conclusion of asthma case study

Case Study: Managing Severe Asthma in an Adult

—he follows his treatment plan, but this 40-year-old male athlete has asthma that is not well-controlled. what’s the next step.

By Kirstin Bass, MD, PhD Reviewed by Michael E. Wechsler, MD, MMSc

This case presents a patient with poorly controlled asthma that remains refractory to treatment despite use of standard-of-care therapeutic options. For patients such as this, one needs to embark on an extensive work-up to confirm the diagnosis, assess for comorbidities, and finally, to consider different therapeutic options.

Case presentation and patient history

Mr. T is a 40-year-old recreational athlete with a medical history significant for asthma, for which he has been using an albuterol rescue inhaler approximately 3 times per week for the past year. During this time, he has also been waking up with asthma symptoms approximately twice a month, and has had three unscheduled asthma visits for mild flares. Based on the National Asthma Education and Prevention Program guidelines , Mr. T has asthma that is not well controlled. 1

As a result of these symptoms, spirometry was performed revealing a forced expiratory volume in the first second (FEV1) of 78% predicted. Mr. T then was prescribed treatment with a low-dose corticosteroid, fluticasone 44 mcg at two puffs twice per day. However, he remained symptomatic and continued to use his rescue inhaler 3 times per week. Therefore, he was switched to a combination inhaled steroid and long-acting beta-agonist (LABA) (fluticasone propionate 250 mcg and salmeterol 50 mcg, one puff twice a day) by his primary care doctor.

Initial pulmonary assessment Even with this step up in his medication, Mr. T continued to be symptomatic and require rescue inhaler use. Therefore, he was referred to a pulmonologist, who performed the initial work-up shown here:

Spirometry, pre-albuterol: FEV1 79%, post-albuterol: 12% improvement
Methacholine challenge: PC 20 : 1.0 mg/mL
Chest X-ray: Within normal limits

Continued pulmonary assessment His dose of inhaled corticosteroid (ICS) and LABA was increased to fluticasone 500 mcg/salmeterol 50 mcg, one puff twice daily. However, he continued to have symptoms and returned to the pulmonologist for further work-up, shown here:

Chest computed tomography (CT): Normal lung parenchyma with no scarring or bronchiectasis
Sinus CT: Mild mucosal thickening
Complete blood count (CBC): Within normal limits, white blood cells (WBC) 10.0 K/mcL, 3% eosinophils
Immunoglobulin E (IgE): 25 IU/mL
Allergy-skin test: Positive for dust, trees
Exhaled NO: Fractional exhaled nitric oxide (FeNO) 53 parts per billion (pbb)

Assessment for comorbidities contributing to asthma symptoms After this work-up, tiotropium was added to his medication regimen. However, he remained symptomatic and had two more flares over the next 3 months. He was assessed for comorbid conditions that might be affecting his symptoms, and results showed:

Esophagram/barium swallow: Negative
Esophageal manometry: Negative
Esophageal impedance: Within normal limits
ECG: Within normal limits
Genetic testing: Negative for cystic fibrosis, alpha1 anti-trypsin deficiency

The ear, nose, and throat specialist to whom he was referred recommended only nasal inhaled steroids for his mild sinus disease and noted that he had a normal vocal cord evaluation.

Following this extensive work-up that transpired over the course of a year, Mr. T continued to have symptoms. He returned to the pulmonologist to discuss further treatment options for his refractory asthma.

Diagnosis Mr. T has refractory asthma. Work-up for this condition should include consideration of other causes for the symptoms, including allergies, gastroesophageal reflux disease, cardiac disease, sinus disease, vocal cord dysfunction, or genetic diseases, such as cystic fibrosis or alpha1 antitrypsin deficiency, as was performed for Mr. T by his pulmonary team.

Treatment options When a patient has refractory asthma, treatment options to consider include anticholinergics (tiotropium, aclidinium), leukotriene modifiers (montelukast, zafirlukast), theophylline, anti-immunoglobulin E (IgE) antibody therapy with omalizumab, antibiotics, bronchial thermoplasty, or enrollment in a clinical trial evaluating the use of agents that modulate the cell signaling and immunologic responses seen in asthma.

Treatment outcome Mr. T underwent bronchial thermoplasty for his asthma. One year after the procedure, he reports feeling great. He has not taken systemic steroids for the past year, and his asthma remains controlled on a moderate dose of ICS and a LABA. He has also been able to resume exercising on a regular basis.

Approximately 10% to 15% of asthma patients have severe asthma refractory to the commonly available medications. 2 One key aspect of care for this patient population is a careful workup to exclude other comorbidities that could be contributing to their symptoms. Following this, there are several treatment options to consider, as in recent years there have been several advances in the development of asthma therapeutics. 2

Treatment options for refractory asthma There are a number of currently approved therapies for severe, refractory asthma. In addition to therapy with ICS or combination therapies with ICS and LABAs, leukotriene antagonists have good efficacy in asthma, especially in patients with prominent allergic or exercise symptoms. 2 The anticholinergics, such as tiotropium, which was approved for asthma in 2015, enhance bronchodilation and are useful adjuncts to ICS. 3-5 Omalizumab is a monoclonal antibody against IgE recommended for use in severe treatment-refractory allergic asthma in patients with atopy. 2 A nonmedication therapeutic option to consider is bronchial thermoplasty, a bronchoscopic procedure that uses thermal energy to disrupt bronchial smooth muscle. 6,7

Personalizing treatment for each patient It is important to personalize treatment based on individual characteristics or phenotypes that predict the patient's likely response to treatment, as well as the patient's preferences and practical issues, such as adherence and cost. 8

In this case, tiotropium had already been added to Mr. T's medications and his symptoms continued. Although addition of a leukotriene modifier was an option for him, he did not wish to add another medication to his care regimen. Omalizumab was not added partly for this reason, and also because of his low IgE level. As his bronchoscopy was negative, it was determined that a course of antibiotics would not be an effective treatment option for this patient. While vitamin D insufficiency has been associated with adverse outcomes in asthma, T's vitamin D level was tested and found to be sufficient.

We discussed the possibility of Mr. T's enrollment in a clinical trial. However, because this did not guarantee placement within a treatment arm and thus there was the possibility of receiving placebo, he opted to undergo bronchial thermoplasty.

Bronchial thermoplasty Bronchial thermoplasty is effective for many patients with severe persistent asthma, such as Mr. T. This procedure may provide additional benefits to, but does not replace, standard asthma medications. During the procedure, thermal energy is delivered to the airways via a bronchoscope to reduce excess airway smooth muscle and limit its ability to constrict the airways. It is an outpatient procedure performed over three sessions by a trained physician. 9

The effects of bronchial thermoplasty have been studied in several trials. The first large-scale multicenter randomized controlled study was the Asthma Intervention Research (AIR) Trial , which enrolled patients with moderate to severe asthma. 10 In this trial, patients who underwent the procedure had a significant improvement in asthma symptoms as measured by symptom-free days and scores on asthma control and quality of life questionnaires, as well as reductions in mild exacerbations and increases in morning peak expiratory flow. 10 Shortly after the AIR trial, the Research in Severe Asthma (RISA) trial was conducted to evaluate bronchial thermoplasty in patients with more severe, symptomatic asthma. 11 In this population, bronchial thermoplasty resulted in a transient worsening of asthma symptoms, with a higher rate of hospitalizations during the treatment period. 11 Hospitalization rate equalized between the treatment and control groups in the posttreatment period, however, and the treatment group showed significant improvements in rescue medication use, prebronchodilator forced expiratory volume in the first second (FEV1) % predicted, and asthma control questionnaire scores. 11

The AIR-2 trial followed, which was a multicenter, randomized, double-blind, sham-controlled study of 288 patients with severe asthma. 6 Similar to the RISA trial, patients in the treatment arm of this trial experienced an increase in adverse respiratory effects during the treatment period, the most common being airway irritation (including wheezing, chest discomfort, cough, and chest pain) and upper respiratory tract infections. 6

The majority of adverse effects occurred within 1 day of the procedure and resolved within 7 days. 6 In this study, bronchial thermoplasty was found to significantly improve quality of life, as well as reduce the rate of severe exacerbations by 32%. 6 Patients who underwent the procedure also reported fewer adverse respiratory effects, fewer days lost from work, school, or other activities due to asthma, and an 84% risk reduction in emergency department visits. 6

Long-term (5-year) follow-up studies have been conducted for patients in both the AIR and the AIR-2 trials. In patients who underwent bronchial thermoplasty in either study, the rate of adverse respiratory effects remained stable in years 2 to 5 following the procedure, with no increase in hospitalizations or emergency department visits. 7,12 Additionally, FEV1 remained stable throughout the 5-year follow-up period. 7,12 This finding was maintained in patients enrolled in the AIR-2 trial despite decreased use of daily ICS. 7

Bronchial thermoplasty is an important addition to the asthma treatment armamentarium. 7 This treatment is currently approved for individuals with severe persistent asthma who remain uncontrolled despite the use of an ICS and LABA. Several clinical trials with long-term follow-up have now demonstrated its safety and ability to improve quality of life in patients with severe asthma, such as Mr. T.

Severe asthma can be a challenge to manage. Patients with this condition require an extensive workup, but there are several treatments currently available to help manage these patients, and new treatments are continuing to emerge. Managing severe asthma thus requires knowledge of the options available as well as consideration of a patient's personal situation-both in terms of disease phenotype and individual preference. In this case, the patient expressed a strong desire to not add any additional medications to his asthma regimen, which explained the rationale for choosing to treat with bronchial thermoplasty. Personalized treatment necessitates exploring which of the available or emerging options is best for each individual patient.

Published: April 16, 2018

1. National Asthma Education and Prevention Program: Asthma Care Quick Reference.
2. Olin JT, Wechsler ME. Asthma: pathogenesis and novel drugs for treatment. BMJ . 2014;349:g5517.
3. Boehringer Ingelheim. Asthma: U.S. FDA approves new indication for SPIRIVA Respimat [press release]. September 16, 2015.
4. Peters SP, Kunselman SJ, Icitovic N, et al. Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N Engl J Med . 2010;363:1715-1726.
5. Kerstjens HA, Engel M, Dahl R. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med . 2012;367:1198-1207.
6. Castro M, Rubin AS, Laviolette M, et al. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med . 2010;181:116-124.
7. Wechsler ME, Laviolette M, Rubin AS, et al. Bronchial thermoplasty: long-term safety and effectiveness in patients with severe persistent asthma. J Allergy Clin Immunol . 2013;132:1295-1302.
8. Global Initiative for Asthma: Pocket Guide for Asthma Management and Prevention (for Adults and Children Older than 5 Years).
10. Cox G, Thomson NC, Rubin AS, et al. Asthma control during the year after bronchial thermoplasty. N Engl J Med . 2007;356:1327-1337.
11. Pavord ID, Cox G, Thomson NC, et al. Safety and efficacy of bronchial thermoplasty in symptomatic, severe asthma. Am J Respir Crit Care Med . 2007;176:1185-1191.
12. Thomson NC, Rubin AS, Niven RM, et al. Long-term (5 year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial. BMC Pulm Med . 2011;11:8.

A woman with asthma: a whole systems approach to supporting self-management

Hilary Pinnock 1 ,
Elisabeth Ehrlich 1 ,
Gaylor Hoskins 2 &
Ron Tomlins 3

npj Primary Care Respiratory Medicine volume 24 , Article number: 14063 ( 2014 ) Cite this article

16k Accesses

2 Citations

6 Altmetric

Metrics details

Health care

A 35-year-old lady attends for review of her asthma following an acute exacerbation. There is an extensive evidence base for supported self-management for people living with asthma, and international and national guidelines emphasise the importance of providing a written asthma action plan. Effective implementation of this recommendation for the lady in this case study is considered from the perspective of a patient, healthcare professional, and the organisation. The patient emphasises the importance of developing a partnership based on honesty and trust, the need for adherence to monitoring and regular treatment, and involvement of family support. The professional considers the provision of asthma self-management in the context of a structured review, with a focus on a self-management discussion which elicits the patient’s goals and preferences. The organisation has a crucial role in promoting, enabling and providing resources to support professionals to provide self-management. The patient’s asthma control was assessed and management optimised in two structured reviews. Her goal was to avoid disruption to her work and her personalised action plan focused on achieving that goal.

Barriers to implementing asthma self-management in Malaysian primary care: qualitative study exploring the perspectives of healthcare professionals

The self-management abilities test (SMAT): a tool to identify the self-management abilities of adults with bronchiectasis

Improving primary care management of asthma: do we know what really works?

A 35-year-old sales representative attends the practice for an asthma review. Her medical record notes that she has had asthma since childhood, and although for many months of the year her asthma is well controlled (when she often reduces or stops her inhaled steroids), she experiences one or two exacerbations a year requiring oral steroids. These are usually triggered by a viral upper respiratory infection, though last summer when the pollen count was particularly high she became tight chested and wheezy for a couple of weeks.

Her regular prescription is for fluticasone 100 mcg twice a day, and salbutamol as required. She has a young family and a busy lifestyle so does not often manage to find time to attend the asthma clinic. A few weeks previously, an asthma attack had interfered with some important work-related travel, and she has attended the clinic on this occasion to ask about how this can be managed better in the future. There is no record of her having been given an asthma action plan.

What do we know about asthma self-management? The academic perspective

Supported self-management reduces asthma morbidity.

The lady in this case study is struggling to maintain control of her asthma within the context of her busy professional and domestic life. The recent unfortunate experience which triggered this consultation offers a rare opportunity to engage with her and discuss how she can manage her asthma better. It behoves the clinician whom she is seeing (regardless of whether this is in a dedicated asthma clinic or an appointment in a routine general practice surgery) to grasp the opportunity and discuss self-management and provide her with a (written) personalised asthma action plan (PAAP).

The healthcare professional advising the lady is likely to be aware that international and national guidelines emphasise the importance of supporting self-management. 1 – 4 There is an extensive evidence base for asthma self-management: a recent synthesis identified 22 systematic reviews summarising data from 260 randomised controlled trials encompassing a broad range of demographic, clinical and healthcare contexts, which concluded that asthma self-management reduces emergency use of healthcare resources, including emergency department visits, hospital admissions and unscheduled consultations and improves markers of asthma control, including reduced symptoms and days off work, and improves quality of life. 1 , 2 , 5 – 12 Health economic analysis suggests that it is not only clinically effective, but also a cost-effective intervention. 13

Personalised asthma action plans

Key features of effective self-management approaches are:

Self-management education should be reinforced by provision of a (written) PAAP which reminds patients of their regular treatment, how to monitor and recognise that control is deteriorating and the action they should take. 14 – 16 As an adult, our patient can choose whether she wishes to monitor her control with symptoms or by recording peak flows (or a combination of both). 6 , 8 , 9 , 14 Symptom-based monitoring is generally better in children. 15 , 16

Plans should have between two and three action points including emergency doses of reliever medication; increasing low dose (or recommencing) inhaled steroids; or starting a course of oral steroids according to severity of the exacerbation. 14

Personalisation of the action plan is crucial. Focussing specifically on what actions she could take to prevent a repetition of the recent attack is likely to engage her interest. Not all patients will wish to start oral steroids without advice from a healthcare professional, though with her busy lifestyle and travel our patient is likely to be keen to have an emergency supply of prednisolone. Mobile technology has the potential to support self-management, 17 , 18 though a recent systematic review concluded that none of the currently available smart phone ‘apps’ were fit for purpose. 19

Identification and avoidance of her triggers is important. As pollen seems to be a trigger, management of allergic rhinitis needs to be discussed (and included in her action plan): she may benefit from regular use of a nasal steroid spray during the season. 20

Self-management as recommended by guidelines, 1 , 2 focuses narrowly on adherence to medication/monitoring and the early recognition/remediation of exacerbations, summarised in (written) PAAPs. Patients, however, may want to discuss how to reduce the impact of asthma on their life more generally, 21 including non-pharmacological approaches.

Supported self-management

The impact is greater if self-management education is delivered within a comprehensive programme of accessible, proactive asthma care, 22 and needs to be supported by ongoing regular review. 6 With her busy lifestyle, our patient may be reluctant to attend follow-up appointments, and once her asthma is controlled it may be possible to make convenient arrangements for professional review perhaps by telephone, 23 , 24 or e-mail. Flexible access to professional advice (e.g., utilising diverse modes of consultation) is an important component of supporting self-management. 25

The challenge of implementation

Implementation of self-management, however, remains poor in routine clinical practice. A recent Asthma UK web-survey estimated that only 24% of people with asthma in the UK currently have a PAAP, 26 with similar figures from Sweden 27 and Australia. 28 The general practitioner may feel that they do not have time to discuss self-management in a routine surgery appointment, or may not have a supply of paper-based PAAPs readily available. 29 However, as our patient rarely finds time to attend the practice, inviting her to make an appointment for a future clinic is likely to be unsuccessful and the opportunity to provide the help she needs will be missed.

The solution will need a whole systems approach

A systematic meta-review of implementing supported self-management in long-term conditions (including asthma) concluded that effective implementation was multifaceted and multidisciplinary; engaging patients, training and motivating professionals within the context of an organisation which actively supported self-management. 5 This whole systems approach considers that although patient education, professional training and organisational support are all essential components of successful support, they are rarely effective in isolation. 30 A systematic review of interventions that promote provision/use of PAAPs highlighted the importance of organisational systems (e.g., sending blank PAAPs with recall reminders). 31 A patient offers her perspective ( Box 1 ), a healthcare professional considers the clinical challenge, and the challenges are discussed from an organisational perspective.

Box 1: What self-management help should this lady expect from her general practitioner or asthma nurse? The patient’s perspective

The first priority is that the patient is reassured that her condition can be managed successfully both in the short and the long term. A good working relationship with the health professional is essential to achieve this outcome. Developing trust between patient and healthcare professional is more likely to lead to the patient following the PAAP on a long-term basis.

A review of all medication and possible alternative treatments should be discussed. The patient needs to understand why any changes are being made and when she can expect to see improvements in her condition. Be honest, as sometimes it will be necessary to adjust dosages before benefits are experienced. Be positive. ‘There are a number of things we can do to try to reduce the impact of asthma on your daily life’. ‘Preventer treatment can protect against the effect of pollen in the hay fever season’. If possible, the same healthcare professional should see the patient at all follow-up appointments as this builds trust and a feeling of working together to achieve the aim of better self-management.

Is the healthcare professional sure that the patient knows how to take her medication and that it is taken at the same time each day? The patient needs to understand the benefit of such a routine. Medication taken regularly at the same time each day is part of any self-management regime. If the patient is unused to taking medication at the same time each day then keeping a record on paper or with an electronic device could help. Possibly the patient could be encouraged to set up a system of reminders by text or smartphone.

Some people find having a peak flow meter useful. Knowing one's usual reading means that any fall can act as an early warning to put the PAAP into action. Patients need to be proactive here and take responsibility.

Ongoing support is essential for this patient to ensure that she takes her medication appropriately. Someone needs to be available to answer questions and provide encouragement. This could be a doctor or a nurse or a pharmacist. Again, this is an example of the partnership needed to achieve good asthma control.

It would also be useful at a future appointment to discuss the patient’s lifestyle and work with her to reduce her stress. Feeling better would allow her to take simple steps such as taking exercise. It would also be helpful if all members of her family understood how to help her. Even young children can do this.

From personal experience some people know how beneficial it is to feel they are in a partnership with their local practice and pharmacy. Being proactive produces dividends in asthma control.

What are the clinical challenges for the healthcare professional in providing self-management support?

Due to the variable nature of asthma, a long-standing history may mean that the frequency and severity of symptoms, as well as what triggers them, may have changed over time. 32 Exacerbations requiring oral steroids, interrupting periods of ‘stability’, indicate the need for re-assessment of the patient’s clinical as well as educational needs. The patient’s perception of stability may be at odds with the clinical definition 1 , 33 —a check on the number of short-acting bronchodilator inhalers the patient has used over a specific period of time is a good indication of control. 34 Assessment of asthma control should be carried out using objective tools such as the Asthma Control Test or the Royal College of Physicians three questions. 35 , 36 However, it is important to remember that these assessment tools are not an end in themselves but should be a springboard for further discussion on the nature and pattern of symptoms. Balancing work with family can often make it difficult to find the time to attend a review of asthma particularly when the patient feels well. The practice should consider utilising other means of communication to maintain contact with patients, encouraging them to come in when a problem is highlighted. 37 , 38 Asthma guidelines advocate a structured approach to ensure the patient is reviewed regularly and recommend a detailed assessment to enable development of an appropriate patient-centred (self)management strategy. 1 – 4

Although self-management plans have been shown to be successful for reducing the impact of asthma, 21 , 39 the complexity of managing such a fluctuating disease on a day-to-day basis is challenging. During an asthma review, there is an opportunity to work with the patient to try to identify what triggers their symptoms and any actions that may help improve or maintain control. 38 An integral part of personalised self-management education is the written PAAP, which gives the patient the knowledge to respond to the changes in symptoms and ensures they maintain control of their asthma within predetermined parameters. 9 , 40 The PAAP should include details on how to monitor asthma, recognise symptoms, how to alter medication and what to do if the symptoms do not improve. The plan should include details on the treatment to be taken when asthma is well controlled, and how to adjust it when the symptoms are mild, moderate or severe. These action plans need to be developed between the doctor, nurse or asthma educator and the patient during the review and should be frequently reviewed and updated in partnership (see Box 1). Patient preference as well as clinical features such as whether she under- or over-perceives her symptoms should be taken into account when deciding whether the action plan is peak flow or symptom-driven. Our patient has a lot to gain from having an action plan. She has poorly controlled asthma and her lifestyle means that she will probably see different doctors (depending who is available) when she needs help. Being empowered to self-manage could make a big difference to her asthma control and the impact it has on her life.

The practice should have protocols in place, underpinned by specific training to support asthma self-management. As well as ensuring that healthcare professionals have appropriate skills, this should include training for reception staff so that they know what action to take if a patient telephones to say they are having an asthma attack.

However, focusing solely on symptom management strategies (actions) to follow in the presence of deteriorating symptoms fails to incorporate the patients’ wider views of asthma, its management within the context of her/his life, and their personal asthma management strategies. 41 This may result in a failure to use plans to maximise their health potential. 21 , 42 A self-management strategy leading to improved outcomes requires a high level of patient self-efficacy, 43 a meaningful partnership between the patient and the supporting health professional, 42 , 44 and a focused self-management discussion. 14

Central to both the effectiveness and personalisation of action plans, 43 , 45 in particular the likelihood that the plan will lead to changes in patients’ day-to-day self-management behaviours, 45 is the identification of goals. Goals are more likely to be achieved when they are specific, important to patients, collaboratively set and there is a belief that these can be achieved. Success depends on motivation 44 , 46 to engage in a specific behaviour to achieve a valued outcome (goal) and the ability to translate the behavioural intention into action. 47 Action and coping planning increases the likelihood that patient behaviour will actually change. 44 , 46 , 47 Our patient has a goal: she wants to avoid having her work disrupted by her asthma. Her personalised action plan needs to explicitly focus on achieving that goal.

As providers of self-management support, health professionals must work with patients to identify goals (valued outcomes) that are important to patients, that may be achievable and with which they can engage. The identification of specific, personalised goals and associated feasible behaviours is a prerequisite for the creation of asthma self-management plans. Divergent perceptions of asthma and how to manage it, and a mismatch between what patients want/need from these plans and what is provided by professionals are barriers to success. 41 , 42

What are the challenges for the healthcare organisation in providing self-management support?

A number of studies have demonstrated the challenges for primary care physicians in providing ongoing support for people with asthma. 31 , 48 , 49 In some countries, nurses and other allied health professionals have been trained as asthma educators and monitor people with stable asthma. These resources are not always available. In addition, some primary care services are delivered in constrained systems where only a few minutes are available to the practitioner in a consultation, or where only a limited range of asthma medicines are available or affordable. 50

There is recognition that the delivery of quality care depends on the competence of the doctor (and supporting health professionals), the relationship between the care providers and care recipients, and the quality of the environment in which care is delivered. 51 This includes societal expectations, health literacy and financial drivers.

In 2001, the Australian Government adopted a programme developed by the General Practitioner Asthma Group of the National Asthma Council Australia that provided a structured approach to the implementation of asthma management guidelines in a primary care setting. 52 Patients with moderate-to-severe asthma were eligible to participate. The 3+ visit plan required confirmation of asthma diagnosis, spirometry if appropriate, assessment of trigger factors, consideration of medication and patient self-management education including provision of a written PAAP. These elements, including regular medical review, were delivered over three visits. Evaluation demonstrated that the programme was beneficial but that it was difficult to complete the third visit in the programme. 53 – 55 Accordingly, the programme, renamed the Asthma Cycle of Care, was modified to incorporate two visits. 56 Financial incentives are provided to practices for each patient who receives this service each year.

Concurrently, other programmes were implemented which support practice-based care. Since 2002, the National Asthma Council has provided best-practice asthma and respiratory management education to health professionals, 57 and this programme will be continuing to 2017. The general practitioner and allied health professional trainers travel the country to provide asthma and COPD updates to groups of doctors, nurses and community pharmacists. A number of online modules are also provided. The PACE (Physician Asthma Care Education) programme developed by Noreen Clark has also been adapted to the Australian healthcare system. 58 In addition, a pharmacy-based intervention has been trialled and implemented. 59

To support these programmes, the National Asthma Council ( www.nationalasthma.org.au ) has developed resources for use in practices. A strong emphasis has been on the availability of a range of PAAPs (including plans for using adjustable maintenance dosing with ICS/LABA combination inhalers), plans for indigenous Australians, paediatric plans and plans translated into nine languages. PAAPs embedded in practice computer systems are readily available in consultations, and there are easily accessible online paediatric PAAPs ( http://digitalmedia.sahealth.sa.gov.au/public/asthma/ ). A software package, developed in the UK, can be downloaded and used to generate a pictorial PAAP within the consultation. 60

One of the strongest drivers towards the provision of written asthma action plans in Australia has been the Asthma Friendly Schools programme. 61 , 62 Established with Australian Government funding and the co-operation of Education Departments of each state, the Asthma Friendly Schools programme engages schools to address and satisfy a set of criteria that establishes an asthma-friendly environment. As part of accreditation, the school requires that each child with asthma should have a written PAAP prepared by their doctor to assist (trained) staff in managing a child with asthma at school.

The case study continues...

The initial presentation some weeks ago was during an exacerbation of asthma, which may not be the best time to educate a patient. It is, however, a splendid time to build on their motivation to feel better. She agreed to return after her asthma had settled to look more closely at her asthma control, and an appointment was made for a routine review.

At this follow-up consultation, the patient’s diagnosis was reviewed and confirmed and her trigger factors discussed. For this lady, respiratory tract infections are the usual trigger but allergic factors during times of high pollen count may also be relevant. Assessment of her nasal airway suggested that she would benefit from better control of allergic rhinitis. Other factors were discussed, as many patients are unaware that changes in air temperature, exercise and pets can also trigger asthma exacerbations. In addition, use of the Asthma Control Test was useful as an objective assessment of control as well as helping her realise what her life could be like! Many people with long-term asthma live their life within the constraints of their illness, accepting that is all that they can do.

After assessing the level of asthma control, a discussion about management options—trigger avoidance, exercise and medicines—led to the development of a written PAAP. Asthma can affect the whole family, and ways were explored that could help her family understand why it is important that she finds time in the busy domestic schedules to take her regular medication. Family and friends can also help by understanding what triggers her asthma so that they can avoid exposing her to perfumes, pollens or pets that risk triggering her symptoms. Information from the national patient organisation was provided to reinforce the messages.

The patient agreed to return in a couple of weeks, and a recall reminder was set up. At the second consultation, the level of control since the last visit will be explored including repeat spirometry, if appropriate. Further education about the pathophysiology of asthma and how to recognise early warning signs of loss of control can be given. Device use will be reassessed and the PAAP reviewed. Our patient’s goal is to avoid disruption to her work and her PAAP will focus on achieving that goal. Finally, agreement will be reached with the patient about future routine reviews, which, now that she has a written PAAP, could be scheduled by telephone if all is well, or face-to-face if a change in her clinical condition necessitates a more comprehensive review.

Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2012. Available from: http://www.ginasthma.org (accessed July 2013).

British Thoracic Society/Scottish Intercollegiate Guideline Network British Guideline on the Management of Asthma. Thorax 2008; 63 (Suppl 4 iv1–121, updated version available from: http://www.sign.ac.uk (accessed January 2014).

Article Google Scholar

National Asthma Council Australia. Australian Asthma Handbook. Available from: http://www.nationalasthma.org.au/handbook (accessed May 2014).

National Asthma Education and Prevention Program (NAEPP) Coordinating Committee. Expert Panel Report 3 (EPR3): Guidelines for the Diagnosis and Management of Asthma. Available from: https://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm (accessed May 2014).

Taylor SJC, Pinnock H, Epiphaniou E, Pearce G, Parke H . A rapid synthesis of the evidence on interventions supporting self-management for people with long-term conditions. (PRISMS Practical Systematic Review of Self-Management Support for long-term conditions). Health Serv Deliv Res (in press).

Gibson PG, Powell H, Wilson A, Abramson MJ, Haywood P, Bauman A et al. Self-management education and regular practitioner review for adults with asthma. Cochrane Database Syst Rev 2002: (Issue 3) Art No. CD001117.

Tapp S, Lasserson TJ, Rowe BH . Education interventions for adults who attend the emergency room for acute asthma. Cochrane Database Syst Rev 2007: (Issue 3) Art No. CD003000.

Powell H, Gibson PG . Options for self-management education for adults with asthma. Cochrane Database Syst Rev 2002: (Issue 3) Art No: CD004107.

Toelle B, Ram FSF . Written individualised management plans for asthma in children and adults. Cochrane Database Syst Rev 2004: (Issue 1) Art No. CD002171.

Lefevre F, Piper M, Weiss K, Mark D, Clark N, Aronson N . Do written action plans improve patient outcomes in asthma? An evidence-based analysis. J Fam Pract 2002; 51 : 842–848.

PubMed Google Scholar

Boyd M, Lasserson TJ, McKean MC, Gibson PG, Ducharme FM, Haby M . Interventions for educating children who are at risk of asthma-related emergency department attendance. Cochrane Database Syst Rev 2009: (Issue 2) Art No.CD001290.

Bravata DM, Gienger AL, Holty JE, Sundaram V, Khazeni N, Wise PH et al. Quality improvement strategies for children with asthma: a systematic review. Arch Pediatr Adolesc Med 2009; 163 : 572–581.

Bower P, Murray E, Kennedy A, Newman S, Richardson G, Rogers A . Self-management support interventions to reduce health care utilisation without compromising outcomes: a rapid synthesis of the evidence. Available from: http://www.nets.nihr.ac.uk/projects/hsdr/11101406 (accessed April 2014).

Gibson PG, Powell H . Written action plans for asthma: an evidence-based review of the key components. Thorax 2004; 59 : 94–99.

Article CAS Google Scholar

Bhogal SK, Zemek RL, Ducharme F . Written action plans for asthma in children. Cochrane Database Syst Rev 2006: (Issue 3) Art No. CD005306.

Zemek RL, Bhogal SK, Ducharme FM . Systematic review of randomized controlled trials examining written action plans in children: what is the plan?. Arch Pediatr Adolesc Med 2008; 162 : 157–163.

Pinnock H, Slack R, Pagliari C, Price D, Sheikh A . Understanding the potential role of mobile phone based monitoring on asthma self-management: qualitative study. Clin Exp Allergy 2007; 37 : 794–802.

de Jongh T, Gurol-Urganci I, Vodopivec-Jamsek V, Car J, Atun R . Mobile phone messaging for facilitating self-management of long-term illnesses. Cochrane Database Syst Rev 2012: (Issue 12) Art No. CD007459.

Huckvale K, Car M, Morrison C, Car J . Apps for asthma self-management: a systematic assessment of content and tools. BMC Med 2012; 10 : 144.

Allergic Rhinitis and its Impact on Asthma. Management of Allergic Rhinitis and its Impact on Asthma: Pocket Guide. ARIA 2008. Available from: http://www.whiar.org (accessed May 2014).

Ring N, Jepson R, Hoskins G, Wilson C, Pinnock H, Sheikh A et al. Understanding what helps or hinders asthma action plan use: a systematic review and synthesis of the qualitative literature. Patient Educ Couns 2011; 85 : e131–e143.

Moullec G, Gour-Provencal G, Bacon SL, Campbell TS, Lavoie KL . Efficacy of interventions to improve adherence to inhaled corticosteroids in adult asthmatics: Impact of using components of the chronic care model. Respir Med 2012; 106 : 1211–1225.

Pinnock H, Bawden R, Proctor S, Wolfe S, Scullion J, Price D et al. Accessibility, acceptability and effectiveness of telephone reviews for asthma in primary care: randomised controlled trial. BMJ 2003; 326 : 477–479.

Pinnock H, Adlem L, Gaskin S, Harris J, Snellgrove C, Sheikh A . Accessibility, clinical effectiveness and practice costs of providing a telephone option for routine asthma reviews: phase IV controlled implementation study. Br J Gen Pract 2007; 57 : 714–722.

PubMed PubMed Central Google Scholar

Kielmann T, Huby G, Powell A, Sheikh A, Price D, Williams S et al. From support to boundary: a qualitative study of the border between self care and professional care. Patient Educ Couns 2010; 79 : 55–61.

Asthma UK . Compare your care report. Asthma UK, 2013. Available from: http://www.asthma.org.uk (accessed January 2014).

Stallberg B, Lisspers K, Hasselgren M, Janson C, Johansson G, Svardsudd K . Asthma control in primary care in Sweden: a comparison between 2001 and 2005. Prim Care Respir J 2009; 18 : 279–286.

Reddel H, Peters M, Everett P, Flood P, Sawyer S . Ownership of written asthma action plans in a large Australian survey. Eur Respir J 2013; 42 . Abstract 2011.

Wiener-Ogilvie S, Pinnock H, Huby G, Sheikh A, Partridge MR, Gillies J . Do practices comply with key recommendations of the British Asthma Guideline? If not, why not? Prim Care Respir J 2007; 16 : 369–377.

Kennedy A, Rogers A, Bower P . Support for self care for patients with chronic disease. BMJ 2007; 335 : 968–970.

Ring N, Malcolm C, Wyke S, Macgillivray S, Dixon D, Hoskins G et al. Promoting the Use of Personal Asthma Action Plans: A Systematic Review. Prim Care Respir J 2007; 16 : 271–283.

Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, Casale TB et al. A new perspective on concepts of asthma severity and control. Eur Respir J 2008; 32 : 545–554.

Horne R . Compliance, adherence, and concordance: implications for asthma treatment. Chest 2006; 130 (suppl): 65S–72S.

Reddel HK, Taylor DR, Bateman ED, Boulet L-P, Boushey HA, Busse WW et al. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med 2009; 180 : 59–99.

Thomas M, Kay S, Pike J, Rosenzweig JR, Hillyer EV, Price D . The Asthma Control Test (ACT) as a predictor of GINA guideline-defined asthma control: analysis of a multinational cross-sectional survey. Prim Care Respir J 2009; 18 : 41–49.

Hoskins G, Williams B, Jackson C, Norman P, Donnan P . Assessing asthma control in UK primary care: use of routinely collected prospective observational consultation data to determine appropriateness of a variety of control assessment models. BMC Fam Pract 2011; 12 : 105.

Pinnock H, Fletcher M, Holmes S, Keeley D, Leyshon J, Price D et al. Setting the standard for routine asthma consultations: a discussion of the aims, process and outcomes of reviewing people with asthma in primary care. Prim Care Respir J 2010; 19 : 75–83.

McKinstry B, Hammersley V, Burton C, Pinnock H, Elton RA, Dowell J et al. The quality, safety and content of telephone and face-to-face consultations: a comparative study. Qual Saf Health Care 2010; 19 : 298–303.

Gordon C, Galloway T . Review of Findings on Chronic Disease Self-Management Program (CDSMP) Outcomes: Physical, Emotional & Health-Related Quality of Life, Healthcare Utilization and Costs . Centers for Disease Control and Prevention and National Council on Aging: Atlanta, GA, USA, 2008.

Beasley R, Crane J . Reducing asthma mortality with the self-management plan system of care. Am J Respir Crit Care Med 2001; 163 : 3–4.

Ring N, Jepson R, Pinnock H, Wilson C, Hoskins G, Sheikh A et al. Encouraging the promotion and use of asthma action plans: a cross study synthesis of qualitative and quantitative evidence. Trials 2012; 13 : 21.

Jones A, Pill R, Adams S . Qualitative study of views of health professionals and patients on guided self-management plans for asthma. BMJ 2000; 321 : 1507–1510.

Bandura A . Self-efficacy: toward a unifying theory of behavioural change. Psychol Rev 1977; 84 : 191–215.

Gollwitzer PM, Sheeran P . Implementation intentions and goal achievement: a meta-analysis of effects and processes. Adv Exp Soc Psychol 2006; 38 : 69–119.

Google Scholar

Hardeman W, Johnston M, Johnston DW, Bonetti D, Wareham NJ, Kinmonth AL . Application of the theory of planned behaviour change interventions: a systematic review. Psychol Health 2002; 17 : 123–158.

Schwarzer R . Modeling health behavior change: how to predict and modify the adoption and maintenance of health behaviors. Appl Psychol 2008; 57 : 1–29.

Sniehotta F . Towards a theory of intentional behaviour change: plans, planning, and self-regulation. Br J Health Psychol 2009; 14 : 261–273.

Okelo SO, Butz AM, Sharma R, Diette GB, Pitts SI, King TM et al. Interventions to modify health care provider adherence to asthma guidelines: a systematic review. Pediatrics 2013; 132 : 517–534.

Grol R, Grimshaw RJ . From best evidence to best practice: effective implementation of change in patients care. Lancet 2003; 362 : 1225–1230.

Jusef L, Hsieh C-T, Abad L, Chaiyote W, Chin WS, Choi Y-J et al. Primary care challenges in treating paediatric asthma in the Asia-Pacific region. Prim Care Respir J 2013; 22 : 360–362.

Donabedian A . Evaluating the quality of medical care. Milbank Q 2005; 83 : 691–729.

Fardy HJ . Moving towards organized care of chronic disease. The 3+ visit plan. Aust Fam Physician 2001; 30 : 121–125.

CAS PubMed Google Scholar

Glasgow NJ, Ponsonby AL, Yates R, Beilby J, Dugdale P . Proactive asthma care in childhood: general practice based randomised controlled trial. BMJ 2003; 327 : 659.

Douglass JA, Goemann DP, Abramson MJ . Asthma 3+ visit plan: a qualitative evaluation. Intern Med J 2005; 35 : 457–462.

Beilby J, Holton C . Chronic disease management in Australia; evidence and policy mismatch, with asthma as an example. Chronic Illn 2005; 1 : 73–80.

The Department of Health. Asthma Cycle of Care. Accessed on 14 May 2014 at http://www.health.gov.au/internet/main/publishing.nsf/Content/asthma-cycle .

National Asthma Council Australia. Asthma and Respiratory Education Program. Accessed on 14 May 2014 at http://www.nationalasthma.org.au/health-professionals/education-training/asthma-respiratory-education-program .

Patel MR, Shah S, Cabana MD, Sawyer SM, Toelle B, Mellis C et al. Translation of an evidence-based asthma intervention: Physician Asthma Care Education (PACE) in the United States and Australia. Prim Care Respir J 2013; 22 : 29–34.

Armour C, Bosnic-Anticevich S, Brilliant M, Burton D, Emmerton L, Krass I et al. Pharmacy Asthma Care Program (PACP) improves outcomes for patients in the community. Thorax 2007; 62 : 496–502.

Roberts NJ, Mohamed Z, Wong PS, Johnson M, Loh LC, Partridge MR . The development and comprehensibility of a pictorial asthma action plan. Patient Educ Couns 2009; 74 : 12–18.

Henry RL, Gibson PG, Vimpani GV, Francis JL, Hazell J . Randomised controlled trial of a teacher-led asthma education program. Pediatr Pulmonol 2004; 38 : 434–442.

National Asthma Council Australia. Asthma Friendly Schools program. Accessed on 14 May 2014 at http://www.asthmaaustralia.org.au/Asthma-Friendly-Schools.aspx .

Download references

Author information

Authors and affiliations.

Asthma UK Centre for Applied Research, Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK,

Hilary Pinnock & Elisabeth Ehrlich

NMAHP-RU, University of Stirling, Stirling, UK,

Gaylor Hoskins

Discipline of General Practice, University of Sydney, Sydney, NSW, Australia

Ron Tomlins

You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hilary Pinnock .

Ethics declarations

Competing interests.

The authors declare no conflict of interest.

Rights and permissions

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

Reprints and permissions

About this article

Cite this article.

Pinnock, H., Ehrlich, E., Hoskins, G. et al. A woman with asthma: a whole systems approach to supporting self-management. npj Prim Care Resp Med 24 , 14063 (2014). https://doi.org/10.1038/npjpcrm.2014.63

Download citation

Received : 23 June 2014

Revised : 15 July 2014

Accepted : 15 July 2014

Published : 16 October 2014

DOI : https://doi.org/10.1038/npjpcrm.2014.63

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Quick links

Explore articles by subject
Guide to authors
Editorial policies

Case report
Open access
Published: 21 February 2018

Pediatric severe asthma: a case series report and perspectives on anti-IgE treatment

Virginia Mirra 1 ,
Silvia Montella 1 &
Francesca Santamaria 1

BMC Pediatrics volume 18 , Article number: 73 ( 2018 ) Cite this article

11k Accesses

11 Citations

12 Altmetric

Metrics details

The primary goal of asthma management is to achieve disease control for reducing the risk of future exacerbations and progressive loss of lung function. Asthma not responding to treatment may result in significant morbidity. In many children with uncontrolled symptoms, the diagnosis of asthma may be wrong or adherence to treatment may be poor. It is then crucial to distinguish these cases from the truly “severe therapy-resistant” asthmatics by a proper filtering process. Herein we report on four cases diagnosed as difficult asthma, detail the workup that resulted in the ultimate diagnosis, and provide the process that led to the prescription of omalizumab.

Case presentation

All children had been initially referred because of asthma not responding to long-term treatment with high-dose inhaled steroids, long-acting β 2 -agonists and leukotriene receptor antagonists. Definitive diagnosis was severe asthma. Three out four patients were treated with omalizumab, which improved asthma control and patients’ quality of life. We reviewed the current literature on the diagnostic approach to the disease and on the comorbidities associated with difficult asthma and presented the perspectives on omalizumab treatment in children and adolescents. Based on the evidence from the literature review, we also proposed an algorithm for the diagnosis of pediatric difficult-to-treat and severe asthma.

Conclusions

The management of asthma is becoming much more patient-specific, as more and more is learned about the biology behind the development and progression of asthma. The addition of omalizumab, the first targeted biological treatment approved for asthma, has led to renewed optimism in the management of children and adolescents with atopic severe asthma.

Peer Review reports

Children with poor asthma control have an increased risk of severe exacerbations and progressive loss of lung function, which results in the relevant use of health resources and impaired quality of life (QoL) [ 1 ]. Therefore, the primary goal of asthma management at all ages is to achieve disease control [ 2 , 3 , 4 ].

According to recent international guidelines, patients with uncontrolled asthma require a prolonged maintenance treatment with high-dose inhaled corticosteroids (ICS) in association with a long-acting β 2 -agonist (LABA) plus oral leukotriene receptor antagonist (LTRA) (Table 1 ) [ 5 ].

Nevertheless, in the presence of persistent lack of control, reversible factors such as adherence to treatment or inhalation technique should be first checked for, and diseases that can masquerade as asthma should be promptly excluded. Finally, additional strategies, in particular anti-immunoglobulin E (anti-IgE) treatment (omalizumab), are suggested for patients with moderate or severe allergic asthma that remains uncontrolled in Step 4 [ 5 ].

Herein, we reviewed the demographics, clinical presentation and treatment of four patients with uncontrolled severe asthma from our institution in order to explain why we decided to prescribe omalizumab. We also provided a review of the current literature that focuses on recent advances in the diagnosis of pediatric difficult asthma and the associated comorbidities, and summarizes the perspectives on anti-IgE treatment in children and adolescents.

Case presentations

Table 2 summarizes the clinical characteristics and the triggers/comorbidities of the cases at referral to our Institution. Unfortunately, data on psychological factors, sleep apnea, and hyperventilation syndrome were not available in any case. Clinical, lung function and airway inflammation findings at baseline and after 12 months of follow-up are reported in Table 3 . In the description of our cases, we used the terminology recommended by the ERS/ATS guidelines on severe asthma [ 6 ].

A full-term male had severe preschool wheezing and, since age 3, recurrent, severe asthma exacerbations with frequent hospital admissions. At age 11, severe asthma was diagnosed. Sensitization to multiple inhalant allergens (i.e., house dust mites, dog dander, Graminaceae pollen mix, and Parietaria judaica ) and high serum IgE levels (1548 KU/l) were found. Body mass index (BMI) was within normal range. Combined treatment with increasing doses of ICS (fluticasone, up to 1000 μg/day) in association with LABA (salmeterol, 100 μg/day) plus LTRA (montelukast, 5 mg/day) has been administered over 2 years. Nevertheless, persistent symptoms and monthly hospital admissions due to asthma exacerbations despite correct inhaler technique and good adherence were reported. Parents refused to perform any test to exclude gastroesophageal reflux (GER) as comorbidity [ 6 ]. However, an ex-juvantibus 2-month-course with omeprazole was added to asthma treatment [ 7 ], but poor control persisted. Anterior rhinoscopy revealed rhinosinusitis that was treated with nasal steroids for six months [ 8 ], but asthma symptoms were unmodified. Treatment with omalizumab was added at age 12. Reduced hospital admissions for asthma exacerbations, no further need for systemic steroids, and improved QoL score (from 2.0 up to 6.7 out of a maximum of 7 points) were documented over the following months. Unfortunately, after one year of treatment, adherence to omalizumab decreased because of family complaints, and eventually parents withdrew their informed consent and discontinued omalizumab. Currently, by age 17, treatment includes inhaled salmeterol/fluticasone (100 μg/500 μg∙day -1 , respectively) plus oral montelukast (10 mg/day). Satisfactory symptom control is reported, with no asthma exacerbations.

A full-term male, who had a recurrent severe preschool wheezing, at 6 years of age developed exercise-induced asthma. At age 10, severe asthma was diagnosed. High serum IgE levels (1300 KU/l) and skin prick tests positive to house dust mites were found. Despite a 3-year treatment with progressively increasing doses of inhaled fluticasone (up to 1000 μg/day) combined with salmeterol (100 μg/day) and oral montelukast (5 mg/day), monthly hospital admissions with systemic steroids use were reported. At age 13, a 24-h esophageal impedance/pH study demonstrated the presence of acid and non-acid GER [ 7 ]. Esomeprazole was added to asthma medications, but with an incomplete clinical benefit for respiratory symptoms. Esomeprazole was withdrawn after 3 months, and parents refused to re-test for GER. As respiratory symptoms persisted uncontrolled despite treatment, severe asthma was definitively diagnosed [ 6 ]. BMI was within the normal range and anterior rhinoscopy excluded rhinosinusitis. Inhaler technique and adherence were good; thus we considered the anti-IgE treatment option [ 9 ]. Subcutaneous omalizumab was started, with fast improvement of both symptoms and QoL score (from 3.9 up to 6.5). Seventeen months later, the dose of ICS had been gradually tapered and oral montelukast definitely discontinued. Currently, at age 14, treatment includes the combined administration of bimonthly subcutaneous omalizumab and of daily inhaled salmeterol/fluticasone (50 μg/100 μg∙day - 1 , respectively). Asthma control is satisfactory and no side effects are reported. Omalizumab has been continuously administered for 2.6 years and is still ongoing.

A full-term male had severe preschool wheezing and, since age 3, recurrent, severe asthma exacerbations with acute respiratory failure that frequently required intensive care unit (ICU) admission. At age 6, sensitization to multiple perennial inhalant (i.e., house dust mites, dog and cat danders, Alternaria alternata , Graminaceae pollen mix, Artemisia vulgaris , Parietaria judaica , and Olea europaea pollen) and food allergens (i.e., egg, milk, and peanut) was diagnosed. Serum IgE levels were 2219 KU/l. Weight and height were appropriate for age and sex. The patient has been treated over 3 years with a combined scheme of high-dose inhaled fluticasone (up to 1000 μg/day) plus salmeterol (100 μg/day) and oral montelukast (5 mg/day), with correct inhaler technique and good adherence. Despite this, monthly hospital admissions with systemic steroids use were recorded. Rhinosinusitis and GER were excluded on the basis of appropriate testing; thus treatment with omalizumab was started when the patient was 9 years old. At age 11, adherence to treatment is satisfactory, with no side effects. More importantly, reduced hospital admissions for asthma exacerbations, no further need for systemic steroids, and improved QoL score (from 6.4 to 6.8) were reported. Finally, progressive step-down of anti-asthma treatment was started, and at present (by 11.5 years) inhaled fluticasone (200 μg/day) plus bimonthly subcutaneous omalizumab provide good control of symptoms. Omalizumab has been continuously administered for 2.6 years and is still ongoing.

A full-term male had severe preschool wheezing and, since age 4, recurrent, severe asthma exacerbations with frequent hospital admissions. At age 8, multiple perennial inhalants and food sensitization (i.e., house dust mites, dog dander, Graminaceae pollen mix, Olea europaea pollen, tomatoes, beans, shrimps, and peas) and high serum IgE levels (1166 KU/l) were found. The patient has been treated over 5 years with inhaled fluticasone (up to 1000 μg/day) in association with salmeterol (100 μg/day) and oral montelukast (5 mg/day). Despite this, monthly hospital admissions with systemic steroids need were recorded. After checking the inhaler technique and adherence to treatment, comorbidities including obesity, rhinosinusitis and GER were excluded. Omalizumab was proposed, but parents refused it. By 13.6 years, despite a treatment including the association of inhaled salmeterol/fluticasone (100 μg/1000 μg∙day − 1 , respectively) plus oral montelukast (10 mg/day), monthly exacerbations requiring systemic steroids are reported.

Discussion and conclusions

Most children and adolescents with asthma respond well to inhaled short-acting beta 2 -agonists (SABA) on demand if symptoms are intermittent, or to low dose controller drugs plus as-needed SABA if the risk of exacerbations increases [ 1 ]. Nevertheless, a proportion of patients is referred to specialists because this strategy is not working and asthma is persistently uncontrolled [ 4 ]. For these children, assessment is primarily aimed at investigating the reasons for poor control. Indeed, when the child is initially referred, before the label of “severe, therapy-resistant asthma” (i.e., not responding to treatment even when factors as exposure to allergens and tobacco smoke have been considered) is assigned, three main categories need to be identified: 1) “not asthma at all”, in which response to treatment is suboptimal because the diagnosis is wrong; 2) “asthma plus ”, when asthma is mild but exacerbated by one or more comorbidities; and 3) “difficult-to-treat asthma”, when asthma is uncontrolled because of potentially reversible factors [ 10 ].

The reported cases highlight some aspects of the disease process that may expand the diagnosis and improve patients’ care. At our institution, the severe asthma program includes a multidisciplinary approach with consultations by gastroenterologists as well as ear, nose and throat experts. Recently, sleep medicine experts joined this multidisciplinary team; thus, unfortunately, sleep-disordered breathing (SDB) could not be excluded at the time of our patients’ assessment. Inhalation technique is periodically evaluated by nurses or doctors in each patient. Unfortunately, in Italy an individual prescription database is not available and thus we cannot assess patients’ use of medication. In two cases, the filtering process eventually identified GER and rhinosinusitis, but poor control of asthma persisted even after comorbidities were treated. In all subjects, inhaler skills, treatment adherence, and environmental exposure to indoor/outdoor allergens as well as to second- and third-hand smoke were excluded as cause of lack of control. Eventually, three out of four patients started anti-IgE treatment; asthma control was obtained and maintenance drugs were progressively reduced. In the case that refused omalizumab therapy, pulmonary function, clinical features and controller treatment including high-dose ICS were unchanged.

Previous studies have highlighted an association between increasing asthma severity in children and reduced QoL [ 11 , 12 , 13 ]. Uncontrolled asthma symptoms not only affect children physically, but can impair them socially, emotionally, and educationally [ 13 ]. In line with previous observations, 3 out 4 of our cases had poor QoL, assessed by a standardized questionnaire [ 14 ]. It is well known that improving QoL in difficult asthma is not an easy task, despite a variety of treatments aimed at achieving control [ 12 ], and much more remains to be done to address the problem. Nevertheless, 2 of our 3 cases showed a remarkable improvement of QoL after one year of treatment with omalizumab.

Reduction in forced expiratory volume in the first second (FEV 1 ) is often used to define childhood asthma severity in treatment guidelines and clinical studies [ 5 , 11 , 15 ]. Nevertheless, children with severe asthma often have a normal FEV 1 that does not improve after bronchodilators, indicating that spirometry may be a poor predictor of asthma severity in childhood [ 6 , 16 , 17 ]. Actually, children with a normal FEV 1 , both before and after β 2 -agonist, may show a bronchodilator response in terms of forced expiratory flow between 25% and 75% (FEF 25–75 ) [ 18 ]. However, the utility of FEF 25–75 in the assessment or treatment of severe asthma is currently unknown. Interestingly, all the reported cases showed normal or slightly reduced values of FEV 1 but severe impairment of FEF 25–75 . Two cases showed a bronchodilator response in terms of FEV 1 (subjects 3 and 4), while 3 patients had a significant increase of FEF 25–75 (cases 1, 3 and 4). Unfortunately, we could not provide the results of bronchodilator response during or after the treatment with omalizumab in any case.

Available literature on the diagnostic approach to difficult asthma in children offers a number of reviews which basically summarize the steps needed to fill the gap between a generic diagnosis of “difficult asthma” and more specific labels (i.e., “severe” asthma, “difficult-to-treat” asthma, or even different diagnoses) [ 3 , 5 , 6 , 8 , 10 , 19 , 20 , 21 ]. So far, few original articles and case reports have been published, probably due to the peculiarity of the issue, which makes retrospective discussion of cases easier than the design of a prospective clinical study [ 4 , 22 , 23 , 24 , 25 , 26 ]. Available knowledge mainly derives from the experience of specialized centers.

The evaluation of a child referred for uncontrolled asthma should start with a careful history focused on typical respiratory symptoms and on the definition of possible triggers. In the “severe asthma” process, it is crucial for clinicians to maintain a high degree of skepticism about the ultimate diagnosis, particularly in the presence of relevant discrepancies between history, physical features and lung function, as many conditions may be misdiagnosed as asthma. In order to simplify this process, herein we propose an algorithm for the diagnosis of difficult-to-treat and severe asthma (Fig. 1 ). Confirmation of the diagnosis through a detailed clinical and laboratory re-evaluation is important because in 12–50% of cases assumed to have severe asthma this might not be the correct diagnosis [ 10 ]. Several documents have indicated the main steps of the process that should be followed in children with uncontrolled asthma [ 3 , 8 , 10 ]. The translation of these procedures into real life practice may deeply change from one subject to another due to the variability of individual patients’ history and clinical features, which will often lead the diagnostic investigations towards the most likely reason for uncontrolled asthma. For children with apparently severe asthma, the first step is to confirm the diagnosis and, before proceeding to broader investigations, to verify that the poor control is not simply determined by poor adherence to treatment, inadequate inhaler skills and/or environmental exposure to triggers. A nurse-led assessment, including a home visit, despite not being applicable in all settings, may be useful for identifying potentially modifiable factors in uncontrolled pediatric asthma [ 27 ].

A practical algorithm for the diagnosis of difficult-to-treat and severe asthma. ICS, inhaled corticosteroids; OCS, oral corticosteroids

A number of comorbidities have been increasingly recognized as factors that may impact asthma clinical expression and control in childhood [ 10 , 28 ]. Children with uncontrolled disease should be investigated for GER, rhinosinusitis, dysfunctional breathing and/or vocal cord dysfunction, obstructive sleep apnea, obesity, psychological factors, smoke exposure, hormonal influences, and ongoing drugs [ 3 , 6 , 8 , 20 ]. Indeed, the exact role played by comorbidities in pediatric asthma control is still debated [ 28 ]. The most impressive example is GER. Several pediatric documents recommend assessing for GER because reflux may be a contributing factor to problematic or difficult asthma [ 7 , 29 ]. Nevertheless, GER treatment might not be effective for severe asthma [ 30 , 31 ], as confirmed by current cases 1 and 2. There is an established evidence that chronic rhinosinusitis is associated with more severe asthma in children [ 32 , 33 , 34 ]. Therefore, examination of upper airways and ad hoc treatment if rhinosinusitis is evident are recommended in children with severe asthma [ 3 , 8 , 35 ]. However, intranasal steroids for rhinitis resulted in a small reduction of asthma risk in school-aged children [ 36 ], and actual placebo-controlled studies on the effect of treatment of rhinosinusitis on asthma control in children are lacking [ 10 , 37 ].

Dysfunctional breathing, including hyperventilation and vocal cord dysfunction, is associated with poorer asthma control in children [ 8 , 10 , 38 , 39 ]. Unfortunately, there is scarce literature on the effect of its treatment on the control of severe asthma in children [ 40 ]. SDB ranging from primary snoring to obstructive sleep apnea syndrome is very common in children [ 41 ], and an increased prevalence of SDB together with increasing asthma severity has been reported [ 42 ]. Interestingly, GER may also be worsened by recurrent episodes of upper airway obstruction associated with SDB, and this may further trigger bronchial obstruction. Asthma guidelines recommend the assessment of SDB through nocturnal polysomnography in poorly controlled asthmatics, particularly if they are also obese [ 5 ]. There are no studies examining whether pediatric asthma improves after SDB has been treated, for example, with nasal steroids, adenotonsillectomy, continuous positive airway pressure or weight reduction if the child is also obese [ 43 ]. The parallel increase in obesity and asthma suggests that the two conditions are linked and that they can aggravate each other [ 44 , 45 ], even though the exact mechanisms that underlie this association remain unclear [ 46 ]. Indeed, other coexisting comorbidities such as SDB or GER may play a confounding role in the development of the interactions between obesity and the airways [ 47 , 48 ]. Obesity is associated with increased markers of inflammation in serum and adipose tissue and yet decreased airway inflammation in obese people with asthma [ 49 ]. Several interventions, including behavioral and weight reduction programs or bariatric surgery, may result in improved asthma control, quality of life and lung function in adult obese asthmatics [ 50 ]. Although reports of adolescent bariatric surgery demonstrate a significant body weight decrease, this approach is not widely available and there are no published reports on its effect on pediatric severe asthma control [ 51 ]. Finally, although it is still unclear whether food allergy is causative or shares a common pathway with difficult asthma, it might explain the loss of asthma control at least in some children and thus be considered as a comorbid condition [ 10 , 16 , 52 ].

In conclusion, establishing the impact of comorbidities on asthma control may be cumbersome, and an ex-juvantibus treatment is sometimes necessary to assess their role. Comorbid conditions can also worsen each other, and symptoms arising from some of them may mimic asthma [ 6 ]. Although the ability to improve pediatric severe asthma by treating comorbidities remains unconfirmed, they should be treated appropriately [ 9 ].

The vast majority of asthmatic children exhibit a mild or at most a moderate disease that can be fully controlled with low-to-medium dose ICS associated or not with other controllers [ 5 , 6 ]. However, a subset of asthmatics remains difficult-to-treat [ 5 , 6 ]. With the advent of biologics, these severe steroid-dependent asthmatics have alternative options for treatment, as steroid-related adverse events are common in severe asthma [ 53 ]. Omalizumab, an anti-IgE monoclonal antibody, is the only biologic therapy recommended in children with moderate-to-severe asthma by the recent guidelines [ 5 , 6 ]. In Italy, this treatment is fully covered by the National Health System. Therefore, there is no influence by any funding on treatment decisions. It was approved by the US (Food and Drug Administration) in 2003 and by the European Union (European Medicines Agency) in 2005 as an add-on treatment for patients aged > 12 years with severe persistent allergic asthma and who have a positive skin test or in-vitro reactivity to a perennial aeroallergen, FEV 1 < 80% predicted, frequent daytime symptoms or nighttime awakenings, and multiple documented severe asthma exacerbations despite daily ICS plus a LABA [ 54 , 55 ]. In 2009, it also received approval in Europe for treating patients aged 6–12 years. Figure 2 illustrates current indications for treatment with omalizumab in children and adolescents with severe asthma.

Indications for omalizumab in children and adolescents with severe asthma

IgE antibodies, Th 2 -derived cytokines and eosinophils play a major role in the development of chronic airway inflammation in asthmatic subjects [ 56 ]. Once released from plasma cells, IgE binds principally to the high-affinity IgE receptor (FcεRI) on mast cells, triggering different effector responses, including the release of mediators leading to allergic inflammatory reactions [ 56 ]. The activation of the allergic cascade by IgE, under constant allergen stimulation, leads to the establishment of chronic allergic inflammation in the airways of asthmatic patients, with IgE being a key element of the vicious circle that maintains it. Cytokines produced during the late phase and subsequent chronic inflammation stage have been directly associated with the induction of airway remodelling, indirectly implicating IgE in the process [ 56 ]. At present, omalizumab is the only commercially available recombinant humanized anti-IgE monoclonal antibody that specifically binds serum free IgE at its CH 3 domain, in the proximity of the binding site for FcεRI, thus preventing IgE from interacting with its receptor on mast cells, basophils, antigen-presenting cells and other inflammatory cells [ 57 ]. The rapid reduction of free IgE levels leads to a downregulation of the FcεRI expression on inflammatory cells and an interruption of the allergic cascade, which results in the reduction of peripheral and bronchial tissue eosinophilia and of levels of granulocyte macrophage colony stimulating factor, interleukin (IL)-2, IL-4, IL-5, and IL-13 [ 58 ]. Moreover, basophils have a relevant role in the initiation and progression of allergic inflammation, suggesting that they may represent a viable therapeutic target. Indeed, in children with severe asthma, it has been reported that omalizumab therapy is associated with a significant reduction in circulating basophil numbers, a finding that is concurrent with improved clinical outcomes [ 59 ]. This finding supports a mechanistic link between IgE levels and circulating basophil populations, and may provide new insights into one mechanism by which omalizumab improves asthma symptoms.

Several clinical controlled and real-life studies of adults with severe, inadequately controlled allergic asthma have demonstrated the efficacy and safety of omalizumab in reducing asthma-related symptoms, corticosteroid use, exacerbation rates, and healthcare resource utilization, and in improving QoL and lung function [ 60 , 61 , 62 , 63 ]. Fewer studies have been published in children. In two double-blind, randomized, placebo-controlled trials (RCTs) of children aged 6 to 12 years with moderate-to-severe allergic asthma, treatment with omalizumab reduced the requirement for ICS and protected against disease exacerbations, but there was little change in asthma symptom scores or spirometry [ 9 , 64 ]. These findings were confirmed and extended in older children [ 65 , 66 , 67 ].

The results of the ICATA study, a multicenter RCT of 419 inner-city children, adolescents and young adults with persistent allergic asthma, showed that, compared to placebo, omalizumab reduces the number of days with asthma symptoms and the proportion of participants with at least one exacerbation by approximately 25% and 19%, respectively ( p < 0.001), thus reducing the need for asthmatic symptom controllers [ 68 ]. Another multicenter RCT of inner-city children and adolescents showed that the addition of omalizumab to ongoing guidelines-based care before patients return to school reduces fall asthma exacerbations (odds ratio, 0.48), particularly in subjects with a recent exacerbation [ 69 ]. Moreover, in a real-life study of 104 children and adolescents with severe allergic refractory asthma followed over 1 year, treatment with omalizumab resulted in good asthma control in 67% of the cases ( p < 0.001), while FEV 1 improved by 4.9% ( p = 0.02) and exacerbation rates and healthcare utilisation decreased approximately by 30% ( p < 0.001) [ 70 ]. The same authors also showed that, after two years of treatment, exacerbation rate and healthcare utilisation were further decreased by 83% and 100%, respectively, while level of asthma control, steroid use and lung function remained unchanged [ 71 ].

A systematic review of pediatric RCTs pooled the data of 1381 children and adolescents with moderate-to-severe allergic asthma in order to establish the efficacy of omalizumab as an add-on therapy [ 72 ]. During the stable-steroid phase, omalizumab decreased the number of patients with at least one exacerbation (risk ratio, 0.69; p < 0.001), the mean number of asthma exacerbations per patient (risk ratio, 0.35; p < 0.001), and the asthma symptom score (mean difference, 0.12; p = 0.005) when compared to placebo. During the steroid reduction phase, omalizumab further reduced the number of patients with at least one exacerbation (risk ratio, 0.48; p < 0.001) and the mean number of asthma exacerbations per patient (mean difference, 0.12; p < 0.05).

Given the cost of omalizumab, many authors have argued for the importance of identifying specific asthma populations who will have significant benefit from it [ 68 , 73 , 74 ]. In the ICATA study, baseline predictors of good response to treatment were sensitization and exposure to cockroach allergen, sensitization to house dust mite allergens, a serum IgE level of more than 100 IU per milliliter, a BMI of 25 or more, and a history of at least one unscheduled medical visit in the previous year [ 68 ].

Several studies have assessed the long-term safety of omalizumab in children and adults. A pooled analysis of 67 RCTs conducted over 2 decades on 4254 children and adults treated with omalizumab showed no association between omalizumab treatment and risk of malignancy [ 75 ]. In an RCT evaluating 225 school-aged children, omalizumab was well tolerated, there were no serious adverse events, and the frequency and types of all adverse events were similar to the placebo group [ 9 ]. These results have been further confirmed by a recent systematic review of RCTs that concluded that treatment with omalizumab does not result in increased risk of malignancy or hypersensitivity reactions [ 72 ].

While the rationale for long-term treatment with omalizumab is supported by pharmacokinetic-pharmacodynamic models [ 76 ], the duration of treatment is still under discussion. Results from published studies suggest that omalizumab should be continued for > 1 year [ 77 , 78 ]. In a retrospective study of adults and children with uncontrolled severe asthma treated with omalizumab, the response to treatment was ‘excellent’ in 52.5% of patients, particularly in the subgroup of children aged 6 to 11 years [ 77 ]. After the discontinuation of treatment, loss of asthma control was documented in 69.2% of the patients who had received omalizumab for < 1 year, 59.1% of the subjects treated for 1–2 years, and 46.1% of the cases treated for > 2 years. Time to loss of control was shorter in younger children and longer in patients with an ‘excellent’ response compared with patients with a ‘good’ response. No early loss of control (within 6 months) was observed among patients with > 3.5 years of continuous treatment with omalizumab. Finally, 20% of patients in whom omalizumab was re-prescribed because of loss of control did not respond to the treatment anymore [ 77 ]. Despite these encouraging findings, the impact of omalizumab on the natural history of severe asthma in children deserves to be further investigated by long-term studies that will also define the criteria and timing for discontinuing the treatment.

It is well known that asthma pharmacotherapy is effective in controlling symptoms and bronchial inflammation, but cannot affect the underlying immune response, thus leading to the possibility of symptom reappearance after its discontinuation [ 79 ]. In this scenario, allergen-specific immunotherapy (AIT) has been proposed as the only therapeutic method that can modulate the underlying immune pathophysiology in allergic asthma [ 80 ].

AIT is currently indicated in children and adults with mild-moderate allergic asthma that is completely or partially controlled by pharmacotherapy and with the evidence of a clear relationship between symptoms and exposure to a specific allergen [ 81 , 82 , 83 , 84 ]. However, according to recent guidelines, the efficacy of AIT in asthmatic subjects is limited, and its potential benefits must be weighed against the risk of side effects and the inconvenience and costs of the prolonged therapy [ 5 ]. Moreover, severe or uncontrolled asthma (regardless of its severity) is a major independent risk factor for non-fatal or even fatal adverse reactions, thus representing a contraindication for AIT [ 85 , 86 , 87 ]. Finally, children with severe asthma are often sensitized to multiple allergens, thus making AIT prescription even more complicated [ 88 ].

In subjects with uncontrolled and/or severe allergic asthma, a combination of omalizumab and AIT has been proposed [ 88 ]. Surprisingly, only a few studies have addressed this issue [ 89 , 90 , 91 , 92 ]. However, pre-treatment with omalizumab seems to improve the efficacy and tolerability of subcutaneous AIT in children and adults with severe allergic asthma both during omalizumab treatment and after its discontinuation [ 89 , 91 , 92 ]. Omalizumab has also been successfully used as a supplementary treatment to AIT in order to improve asthma control in children ≥6 years with severe persistent allergic asthma [ 90 ]. Given the scarcity of studies on AIT plus omalizumab in children with severe allergic asthma, further research is warranted to assess risks and benefits of the combined treatment.

Children with severe asthma require a detailed and individualized approach including re-assessment for differential diagnoses, comorbidities and contributory factors, environmental triggers, lung function and inflammation, adherence and response to therapy, and QoL. Treatment of pediatric severe asthma still relies on the maximal optimal use of corticosteroids, bronchodilators and other controllers recommended for moderate-to-severe disease. However, the management of asthma is becoming much more patient-specific, as more and more is learned about the biology behind the development and progression of asthma.

In the current paper, we described the characteristics of four children with severe asthma in whom omalizumab was prescribed. A review of the relevant literature on the topic was also performed. Finally, we provided an algorithm for the diagnosis of difficult-to-treat and severe asthma in children and adolescents, based on the evidence from the literature review. As all algorithms, it is not meant to replace clinical judgment, but it should drive physicians to adopt a systematic approach towards difficult and severe asthma and provide a useful guide to the clinician.

The addition of omalizumab, the first targeted biological treatment approved for asthma, has led to renewed optimism of outcome improvements in patients with allergic severe asthma. As severe asthma is a heterogeneous condition consisting of different phenotypes, the future of asthma management will likely involve phenotypic and potentially even genotypic characterization in selected cases in order to determine appropriate therapy and thus to provide the highest possible benefit, especially if specific responder phenotypes can be identified and selected for this highly specific treatment.

Abbreviations

Anti-immunoglobulin E

Body mass index

IgE receptor

Forced expiratory flow between 25% and 75%

Forced expiratory volume in the first second

Gastroesophageal reflux

Inhaled corticosteroids

Intensive care unit

Interleukin

Long-acting β 2 -agonist

Oral leukotriene receptor antagonist

Quality of life

Randomized controlled trials

Short-acting β 2 -agonists

Sleep-disordered breathing

O'Byrne PM, Pedersen S, Schatz M, Thoren A, Ekholm E, Carlsson LG, et al. The poorly explored impact of uncontrolled asthma. Chest. 2013;143:511–3.

Article PubMed Google Scholar

National Asthma Education and Prevention Program. Expert panel report 3 (EPR-3): guidelines for the diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol. 2007;120:S94–8.

Article Google Scholar

Hedlin G. Management of severe asthma in childhood-state of the art and novel perspectives. Pediatr Allergy Immunol. 2014;25:111–21.

Konradsen JR, Nordlund B, Lidegran M, Pedroletti C, Grönlund H, van Hage M, et al. Problematic severe asthma: a proposed approach to identifying children who are severely resistant to therapy. Pediatr Allergy Immunol. 2011;22:9–18.

Global Initiative for Asthma Report. Global strategy for asthma management and prevention (updated 2016). https://www.ginasthma.org . Accessed 07 June 2017.

Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343–53.

Article CAS PubMed Google Scholar

Vandenplas Y, Rudolph CD, Di Lorenzo C, Hassall E, Liptak G, Mazur L, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the north American Society for Pediatric Gastroenterology, Hepatology, and nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. 2009;49:498–507.

Lødrup Carlsen KC, Hedlin G, Bush A, Wennergren G, de Benedictis FM, De Jongste JC, et al. Assessment of problematic severe asthma in children. Eur Respir J. 2011;37:432–40.

Milgrom H, Berger W, Nayak A, Gupta N, Pollard S, McAlary M, et al. Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics. 2001;108:E36.

Bush A, Saglani S. Management of severe asthma in children. Lancet. 2010;376:814–5.

Article CAS PubMed PubMed Central Google Scholar

Lang A, Mowinckel P, Sachs-Olsen C, Riiser A, Lunde J, Carlsen KH, et al. Asthma severity in childhood, untangling clinical phenotypes. Pediatr Allergy Immunol. 2010;21:945–53.

Nordlund B, Konradsen JR, Pedroletti C, Kull I, Hedlin G. The clinical benefit of evaluating health-related quality-of-life in children with problematic severe asthma. Acta Paediatr. 2011;100:1454–60.

Dean BB, Calimlim BC, Sacco P, Aguilar D, Maykut R, Tinkelman D. Uncontrolled asthma: assessing quality of life and productivity of children and their caregivers using a cross-sectional internet-based survey. Health Qual Life Outcomes. 2010;8:6.

Juniper EF, Guyatt GH, Feeny DH, Ferrie PJ, Griffith LE, Townsend M. Measuring quality of life in children with asthma. Qual Life Res. 1996;5:35–46.

British Thoracic Society. Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma, 2014. https://www.brit-thoracic.org.uk/guidelines-and-quality-standards/asthma-guideline . Accessed 13 Apr 2016.

Montella S, Baraldi E, Cazzato S, Aralla R, Berardi M, Brunetti LM, et al. Severe asthma features in children: a case-control online survey. Ital J Pediatr. 2016;42:9.

Article PubMed PubMed Central Google Scholar

Fitzpatrick AM, Gaston BM, Erzurum SC, Teague WG, National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program. Features of severe asthma in school-age children: Atopy and increased exhaled nitric oxide. J Allergy Clin Immunol. 2006;118:1218–25.

Simon MR, Chinchilli VM, Phillips BR, Sorkness CA, Lemanske RF Jr, Szefler SJ, et al. Forced expiratory flow between 25% and 75% of vital capacity and FEV1/forced vital capacity ratio in relation to clinical and physiological parameters in asthmatic children with normal FEV1 values. J Allergy Clin Immunol. 2010;126:527–34.

Hedlin G, Bush A, Lødrup Carlsen K, Wennergren G, De Benedictis FM, Melén E, et al. Problematic severe asthma in children, not one problem but many: a GA2LEN initiative. Eur Respir J. 2010;36:196–201.

Fitzpatrick AM, Teague WG. Severe asthma in children: insights from the National Heart, Lung, and Blood Institute's severe asthma research program. Pediatr Allergy Immunol Pulmonol. 2010;23:131–8.

Konradsen JR, Caffrey Osvald E, Hedlin G. Update on the current methods for the diagnosis and treatment of severe childhood asthma. Expert Rev Respir Med. 2015;9:769–77.

Lang AM, Konradsen J, Carlsen KH, Sachs-Olsen C, Mowinckel P, Hedlin G, et al. Identifying problematic severe asthma in the individual child—does lung function matter? Acta Paediatr. 2010;99:404–10.

Rao DR, Gaffin JM, Baxi SN, Sheehan WJ, Hoffman EB, Phipatanakul WJ. The utility of forced expiratory flow between 25% and 75% of vital capacity in predicting childhood asthma morbidity and severity. Asthma. 2012;49:586–92.

Eid N, Yandell B, Howell L, Eddy M, Sheikh S. Can peak expiratory flow predict airflow obstruction in children with asthma? Pediatrics. 2000;105:354–8.

Cicutto LC, Chapman KR, Chamberlain D, Downey GP. Difficult asthma: consider all of the possibilities. Can Respir J. 2000;7:415–8.

Wener RR, Bel EH. Severe refractory asthma: an update. Eur Respir Rev. 2013;22:227–35.

Bracken M, Fleming L, Hall P, et al. The importance of nurse-led home visits in the assessment of children with problematic asthma. Arch Dis Child. 2009;94:780–4.

De Groot EP, Kreggemeijer WJ, Brand PL. Getting the basics right resolves most cases of uncontrolled and problematic asthma. Acta Paediatr. 2015;104:916–21.

Grimaldi-Bensouda L, Zureik M, Aubier M, Humbert M, Levy J, Benichou J, et al. Does omalizumab make a difference to the real-life treatment of asthma exacerbations? Results from a large cohort of patients with severe uncontrolled asthma. Chest. 2013;143:398–405.

American Lung Association Asthma Clinical Research Centers, Mastronarde JG, Anthonisen NR, Castro M, Holbrook JT, Leone FT, et al. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med. 2009;360:1487–9.

Article PubMed Central Google Scholar

Writing Committee for the American Lung Association Asthma Clinical Research Centers, Holbrook JT, Wise RA, Gold BD, Blake K, Brown ED, et al. Lansoprazole for children with poorly controlled asthma: a randomized controlled trial. JAMA 2012;307:373-381.

Wright AL, Holberg CJ, Martinez FD, Halonen M, Morgan W, Taussig LM. Epidemiology of physician-diagnosed allergic rhinitis in childhood. Pediatrics. 1994;94:895–901.

CAS PubMed Google Scholar

De Groot EP, Nijkamp A, Duiverman EJ, Brand PL. Allergic rhinitis is associated with poor asthma control in children with asthma. Thorax. 2012;67:582–7.

Rotiroti G, Roberts G, Scadding GK. Rhinitis in children: common clinical presentations and differential diagnoses. Pediatr Allergy Immunol. 2015;26:103–10.

Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic rhinitis and its impact on asthma (ARIA). 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008;63:S8–160.

Deliu M, Belgrave D, Simpson A, Murray CS, Kerry G, Custovic A. Impact of rhinitis on asthma severity in school-age children. Allergy. 2014;69:1515–21.

Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW, Casale TB, et al. Allergic rhinitis and its impact on asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol. 2010;126:466–76.

Weinberger M, Abu-Hasan M. Pseudo-asthma: when cough, wheezing, and dyspnea are not asthma. Pediatrics. 2007;120:855–64.

De Groot EP, Duiverman EJ, Brand PL. Dysfunctional breathing in children with asthma: a rare but relevant comorbidity. Eur Respir J. 2013;41:1068–73.

Barker NJ, Jones M, O'Connell NE, Everard ML. Breathing exercises for dysfunctional breathing/hyperventilation syndrome in children. Cochrane Database Syst Rev. 2013;12:CD010376.

Google Scholar

Section on Pediatric Pulmonology, Subcommittee on Obstructive Sleep Apnea Syndrome, American Academy of Pediatrics. Clinical practice guideline: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2002;109:704–12.

Goldstein NA, Aronin C, Kantrowitz B, Hershcopf R, Fishkin S, Lee H, Weaver DE, et al. The prevalence of sleep-disordered breathing in children with asthma and its behavioral effects. Pediatr Pulmonol. 2015;50:1128–36.

Ross KR, Storfer-Isser A, Hart MA, Kibler AM, Rueschman M, Rosen CL, et al. Sleep-disordered breathing is associated with asthma severity in children. J Pediatr. 2012;160:736–42.

Santamaria F, Montella S, Greco L, Valerio G, Franzese A, Maniscalco M, et al. Obesity duration is associated to pulmonary function impairment in obese subjects. Obesity (Silver Spring). 2011;19:1623–8.

Sivapalan P, Diamant Z, Ulrik CS. Obesity and asthma: current knowledge and future needs. Curr Opin Pulm Med. 2015;21:80–5.

Rasmussen F, Hancox RJ. Mechanisms of obesity in asthma. Curr Opin Allergy Clin Immunol. 2014;14:35–43.

Santamaria F, Montella S, Pietrobelli A. Obesity and pulmonary disease: unanswered questions. Obes Rev. 2012;13:822–33.

Lang JE, Hossain J, Holbrook JT, Teague WG, Gold BD, Wise RA, et al. Gastro-oesophageal reflux and worse asthma control in obese children: a case of symptom misattribution? Thorax. 2016;71:238–46.

Santamaria F, Montella S, De Stefano S, Sperlì F, Barbarano F, Valerio G. Relationship between exhaled nitric oxide and body mass index in children and adolescents. J Allergy Clin Immunol. 2005;116:1163–4.

Van Huisstede A, Rudolphus A, Castro Cabezas M, Biter LU, van de Geijn GJ, Taube C, et al. Effect of bariatric surgery on asthma control, lung function and bronchial and systemic inflammation in morbidly obese subjects with asthma. Thorax. 2015;70:659–67.

Katzmarzyk PT, Bouchard C. Where is the beef? Waist circumference is more highly correlated with BMI and total body fat than with abdominal visceral fat in children. Int J Obes. 2014;38:753–4.

Article CAS Google Scholar

De Groot EP, Duiverman EJ, Brand PL. Comorbidities of asthma during childhood: possibly important, yet poorly studied. Eur Respir J. 2010;36:671–8.

Sweeney J, Patterson CC, Menzies-Gow A, Niven RM, Mansur AH, Bucknall C, et al. Comorbidity in severe asthma requiring systemic corticosteroid therapy: cross-sectional data from the optimum patient care research database and the British thoracic difficult asthma registry. Thorax. 2016; https://doi.org/10.1136/thoraxjnl-2015-207630 .

Federal Drug Administration Advisory for Omalizumab. Available at: https://wayback.archive-it.org/7993/20170111075347/ . http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/default.htm . Accessed 4 Feb 2018.

European Medicines Agency: assessment report for Xolair. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000606/human_med_001162.jsp&mid=WC0b01ac058001d124 . Accessed 7 June 2017.

Chung KF. Targeting the interleukin pathway in the treatment of asthma. Lancet. 2015;386:1086–96.

Jensen RK, Plum M, Tjerrild L, Jakob T, Spillner E, Andersen GR. Structure of the omalizumab Fab. Acta Crystallogr F Struct Biol Commun. 2015;71:419–26.

Holgate S, Smith N, Massanari M, Jimenez P. Effects of omalizumab on markers of inflammation in patients with allergic asthma. Allergy. 2009;64:1728–36.

Hill DA, Siracusa MC, Ruymann KR, Tait Wojno ED, Artis D, Spergel JM. Omalizumab therapy is associated with reduced circulating basophil populations in asthmatic children. Allergy. 2014;69:674–7.

Humbert M, Beasley R, Ayres J, Slavin R, Hébert J, Bousquet J, et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy. 2005;60:309–16.

Normansell R, Walker S, Milan SJ, Walters EH, Nair P. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev. 2014;1:CD003559.

Lai T, Wang S, Xu Z, Zhang C, Zhao Y, Hu Y, Cao C, et al. Long-term efficacy and safety of omalizumab in patients with persistent uncontrolled allergic asthma: a systematic review and meta-analysis. Sci Rep. 2015;5:8191.

Abraham I, Alhossan A, Lee CS, Kutbi H, MacDonald K. “real-life” effectiveness studies of omalizumab in adult patients with severe allergic asthma: systematic review. Allergy. 2015; https://doi.org/10.1111/all.12815 .

Lanier B, Bridges T, Kulus M, Taylor AF, Berhane I, Vidaurre CF. Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. J Allergy Clin Immunol. 2009;124:1210–6.

Solèr M, Matz J, Townley R, Buhl R, O'Brien J, Fox H, et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J. 2001;18:254–61.

Holgate ST. Cytokine and anti-cytokine therapy for the treatment of asthma and allergic disease. Cytokine. 2004;28:152–7.

Odajima H, Ebisawa M, Nagakura T, Fujisawa T, Akasawa A, Ito K, et al. Omalizumab in Japanese children with severe allergic asthma uncontrolled with standard therapy. Allergol Int. 2015;64:364–70.

Busse WW, Morgan WJ, Gergen PJ, Mitchell HE, Gern JE, Liu AH, et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med. 2011;364:1005–15.

Teach SJ, Gill MA, Togias A, Sorkness CA, Arbes SJ Jr, Calatroni A, et al. Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations. J Allergy Clin Immunol. 2015;136:1476–85.

Deschildre A, Marguet C, Salleron J, Pin I, Rittié JL, Derelle J, et al. Add-on omalizumab in children with severe allergic asthma: a 1-year real life survey. Eur Respir J. 2013;42:1224–33.

Deschildre A, Marguet C, Langlois C, Pin I, Rittié JL, Derelle J, et al. Real-life long-term omalizumab therapy in children with severe allergic asthma. Eur Respir J. 2015;46:856–9.

Rodrigo GJ, Neffen H. Systematic review on the use of omalizumab for the treatment of asthmatic children and adolescents. Pediatr Allergy Immunol. 2015;26:551–6.

Oba Y, Salzman GA. Cost-effectiveness analysis of omalizumab in adults and adolescents with moderate-to-severe allergic asthma. J Allergy Clin Immunol. 2004;114:265–9.

Campbell JD, Spackman DE, Sullivan SD. The costs and consequences of omalizumab in uncontrolled asthma from a USA payer perspective. Allergy. 2010;65:1141–8.

Busse W, Buhl R, Fernandez Vidaurre C, Blogg M, Zhu J, Eisner MD, et al. Omalizumab and the risk of malignancy: results from a pooled analysis. J Allergy Clin Immunol. 2012;129:983–9.

Lowe PJ, Renard D. Omalizumab decreases IgE production in patients with allergic (IgE-mediated) asthma; PKPD analysis of a biomarker, total IgE. Br J Clin Pharmacol. 2011;72:306–10.

Molimard M, Mala L, Bourdeix I, Le Gros V. Observational study in severe asthmatic patients after discontinuation of omalizumab for good asthma control. Respir Med. 2014;108:571–6.

Busse WW, Trzaskoma B, Omachi TA, Canvin J, Rosen K, Chipps BE, et al. Evaluating Xolair persistency of response after long-term therapy (XPORT). Am J Respir Crit Care Med. 2014;189:A6576.

Guilbert TW, Morgan WJ, Zeiger RS, Mauger DT, Boehmer SJ, Szefler SJ, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006;354:1985–97.

Akdis CA. Therapies for allergic inflammation: refining strategies to induce tolerance. Nat Med. 2012;18:736–49.

National Heart, Lung, and Blood Institute. Expert panel report 3: Guidelines for the diagnosis and management of asthma—full report 2007. Available at: https://www.nhlbi.nih.gov/files/docs/guidelines/asthgdln.pdf . Accessed 4 Feb 2018.

Joint Task Force on Practice Parameters, American Academy of Allergy, Asthma and Immunology, American College of Allergy, Asthma and Immunology, Joint Council of Allergy, Asthma and Immunolgy. Allergen immunotherapy: a practice parameter second update. J Allergy Clin Immunol. 2007;120:S25–85.

Zuberbier T, Bachert C, Bousquet PJ, Passalacqua G, Walter Canonica G, Merk H, et al. GA(2) LEN/EAACI pocket guide for allergen-specific immunotherapy for allergic rhinitis and asthma. Allergy. 2010;65:1525–30.

Pajno GB, Bernardini R, Peroni D, Arasi S, Martelli A, Landi M, et al. Clinical practice recommendations for allergen-specific immunotherapy in children: the Italian consensus report. Ital J Pediatr. 2017;43:13.

Pitsios C, Demoly P, Bilo MB, Gerth van Wijk R, Pfaar O, Sturm GJ, et al. Clinical contraindications to allergen immunotherapy: an EAACI position paper. Allergy. 2015;70:897–909.

Tsabouri S, Mavroudi A, Feketea G, Guibas GV. Subcutaneous and sublingual immunotherapy in allergic asthma in children. Front Pediatr. 2017;5:82.

Jutel M, Agache I, Bonini S, Burks AW, Calderon M, Canonica W, et al. International consensus on allergy immunotherapy. J Allergy Clin Immunol. 2015;136:556–68.

Hedlin G, van Hage M. The role of immunotherapy in the management of childhood asthma. Ther Adv Respir Dis. 2012;6:137–46.

Lambert N, Guiddir T, Amat F, Just J. Pre-treatment by omalizumab allows allergen immunotherapy in children and young adults with severe allergic asthma. Pediatr Allergy Immunol. 2014;25:829–32.

Kopp MV, Hamelmann E, Zielen S, Kamin W, Bergmann K-C, Sieder C. Combination of omalizumab and specific immunotherapy is superior to immunotherapy in patients with seasonal allergic rhinoconjunctivitis and co-morbid seasonal allergic asthma. Clin Exp Allergy. 2009;39:271–9.

Massanari M, Nelson H, Casale T, Busse W, Kianifard F, Geba GP. Effect of pretreatment with omalizumab on the tolerability of specific immunotherapy in allergic asthma. J Allergy Clin Immunol. 2010;125:383–9.

Stelmach I, Kaczmarek-Woźniak J, Majak P, Olszowiec-Chlebna M, Jerzynska J. Efficacy and safety of high-doses sublingual immunotherapy in ultra-rush scheme in children allergic to grass pollen. Clin Exp Allergy. 2009;39:401–8.

Download references

Acknowledgements

The authors gratefully thank Dr. Marco Maglione for his contribution in the clinical assessment of the described cases. Medical writing assistance was provided by Stephen Walters on behalf of City Hills Proofreading.

No funding was secured for this study.

Availability of data and materials

All relevant data and materials are published in the manuscript.

Author information

Authors and affiliations.

Department of Translational Medical Sciences, Federico II University, Via Sergio Pansini 5, 80131, Naples, Italy

Virginia Mirra, Silvia Montella & Francesca Santamaria

You can also search for this author in PubMed Google Scholar

Contributions

VM, SM and FS, authors of the current manuscript, declare that they have participated sufficiently in the work to take public responsibility for appropriate portions of the content. VM and SM carried out the initial investigations, drafted the initial manuscript, revised the manuscript, and approved the final manuscript as submitted. FS conceptualized and designed the study, and critically reviewed and approved the final manuscript as submitted. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Francesca Santamaria .

Ethics declarations

Ethics approval and consent to participate.

This study was approved by the ethics committee “Carlo Romano”, Federico II University, Naples, Italy. Children’s parents/legal guardians gave informed written consent to participate. The description of our cases adheres to the CARE standards of reporting checklist.

Consent for publication

Children’s parents/legal guardians provided informed written consent for the case report to be published.

Competing interests

The authors declare that they have no competing interests to disclose. Authors have no financial relationships relevant to this article to disclose.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Cite this article.

Mirra, V., Montella, S. & Santamaria, F. Pediatric severe asthma: a case series report and perspectives on anti-IgE treatment. BMC Pediatr 18 , 73 (2018). https://doi.org/10.1186/s12887-018-1019-9

Download citation

Received : 24 May 2016

Accepted : 29 January 2018

Published : 21 February 2018

DOI : https://doi.org/10.1186/s12887-018-1019-9

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Severe asthma
Adolescents
Asthma exacerbations

BMC Pediatrics

ISSN: 1471-2431

Submission enquiries: [email protected]
General enquiries: [email protected]

Log in using your username and password

Search More Search for this keyword Advanced search
Latest content
Current issue
Hosted content
BMJ Journals More You are viewing from: Google Indexer

J Kolbe a , b ,
W Fergusson a ,
M Vamos c ,
J Garrett a
a Department of Respiratory Medicine, Green Lane Hospital, Auckland, New Zealand, b Department of Medicine, University of Auckland, Auckland, New Zealand, c Department of Psychiatry, John Hunter Hospital, Newcastle, NSW, Australia
Dr J Kolbe, Respiratory Services, Green Lane Hospital, Auckland, New Zealand jkolbe{at}ahsl.co.nz

BACKGROUND Severe life threatening asthma (SLTA) is important in its own right and as a proxy for asthma death. In order to target hospital based intervention strategies to those most likely to benefit, risk factors for SLTA among those admitted to hospital need to be identified. A case-control study was undertaken to determine whether, in comparison with patients admitted to hospital with acute asthma, those with SLTA have different sociodemographic and clinical characteristics, evidence of inadequate ongoing medical care, barriers to health care, or deficiencies in management of the acute attack.

METHODS Seventy seven patients with SLTA were admitted to an intensive care unit (pH 7.17 (0.15), Pa co 2 10.7 (5.0) kPa) and 239 matched controls (by date of index attack) with acute asthma were admitted to general medical wards. A questionnaire was administered 24–48 hours after admission.

RESULTS The risk of SLTA in comparison with other patients admitted with acute asthma increased with age (odds ratio (OR) 1.04/year, 95% CI 1.01 to 1.07) and was less for women (OR 0.36, 95% CI 0.20 to 0.68). These variables were controlled for in all subsequent analyses. There were no differences in other sociodemographic features. Cases were more likely to have experienced a previous SLTA (OR 2.04, 95% CI 1.20 to 3.45) and to have had a hospital admission in the last year (OR 1.86, 95% CI 1.09 to 3.18). There were no differences between cases and controls in terms of indicators of quality of ongoing asthma specific medical care, nor was there evidence of disproportionate barriers to health care. During the index attack cases had more severe asthma at the time of presentation, were less likely to have presented to general practitioners, and were more likely to have called an ambulance or presented to an emergency department. In terms of pharmacological management, those with SLTA were more likely to have been using oral theophylline (OR 2.14, 95% CI 1.35 to 3.68) and less likely to have been using inhaled corticosteroids in the two weeks before the index attack (OR 0.69, 95% CI 0.47 to 0.99). While there was no difference in self-management knowledge or behaviour scores, those with SLTA were more likely to have inappropriately used oral corticosteroids during the acute attack (OR 2.09, 95% CI 1.02 to 4.47).

CONCLUSIONS In comparison with those admitted to hospital with acute severe asthma, patients with SLTA were indistinguishable on sociodemographic criteria (apart from male predominance), were more likely to have had a previous SLTA or hospital admission in the previous year, had similar quality ongoing asthma care, had no evidence of increased physical, economic or other barriers to health care, but had demonstrable deficiencies in the management of the acute index attack. Educational interventions, while not losing sight of the need for good quality ongoing care, should focus on providing individual patients with better advice on self-management of acute exacerbations.

life threatening asthma
socioeconomics
health care
acute attack

https://doi.org/10.1136/thorax.55.12.1007

Statistics from Altmetric.com

Request permissions.

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Severe life threatening asthma (SLTA) is an important entity in its own right. 1 While still numerically rather small, SLTA greatly outnumbers asthma deaths. 1-3 Patients with SLTA are a disproportionate source of subsequent asthma morbidity 2 , 4-6 and health care costs. 7 Previous SLTA clearly defines a population at increased risk of death or SLTA. 2 , 4-6 Because patients who present with SLTA share demographic and other characteristics with those dying of asthma, 1 and also because death would almost certainly ensue in those presenting with SLTA in the absence of prompt medical intervention, SLTA may be regarded as a “proxy for asthma death”. 1 , 8 However, study of SLTA has some practical advantages. The more complete, detailed, and unbiased information available should facilitate the precise definition of specific risk factors for SLTA (and asthma death), as distinct from the risk factors for simple hospital admission for acute severe asthma. In turn, defining risk factors for SLTA within the population of those admitted to hospital with acute asthma should allow the development of specific interventional strategies to reduce the incidence of serious adverse events.

Poor quality, fragmented medical care, or both, has been cited as a cause of asthma death and near fatal asthma in New Zealand 6 , 9-12 and elsewhere. 13-17 Although in previous studies we have shown evidence of good quality ongoing asthma management in patients admitted to hospital with acute asthma, 18 we have also demonstrated that serious self-management errors occur in a high proportion of patients with acute severe asthma requiring hospitalisation. 19 , 20 If such errors were a risk factor for SLTA (and asthma death), then educational and other initiatives which specifically focus on management of the acute severe attack may be the most effective means of reducing asthma mortality and severe morbidity.

The aims of this study were therefore to determine whether or not, in comparison with those admitted to hospital with acute asthma, patients experiencing SLTA had (1) different demographic characteristics, (2) inferior health care, (3) barriers to health, and/or (4) demonstrably inferior self-management of the acute attack.

A case-control study was undertaken because of its efficiency. 21

Cases comprised consecutive patients aged 15–49 years normally resident in the Auckland region who were admitted to one of the two intensive care units (ICUs) in the region with SLTA. 1 For the purposes of this study, SLTA was defined as admission to ICU for acute severe asthma plus at least one of the following: (1) cardiorespiratory arrest, (2) requirement for mechanical ventilation, (3) impaired level of consciousness at presentation, (4) pH <7.2, and (5) arterial carbon dioxide tension (Pa co 2 ) ⩾6.0 kPa.

Exclusion criteria were: (1) age ⩾50 years to avoid major inaccuracies in the diagnosis of asthma in older patients; (2) age <15 years as this is the lower age limit for entry into “adult” clinics and patients aged 15 years and older are generally considered to be of sufficient maturity to assume responsibility for their own health, thus avoiding the need to study the behavioural attitudes and psychosocial features of both parent and child and the parent-child interaction as would be necessary for younger age groups; (3) asthmatics in whom the primary reason for admission to the ICU was not asthma or in whom admission to the ICU was primarily for asthma complications such as pneumothorax rather than SLTA; (4) patients with persisting sequelae of hypoxic encephalopathy preventing completion of questionnaire; and (5) patients whose proficiency in English impaired their ability to complete the questionnaire (lack of proficiency in English was defined as requiring an interpreter when attending a routine doctor's appointment).

Matched hospital control group

This group comprised patients aged 15–49 years normally resident in the Auckland region admitted with acute asthma to a general medical ward of the same hospital as the case, on the same day as the case, on the day before, or within the subsequent two weeks of admission of the case—that is, day –1 to day 14. No other matching was undertaken as it was considered that features traditionally matched for such as age and sex may be important risk factors for SLTA. Up to four matched controls were selected for each case in order to maximise efficiency. 21

Exclusion criteria were: (1) age ⩾50 years; (2) age <15 years; (3) asthmatics for whom the primary reason for admission was not acute asthma; and (4) poor proficiency in English

Both cases and controls satisfied the criteria for reversible airflow obstruction—that is, improvement of ⩾20% in forced expiratory volume in one second (FEV 1 ) or peak expiratory flow (PEF) in response to treatment.

Community comparison group

A random sample of community based asthmatic patients were recruited to provide normative data for asthmatics, to provide a three way comparison for some parameters, and to distinguish between risk factors for hospitalisation and risk factors for SLTA. Potential subjects had been identified in a previous study of the prevalence of adult asthma. 22

QUESTIONNAIRE

A detailed questionnaire was administered to cases and hospital controls within 24–72 hours of admission to general medical wards by the same research associate (WF). Members of the community comparison group were interviewed at home.

Data collected included: (1) Patient demographics. (2) Indicators of quality of health care including: (a) quality of ongoing asthma specific management (acquisition of PEF meter and written action plan, availability of supply of oral steroids, checking of metered dose inhaler (MDI) technique); (b) accessibility of health care: availability of primary health care for routine appointments and during exacerbations, physical accessibility, cost of health care, financial and other barriers to health care; (c) doctor-patient relationship: this is an individual item obtained by factor analysis of the modified Attitudes and Beliefs About Asthma questionnaire. 23 This modification has been described elsewhere 24 and has proved to be feasible, reliable, and acceptable in different patient groups. 19 , 20 , 24 , 25 (3) Asthma severity using a modification of the severity classification of asthma based primarily on drug management by Blanc. 26 (4) Indices of severity of the acute (index) attack. (5) Medication use in the two weeks before admission. (6) Assessment of self-management knowledge using scenarios describing two hypothetical attacks. 25 One described an attack of increasing severity over seven days (slow onset) while the second described an attack which developed over one hour (rapid onset). Both scenarios ended with the subject “experiencing” a severe attack such that he/she was so wheezy and short of breath as to be unable to speak or rise from a chair. At three stages during each of the scenarios subjects were asked to describe what action they would normally undertake if they were actually experiencing such symptoms. The scoring system, in which scores were weighted for strategies considered most important in aborting an attack or to be potentially lifesaving, was based on consensus statements on the management of asthma published by the Thoracic Society of Australia and New Zealand (TSANZ) 27 and the British Thoracic Society (BTS). 28 , 29 (7) Patient self-management behaviour: this methodology has been described elsewhere. 19 Behaviour was assessed by a very detailed history of symptoms and self-management strategies undertaken before admission to hospital. Particular attention was paid to symptoms which defined “stages” in the hypothetical scenarios and the self-management strategies undertaken in relation to those stages in the actual attack. The index attack was then classified as rapid (<6 hours) or slow (⩾6 hours). Because of the relative infrequency of rapid onset attacks (8% based on previous findings 30 ), only those experiencing a slow onset attack were analysed. The subjects' “behaviour” during the index attack was scored using the same system as for the scenarios.

The total possible score for the measures described in (6) and (7) is 25; a score of <15 was considered to represent clinically significant inadequate self-management knowledge/behaviour. Serious errors in management were defined using predefined criteria. 14 Additional information relating to the management of the acute attack was separately obtained—for example, the use of PEF meters, action plans, oral corticosteroids and nebulised bronchodilators, and difficulties experienced during the attack.

The instruments used in (6) and (7) have previously been tested and found to be feasible, acceptable, and reliable in patients attending an asthma clinic, 25 in inpatients, 19 and in different ethnic groups. 24

A detailed assessment of psychological factors will be presented elsewhere. 31

All subjects gave written informed consent to participate in the study which was approved by the Auckland Healthcare ethics committee.

STATISTICAL ANALYSIS

Normally distributed data were expressed as mean (SD). For the matched case and controls, conditional logistic regression was performed to identify factors related to SLTA compared with the matched hospital control group. Initially, basic demographic variables were analysed and any statistically significant variables were included in all further analyses. Variables considered to be the best measures of individual parameters were grouped and analysed in conjunction with the significant demographic variables. Differences between cases and the community comparison group were analysed using unpaired t tests and the Wilcoxon signed rank test on parametric and non-parametric data, respectively. The χ 2 test was used to test the differences in proportions between the groups. A p value of ⩽0.05 was regarded as statistically significant.

Seventy seven patients fulfilled the criteria of cases. Three were excluded because they normally lived outside the Auckland region and two because they were unable to complete the interviewer administered questionnaire, one because of severe mental retardation and one because of severe schizophrenia. One was excluded because of poor English proficiency. Three potential cases were not interviewed; all left hospital after less than 48 hours and two discharged themselves. There were no refusals.

Two hundred and thirty nine matched hospital controls were recruited, representing 1–4 controls per case. Two were excluded because they normally lived outside the Auckland regions, six were excluded because of poor English proficiency, three because of mental retardation, and there was one refusal. Twelve potential controls were not interviewed because of rapid discharge from hospital, three of whom discharged themselves. One hundred subjects were recruited in the community comparison group; a further 45 declined to participate but did not differ from the total group in terms of basic demographic characteristics.

The sociodemographic data of the patients are presented in table 1 . Analysis of SLTA cases and matched hospital controls showed that both age and sex were risk factors for SLTA. The risk of SLTA increased with age (odds ratio (OR) 1.04 per year, 95% confidence interval (CI) 1.01 to 1.07) and was less for women (OR 0.36, 95% CI 0.20 to 0.68). These variables were therefore controlled for in all further analyses. There were no differences in ethnicity or socioeconomic indicators between cases and hospital matched controls. However, the community comparison group were more likely to be European (p<0.01) and less socioeconomically disadvantaged (p<0.05) than the cases and matched hospital controls.

View inline

Demographic data and previous asthma morbidity of cases (SLTA), matched hospital controls and community comparison group

Asthma morbidity is also shown in table 1 . Cases with SLTA were more likely than matched hospital controls ever to have had previous SLTA (OR 2.04, 95% CI 1.20 to 3.45) and to have been admitted to hospital for acute asthma in the last year (OR 1.86, 95% CI 1.09 to 3.18). The community comparison group had markedly lower morbidity indices than either cases or controls (p<0.001 for all).

The community comparison group was assessed to have less severe asthma than cases or hospital controls (table 2 ) but there were no differences between cases, hospital controls, or the community comparison group in terms of chronic prescribed drug management of asthma except for the use of oral theophylline (table 2 ). There were no differences between cases and hospital controls for indicators of quality of ongoing asthma specific medical care (table 2 ). Data on barriers to health care are shown in table 3 . There were no differences between cases and hospital controls in terms of: (1) physical accessibility of health care, (2) financial barriers to health care (both general and asthma specific), and (3) quality of the doctor-patient relationship (either in terms of total factor score (data not shown) or for the individual items). (“Doctor” was defined as the medical professional whom patients considered most important in the management of their asthma.) The community comparison group had fewer financial barriers to health care but less favourable attitudes to their doctor (not statistically significant) (table 3 ).

Severity and asthma management

Barriers to health care

Data pertaining to presentation and management of the index attack for cases and matched hospital controls are presented in table 4 . As expected, cases had evidence of more severe asthma at presentation. Cases were less likely to present initially to general practitioners and were more likely to present to emergency departments or to call an ambulance (p<0.01). Difficulties encountered by the patient in the management of the index attack are shown in table 4 . Cases were more likely to have perceived panic during the attack but were less likely to be concerned about time off work. Otherwise there were no differences in these parameters.

Management of the acute attack

Use of oral theophylline (ongoing and in the two weeks before the index attack) was associated with a higher risk of SLTA (OR 2.14, 95% CI 1.35 to 3.68) while use of inhaled corticosteroids in the two weeks before the index attack (as opposed to prescribed inhaled corticosteroids) was associated with a reduced risk of SLTA (OR 0.69, 95% CI 0.47 to 0.99) compared with hospital controls. However, cases were less likely to have previously run out of their usual medications (48% vs 28%, p<0.01). There were no differences between cases and controls with regard to access to urgent after hours care nor in their previous management of a nocturnal attack (table 5 ).

Asthma self-management

There were no differences in self-management knowledge scores or self-management behaviour scores between cases and hospital controls. Cases were less likely to use standard self-management strategies, but only the lower rate of use of a peak flow meter reached statistical significance (table 5 ). Self-management error in terms of delayed use or non-use of oral steroids during the index attack was associated with an increased risk of SLTA (OR 2.09, 95% CI 1.02 to 4.47). Delayed or non-summoning of an ambulance was not associated with an increased risk of SLTA.

In comparison with those admitted with acute asthma, patients with SLTA are relatively more likely to be men. However, women predominate in most statistics of asthma morbidity and mortality, making up about 60% of deaths and SLTA 1 , 32-37 and a greater proportion of hospital admissions (up to 75% 18 ), although not all series of asthma death 6 and of near fatal asthma 38 , 39 have shown a predominance of women. We have recently reported a predominance of men in those presenting with rapid onset asthma and who are more likely to have SLTA. 29 This may be a partial explanation for the relative predominance of men in the SLTA cases. However, sex is not a particularly useful clinical criteria for identifying patients at increased risk of SLTA. Similarly, although there is a statistically significant increased risk of SLTA with increasing age, even within the limited age range studied, an odds ratio of 1.04 per year age is not likely to represent a useful discriminator for identifying patients at increased risk of SLTA or death. These factors were controlled for in all further analyses.

Previous SLTA and recent admission to hospital were risk factors for SLTA whether the comparison was made with matched hospital controls or the community comparison group. This is consistent with previous results from our group 4-6 and the case-control study of Turner et al , 39 which was smaller but of similar design to the current study. Risk stratification, even within the group admitted to hospital with acute severe asthma, can therefore be undertaken on the basis of previous SLTA and recent admission to hospital. This is of considerable relevance to all doctors managing patients with acute exacerbations of asthma.

Poor quality and/or fragmented ongoing health care is a potential remediable factor in asthma death 6 , 9 , 10 , 13-17 and life threatening asthma. 18 , 32 , 38 One of the postulated reasons for the dramatic decline in asthma morbidity and mortality in New Zealand over the last decade is an improvement in the quality of, and access to, primary health care—both ongoing and emergency care. 11 , 12 In a previous cross sectional study of patients admitted to hospital with acute asthma we found evidence of generally good quality, ongoing, asthma specific medical care 18 but we hypothesised that poor quality care might still be a risk factor for SLTA. However, our results showed that, compared with matched hospital controls, cases with SLTA did not differ in any of the indices of quality of ongoing medical care. Data on quality of health care were not available for the community group and the possibility still exists that deficiencies in health care may operate to increase the risk of an acute attack and admission to hospital, although not increasing the risk of SLTA per se.

Barriers to health care may take a variety of forms—for example, physical inaccessibility, financial barriers, and attitudinal factors. Inaccessibility to health care is one of the reasons why asthma deaths and SLTA are more likely to occur outside usual working hours. 1 Jones and Bentham 40 showed that geographical barriers to acute hospital services were an independent risk factor for asthma death, although this association was based on population statistics rather than on data of individuals with asthma. In the current study none of the geographical or organisational factors differed significantly between SLTA cases and hospital controls. Indeed, the data in table 3 argue against an important role for physical barriers in both groups. Analysis of the reasons for difficulty in managing the index attack (table 4 ) suggests that non-availability of a telephone or a car was not an issue for >90% of patients in both groups. However, the current study was undertaken in an urban region, albeit a sprawling one, and thus the results may not be applicable to other regions, particularly if they contain a substantial rural population.

The results of this study do not support the contention that financial barriers to health care are a risk factor for SLTA when comparison is made with hospital controls. This does not imply that financial barriers are not important and operational in patients with asthma, merely that they influence both of these groups in a similar fashion. This is shown in table 3 by the considerable differences between the community group and both cases and hospital controls in terms of general and asthma specific financial factors. We have recently demonstrated a very close relationship between hospital admissions, SLTA and asthma death and an index of socioeconomic deprivation (SED) in the Auckland region. 41 There was a stronger influence of SED on the more severe undesirable adverse outcomes. Although there are no differences between cases (SLTA) and hospital controls in any of the indicators of socioeconomic status, both groups had evidence of significant socioeconomic disadvantage (consistent with results of a previous cross sectional study of patients admitted with acute asthma 18 ).

Successful management of a chronic illness such as asthma requires the establishment of a therapeutic alliance and partnership between the patient and doctor. Deficiencies in this relationship have adverse effects on the acquisition of self-management knowledge and patient self-management behaviour during an acute attack. 19 , 20 The doctor's level of sensitivity to the emotional needs of the asthmatic patient may influence clinical decisions; doctors too much in tune with the patient's psychological distress tended to overtreat while doctors who paid inadequate attention to such issues discharged inappropriately early. 42 In this study all indications were that there was generally an excellent relationship between the patient and the doctor regarded as most important in the management of their asthma, and no evidence that the quality of the doctor-patient relationship was an identifiable risk factor for SLTA.

Factors related to patient self-management strategies shortly before and during the index attack were significantly associated with the risk of SLTA, those with SLTA being (1) less likely to have used inhaled corticosteroids in the two weeks before the index attack, (2) more likely to have used oral theophylline, (3) less likely to have monitored peak flow, and (4) less likely to have appropriately used oral corticosteroids during the acute attack. In part, these results are consistent with our previous results which showed a high rate of errors in the management of severe attacks of asthma, the errors being generally made by the patient rather than the doctor and more likely to occur in relation to strategies that may abort the attack or be potentially life saving. 20 We have also shown considerable disparity between the patients' knowledge of what to do in the event of an acute attack and what is acutely done—that is, their behaviour. 19 The patients' self-management knowledge, their behaviour during an acute attack, and self-management errors are all influenced by a variety of socioeconomic and health care factors. 19 , 20 , 25 Thus, while deficiencies in quality of ongoing asthma care have been cited as a cause of SLTA/asthma death, 1-10 efforts directed towards improving patient self-management of acute exacerbations of asthma may be more likely to produce improved outcomes in terms of reductions in asthma mortality and severe morbidity, and should be the focus of intervention strategies and be an essential component of asthma education. 43

The results of this study raise issues about the perceived role of the general practitioner in the management of acute severe asthma. Cases with SLTA were more likely to present directly to an emergency department or to call an ambulance; only 29% presented initially to the general practitioner compared with 51% of hospital controls. Similar reliance on emergency departments was noted in the study by Turner et al . 39 This behaviour would seem entirely appropriate in the context of a more severe attack of asthma. However, few attacks leading to hospital are rapid (<6 hours) 30 and the behaviour during the index attack is reflected in the responses to questions on the previous management of nocturnal exacerbations of asthma; only 4% of those who presented with SLTA and 7% of hospital controls had telephoned their general practitioner during previous acute episodes. Perhaps most disturbing is the fact that, on previous occasions, over 80% had not summoned any form of help nor sought any advice. Previous studies have shown that, in the event of an acute attack of asthma, there were delays in summoning emergency services 20 and also delays in attendance at the emergency department; the latter was indicated by more severe asthma on presentation in Auckland than in Toronto. 44 This underuse of primary health care, particularly after hours when there may be organisational and other barriers to community care, was one of the factors thought to contribute to asthma morbidity and mortality in New Zealand. 1 , 9-12 These data seem to reflect a perception by the patient of a lack of role for the general practitioner in the management of acute asthma. This may be appropriate in the event of a rapid onset or very severe attack (along with the lower rate of use of a peak flow meter), but may also be influenced by the perceived availability of general practitioners after hours and of other barriers to acute health care (including financial, as primary health care is delivered on a fee-for-service basis in New Zealand). Such patient behaviour needs to be considered when providing advice to individual patients and when devising acute asthma management guidelines. Unfortunately, a similar situation seems to exist for patients admitted to hospital with chronic obstructive pulmonary disease (COPD) as only 25% had sought medical help from their general practitioner in the two weeks before admission. 45

One of the major aims of asthma education is to increase patients' self-management knowledge and skills, 19 , 25 although this does not necessarily translate into improved self-management behaviour. 19 , 20 In this study there were no differences between cases and controls in the total scores for self-management knowledge (table 5 ) although scores for both groups were higher than those obtained from a community based comparison group (data not presented). This suggests that educational strategies directed solely at increasing patient knowledge are unlikely to reduce the risk of SLTA. A critical component of self-management educational initiatives is instruction on action to be undertaken in the event of an acute attack, specifically the indications for use of oral corticosteroids. Delay or non-use of oral corticosteroids was a risk factor for SLTA, thus reinforcing the importance of that single piece of advice in attempts to reduce serious asthma morbidity.

Inhaled corticosteroids are the linchpin of preventive therapy in adult asthma; these agents modulate the inflammatory response in airways, 46-49 reduce the level of airway responsiveness, 50-52 improve various parameters of asthma control, 52-54 and reduce asthma morbidity. 55 Although we have previously shown that the use of all forms of asthma drugs was associated with increased risk of death or SLTA, and that confounding by severity was present, it was only for higher doses of inhaled steroids that the risk ratio (RR) for SLTA or death fell below 1 after adjustment for multiple severity indicators. 5 Other pharmacoepidemiological studies have reported similar findings of a reduced risk of adverse outcomes in association with the use of inhaled corticosteroids. 56 , 57 Although the rate of use of inhaled corticosteroids was much higher than in the Canadian study of Turner et al , 39 this study showed that it was recent use (within two weeks) and not prescribed use that was associated with the reduced risk of a serious adverse event. In view of the similarities in most other respects between the cases and matched hospital controls, these data suggest that recent use of inhaled corticosteroids may prevent SLTA. The importance of the distinction between prescribed and actual use of medications is also highlighted.

In pharmacoepidemiological studies theophylline has been consistently associated with an increased OR for serious adverse events 5 , 56 , 57 and, even after adjusting for multiple severity markers, the OR remained significantly raised. 5 While this may be due to residual confounding (with theophylline use being a marker of poorly controlled asthma for whatever reason or inappropriate medical management), direct or indirect effects of the drug are not excluded. Whatever the mechanism and whatever the indication for administration, the results of this study support the contention that the use of oral theophylline does indicate a patient at increased risk of a serious adverse event.

The lack of information in the literature regarding the possible impact of panic by the patient during the acute attack reflects the general paucity of research in the area of patient behaviour, especially at times when self-management decisions are most crucial. High rates of anxiety, not necessarily related to acute exacerbations, are well documented in those with severe asthma 19 , 43 and have been shown to be associated with higher rates of hospitalisation and greater use of “as required” medication and oral steroids. 58 It has been suggested that symptoms of panic/fear occurring during an attack of asthma may lead to more inappropriate action by the patient. 59 , 60 While heightened awareness may help to focus the patient on making correct self-management decisions, a high level of anxiety/fear may incapacitate the patient and lead to no action rather than incorrect but deliberate action, precisely what was found to occur in this study and in previous studies. 19 , 20

In this study patients admitted to hospital with an acute attack of asthma were used as controls, thus allowing interview of both cases and controls using the same procedure and controlling to a large extent for the impact of the acute exacerbation, drug treatment, and the effect of hospitalisation. Matching, apart from date of attack and hospital of presentation, was not undertaken as it was argued that some of the features traditionally matched for may be significant risk factors. As it turned out, this was entirely appropriate as both age and sex were statistically significant risk factors and were controlled for in all subsequent analyses. While the use of patients admitted acutely to hospital to a large extent controls for severity of asthma 4 , 5 and the effects of acute treatment, the use of hospital controls may represent “over-matching”—that is, the cases and controls were both derived from the same subgroup of asthmatic patients and hence were unlikely to differ in measurable ways. However, the major consideration in the choice of controls was the highly relevant clinical aim to distinguish those at highest risk of SLTA (and death) from the larger group of patients admitted acutely to hospital, rather than distinction from the much larger population of community based asthmatics. In other words, we aimed to distinguish between risk factors for SLTA and risk factors for hospitalisation for acute asthma. Most patients who die of asthma or experience SLTA have had contact with hospital services in the previous year and thus present an opportunity for intervention. 4-6 Furthermore, any intervention strategies to reduce morbidity and mortality would be likely be hospital based, at least initially.

It has been argued that patients with SLTA to some extent represent a population of survivors and are thus a highly biased sample. 8 However, during the conduct of this study there were only four asthma deaths in this age range in the region and thus the cases in this study are a reasonably unbiased population of all patients having very severe attacks in the region.

Suitable controls in a case-control study should accurately reflect that population from which the cases were derived. However, obtaining a random sample of patients having an acute exacerbation of asthma in the community presented insurmountable logistical difficulties, not only because of the range of sources of acute health care in New Zealand but also because a substantial proportion of patients do not obtain medical help for an acute attack which occurs outside usual working hours (table 5 ). The conduct of an epidemiological study of asthma prevalence 22 provided the opportunity to obtain a random sample of community based asthmatic subjects to provide normative data for some of the instruments used and for comparison with the cases and controls. This comparison reinforced the fact that community based asthmatic subjects differ markedly from those who are admitted to hospital with acute asthma.

Although not a primary aim, this study provides data on risk factors for admission to hospital for acute asthma; these included non-European ethnicity, socioeconomic deprivation (either general or directly related to asthma, confirming our previous results 18 , 40 ), more severe asthma, previous SLTA, and recent admission to hospitals or presentation at the emergency department. This highlights the fact that risk factors for death (and SLTA) may differ according to the control subgroup studied, an important consideration in discussions relating to controlling for severity in the debate about the relationship between fenoterol and asthma deaths. 4-6

Thus, in comparison with patients admitted to hospital with acute severe asthma, those with SLTA are (1) indistinguishable on sociodemographic criteria (apart from relative male predominance), (2) are more likely to have had previous SLTA or hospital admission in the last year, (3) have similar quality ongoing asthma care, (4) have no evidence of physical, economic, or other barriers to health care, and (5) have demonstrable deficiencies in management shortly before and during the index attack in terms of being more likely to have been using oral theophylline, less prior use of inhaled corticosteroids, less likely to have monitored PEF and to have appropriately used oral steroids during the attack.

These findings have major implications for asthma education and management. Following an acute attack, particularly one of sufficient severity to necessitate admission to hospital, it is important to review carefully the patients' self-management strategies, to identify errors particularly of omission or delays in undertaking appropriate action, and to institute corrective advice. Educational strategies, while not losing sight of the need for good quality ongoing care, need to focus more on providing individual patients with rational, relevant, and realistic advice on self-management of acute exacerbations and this advice needs to be repeatedly reinforced and refined—the “5 Rs” of asthma education.

Acknowledgments

The authors wish to thank the medical nursing and other staff of the general medical wards and intensive care units of the Auckland hospitals for their assistance and cooperation during the conduct of this study. We also thank Mrs Josephine Ratnasabapathy for her patience and diligence in preparing the manuscript. We are extremely grateful to Joanna Stewart for her assistance in performing the statistical analyses and to Dr Julian Crane for assistance in the recruitment of the community comparison group.

Richards GN ,
Fenwick J ,
Marquette CH ,
Sauliner F ,
Spitzer WO ,
Garrett JE ,
Jackson R ,
Barnes PJ ,
Jansson B ,
Beasley R ,
Beaglehole R ,
Beaglehole R
Garrett J ,
Richards G ,
Westerman DE ,
Benatar SR ,
Potgieter PD ,
British Thoracic Association
MacDonald JB ,
Williams DA
Miller BD ,
Fergusson W
Fergusson W ,
Sibbald B ,
Collier J ,
Woolcock A ,
Rubinfeld AR ,
↵ Kolbe J, Fergusson W, Vamos M, et al . Case-control study of severe life-threatening asthma (SLTA) in adults: psychological factors. Thorax 2000; 55 :(in review).
Benator SR ,
Cochrane GM ,
Ormerod LP ,
Stableforth DE
Wasserfallen JB ,
Schaller MD ,
Wareham NJ ,
Harrison BDW ,
Jenkins PF ,
Campbell DA ,
McLennan G ,
Turner MO ,
Noertjojo K ,
↵ Garrett JE, Poyser M, Kolbe J. The relationship between social and economic deprivation and asthma morbidity/mortality in New Zealand. Eur Respir J 1999; 12 (abstract).
Horton DJ ,
Kinsman RA ,
Brodie SM ,
Manolitsais ND ,
van Krieken JHJM ,
Evertse CE ,
Laitinen LA ,
Laitinen A ,
Schleimer RP ,
Schwebert L ,
Woolcock AJ ,
K Kerrebijn KF ,
van Essen-Zandvbet EEM ,
Juniper EF ,
Vanzielegham MA ,
Haaktela T ,
Jarvinen M ,
Taylor DR ,
Donahue JG ,
Livingstone JM ,
Burgess C ,
Thiruchelvan R ,
Staudenmeyer H ,

Funding: This study was supported by grants from Lottery Health Research and New Zealand Health Research Council.

Read the full text or download the PDF:

How do you diagnose asthma? A multiple case study design to understand and explain current use of national guidelines by primary care clinicians

Affiliations.

1 Betsi Cadwaladr University Health Board.
2 Glan Clwyd Hospital.
3 Bangor University.
PMID: 32554672
DOI: 10.3399/bjgp20X711485

Background: Clinical guidelines for asthma are available to UK clinicians but implementation is not straightforward. Diagnostic and treatment inadequacy contribute to patient morbidity and mortality and lack of adherence to guidelines is a component of this.

Aim: This qualitative study sought to explore and understand the use of asthma guidelines by primary care clinicians in two geographically bounded regions of Wales.

Method: Multiple case study design was used. Data was collected using semi-structured interviews with a purposively sampled group of clinical staff from GP practices. Interview transcripts were thematically analysed to produce a detailed picture of practice.

Results: Asthma care in the studied areas operated as a social network of clinicians who often used guidelines as boundary objects. Practice and local service design was influenced and dependent on regular input from local secondary care providers. Clinicians looked to British Thoracic Society and Scottish Intercollegiate Guideline Network (BTS/SIGN) 2016 guidelines. There was limited use of National Institute for Health and Care Excellence (NICE) 2017 guidelines. Barriers to guideline recommended diagnostic asthma care included: lack of acceptability, financial costs and disempowerment of nursing staff.

Conclusion: The findings from this study replicate and reinforce the findings of previous work. It is striking and concerning that the thematic outcomes of this study bear a strong resemblance to that which was demonstrated over a decade ago. The guideline-implementation gap in asthma diagnostics will likely persist unless there is significant restructuring, financial investment and greater empowerment of nursing staff in primary care.

Open access
Published: 13 November 2023

Validation of adult asthma case definitions for primary care sentinel surveillance

Max Moloney ORCID: orcid.org/0000-0003-2293-910X 1 , 2 ,
Alison Morra 1 , 2 ,
Rachael Morkem 4 ,
John Queenan 3 ,
Samir Gupta 5 , 6 ,
Teresa To 7 , 8 ,
Geneviève Digby 2 ,
David Barber 3 , 4 &
M. Diane Lougheed 1 , 2

Allergy, Asthma & Clinical Immunology volume 19 , Article number: 95 ( 2023 ) Cite this article

778 Accesses

Metrics details

Most asthma diagnoses and patient care take place in primary care settings. Electronic medical records (EMRs) offer an opportunity to utilize technology to improve asthma diagnosis and care. The purpose of this study was to create and validate separate case definitions for suspected and confirmed asthma in primary care EMRs, to enable surveillance, benchmarking, and quality improvement in primary care settings. The objective of this study was to develop a case definition for suspected and confirmed asthma for use in a primary care sentinel surveillance system.

A single chart abstractor conducted a manual audit of 776 randomly selected patient charts from an academic primary care practice EMR in Kingston, Ontario. Following the single chart abstractor classification, a consensus on chart classification as “not asthma”, “suspected asthma”, or “confirmed asthma” was achieved between the abstractor, a family physician, and a respirologist using Canadian Thoracic Society (CTS) criteria. Case definition algorithms based on billing codes, clinical data elements and medications were applied to the site’s Canadian Primary Care Sentinel Surveillance Network (CPCSSN) data for the same charts and compared to abstractor classifications to determine each algorithm’s measurement properties.

The prevalence of suspected and confirmed asthma were 7.3% (n = 54) and 2.4% (n = 18), respectively. None of the proposed case definitions could differentiate between suspected and confirmed asthma. One algorithm consisting of billing, clinical, and medication elements had the highest Youden’s Index for either suspected or confirmed asthma. The algorithm had a sensitivity of 81%, a specificity of 96%, positive predictive value of 71%, negative predictive value of 98%, and a Youden’s Index of 0.77 for combined suspected or confirmed asthma cases.

An EMR case definition for suspected or confirmed adult asthma has been validated for use in CPCSSN. Implementation of this case definition will enable the development of a surveillance electronic tool (eTool) for adult asthma that can foster quality improvement.

Asthma is diagnosed based on a combination of patient history, physical examination, and objective tests. There are over 3 million Canadians diagnosed with asthma and the prevalence of asthma in Canada is approximately 8.5% [ 1 ]. The Canadian Thoracic Society (CTS) defines asthma as the combination of a compatible clinical history of asthma and reversible airflow obstruction or airway hyperresponsiveness on lung function tests, or alternatively, a specialist diagnosis of asthma [ 2 , 3 ]. Accordingly, although confirmed asthma requires objective testing, a “suspected asthma” case is defined as a compatible clinical history without objective measures of lung function consistent with asthma or specialist diagnosis [ 2 , 3 ]. Most asthma diagnoses and care occur in primary care settings [ 4 ]. Despite available guidelines, less than half of patients diagnosed with asthma have undergone appropriate pulmonary function testing to confirm their diagnosis [ 5 ]. As such, the majority of real-world diagnoses in primary care are more accurately classified as cases of suspected asthma. This failure to use objective testing has led to a high degree of misdiagnosis of asthma [ 6 ].

Electronic medical records (EMRs) offer an opportunity to utilize technology to improve the process of asthma diagnosis. Potential benefits of using electronic tools (eTools) within EMRs include improved quality of care, outcome monitoring, and performance measurement [ 7 , 8 ]. The Canadian Primary Care Sentinel Surveillance Network (CPCSSN) is the first and only pan-Canadian chronic disease surveillance system based on primary care EMR data [ 9 ]. CPCSSN has validated case definitions for 13 chronic conditions, including COPD [ 10 ]. There have also been efforts to create case definitions for adult asthma using EMR data directly by Xi et al. [ 11 ], and using EMR data extracted into the CPCSSN database by Cave et al. [ 12 ]. To date, there remains no standardized case definition for diagnosis of asthma in primary care that can be applied to EMRs and databases across Canada. As primary care EMR data are increasingly being used for disease surveillance, validated case definitions are required [ 13 , 14 ]. A recent literature review on asthma case definitions identified the need to create a case definition that differentiates between suspected and confirmed asthma in primary care EMRs [ 15 ]. The purpose of this study was to create and validate separate case definitions for suspected and confirmed asthma in adults in primary care EMRs, and to determine the ability to distinguish between suspected and confirmed asthma using primary care EMR data.

Study design

A retrospective chart analysis was conducted at the Queen’s Family Health Team (QFHT) in Kingston, Ontario. The QFHT uses the open-source OSCAR EMR developed by McMaster University that is used across Canada, in the care of over 1 million patients [ 16 ]. CPCSSN collects de-identified patient data from source EMRs, including but not limited to demographics, visit dates, reason for encounter, medical conditions, billing history, procedure history, prescribed medications, laboratory results, and patient referrals. This study used coded and processed QFHT data in CPCSSN, stored at the Centre for Advanced Computing at Queen’s University. The random sample in this study was derived from a list of patient charts from CPCSSN data holdings generated by a computer algorithm. Patients that elected to opt-out of research from CPCSSN were removed from the list of patient charts for review.

QFHT patients were notified of the study and given the option to withdraw from the study. The study was approved by the Health Sciences and Affiliated Teaching Hospitals Research Ethics Board (HSERB) at Queen’s University. All data were recorded as non-identifiable information.

Chart abstraction and data collection

The criteria for generation of the patient list were age ≥ 18 years and currently registered at QFHT. Charts were excluded if there was no recorded visit to a physician in the previous 5 years or if a chart was marked as inactive by QFHT. A single chart abstractor conducted a manual audit of the 776 randomly selected patient charts for 776 patients. The sample of 776 patient charts was determined based on a power calculation assuming 8% prevalence of asthma in adults [ 17 , 18 ], along with a projected case definition algorithm with 80% sensitivity, 10% precision and 95% CIs. Given these parameters, the minimum sample size was determined to be 776. The abstractor collected 96 data points selected a priori by consensus of the lead investigators relevant to asthma diagnosis and management, and classified each chart as “not asthma”, “suspected asthma”, or “confirmed asthma”. The categories of data collected included patient demographics, prescribed medications, asthma symptom history, comorbidities, smoking status, documentation of asthma diagnosis, asthma exacerbation history, pulmonary function tests, and referral notes. Data collected included a lookback time frame of the entire patient’s history, with the exception of medication data, which was separated into expired (> 2 years) and current (≤ 2 years). The abstractor used a chart abstraction manual to ensure data entry accuracy and consistency. All data were collected using an online abstraction form created on Qualtrics™ software.

Asthma classification definition

The definition of “confirmed asthma” was based on the CTS guideline for asthma diagnosis [ 2 , 3 ]. Confirmed asthma was defined as a compatible clinical history plus pulmonary function tests (PFTs) confirming asthma, and/or a specialist diagnosis. “Suspected asthma” was defined as a compatible clinical history without PFTs consistent with asthma or a specialist diagnosis. All other patient charts were classified as “not asthma.” Following the single chart abstractor classification, each chart classified as suspected or confirmed asthma and 12 charts classified as not asthma which the abstractor thought required additional input for classification, were reviewed by a QFHT family physician and a respirologist to achieve consensus on the final classification. All chart classification reviews were completed on the original OSCAR EMR charts at QFHT.

Case definition development

Case definitions were developed and tested on the CPCSSN data holdings for the same charts reviewed and classified by the abstractor and expert physicians in the OSCAR EMR at QFHT. Case definitions tested in this study were developed by members of the study team. They included 3 case definitions for adult asthma previously published in the literature, in addition to new case definitions designed by the research team [ 11 , 12 ]. The proposed case definitions were developed based on all data fields possibly relevant for diagnosis in CPCSSN, including billing information, health condition, encounter diagnosis, and medication data. In total, 21 case definitions were developed and tested through an iterative process. Case definition criteria within the search fields used a combination of: text strings (in encounter diagnosis or health condition fields); International Classification of Disease, Ninth Revision (ICD-9) codes (used by QFHT) in billing diagnosis, encounter diagnosis, or health condition fields); and medication prescription information of the CPCSSN data. The complete list of case definitions and the specific search criteria tested are available in Table 1 .

Statistical analysis

The results of the proposed case definitions were compared to the confirmed asthma classification definition (reference standard). For each proposed case definition, sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and Youden’s Index (YI) [(sensitivity + specificity) – 1] were calculated in the (i) confirmed asthma subset, (ii) suspected asthma subset, and (iii) combined confirmed or suspected asthma subset. An ROC curve was plotted for combined confirmed or suspected asthma. Additionally, descriptive statistics were calculated for each of the 96 data points abstracted during the study. Statistical analysis was completed using Microsoft Excel™ and SAS™ software.

Sample characteristics

A total of 743 patient charts were included in the study's final analysis. Thirty-three charts were excluded (Fig. 1 ). The date cut off for chart inclusion was an entry into the EMR within the last two years.

Sample derivation

The characteristics of the sample are detailed in Table 1 . The estimated prevalence of suspected or confirmed asthma based on the 743 charts that met inclusion criteria was 9.7% (n = 72). Of the 72 charts determined to have suspected or confirmed asthma, 54 (7.4%) were classified as suspected and 18 (2.3%) were classified as confirmed.

In the study sample, 416 of 743 (56.0%) patients’ charts reviewed were female and 327 charts (44.0%) reviewed were male. The mean (± SD) age of patients reviewed was 50.3 (± 8.7). Additional patient characteristics are outlined in Additional file 1 : Table S2. In assessing rates of objective measures to confirm asthma diagnosis, spirometry was completed in 114 (15.3%) of charts reviewed. Completion of spirometry with bronchodilator testing was documented in 86 charts (11.6%). Documentation of a methacholine challenge test was completed in 15 charts (2.0%)., and evidence of a specialist diagnosis was present in 22 charts (3.0%).

Case definition results

The case definition algorithm determined to have the highest Youden’s Index for the combination of suspected or confirmed asthma was Case Definition 10, which used a combination of text strings and ICD-9 codes from the billing, encounter diagnosis, and health condition within CPCSSN (Table 2 and Fig. 2 ). This definition had a SN of 81%, a SP of 96%, PPV of 71%, NPV of 98%, and a Youden’s Index of 0.77. For suspected asthma, the case definition had a SN of 76%, a SP of 94%, PPV of 50%, NPV of 98%, and a Youden’s Index of 0.70. For confirmed asthma, the case definition had a SN of 94%, a SP of 91%, PPV of 21%, NPV of 99%, and a Youden’s Index of 0.85. None of the case definitions assessed in this study met the minimum standard (sensitivity and specificity > 70%) to differentiate between suspected and confirmed asthma. Complete results are available in Additional file 1 : Table S3–S5.

ROC curve of proposed case definitions for suspected and confirmed asthma

We validated a case definition for combined suspected or confirmed asthma in primary care. This study's proposed case definitions had similar results for both suspected and confirmed asthma. Case definitions could not discriminate between suspected and confirmed asthma because the use of objective measures to confirm asthma diagnosis was either not completed or not documented. Our findings of a combined prevalence of suspected and confirmed asthma of 9,7% is comparable to current national statistics [ 18 ]. However, 75% of the cases in our study were suspected not confirmed. This highlights the importance of confirming and documenting the status of asthma diagnoses in EMRs. National statistics based on population surveys that rely on self-report of physician diagnosis or billing data may also be subject to considerable misclassification. Until EMR data elements are adopted that allow for the distinction between suspected and confirmed asthma [ 19 ], one case definition that can be used for combined suspected or confirmed asthma is recommended.

Our proposed case definitions had similar operating characteristics to those reported previously. However, in replicating case definition algorithms from both Xi et al. [ 11 ] and Cave et al. [ 12 ] (Table 1 ), we found different results across all metrics calculated. For example, for Case Definition 1, Xi et al. (2015) report a SN of 78% and SP of 89%, compared to a SN of 35% and SP of 99% in our study. For Case Definition 3, Xi (2015) reported a SN of 7% and SP of 99%, compared to a SN of 4% and SP of 100% in our study [ 11 ]. Case Definitions 1 and 3 were attempts to replicate their algorithms and were considered approximated because the original case definition algorithms used information directly from the source EMR in OSCAR. For Cave et al., the metrics were similar, with a reported a SN of 83%, SP of 99%, PPV of 74%, NPV of 99%, and a Youden’s Index of 0.82, compared to a SN of 78%, SP of 97%, PPV of 75%, NPV of 98%, and YI of 0.73 in our study. [ 12 ]

This variability can likely be attributed to the variation in the data sources used for case definition analysis and the variation in charting behaviour between clinical sites. Xi et al. (2015) created a cohort with a high proportion of patients with asthma and COPD for analysis. In contrast, we used a population-based sample, thus having a lower asthma prevalence, reducing SP and PPV while improving SN and NPV. In Cave et al.’s (2020) study, the authors used data from the Southern Alberta Primary Care Research Network of CPCSSN (SAPCReN-CPCSSN) to classify cases of asthma. In this study, reviewers used the source EMR for classification, allowing for a complete review of the patient’s entire medical history.

The results of this study highlight the importance of having discrete data elements for asthma diagnostic tests in EMRs, particularly given that there were no searchable data elements that enabled us to differentiate between suspected and confirmed asthma. In addition, in EMRs, there is no requirement for confirming asthma diagnosis through objective measures such as spirometry or a methacholine challenge test. EMRs should incorporate data elements such as those proposed by the Pan-Canadian Respiratory Standards Initiative for Electronic Health Records (PRESTINE) so that providers are able to document whether asthma is suspected or confirmed, and if confirmed by what method [ 7 , 20 ]. Data elements that capture if asthma has been confirmed would enable case definition search strategies to differentiate between suspected and confirmed asthma [ 19 ]. By adopting these data elements, knowledge translation eTools could provide decision support to healthcare providers on cases of suspected asthma that require objective testing, while simultaneously improving asthma surveillance by ensuring cases of asthma are confirmed asthma [ 21 ].

In our study, although we included every medication combination presented in the CTS guidelines for asthma management [ 3 ] (Case Definitions M1-M7), medication data did not improve the operating characteristics of detection algorithms (Table 1 ). The proposed case definitions that included medication data had a wide sensitivity range, from 0 to 76%. This result differs from previous literature on asthma case definitions, which discuss adding medications as an effective way to improve case definitions [ 22 ]. We believe that this may be because many medications are now being used for both asthma and COPD, and as could contribute to misdiagnosis of asthma and COPD if used as part of EMR algorithms. Additionally, this finding suggests that researchers creating asthma case definitions must be very specific in their inclusion or exclusion of medications in case definitions.

The findings of our study fit well within the existing literature on the validation of asthma diagnoses using EMRs. A recent study from Howell et al. [ 23 ] developed a case definition algorithm for asthma using EMR data from a pulmonary specialty clinic. This study’s best-case definition had a SN of 94% and a SP of 85%. These results are slightly higher than the results of our study. In this case, the slightly higher SN and SP can be attributed to using a specialty clinic, which would be more likely to have confirmed cases of asthma, improving specificity, and a higher relative proportion of patients with asthma, improving sensitivity. Another systematic review of literature on the validation of asthma diagnoses in electronic health records by Nissen et al. described 13 studies on the subject [ 22 ]. The authors found that most studies were able to demonstrate a high positive predictive value (PPV > 80%), with a high degree of variation based on methodology used. Our study builds upon the systematic review by using a national database that can utilize the case definition in primary care practices across Canada.

We were able to directly replicate the case definition proposed by Cave et al., given that it also used CPCSSN data holdings. For case definition 13, Cave et al. (2020) reported a SN of 83% (+ 5%), a SP of 99% (+ 2%), PPV of 74% (-1%), NPV of 99% (-1%), and a Youden’s Index of 0.82 (+ 0.09), which are nearly identical to our results. The discrepancy between the findings can be attributed to the data source used for classifying cases of asthma and the data source used for validating the case definition.

The clinical implications of using a combined case definition for asthma in primary care EMRs for suspected and confirmed asthma are important to consider. Until EMR data elements that document whether asthma has been confirmed by objective lung function tests are widely adopted, surveillance data utilizing an asthma EMR case definition that cannot differentiate between suspected and confirmed asthma may over-estimate true asthma prevalence. Separate case definitions would provide more accurate information on disease patterns, prevalence, and performance measurement for quality improvement. Future knowledge translation initiatives should focus on adoption of EMR data elements that would allow separate EMR case definitions for the suspected and confirmed asthma.

Strengths of this study include using the original EMR source data for chart abstraction and classification. By manually reviewing the patient chart, the abstractor and physicians had the entire medical record of a patient available to accurately classify the charts based on all information available. Another strength of this study is the use of CPCSSN data holdings for testing and validating case definitions. CPCSSN data is more granular than health administrative data that has been used for case definitions of asthma in the past. This is due to CPCSSN’s data being derived from primary care medical records which have more specific information than health administrative data. In addition to CPCSSN’s added specificity, CPCSSN remains more broadly applicable than data from a single EMR as it compiles data from multiple EMR platforms [ 24 ]. Another strength of utilizing CPCSSN as a database is to improve the generalizability of the study, as CPCSSN can analyze data from all major EMR providers in Canada. This allows the proposed case definition to be applied across the country to various primary care settings and EMR providers. Additional strengths of this study are the use of a single abstractor and experts for classification purposes, which ensured consistency in both data collection and final classification of cases.

Limitations

Limitations of this study include generalizability and the data source. This exercise was conducted at a single academic clinical site that is a member of CPCSSN. It may be difficult to generalize the findings at this academic primary care practice to community practices, as the case mix may differ, and this particular practice may have unique charting, billing, and data entry patterns. Additionally, this study used information from one EMR, OSCAR. As a result, the case definitions developed in this study may have different results when applied to other EMRs, although the criteria used in the CPCSSN database applies to sites across Canada.

An EMR case definition for confirmed or suspected adult asthma has been validated against original primary care EMR data for use in primary care, including CPCSSN. Implementation of this case definition will enable surveillance and quality improvement of adult asthma care in primary care sites across Canada. Currently, it is not possible to differentiate between suspected and confirmed asthma in primary care EMRs or CPCSSN datasets. As such, adoption of Pan-Canadian standards for EMR elements and algorithms, as proposed by PRESTINE, that identify suspected but unconfirmed asthma and prompt further investigations, is critical to improving the diagnostic accuracy of primary care surveillance and quality improvement systems. Incorporating these data elements into EMR platforms will enable validation of more specific asthma case definitions, and improve surveillance, and quality improvement opportunities for primary care practices.

Availability of data and materials

The datasets used during the study are available from the corresponding author upon reasonable request.

Abbreviations

Canadian Primary Care Sentinel Surveillance Network

Canadian Thoracic Society

Electronic medical records

Electronic tools

Health Sciences and Affiliated Teaching Hospitals Research Ethics Board

International Classification of Disease, Ninth Revision

Negative predictive value

Positive predictive value

Pan-Canadian Respiratory Standards Initiative for Electronic Health Records

Queen’s University Family Health Team

Sensitivity

Specificity

Youden’s index

Canada S. Asthma in Canada, by Age Group. Stat Canada, 2021.

Lougheed MD, et al. Canadian Thoracic Society 2012 guideline update: diagnosis and management of asthma in preschoolers, children and adults. Can Respir J. 2012;19:127–64.

Article PubMed PubMed Central Google Scholar

Yang CL, et al. Canadian Thoracic Society 2021 Guideline update: diagnosis and management of asthma in preschoolers, children and adults. Can J Respir Crit Care Sleep Med. 2021;5:348–61.

Google Scholar

Wu TD, Brigham EP, McCormack MC. Asthma in the primary care setting. Med Clin North Am. 2019;103:435–44.

Gershon AS, Victor JC, Guan J, Aaron SD, To T. Pulmonary function testing in the diagnosis of asthma: a population study. Chest. 2012;141:1190–6.

Article PubMed Google Scholar

Aaron SD, Boulet LP, Reddel HK, Gershon AS. Underdiagnosis and overdiagnosis of asthma. Am J Respir Crit Care Med. 2018;198:1012–20.

Taite A, Minard J, Morra A, Lougheed MD. Supporting asthma and COPD best practices in Ontario through primary care electronic medical records. Healthc Q. 2020;23:67–74.

To T, et al. Evidence-based performance indicators of primary care for asthma: a modified RAND Appropriateness Method. Int J Qual Heal Care. 2010;22:476–85.

Article Google Scholar

Garies S, Birtwhistle R, Drummond N, Queenan J, Williamson T. Data Resource Profile: national electronic medical record data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). Int J Epidemiol. 2017;46:1091–9.

Cave A, et al. Chronic obstructive pulmonary disease as a risk factor in primary care: a Canadian retrospective cohort study. NPJ Prim Care Respir Med. 2021;31:1–4.

Xi N, et al. Identifying patients with asthma in primary care electronic medical record systems: chart analysis-based electronic algorithm validation study. Can Fam Physician. 2015;61:474–83.

Cave AJ, et al. Validating a case definition for adult asthma in primary care electronic medical records. Prim Care Respir Med. 2020;30:1–4.

McBrien KA, et al. Identification of validated case definitions for medical conditions used in primary care electronic medical record databases: a systematic review. J Am Med Inform Assoc. 2018;25:1567–78.

Birtwhistle R, Williamson T. Primary care electronic medical records: a new data source for research in Canada. CMAJ. 2015;187:239–40.

Moloney M, et al. Primary care asthma surveillance: a review of knowledge translation tools and strategies for quality improvement. Allergy Asthma Clin Immunol. 2023;19:3.

Safadi H, Chan D, Dawes M, Roper M, Faraj S. Open-source health information technology: a case study of electronic medical records. Heal Policy Technol. 2015;4:14–28.

Crighton EJ, Feng J, Gershon A, Guan J, To T. A spatial analysis of asthma prevalence in Ontario. Can J Public Heal. 2012;2012(103):384–9.

Public Health Agency of Canada. Report from the Canadian Chronic Disease Surveillance System: asthma and chronic obstructive pulmonary disease (COPD) in Canada. 2018.

Lougheed MD, et al. Pan-Canadian asthma and COPD standards for electronic health records: a Canadian thoracic society expert working group report. Can J Respir Crit Care Sleep Med. 2018;2:244–50.

Moloney M, et al. Integrating user preferences for asthma tools and clinical guidelines into primary care electronic medical records: mixed methods study. JMIR Form Res. 2023. https://doi.org/10.2196/42767 .

Lougheed MD. Pan-Canadian standards for severe asthma in electronic medical records. 2021; 5 :391–399.

Nissen F, et al. Validation of asthma recording in electronic health records: a systematic review. Clin Epidemiol. 2017;9:643–56.

Howell D, Rogers L, Kasarskis A, Twyman K. Comparison and validation of algorithms for asthma diagnosis in an electronic medical record system. Ann Allergy Asthma Immunol. 2022;128:677–81.

Gershon AS, Guan J, Wang C, To T. Trends in asthma prevalence and incidence in Ontario, Canada, 1996–2005: a population study. Am J Epidemiol. 2010;172:728–36.

Download references

Acknowledgements

Not applicable.

This study was funded by the Southeastern Ontario Academic Medical Organization Innovation Fund Grant.

Author information

Authors and affiliations.

Asthma Research Unit, Kingston General Hospital, Kingston Health Sciences Centre at Queen’s University, 72 Stuart Street, Kingston, ON, K7L 2V7, Canada

Max Moloney, Alison Morra & M. Diane Lougheed

Division of Respirology, Department of Medicine, Queen’s University, Kingston, ON, Canada

Max Moloney, Alison Morra, Geneviève Digby & M. Diane Lougheed

Department of Family Medicine, Queen’s University, Kingston, ON, Canada

John Queenan & David Barber

Canadian Primary Care Sentinel Surveillance Network (Eastern Ontario Network), Kingston, ON, Canada

Rachael Morkem & David Barber

Division of Respirology, Department of Medicine, St. Michael’s Hospital, Toronto, ON, Canada

Samir Gupta

Department of Medicine, University of Toronto, Toronto, ON, Canada

Child Health Evaluative Science, The Hospital for Sick Children, Toronto, ON, Canada

Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

You can also search for this author in PubMed Google Scholar

Contributions

MDL conceived the premise of this study. MM, DB, and RM conducted the data analysis. MM wrote the first draft of the manuscript with revisions from MDL and AM. JQ, SG, TT, and GD provided guidance, suggestions, and revisions for this manuscript.

Corresponding author

Correspondence to Max Moloney .

Ethics declarations

Ethics approval and consent to participate.

The study was reviewed for ethical compliance by the Queen’s University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board (Reference #6029444).

Consent for publication

Competing interests.

The authors declare that they have no competing interests.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1:.

Table S1. Asthma Medications List. Table S2. Additional Sample Characteristics (n=743). Table S3. Case Definition Results (Combined Suspected or Confirmed Asthma). Table S4. Case Definition Results (Suspected Asthma). Table S5. Case Definition Results (Confirmed Asthma).

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Moloney, M., Morra, A., Morkem, R. et al. Validation of adult asthma case definitions for primary care sentinel surveillance. Allergy Asthma Clin Immunol 19 , 95 (2023). https://doi.org/10.1186/s13223-023-00854-8

Download citation

Received : 28 June 2023

Accepted : 01 November 2023

Published : 13 November 2023

DOI : https://doi.org/10.1186/s13223-023-00854-8

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Quality improvement
Knowledge translation

Allergy, Asthma & Clinical Immunology

ISSN: 1710-1492

Submission enquiries: [email protected]
General enquiries: [email protected]

Join our Mailing List

Working locally in primary care and collaborating globally to improve respiratory health

Clinical case study - asthma, clinical case study - asthma, resource information.

Disease management

Open access
Published: 01 December 2023

Prediction of the number of asthma patients using environmental factors based on deep learning algorithms

Hyemin Hwang 1 ,
Jae-Hyuk Jang 2 ,
Eunyoung Lee 3 ,
Hae-Sim Park 2 &
Jae Young Lee 4

Respiratory Research volume 24 , Article number: 302 ( 2023 ) Cite this article

993 Accesses

3 Altmetric

Metrics details

Air pollution, weather, pollen, and influenza are typical aggravating factors for asthma. Previous studies have identified risk factors using regression-based and ensemble models. However, studies that consider complex relationships and interactions among these factors have yet to be conducted. Although deep learning algorithms can address this problem, further research on modeling and interpreting the results is warranted.

In this study, from 2015 to 2019, information about air pollutants, weather conditions, pollen, and influenza were utilized to predict the number of emergency room patients and outpatients with asthma using recurrent neural network, long short-term memory (LSTM), and gated recurrent unit models. The relative importance of the environmental factors in asthma exacerbation was quantified through a feature importance analysis.

We found that LSTM was the best algorithm for modeling patients with asthma. Our results demonstrated that influenza, temperature, PM 10 , NO 2, CO, and pollen had a significant impact on asthma exacerbation. In addition, the week of the year and the number of holidays per week were an important factor to model the seasonality of the number of asthma patients and the effect of holiday clinic closures, respectively.

LSTM is an excellent algorithm for modeling complex epidemiological relationships, encompassing nonlinearity, lagged responses, and interactions. Our study findings can guide policymakers in their efforts to understand the environmental factors of asthma exacerbation.

Asthma is one of the most prevalent respiratory diseases that have a significant public health burden. According to the Global Asthma Report 2022, 262 million people were affected by asthma, and 461 thousand people died from asthma worldwide in 2019 [ 1 ]. In addition, asthma is a chronic disease that seriously reduces patients’ quality of life but has no definitive cure [ 2 ].

Due to the severity of asthma, many previous studies have attempted to understand the risk factors that exacerbate asthma, and various environmental factors such as air pollution, tobacco smoke, weather, allergens such as pollen, and pathogens such as influenza viruses have been identified as culprits for asthma exacerbation [ 3 ]. These studies mostly used regression-based statistical models such as the generalized linear model (GLM) [ 4 ], generalized additive model (GAM) [ 5 ], and distributed lag nonlinear model (DLNM) [ 6 ] and ensemble-based machine learning models such as the random forest (RF) [ 7 ] and gradient boosting machine (GBM) [ 8 ]. Cassino et al. analyzed tobacco use and O 3 -associated emergency room visits for asthma in New York City based on a Poisson regression model [ 9 ]. Lee et al. studied the effects of air pollutants, pollen, weather conditions, and viruses on the number of emergency room patients with asthma in Seoul, South Korea, using DLNM [ 10 ]. Chen et al. studied the lagged nonlinear relationship between temperature and adult asthma hospitalizations in Beijing using the DLNM [ 2 ]. Sun et al. studied the association between pollen (trees, weeds, and grasses) and asthma in North Carolina using DLNM [ 11 ]. Jeddi et al. compared machine learning models for pediatric asthma diagnosis by considering environmental factors such as mites, cold air, strong odors, and mold [ 12 ]. Although previous studies have succeeded in identifying risk factors and modeling the risk of asthma using conventional statistical and machine learning algorithms, our understanding and modeling accuracy remain insufficient because of the complexities associated with nonlinearity, lagged relationships, interactions between factors, multicollinearity, and various confounders.

To model the relationship with higher accuracy, researchers have started to utilize state-of-the-art deep learning algorithms such as recurrent neural networks (RNNs) [ 13 ], long short-term memory (LSTM) [ 14 ], and gated recurrent units (GRUs) [ 15 ]. Woo et al. predicted the peak expiratory flow rate in children with asthma using real-time indoor air pollution data using RNN, GRU, and deep neural network [ 16 ]. Kim et al. studied the association between indoor particulate matter (PM) and asthma attacks in children in South Korea using the LSTM [ 17 ]. Chang and Ku used LSTM to predict the daily number of patients with asthma affected by weather and air pollution in Seoul, South Korea [ 18 ]. As research based on deep learning algorithms in the field of public health is still in its early stages, more research on modeling methodologies and epidemiological results from the models is necessary.

This study examined the association between the number of patients with asthma and 18 environmental factors in South Korea between 2015 and 2019 using the RNN, LSTM, and GRU algorithms. Eighteen environmental factors were categorized into air pollution, weather, pollen, and influenza. The accuracy of the model developed in this study was compared with that of conventional algorithms (GLM, GAM, RF, and GBM), and permutation feature importance analysis was performed to identify the critical factors in asthma exacerbation and understand the interaction between various factors.

Data collection

Weekly counts of patients with asthma in South Korea from 2015 to 2019 were collected by the Health Insurance Review and Assessment Service. Patients with asthma were defined as those aged 17 years or older who visited a healthcare facility and were diagnosed with asthma (ICD-10 codes J45, J46, J820, and J828). The number of outpatients and emergency room (ER) patients with asthma was determined separately. Environmental data were collected from South Korea from 2015 to 2019. Daily air pollutant concentrations of CO, NO 2 , O 3 , PM 10 , PM 2.5 , and SO 2 were collected from 556 nationwide measurement stations by the Korea Environment Corporation. Daily meteorological data on mean temperature, minimum temperature, maximum temperature, diurnal temperature range, humidity, precipitation, solar radiation, and wind speed were collected from 100 measurement stations in South Korea by the Korea Meteorological Administration. The data collected from multiple measurement stations spread across the entire nation were averaged to obtain national air pollution and meteorological data. Any missing values, if present, from the measurement stations were excluded during the averaging. Data regarding the hazard index of the daily pollen concentration from oaks, pines, and grasses were obtained from the Korea Meteorological Administration. This index was designed to forecast pollen concentrations based on meteorological and environmental factors (see Additional file 1 : Table S1 for a detailed description). Weekly numbers of influenza and Middle East respiratory syndrome (MERS) patients were collected by the Korea Centers for Disease Control and Prevention. Patients with influenza were defined as those diagnosed with influenza (ICD-10 codes J10.0–J11.8) or those who had an influenza-like illness (ILI). ILI is defined by WHO as a respiratory infection with onset within the past ten days and a fever of ≥ 38 °C and cough or sore throat. Daily and regional data were averaged and converted into weekly national data for South Korea.

Prediction of patients with asthma using environmental factors based on deep learning algorithms

To model the relationship between the number of patients with asthma (outpatients or ER patients) and environmental factors, we used 18 environmental factors and four potential confounders as input data. The 18 environmental factors included six air pollutant concentrations (CO, NO 2 , O 3 , PM 10 , PM 2.5 , and SO 2 ), three pollen concentrations (pollen from oaks, pines, and grasses), eight meteorological conditions (mean temperature, minimum temperature, maximum temperature, diurnal temperature range, humidity, precipitation, solar radiation, and wind speed), and the number of patients with influenza. The four confounders were the week of the year, date, number of holidays per week, and number of patients with MERS. The week of the year is an indicator of where a particular week falls numerically within a year. The first week (week 1) of the year is defined as the week containing the first Wednesday of the year. For each year from 2015 to 2019, the week of the year is numbered from 1 to 52. The date is a number that incidates a specific point in time, and it is calculated as the number of days that have passed since January 1, 1970. These were used to model the confounding effects of seasonality, long-term trends, holidays, and the 2015 MERS outbreak. All input factors were preprocessed with minimum–maximum normalization before modeling.

We used the RNN, LSTM, and GRU as the deep learning algorithms. The model consisted of four layers: an input layer, two hidden layers, and an output layer. Recurrent cells were used only in the input layer, whereas simple, fully connected neural network cells without recurrent connections were used in the hidden and output layers to simplify the model (see Additional file 1 : Figure S1 for the topology). Dropout techniques were applied to all layers to prevent overfitting [ 19 , 20 ]. The optimum model size and dropout rates were selected empirically by finding the best model among various candidates (see Additional file 1 : Table S2 for the hyperparameter candidates). We used walk-forward expanding window cross-validation, where data from 2015–2016, 2015–2017, and 2015–2018 were used for training and data from 2017, 2018, and 2019 were used for testing, respectively. Walk-forward cross-validation is a well-known validation method for time-series data to remove the possibility of prediction leakage [ 21 , 22 ]. The length of time steps in RNN, LSTM, and GRU was set as 5 weeks to model the long-term lagged effects of environmental factors on asthma, and the training learning rate was set as 0.004. During training, the mean squared error (MSE) for the test set was monitored, and training was stopped when the observed MSE did not improve after 50 epochs. The modeling and training were implemented using the Python packages “keras” and “tensorflow” [ 23 , 24 ].

Comparison with conventional modeling methods

We compared the R 2 values of the neural network models with those of the GLM, GAM, RF, and GBM. The input and output variables used for modeling were identical to those used for the deep learning algorithms. The GLM and GAM were fitted using the maximum likelihood method under the assumption of a quasi-Poisson distribution. For the modeling and training of RF and GBM, the “sklearn” package of Python was used. The model hyperparameters for RF and GBM were optimized using “best_estimator_” of the “Grid method for the model’s trainingSearchCV” function (see Additional file 1 : Table S3 for the candidates) [ 25 ].

Permutation feature importance

After modeling, we evaluated the importance of all input features in the final model based on the permutation feature importance method [ 26 ], where feature importance is defined as the increase in the MSE when the values of a single feature are temporally shuffled. This method helps identify features with high contributions in predicting the output. In addition, we define the interaction between the two features as follows:

here, I is the interaction between two features, A and B, FI AB is the increase in MSE with both A and B shuffled, FI A is the increase in MSE with A shuffled, and FI B is the increase in MSE with B shuffled.

General analysis of the number of patients with asthma

Figure 1 shows the weekly numbers of outpatients and ER patients with asthma in South Korea for each year from 2015 to 2019 (see Additional file 1 : Figure S2 for the 5-year curves and Additional file 1 : Table S4 for descriptive statistics). From 2015 to 2019, the number of outpatients with asthma decreased, whereas the number of ER patients with asthma increased. The number of patients with asthma showed seasonal variability (Fig. 1 ), with the lowest in summer (July and August) and the highest in winter (December and January) and spring (March and April). Additional file 1 : Figures S3-S8 show the time-series curves of various independent variables, and Additional file 1 : Tables S5 and S6 show the descriptive statistics for air pollutant concentrations and climate conditions in South Korea during the study period.

The number of outpatients and ER patients with asthma in South Korea each year from 2015 to 2019. The areas shaded in green, red, and blue highlighted the weeks when the numbers of influenza patients, patients with MERS, and holidays surged, respectively. The peaks in the green and blue periods correspond to the peaks in the number of influenza patients and the number of holidays in a week. The smaller number of ER visits during the red period in 2015 compared to 2016–2019 can be attributed to the MERS outbreak that occurred in 2015

The areas shaded in green in Fig. 1 (between Weeks 1 and 4, and between Weeks 48 and 52) show the weeks when the number of influenza patients surged, especially in 2018 (see Additional file 1 : Figure S3 to find the surge in influenza patients). As shown in the figure, the number of patients with asthma increased during this period. The areas shaded in blue show the weeks in which the two biggest holidays in Korea, Lunar New Year’s Day (between Weeks 4 and 8) and Korean Thanksgiving Day (between Weeks 36 and 41), were located. During the holidays, the number of outpatients shows downward spikes due to the holiday clinic closures. In contrast, the number of ER patients shows upward spikes due to the “balloon effect” of the holiday clinic closures. This study used the number of holidays per week (Additional file 1 : Figure S3) to model the confounding effects of holidays. The area shaded in darker red in Fig. 1 (between weeks 21 and 28) represents the weeks in 2015 when the MERS outbreak occurred in South Korea (see Additional file 1 : Figure S3 for the number of patients with MERS). MERS is one of the 16 diseases classified as a “Class 1 infectious disease,” a term used for diseases of significant health importance owing to its high mortality rates; it was the only Class 1 infectious disease that caught public attention in South Korea during the study period. The area in lighter red (between weeks 28 and 32) shows the weeks between the last identification of patients with MERS and South Korea’s official declaration of a “de facto end” to MERS (July 28, 2015). During this period, the number of ER visits in many tertiary hospitals where patients with MERS were admitted was significantly reduced in 2015 because people were afraid of being infected. Since the MERS outbreak only occurred in 2015, the number of ER visits between weeks 21 and 32 in 2015 was apparently smaller than those during 2016–2019 as shown in Fig. 1 .

This is a confounding effect of Class 1 infectious diseases, such as MERS, and we attempted to model this effect using the number of patients as an independent variable. Note that there is a four-week lag between the last identification of the patient with MERS (Week 28) and getting back to normal with the declaration of “de facto end” (Week 32). LSTM and GRU are suitable for modeling such long lags using their long-term memory.

Modeling patients with asthma based on deep learning algorithms

To determine the best model for predicting the number of patients with asthma, we generated and trained 648 models of RNN, LSTM, and GRU (216 models each) and evaluated them with R 2 based on a walk-forward cross-validation framework. Figure 2 shows the R 2 histograms of 216 RNN, LSTM, and GRU models. The LSTM and GRU models performed better than the RNN models in predicting the number of patients with asthma. This may be due to the internal gates that solve the vanishing gradient problem in the RNN. Our results show that, in general, LSTM models perform slightly better than GRU models. This may be due to the higher number of gates in the LSTM model than in the GRU model (three in LSTM and two in GRU), providing more flexibility in modeling.

Performance (R 2 ) histograms of 216 RNN, LSTM, and GRU models

Additional file 1 : Figure S9 shows the performance (R 2 ) scatter plot for the 648 RNN, LSTM, and GRU models. The top 10% of the models are located in Area 1. Additional file 1 : Table S7 lists all hyperparameter values of the models in Area 1. For the final model, we selected the model that provided the best average performance for outpatients and ER patients (R 2 values of 0.723 for outpatients and 0.650 for ER patients).

Performance comparison of asthma patient predictive models

Table 1 compares the performances of the final RNN, LSTM, and GRU models with those of conventional algorithms. The hyperparameters used in the final model are listed in Additional file 1 : Table S7. Based on our results, LSTM was the best model for outpatients and ER patients, with R 2 of 0.723 and 0.650, respectively. This algorithm performed better than the other algorithms investigated in this study. The ensemble-based models (RF and GBM) performed the worst for both outpatients and ER patients (R 2 of − 0.321–0.583), whereas the regression-based models (GLM and GAM) ranked in the middle (R 2 of 0.631–0.706).

The R 2 gap between the training and test sets was the smallest for the GLM, indicating the least overfitting among all algorithms. This is likely the result of linear modeling, which has a lower chance of overfitting than nonlinear modeling. The R 2 gap was most significant for RF and GBM, indicating considerable overfitting. The gaps for RNN, LSTM, and GRU were smaller than those for GAM, RF, and GBM, despite the complexity and flexibility of the models. This results from the dropout and early stopping techniques implemented in training.

Feature importance analysis

Figure 3 shows the results of the feature importance analysis for outpatients and patients in the ER. In Fig. 3 , the blue dashed line shows the model’s baseline MSE, and any feature that yielded a higher MSE than the baseline after shuffling was considered significant (the higher the value, the more important it is). Influenza was one of the most important factors for outpatients and ER patients among the various environmental factors. Influenza can cause airway swelling, trigger asthma attacks, and exacerbate symptoms [ 27 ]. Temperature substantially impacted the number of outpatient visits and had little effect on the number of ER visits. This can be interpreted as the temperature being associated more with the gradual development of asthma than the acute development of asthma, which causes patients to visit non-emergency care facilities. Among four temperature-related factors (mean, maximum, minimum, and diurnal temperature range), the diurnal temperature range and minimum temperature were the two most critical factors affecting outpatients with asthma. Air pollutants such as NO 2 , CO, and PM 10 had a significant impact on outpatients while they had little impact on ER patients. This may indicate that asthma exacerbation attributable to NO 2 , CO, and PM 10 is not severe enough for patients to visit ER. Pine pollen had a substantial impact on the number of ER patients with asthma, whereas it had a relatively smaller impact on the number of outpatients with asthma. The association between pine pollen and ER patients with asthma can be observed in Additional file 1 : Figure S8 during the pine pollen season (between weeks 16 and 20). The week of the year and the number of holidays per week were also important in modeling the seasonal variability and confounding effect of holiday clinic closure, respectively. Additional file 1 : Figure S10 shows the two-dimensional feature importance analysis. Our result indicates that the simultaneous exposure to both NO 2 and CO has a synergic effect on asthma exacerbation. However, there is no significant interaction effect among other environmental factors.

Feature importance of ( a ) outpatients and ( b ) ER patients

The climate is known for impacting asthma directly through the airway response to climate or indirectly through altered exposure to air pollutants, allergens, and pathogens [ 28 ]. For example, high temperatures increase the ambient ozone through a photochemical reaction [ 29 ]. In addition, abrupt changes in weather and an extensive diurnal temperature range can increase the risk of asthma by affecting inflammatory responses and immunity [ 30 , 31 , 32 ]. In this study, we examined the association between outpatients with asthma and climate, and we showed that diurnal temperature range and minimum temperature are important factors in modeling. This result agrees with the results of previous studies. Chen et al. showed that both low and high temperatures were associated with an increased risk of asthma, whereas the majority of the burden was attributable to moderate cold exposures [ 2 ]. Xu et al. and Kim et al. studied the relationship between the diurnal temperature difference and asthma [ 33 , 34 ].

Air pollutants are associated with asthma through both direct and indirect mechanisms [ 35 ]. The infiltration of air pollutants can directly trigger inflammation and increase oxidative stress, which may lead to cell and tissue damage in airways [ 36 , 37 , 38 ]. Air pollutants can also be involved in indirect mechanisms interacting with inhaled pathogens and allergens, thereby increasing the risk of infections and allergic reactions [ 35 ]. The influence of NO 2 and CO on asthma patients was observed in this study, which agrees with a previous study demonstrating the impact of exposure to traffic emissions such as NO 2 and CO on asthma [ 39 ]. Additionally, PMs may act as a container for allergens and pathogens such as pollen, fungal spores, and viruses, delivering them deep into the airways [ 40 , 41 ]. In this study, the risk of asthma exacerbation with PM 10 was higher than that with PM 2.5 , which is consistent with the results of a previous study by Tecer et al. [ 42 ].

Influenza infection can trigger an immune response by releasing cytokines and increasing susceptibility to asthma [ 27 , 43 ]. Several studies have reported that influenza is associated with asthma exacerbation in adults [ 10 , 44 , 45 ].

This study had a few limitations. First, public environmental data was measured at official stations, instead of personal exposure data. This may have resulted in the underestimation of the actual impact of exposure to asthma-exacerbating environments. Second, demographic factors (such as age, gender, and sex) and socioeconomic conditions (such as occupation, income level, and educational attainment) were not considered in this study because such information was unavailable. Additional studies are warranted to consider such factors in modeling to increase the accuracy.

Conclusions

This study is the first to analyze the association between outpatients and ER patients with asthma and 18 environmental factors, including air pollutants, weather conditions, pollen, and influenza, in South Korea. Additionally, it proved the relative and quantitative importance of all 18 factors in terms of asthma exacerbation. Models with various hyperparameter values were evaluated to optimize the deep learning algorithm. With the optimal hyperparameters, we found that LSTM was the best model for predicting patients with asthma among the eight algorithms studied. It can model nonlinear lagged relationships with interactions between features without causing multicollinearity and overfitting problems. From feature importance analysis, we found out that influenza and pine pollen were the two most important factors exacerbating asthma in outpatients and ER patients.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Generalized linear model

Generalized additive model

Distributed lag nonlinear model

Random forest

Gradient boosting machine

Recurrent neural network
Long short-term memory
Gated recurrent unit

Particulate matter

Emergency room

Influenza-like illness

Middle East respiratory syndrome

Mean squared error

Coefficient of determination

Network TGA. The global asthma report 2022. Int J Tuberc Lung Dis. 2022;26:1–104.

Article Google Scholar

Chen Y, Kong D, Fu J, Zhang Y, Zhao Y, Liu Y, Chang Z, Liu Y, Liu X, Xu K, Jiang C, Fan Z. Associations between ambient temperature and adult asthma hospitalizations in Beijing, China: a time-stratified case-crossover study. Respir Res. 2022;23:1–2.

D’Amato G, Holgate ST, Pawankar R, Ledford DK, Cecchi L, Al-Ahmad M, Al-Enezi F, Al-Muhsen S, Ansotegui I, Baena-Cagnani CE, Baker DJ, Bayram H, Bergmann KC, Boulet LP, Buters JT, D’Amato M, Dorsano S, Douwes J, Finlay SE, Garrasi D, Gómez M, Haahtela T, Halwani R, Hassani Y, Mahboub B, Marks G, Michelozzi P, Montagni M, Nunes C, Oh JJ, Popov TA, Portnoy J, Ridolo E, Rosário N, Rottem M, Sánchez-Borges M, Sibanda E, Sienra-Monge JJ, Vitale C, Annesi-Maesano I. Meteorological conditions, climate change, new emerging factors, and asthma and related allergic disorders. A statement of the World Allergy Organization. World Allergy Organ J. 2015;8:1–52.

McCullagh P, Nelder JA. Generalized linear models. USA: Springer; 1983.

Book Google Scholar

Wood SN. Generalized additive models: an Introduction with R. 2nd ed. Boca Raton: CRC Press; 2017.

Gasparrini A. Distributed lag linear and non-linear models in R: the package dlnm. J Stat Softw. 2011;43:1–20.

Article PubMed PubMed Central Google Scholar

Ayyadevara VK. Random forest. In: Pro machine learning algorithms: a hands-on approach to implementing algorithms in Python and R. Berkeley, CA: Apress; 2018. p. 105–16.

Prettenhofer P, Louppe G. Gradient boosted regression trees in scikit-learn. InPyData 2014;2014.

Cassino C, Ito K, Bader IR, Ciotoli C, Thurston G, Reibman JO. Cigarette smoking and ozone-associated emergency department use for asthma by adults in New York City. Am J Respir Crit Care Med. 1999;159:1773–9.

Article CAS PubMed Google Scholar

Lee SW, Yon DK, James CC, Lee S, Koh HY, Sheen YH, Oh JW, Han MY, Sugihara G. Short-term effects of multiple outdoor environmental factors on risk of asthma exacerbations: age-stratified time-series analysis. J Allergy Clin Immunol. 2019;144:1542-50.e1.

Sun X, Waller A, Yeatts KB, Thie L. Pollen concentration and asthma exacerbations in Wake County, North Carolina, 2006–2012. Sci Total Environ. 2016;544:185–91.

Jeddi Z, Gryech I, Ghogho M, El Hammoumi M, Mahraoui C. Machine learning for predicting the risk for childhood asthma using prenatal, perinatal, postnatal and environmental factors. Healthcare (Basel). 2021;9:1464.

Article PubMed Google Scholar

Medsker LR, Jain LC, editors. Recurrent neural networks: design and applications. Boca Raton: CRC Press; 1999.

Google Scholar

Hochreiter S, Schmidhuber J. Long short-term memory. Neural Comput. 1997;9:1735–80.

Cho K, van Merrienboer B, Bahdanau D, Bengio Y. On the properties of neural machine translation: Encoder-decoder approaches. arXiv preprint arXiv:1409.1259 ; 2014.

Woo J, Lee JH, Kim Y, Rudasingwa G, Lim DH, Kim S. Forecasting the effects of real-time indoor PM2.5 on peak expiratory flow rates (PEFR) of asthmatic children in Korea: a deep learning approach. IEEE Access. 2022;10:19391–400.

Kim D, Cho S, Tamil L, Song DJ, Seo S. Predicting asthma attacks: effects of indoor PM concentrations on peak expiratory flow rates of asthmatic children. IEEE Access. 2019;8:8791–7.

Chang M, Ku Y. LSTM model for predicting the daily number of asthma patients in Seoul, South Korea, using meteorological and air pollution data. Environ Sci Pollut Res Int. 2023;30:37440–8.

Billa J. Dropout approaches for LSTM based speech recognition systems. In: 2018 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP). IEEE; 2018. p. 5879–83.

Pham V, Bluche T, Kermorvant C, Louradour J. Dropout improves recurrent neural networks for handwriting recognition. In: 2014 14th International Conference on Frontiers in Handwriting Recognition. IEEE; 2014. p. 285–90.

Yoon H. Time series data analysis using wavenet and walk forward validation. J Korea Soc Simul. 2021;30:1–8.

Tran TN, Phuc DT. Grid search of multilayer perceptron based on the walk-forward validation methodology. Int J Electr Comput Eng. 2021;11:1742.

Gulli A, Pal S. Deep learning with Keras. Birmingham: Packt Publishing Ltd; 2017.

Raschka S, Mirjalili V. Python machine learning: machine learning and deep learning with Python, scikit-learn, and TensorFlow 2. Birmingham: Packt Publishing Ltd.; 2019.

Pedregosa F, Varoquaux G, Gramfort A, Michel V, Thirion B, Grisel O, Blondel M, Prettenhofer P, Weiss R, Dubourg V, Vanderplas J, Passos A, Cournapeau D, Brucher M, Perrot M, Duchesnay E. Scikit-learn: machine learning in Python. J Mach Learn Res. 2011;12:2825–30.

Altmann A, Toloşi L, Sander O, Lengauer T. Permutation importance: a corrected feature importance measure. Bioinformatics. 2010;26:1340–7.

Xiong X, Wei Y, Lam HCY, Wong CKH, Lau SYF, Zhao S, Ran J, Li C, Jiang X, Yue Q, Cheng W, Wang H, Wang Y, Chong KC. Association between cold weather, influenza infection, and asthma exacerbation in adults in Hong Kong. Sci Total Environ. 2023;857: 159362.

Hales S, Lewis S, Slater T, Crane J, Pearce N. Prevalence of adult asthma symptoms in relation to climate in New Zealand. Environ Health Perspect. 1998;106:607–10.

Article CAS PubMed PubMed Central Google Scholar

Bloomer BJ, Stehr JW, Piety CA, Salawitch RJ, Dickerson RR. Observed relationships of ozone air pollution with temperature and emissions. Geophys Res Lett 2009;36.

Bull GM. The weather and deaths from pneumonia. Lancet. 1980;1:1405–8.

Graudenz GS, Landgraf RG, Jancar S, Tribess A, Fonseca SG, Faé KC, Kalil J. The role of allergic rhinitis in nasal responses to sudden temperature changes. J Allergy Clin Immunol. 2006;118:1126–32.

Togias AG, Naclerio RM, Proud D, Fish JE, Adkinson NF Jr, Kagey-Sobotka A, Norman PS, Lichtenstein LM. Nasal challenge with cold, dry air results in release of inflammatory mediators. Possible mast cell involvement. J Clin Invest. 1985;76:1375–81.

Xu Z, Huang C, Su H, Turner LR, Qiao Z, Tong S. Diurnal temperature range and childhood asthma: a time-series study. Environ Health. 2013;12:12.

Kim J, Lim Y, Kim H. Outdoor temperature changes and emergency department visits for asthma in Seoul, Korea: a time-series study. Environ Res. 2014;135:15–20.

Bronte-Moreno O, González-Barcala FJ, Muñoz-Gall X, Pueyo-Bastida A, Ramos-González J, Urrutia-Landa I. Impact of air pollution on asthma: a scoping review. Open Respir Arch. 2023;5: 100229.

Cohen AJ, Brauer M, Burnett R, Anderson HR, Frostad J, Estep K, Balakrishnan K, Brunekreef B, Dandona L, Dandona R, Feigin V, Freedman G, Hubbell B, Jobling A, Kan H, Knibbs L, Liu Y, Martin R, Morawska L, Pope CA 3rd, Shin H, Straif K, Shaddick G, Thomas M, van Dingenen R, van Donkelaar A, Vos T, Murray CJL, Forouzanfar MH. Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015. Lancet. 2017;389:1907–18.

Kelly FJ. Oxidative stress: its role in air pollution and adverse health effects. Occup Environ Med. 2003;60:612–6.

Li XY, Gilmour PS, Donaldson K, Macnee W. In vivo and in vitro proinflammatory effects of particulate air pollution (PM10). Environ Health Perspect. 1997;105(suppl 5):1279–83.

Villeneuve PJ, Chen L, Rowe BH, Coates F. Outdoor air pollution and emergency department visits for asthma among children and adults: a case-crossover study in northern Alberta. Canada Environ Health. 2007;6:1–15.

Delfino RJ, Zeiger RS, Seltzer JM, Street DH, Matteucci RM, Anderson PR, Koutrakis P. The effect of outdoor fungal spore concentrations on daily asthma severity. Environ Health Perspect. 1997;105:622–35.

Ostro B, Lipsett M, Mann J, Braxton-Owens H, White M. Air pollution and exacerbation of asthma in African–American children in Los Angeles. Epidemiology. 2001;12:200–8.

Tecer LH, Alagha O, Karaca F, Tuncel G, Eldes N. Particulate matter (PM(2.5), PM(10–2.5), and PM(10)) and children’s hospital admissions for asthma and respiratory diseases: a bidirectional case-crossover study. J Toxicol Environ Health A. 2008;71:512–20.

Chang YJ, Kim HY, Albacker LA, Baumgarth N, McKenzie AN, Smith DE, Dekruyff RH, Umetsu DT. Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity. Nat Immunol. 2011;12:631–8.

Feldman LY, Zhu J, To T. Estimating age-specific influenza-associated asthma morbidity in Ontario, Canada. Respir Med. 2019;155:104–12.

Gerke AK, Yang M, Tang F, Foster ED, Cavanaugh JE, Polgreen PM. Association of hospitalizations for asthma with seasonal and pandemic influenza. Respirology. 2014;19:116–21.

Download references

This research was supported by the Fine Particle Research Initiative in East Asia Considering National Differences (FRIEND) Project through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT [Grant number NRF-2023M3G1A1090660], and this research was also supported by the National Research Foundation of Korea [Grant number NRF-2021R1C1C1013350].

Author information

Authors and affiliations.

Environmental Engineering Department, Ajou University, Suwon, 16499, Korea

Hyemin Hwang

Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, 16499, Korea

Jae-Hyuk Jang & Hae-Sim Park

Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA

Eunyoung Lee

Environmental and Safety Engineering Department, Ajou University, 206, World Cup-ro, Yeongtong-gu, Suwon, 16499, Korea

Jae Young Lee

You can also search for this author in PubMed Google Scholar

Contributions

HH: Data curation, Formal analysis, Methodology, Software, Visualization, Roles/Writing—original draft. J-HJ: Validation. EL: Data curation. H-SP: Conceptualization, Validation. JYL: Conceptualization, Supervision, Validation, Funding acquisition, Methodology, Writing—review & editing.

Corresponding author

Correspondence to Jae Young Lee .

Ethics declarations

Ethics approval and consent to participate.

Not applicable.

Consent for publication

Competing interests.

The authors declare that they have no competing interests.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1. table s1..

Information on pollen. Table S2. Hyperparameter candidates for the neural network models. Table S3. Hyperparameters considered for RF and GBM. Table S4. Descriptive statistics for the number of asthma patients in South Korea between 2015 and 2019. Table S5. Descriptive statistics for the air pollutant concentrations in South Korea between 2015 and 2019. Table S6. Descriptive statistics for the climate conditions in South Korea between 2015 and 2019. Table S7. The hyperparameter values of models in Area 1 of Figure S9 and the hyperparameter values selected for the final model. Figure S1. Topology of deep learning algorithms. Figure S2. The number of asthma outpatients and ER patients in South Korea between 2015 and 2019. The black line shows the linear regression fit of the patient data. Figure S3. The numbers of asthma patients, influenza patients, MERS patients, holidays in a week in South Korea in each year from 2015 to 2019. The areas shaded in green, red, and blue highlighted the weeks, when the numbers of influenza patients, MERS patients and holidays surged, respectively. Figure S4. The number of asthma patients and pollutant concentrations (CO, O 3 , and SO 2 ) in South Korea in each year from 2015 to 2019. Figure S5. The number of asthma patients and pollutant concentrations (NO 2 , PM 10 , and PM 2·5 ) in South Korea in each year from 2015 to 2019. Figure S6. The number of asthma patients, temperature, and relative humidity in South Korea in each year from 2015 to 2019. Figure S7. The number of asthma patients, precipitation, wind speed, and insolation in South Korea in each year from 2015 to 2019. Figure S8. The number of asthma patients and pollen hazard index in South Korea in each year from 2015 to 2019. Figure S9. Performance (R 2 ) scatter plot of modeling outpatients (x axis) and ER patients (y axis) for 648 models of RNN, LSTM, and GRU. The red dashed lines indicate the 90 percentile of R 2 for outpatients and ER patients. The four areas that were divided with the red dashed lines were denoted as Areas 1 to 4. Figure S10. Observed and predicted number of asthma patients for outpatient and ER patients.

Rights and permissions

Reprints and permissions

About this article

Cite this article.

Hwang, H., Jang, JH., Lee, E. et al. Prediction of the number of asthma patients using environmental factors based on deep learning algorithms. Respir Res 24 , 302 (2023). https://doi.org/10.1186/s12931-023-02616-x

Download citation

Received : 25 August 2023

Accepted : 25 November 2023

Published : 01 December 2023

DOI : https://doi.org/10.1186/s12931-023-02616-x

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Air pollution

Respiratory Research

ISSN: 1465-993X

General enquiries: [email protected]

Gas and propane stoves linked to 50,000 cases of childhood asthma, study finds

Gas stoves, found in more than 40 million U.S. homes, are likely giving some children asthma, new research suggests.

A study published Friday suggests that around 50,000 current cases of pediatric asthma in the U.S. are linked to long-term exposure to nitrogen dioxide from gas and propane stoves.

Nitrogen dioxide forms when natural gas is burned at high temperatures. It is known to irritate airways and worsen existing respiratory problems. Previous studies have also linked long-term exposure to new cases of asthma and chronic lung disease .

The new study, which researchers at Stanford University published in the journal Science Advances, suggests that the average yearly exposure to nitrogen dioxide from gas and propane stoves in U.S. homes may be close to the World Health Organization’s limit.

To reach those conclusions, the researchers measured nitrogen dioxide inside more than 100 U.S. kitchens while stoves were on and monitored how nitrogen dioxide spread to other rooms after the stoves were turned off. They accounted for various scenarios like windows being open or shut, burners on low versus high, and range hoods being on or off.

The team combined that data with information from a U.S. Energy Information Administration survey about how often people use their stoves and what indoor ventilation typically looks like. That yielded an overall estimate of annual exposure to nitrogen dioxide, which the researchers then used to calculate the approximate number of new asthma cases that would be expected as a result, based on past studies.

“If you don’t smoke in your home, then your gas stove is one of the largest sources of air pollution in your home,” said Yannai Kashtan, the study’s lead author and a doctoral candidate at Stanford's Doerr School of Sustainability.

A 2022 study similarly found that 13% of childhood asthma cases in the U.S. were attributable to gas stoves.

On average, the new study found, gas or propane stoves account for a yearly exposure to nitrogen dioxide of around 4 parts per billion. The WHO’s annual limit is about 5.3 parts per billion for indoor and outdoor air combined.

The study also noted that exposures tend to be higher in smaller homes, those where people cook often and homes without a hood to vent air from the kitchen to the outdoors.

Homes under 800 square feet have four times the amount of long-term exposure to nitrogen dioxide compared to homes larger than 3,000 square feet, the research showed. Exposure in those small homes exceeded the WHO’s safe limit.

“We often focus on outdoor air quality, but the indoor sources — stoves being one of them — could be just as important, if not more so, because of the amount of time people spend indoors,” said Susan Anenberg, chair of the environmental and occupational health department at George Washington University's Milken Institute School of Public Health, who was not involved in the research.

The study also revealed racial disparities in nitrogen dioxide exposure from gas stoves. American Indian and Alaska Native households had 60% more long-term exposure relative to the national average, while Black and Hispanic households had 20% more exposure. Poorer families also faced an increased risk.

“We found that poor people breathe dirtier air outdoors and — if they own a gas stove — indoors, too,” said Rob Jackson, a co-author of the study and a professor of Earth science at Stanford. “People in public housing and in poorer neighborhoods who often rent can’t switch their appliances because they don’t own them or they can’t afford to do so.”

The American Gas Association, a trade group representing energy companies that deliver natural gas, questioned some of the past research on which the new study relied.

It pointed to one paper which found that although cooking with gas slightly increased the risk of asthma in children, the result was not statistically significant. Because of that, among other reasons, AGA President and CEO Karen Harbert called the new study’s conclusions “misleading and unsupported.”

(The same paper, however, found that cooking with gas instead of electricity significantly increased the risk of pneumonia and chronic lung disease.)

Dr. Laura Paulin, a pulmonologist at Dartmouth Hitchcock Medical Center, said she often asks patients with lung disease about their cooking habits.

“Some people will say it themselves: ‘Every time I cook or every time my spouse cooks, I feel worse or have to leave the room,’” she said.

Even leaving the kitchen may not be sufficient, Paulin added: “We’re still seeing that the NO2 [nitrogen dioxide] concentrations are high everywhere — not just in the kitchen.”

To reduce exposure, opening windows or installing a range hood that vents outdoors may help, Jackson said, though it won’t eliminate the problem. His team also found that many people don’t use hoods due to the noise, and many hoods simply recirculate polluted air inside the home.

If possible, Jackson said, families with gas stoves could consider using a portable induction cooktop.

“Every time you’re boiling water for rice or noodles and you don’t have to turn your gas stove on, that’s a win for health,” he said.

Another option, Jackson added, would be laws that prohibit new buildings from installing gas stoves.

New York state passed such a policy last year: Electric heating and cooking will be required in some new buildings there by 2026 or 2029, depending on their height. Berkeley, California, also passed an ordinance in 2019 that prohibited natural gas hookups in new homes, but the city repealed the ban in March in response to a lawsuit by the California Restaurant Association.

“There’s such a viable alternative here that works the same way in terms of the use of the stove: electric stoves. It is not the case that we have to be stuck with these gas stoves,” Anenberg said.

However, at least two dozen states have passed laws prohibiting local governments from restricting gas use in buildings, according to an analysis from S&P Global Commodity Insights .

House Republicans have also introduced several bills that would limit regulations on gas stoves. Two of those bills passed in the House last year but stalled in the Senate. A vote on a third, the Hands Off Our Home Appliances Act, is expected next week.

Aria Bendix is the breaking health reporter for NBC News Digital.

An official website of the United States government

The .gov means it's official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you're on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Publications
Account settings
Browse Titles

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

StatPearls [Internet].

Case study: 60-year-old female presenting with shortness of breath.

Deepa Rawat ; Sandeep Sharma .

Affiliations

Last Update: February 20, 2023 .

Case Presentation

The patient is a 60-year-old white female presenting to the emergency department with acute onset shortness of breath. Symptoms began approximately 2 days before and had progressively worsened with no associated, aggravating, or relieving factors noted. She had similar symptoms approximately 1 year ago with an acute, chronic obstructive pulmonary disease (COPD) exacerbation requiring hospitalization. She uses BiPAP ventilatory support at night when sleeping and has requested to use this in the emergency department due to shortness of breath and wanting to sleep.

She denies fever, chills, cough, wheezing, sputum production, chest pain, palpitations, pressure, abdominal pain, abdominal distension, nausea, vomiting, and diarrhea.

She reports difficulty breathing at rest, forgetfulness, mild fatigue, feeling chilled, requiring blankets, increased urinary frequency, incontinence, and swelling in her bilateral lower extremities that are new-onset and worsening. Subsequently, she has not ambulated from bed for several days except to use the restroom due to feeling weak, fatigued, and short of breath.

There are no known ill contacts at home. Her family history includes significant heart disease and prostate malignancy in her father. Social history is positive for smoking tobacco use at 30 pack years. She quit smoking 2 years ago due to increasing shortness of breath. She denies all alcohol and illegal drug use. There are no known foods, drugs, or environmental allergies.

Past medical history is significant for coronary artery disease, myocardial infarction, COPD, hypertension, hyperlipidemia, hypothyroidism, diabetes mellitus, peripheral vascular disease, tobacco usage, and obesity. Past surgical history is significant for an appendectomy, cardiac catheterization with stent placement, hysterectomy, and nephrectomy.

Her current medications include fluticasone-vilanterol 100-25 mcg inhaled daily, hydralazine 50 mg by mouth, 3 times per day, hydrochlorothiazide 25 mg by mouth daily, albuterol-ipratropium inhaled every 4 hours PRN, levothyroxine 175 mcg by mouth daily, metformin 500 mg by mouth twice per day, nebivolol 5 mg by mouth daily, aspirin 81 mg by mouth daily, vitamin D3 1000 units by mouth daily, clopidogrel 75 mg by mouth daily, isosorbide mononitrate 60 mg by mouth daily, and rosuvastatin 40 mg by mouth daily.

Physical Exam

Initial physical exam reveals temperature 97.3 F, heart rate 74 bpm, respiratory rate 24, BP 104/54, HT 160 cm, WT 100 kg, BMI 39.1, and O2 saturation 90% on room air.

Constitutional: Extremely obese, acutely ill-appearing female. Well-developed and well-nourished with BiPAP in place. Lying on a hospital stretcher under 3 blankets.

HEENT:

Head: Normocephalic and atraumatic
Mouth: Moist mucous membranes
Macroglossia
Eyes: Conjunctiva and EOM are normal. Pupils are equal, round, and reactive to light. No scleral icterus. Bilateral periorbital edema present.
Neck: Neck supple. No JVD present. No masses or surgical scarring.
Throat: Patent and moist

Cardiovascular: Normal rate, regular rhythm, and normal heart sound with no murmur. 2+ pitting edema bilateral lower extremities and strong pulses in all four extremities.

Pulmonary/Chest: No respiratory status distress at this time, tachypnea present, (+) wheezing noted, bilateral rhonchi, decreased air movement bilaterally. The patient was barely able to finish a full sentence due to shortness of breath.

Abdominal: Soft. Obese. Bowel sounds are normal. No distension and no tenderness

Skin: Skin is very dry

Neurologic: Alert, awake, able to protect her airway. Moving all extremities. No sensation losses

Initial Evaluation

Initial evaluation to elucidate the source of dyspnea was performed and included CBC to establish if an infectious or anemic source was present, CMP to review electrolyte balance and review renal function, and arterial blood gas to determine the PO2 for hypoxia and any major acid-base derangement, creatinine kinase and troponin I to evaluate the presence of myocardial infarct or rhabdomyolysis, brain natriuretic peptide, ECG, and chest x-ray. Considering that it is winter and influenza is endemic in the community, a rapid influenza assay was obtained as well.

Largely unremarkable and non-contributory to establish a diagnosis.

Showed creatinine elevation above baseline from 1.08 base to 1.81, indicating possible acute injury. EGFR at 28 is consistent with chronic renal disease. Calcium was elevated to 10.2. However, when corrected for albumin, this corrected to 9.8 mg/dL. Mild transaminitis is present as seen in alkaline phosphatase, AST, and ALT measurements which could be due to liver congestion from volume overload.

Initial arterial blood gas with pH 7.491, PCO2 27.6, PO2 53.6, HCO3 20.6, and oxygen saturation 90% on room air, indicating respiratory alkalosis with hypoxic respiratory features.

Creatinine kinase was elevated along with serial elevated troponin I studies. In the setting of her known chronic renal failure and acute injury indicated by the above creatinine value, a differential of rhabdomyolysis is determined.

Influenza A and B: Negative

Normal sinus rhythm with non-specific ST changes in inferior leads. Decreased voltage in leads I, III, aVR, aVL, aVF.

Chest X-ray

Findings: Bibasilar airspace disease that may represent alveolar edema. Cardiomegaly noted. Prominent interstitial markings were noted. Small bilateral pleural effusions

Radiologist Impression: Radiographic changes of congestive failure with bilateral pleural effusions greater on the left compared to the right

Differential Diagnosis
Acute on chronic COPD exacerbation
Acute on chronic renal failure
Bacterial pneumonia
Congestive heart failure
Pericardial effusion
Hypothyroidism
Influenza pneumonia
Pulmonary edema
Pulmonary embolism
Confirmatory Evaluation

On the second day of the admission patient’s shortness of breath was not improved, and she was more confused with difficulty arousing on conversation and examination. To further elucidate the etiology of her shortness of breath and confusion, the patient's husband provided further history. He revealed that she is poorly compliant with taking her medications. He reports that she “doesn’t see the need to take so many pills.”

Testing was performed to include TSH, free T4, BNP, repeated arterial blood gas, CT scan of the chest, and echocardiogram. TSH and free T4 evaluate hypothyroidism. BNP evaluates fluid load status and possible congestive heart failure. CT scan of the chest will look for anatomical abnormalities. An echocardiogram is used to evaluate left ventricular ejection fraction, right ventricular function, pulmonary artery pressure, valvular function, pericardial effusion, and any hypokinetic area.

TSH: 112.717 (H)
Free T4: 0.56 (L)
TSH and Free T4 values indicate severe primary hypothyroidism.

BNP can be falsely low in obese patients due to the increased surface area. Additionally, adipose tissue has BNP receptors which augment the true BNP value. Also, African American patients with more excretion may have falsely low values secondary to greater excretion of BNP. This test is not that helpful in renal failure due to the chronic nature of fluid overload. This allows for desensitization of the cardiac tissues with a subsequent decrease in BNP release.

Repeat arterial blood gas on BiPAP ventilation shows pH 7.397, PCO2 35.3, PO2 72.4, HCO3 21.2, and oxygen saturation 90% on 2 L supplemental oxygen.

CT chest without contrast was primarily obtained to evaluate the left hemithorax, especially the retrocardiac area.

Radiologist Impression: Tiny bilateral pleural effusions. Pericardial effusion. Coronary artery calcification. Some left lung base atelectasis with minimal airspace disease.

Echocardiogram

The left ventricular systolic function is normal. The left ventricular cavity is borderline dilated.

The pericardial fluid is collected primarily posteriorly, laterally but not apically. There appeared to be a subtle, early hemodynamic effect of the pericardial fluid on the right-sided chambers by way of an early diastolic collapse of the RA/RV and delayed RV expansion until late diastole. A dedicated tamponade study was not performed.

The estimated ejection fraction appears to be in the range of 66% to 70%. The left ventricular cavity is borderline dilated.

The aortic valve is abnormal in structure and exhibits sclerosis.

The mitral valve is abnormal in structure. Mild mitral annular calcification is present. There is bilateral thickening present. Trace mitral valve regurgitation is present.

Myxedema coma or severe hypothyroidism
Pericardial effusion secondary to myxedema coma
COPD exacerbation
Acute on chronic hypoxic respiratory failure
Acute respiratory alkalosis
Bilateral community-acquired pneumonia
Small bilateral pleural effusions
Acute mild rhabdomyolysis
Acute chronic, stage IV, renal failure
Elevated troponin I levels, likely secondary to Renal failure
Diabetes mellitus type 2, non-insulin-dependent
Extreme obesity
Hepatic dysfunction

The patient was extremely ill and rapidly decompensating with multisystem organ failure, including respiratory failure, altered mental status, acute on chronic renal failure, and cardiac dysfunction. The primary concerns for the stability of the patient revolved around respiratory failure coupled with altered mental status. In the intensive care unit (ICU), she rapidly began to fail BiPAP therapy. Subsequently, the patient was emergently intubated in the ICU. A systemic review of therapies and hospital course is as follows:

Considering the primary diagnosis of myxedema coma, early supplementation with thyroid hormone is essential. Healthcare providers followed the American Thyroid Association recommendations, which recommend giving combined T3 and T4 supplementation; however, T4 alone may also be used. T3 therapy is given as a bolus of 5 to 20 micrograms intravenously and continued at 2.5 to 10 micrograms every 8 hours. An intravenous loading dose of 300 to 600 micrograms of T4 is followed by a daily intravenous dose of 50 to 100 micrograms. Repeated monitoring of TSH and T4 should be performed every 1 to 2 days to evaluate the effect and to titrate the dose of medication. The goal is to improve mental function. Until coexistent adrenal insufficiency is ruled out using a random serum cortisol measurement, 50 to 100 mg every 8 hours of hydrocortisone should be administered. In this case, clinicians used hydrocortisone 100 mg IV every 8 hours. Dexamethasone 2 to 4 mg every 12 hours is an alternative therapy.

The patient’s mental status rapidly worsened despite therapy. In the setting of her hypothyroidism history, this may be myxedema coma or due to the involvement of another organ system. The thyroid supplementation medications and hydrocortisone were continued. A CT head without contrast was normal.

Respiratory

For worsening metabolic acidosis and airway protection, the patient was emergently intubated. Her airway was deemed high risk due to having a large tongue, short neck, and extreme obesity. As the patient’s heart was preload dependent secondary to pericardial effusion, a 1-liter normal saline bolus was started. Norepinephrine was started at a low dose for vasopressor support, and ketamine with low dose Propofol was used for sedation. Ketamine is a sympathomimetic medication and usually does not cause hypotension as all other sedatives do. The patient was ventilated with AC mode of ventilation, tidal volume of 6 ml/kg ideal body weight, flow 70, initial fio2 100 %, rate 26 per minute (to compensate for metabolic acidosis), PEEP of 8.

Cardiovascular

She was determined to be hemodynamically stable with a pericardial effusion. This patient’s cardiac dysfunction was diastolic in nature, as suggested by an ejection fraction of 66% to 70%. The finding of posterior pericardial effusion further supported this conclusion. The posterior nature of this effusion was not amenable to pericardiocentesis. As such, this patient was preload dependent and showed signs of hypotension. The need for crystalloid fluid resuscitation was balanced against the impact increased intravascular volume would have on congestive heart failure and fluid overload status. Thyroid hormone replacement as above should improve hypotension. However, vasopressor agents may be used to maintain vital organ perfusion targeting a mean arterial pressure of greater than 65 mm Hg as needed. BP improved after fluid bolus, and eventually, the norepinephrine was stopped. Serial echocardiograms were obtained to ensure that the patient did not develop tamponade physiology. Total CK was elevated, which was likely due to Hypothyroidism compounded with chronic renal disease.

Infectious Disease

Blood cultures, urine analysis, and sputum cultures were obtained. The patient's white blood cell count was normal. This is likely secondary to her being immunocompromised due to hypothyroidism and diabetes. In part, the pulmonary findings of diffuse edema and bilateral pleural effusions can be explained by cardiac dysfunction. Thoracentesis of pleural fluid was attempted, and the fluid was analyzed for cytology and gram staining to rule out infectious or malignant causes as both a therapeutic and diagnostic measure. Until these results return, broad-spectrum antibiotics are indicated and may be discontinued once the infection is ruled out completely.

Gastrointestinal

Nasogastric tube feedings were started on the patient after intubation. She tolerated feedings well. AST and ALT were mildly elevated, which was thought to be due to hypothyroidism, and as the TSH and free T4 improved, her AST and ALT improved. Eventually, these values became normal once her TSH level was close to 50.

Her baseline creatinine was found to be close to 1.08 in prior medical records. She presented with a creatinine of 1.8 in the emergency department. Since hypothyroidism causes fluid retention in part because thyroid hormone encourages excretion of free water and partly due to decreased lymphatic function in returning fluid to vascular circulation. Aggressive diuresis was attempted. As a result, her creatinine increased initially but improved on repeated evaluation, and the patient had a new baseline creatinine of 1.6. Overall she had a net change in the fluid status of 10 liters negative by her ten days of admission in the ICU.

Mildly anemic otherwise, WBC and platelet counts were normal. Electrolyte balance should be monitored closely, paying attention to sodium, potassium, chloride, and calcium specifically as these are worsened in both renal failure and myxedema.

Daily sedation vacations were enacted, and the patient's mental status improved and was much better when TSH was around 20. The bilateral pleural effusions improved with aggressive diuresis. Breathing trials were initiated when the patient's fio2 requirements decreased to 60% and a PEEP of 8. She was eventually extubated onto BiPAP and then high-flow nasal cannula while off of BiPAP. Pericardial fluid remained stable, and no cardiac tamponade pathology developed. As a result, it was determined that a pericardial window was unnecessary. Furthermore, she was not a candidate for pericardiocentesis as the pericardial effusion was located posterior to the heart. Her renal failure improved with improved cardiac function, diuretics, and thyroid hormone replacement.

After extubation patient had speech and swallow evaluations and was able to resume an oral diet. The patient was eventually transferred out of the ICU to the general medical floor and eventually to a rehabilitation unit.

Despite the name myxedema coma, most patients will not present in a coma status. This illness is at its core a severe hypothyroidism crisis that leads to systemic multiorgan failure. Thyroid hormones T3, and to a lesser extent, T4 act directly on a cellular level to upregulate all metabolic processes in the body. Therefore, deficiency of this hormone is characterized by systemic decreased metabolism and decreased glucose utilization along with increased production and storage of osmotically active mucopolysaccharide protein complexes into peripheral tissues resulting in diffuse edema and swelling of tissue. [1]

Myxedema coma is an illness that occurs primarily in females at a rate of 4:1 compared to men. It typically impacts the elderly at the age of greater than 60 years old, and approximately 90% of cases occur during the winter months. Myxedema coma is the product of longstanding unidentified or undertreated hypothyroidism of any etiology. Thyroid hormone is necessary throughout the body and acts as a regulatory hormone that affects many organ systems. [2] In cardiac tissues, myxedema coma manifests as decreased contractility with subsequent reduction in stroke volume and overall cardiac output. Bradycardia and hypotension are typically present also. Pericardial effusions occur due to the accumulation of mucopolysaccharides in the pericardial sac, which leads to worsened cardiac function and congestive heart failure from diastolic dysfunction. Capillary permeability is also increased throughout the body leading to worsened edema. Electrocardiogram findings may include bradycardia and low-voltage, non-specific ST waveform changes with possible inverted T waves.

Neurologic tissues are impacted in myxedema coma leading to the pathognomonic altered mental status resulting from hypoxia and decreased cerebral blood flow secondary to cardiac dysfunction as above. Additionally, hypothyroidism leads to decreased glucose uptake and utilization in neurological tissue, thus worsening cognitive function.

The pulmonary system typically manifests this disease process through hypoventilation secondary to the central nervous system (CNS) depression of the respiratory drive with blunting of the response to hypoxia and hypercapnia. Additionally, metabolic dysfunction in the muscles of respiration leads to respiratory fatigue and failure, macroglossia from mucopolysaccharide driven edema of the tongue leads to mechanical obstruction of the airway, and obesity hypoventilation syndrome with the decreased respiratory drive as most hypothyroid patients suffer from obesity.

Renal manifestations include decreased glomerular filtration rate from the reduced cardiac output and increased systemic vascular resistance coupled with acute rhabdomyolysis lead to acute kidney injury. In the case of our patient above who has a pre-existing renal disease status post-nephrectomy, this is further worsened. The net effect is worsened fluid overload status compounding the cardiac dysfunction and edema. [3]

The gastrointestinal tract is marked by mucopolysaccharide-driven edema as well leading to malabsorption of nutrients, gastric ileus, and decreased peristalsis. Ascites is common because of increased capillary permeability in the intestines coupled with coexistent congestive heart failure and congestive hepatic failure. Coagulopathies are common to occur as a result of this hepatic dysfunction.

Evaluation: The diagnosis of myxedema coma, as with all other diseases, is heavily reliant on the history and physical exam. A past medical history including hypothyroidism is highly significant whenever decreased mental status or coma is identified. In the absence of identified hypothyroidism, myxedema coma is a diagnosis of exclusion when all other sources of coma have been ruled out. If myxedema coma is suspected, evaluation of thyroid-stimulating hormone (TSH), free thyroxine (T4), and serum cortisol is warranted. T4 will be extremely low. TSH is variable depending on the etiology of hypothyroidism, with a high TSH indicating primary hypothyroidism and a low or normal TSH indicating secondary etiologies. Cortisol may be low indicating adrenal insufficiency because of hypothyroidism. [4]

Prognosis: Myxedema coma is a medical emergency. With proper and rapid diagnosis and initiation of therapy, the mortality rate is still as high as 25% to 50%. The most common cause of death is due to respiratory failure. The factors which suggest a poorer prognosis include increased age, persistent hypothermia, bradycardia, low score Glasgow Coma Scale, or multi-organ impairment indicated by high APACHE (Acute Physiology and Chronic Health Evaluation) II score. For these reasons, placement in an intensive care unit with a low threshold for intubation and mechanical ventilation can improve mortality outcomes. [3] [5]

Pearls of Wisdom
Not every case of shortness of breath is COPD or congestive heart failure (CHF). While less likely, a history of hypothyroidism should raise suspicion of myxedema coma in a patient with any cognitive changes.
Myxedema is the great imitator illness that impacts all organ systems. It can easily be mistaken for congestive heart failure, COPD exacerbation, pneumonia, renal injury or failure, or neurological insult.
Initial steps in therapy include aggressive airway management, thyroid hormone replacement, glucocorticoid therapy, and supportive measures.
These patients should be monitored in an intensive care environment with continuous telemetry. [6]
Enhancing Healthcare Team Outcomes

This case demonstrates how all interprofessional healthcare team members need to be involved in arriving at a correct diagnosis, particularly in more challenging cases such as this one. Clinicians, specialists, nurses, pharmacists, laboratory technicians all bear responsibility for carrying out the duties pertaining to their particular discipline and sharing any findings with all team members. An incorrect diagnosis will almost inevitably lead to incorrect treatment, so coordinated activity, open communication, and empowerment to voice concerns are all part of the dynamic that needs to drive such cases so patients will attain the best possible outcomes.

Review Questions
Access free multiple choice questions on this topic.
Comment on this article.

Case Study of 60 year old female presenting with Shortness of Breath Contributed by Sandeep Sharma, MD

Disclosure: Deepa Rawat declares no relevant financial relationships with ineligible companies.

Disclosure: Sandeep Sharma declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

Cite this Page Rawat D, Sharma S. Case Study: 60-Year-Old Female Presenting With Shortness of Breath. [Updated 2023 Feb 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

In this Page

Bulk download.

Bulk download StatPearls data from FTP

Related information

PubMed Links to PubMed

Recent Activity

Case Study: 60-Year-Old Female Presenting With Shortness of Breath - StatPearls Case Study: 60-Year-Old Female Presenting With Shortness of Breath - StatPearls

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Connect with NLM

National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894

Web Policies FOIA HHS Vulnerability Disclosure

Help Accessibility Careers

Share full article

Supported by

Gas Stove Pollution Risk Is Greatest in Smaller Homes, Study Finds

Gas-burning ranges, a significant contributor to indoor pollution, can produce and spread particularly high levels of some pollutants in smaller spaces.

Yannai Kashtan leans over a small, white stove, adjusting a knob.

By Hiroko Tabuchi

For decades, scientists have worked to clean up air pollution from factories, cars and power plants. But researchers are increasingly turning their attention to the air that people breathe indoors. And one appliance has come to the fore as a source of pollutants harmful to human health: the humble gas stove.

A new study from researchers at Stanford University sheds light on how much Americans may be exposed, indoors, to nitrogen dioxide, which comes from burning coal and gas and has been linked to asthma and other respiratory conditions.

The researchers found that, across the country, short-term nitrogen dioxide exposure from typical gas stove use frequently exceeded benchmarks set by both the World Health Organization and the United States Environmental Protection Agency. In the longer term, using gas or propane stoves meant that the typical American could breathe in three-quarters of the nitrogen dioxide levels deemed safe by the W.H.O. within their own homes.

As with outdoor pollution , disadvantaged households may be more exposed, the researchers found. Because gas more easily spreads throughout smaller spaces, people in homes smaller than 800 square feet were exposed to four times more nitrogen dioxide in the long term than people in homes larger than 3,000 square feet, the study found. Black and Latino households were exposed to 20 percent more nitrogen dioxide compared with the national average.

“We’ve done a really good job in this country of reducing outdoor pollution,” said Rob Jackson, professor of earth system science at the Stanford Doerr School of Sustainability and a principal investigator on the study, which was published on Friday in Science Advances. “But we’ve ignored the risks that people face indoors. And that’s the air that we’re breathing most of the time.”

And though home cooks who use a gas stove are particularly exposed to nitrogen dioxide, he said, “we’re getting a better handle on the migration of pollution down the hall, to the living room and the bedroom.”

The focus on gas stoves isn’t without critics. When a Biden administration official spoke about the health hazards of gas stoves last year, Republican politicians and their allies accused the administration of overreach and of planning to ban gas stoves outright.

Next week, House Republicans are set to meet on a bill called the Hands Off Our Home Appliances Act, which would make it harder for the Department of Energy to set more stringent energy-efficiency standards on household appliances, including gas stoves.

Health experts say that the health risks posed by gas stoves are significant. “There really is no safe amount of exposure to these toxicants produced by gas or propane, or any fossil fuel, outside or inside,” said Kari Nadeau, chairwoman of the Department of Environmental Health at the Harvard T.H. Chan School of Public Health.

The Stanford study estimated that long-term exposure to nitrogen dioxide from stoves was likely causing up to 50,000 cases of asthma in children.

Some cities and counties have tried to move away from gas altogether, as part of a transition to cleaner forms of energy. Over the past few years, more than 140 cities and local governments have sought to restrict gas hookups in new buildings or have taken other measures to end the use of natural gas in new buildings, though those measures have been challenged in court .

“It isn’t ideal to tell people, they have to rip a perfectly good gas stove out of their home,” Dr. Jackson said. But requiring new homes to install electric stoves, which the study found had virtually no harmful emissions, made sense, he said. “Otherwise, we’re putting dirty polluting infrastructure into the next set of homes, and it will be there and 50 years. No one benefits from that.”

The Stanford team took direct measurements of nitrogen dioxide emissions and concentrations at about 100 homes in San Francisco, Los Angeles, New York City and other major U.S. cities, and used indoor air-quality monitoring and epidemiological risk calculations to estimate exposure and health consequences.

They found that home cooks were exposed to three times more nitrogen dioxide pollution compared to the average, said Yannai Kashtan, a Ph.D. candidate at Stanford and the study’s lead researcher. Mr. Kashtan was the subject of a recent article on the debate at Stanford about fossil fuel funding for climate research.

For this study, the researchers also found that the pollution traveled quickly out of the kitchen, down hallways, and into living rooms and bedrooms.

Good ventilation, for example turning on the range hood or opening a window, helped to reduce exposure. But more than that, the study found that “the kind of stove you cook on matters the most,” Mr. Kashtan said. “Ultimately, the best way is to reduce pollution at the source.”

Hiroko Tabuchi covers the intersection of business and climate for The Times. She has been a journalist for more than 20 years in Tokyo and New York. More about Hiroko Tabuchi

Learn More About Climate Change

Have questions about climate change? Our F.A.Q. will tackle your climate questions, big and small .

Giant batteries are transforming the way the United States uses electricity. Here’s how .

Are carbon offsets for air travel worth it? A lot of them don’t work and some might even be harmful, but there are alternatives .

Cattle ranches have ruled the Amazon for decades. Now, new companies are selling something else: the ability of trees to lock away planet-warming carbon .

“Buying Time,” a series from The New York Times, looks at the risky ways humans are starting to manipulate nature to fight climate change.

Did you know the ♻ symbol doesn’t mean something is actually recyclable ? Read on about how we got here, and what can be done.

IMAGES

Case Study On Asthma
SOLUTION: Case study of bronchial asthma by sue
Asthma case study
Pediactric Asthma HESI Case Study;ANSWERED
Case Study (Asthma)
Asthma

VIDEO

Asthma Case Study
Case Discussion || Acute Asthma
#CASE STUDY ON ASTHMA #NURSING #EDUCATION
#shortvideo on case study in asthma #trendingshorts #youtubeshorts in bsc nursing & gnm students'
Asthma Case Study 3
ASTHMA CASE AND MAGIC OF HOMOEOPATHY

COMMENTS

Case Study: Managing Severe Asthma in an Adult
The majority of adverse effects occurred within 1 day of the procedure and resolved within 7 days. 6. In this study, bronchial thermoplasty was found to significantly improve quality of life, as ...
Educational Case: Asthma: Clinical Features and Morphologic Findings
Primary Objective. Objective: RS4.4: Asthma. Compare and contrast the clinicopathological features and causes of asthma and describe the morphologic changes and consequences that result in airflow obstruction. Competency 2: Organ System Pathology; Topic: Respiratory System (RS); Learning Goal 4: Obstructive Diseases of the Lung.
A woman with asthma: a whole systems approach to supporting ...
Supported self-management reduces asthma morbidity. The lady in this case study is struggling to maintain control of her asthma within the context of her busy professional and domestic life.
Asthma patients' and physicians' perspectives on the burden and
The Asthma Patients' and Physicians' Perspectives on the Burden and Management of Asthma (APPaRENT) study was a multinational, cross-sectional online survey of patients and physicians in four countries: Australia, Canada, China, and the Philippines. Patients and physicians were sampled and recruited from high-quality, non-probability panels.
Case Report: Conundrum in an asthma exacerbation
A 66-year-old man, an asthmatic, presented with symptoms suggestive of an acute exacerbation of asthma. His arterial blood gas revealed type 1 respiratory failure (PaO 2 <8 kPa or 60 mm Hg with normal or low PaCO 2) with a compensated lactic acidosis. He was treated for an asthma exacerbation and sepsis. Despite treatment, his respiratory rate ...
Pediatric severe asthma: a case series report and perspectives on anti
Moreover, in a real-life study of 104 children and adolescents with severe allergic refractory asthma followed over 1 year, treatment with omalizumab resulted in good asthma control in 67% of the cases (p < 0.001), while FEV 1 improved by 4.9% (p = 0.02) and exacerbation rates and healthcare utilisation decreased approximately by 30% (p < 0.001) .
Management of A Case of Uncontrolled Bronchial Asthma
CASE PRESENTATION: A 58 years old Caucasian male, non smoker, with late onset allergic asthma was referred to our pulmonary rehabilitation clinic because of deconditioning, wheezing and recurrent asthma exacerbations despite treatment with budesonide-formoterol 200/6 mcg b.i.d., montelukast 10 mg q.i.d. He had daily complaints of dyspnea both at rest and on exertion using almost 200 ...
Asthma: a case study, review of pathophysiology, and management
Purpose: To review the pathophysiology of asthma, present a case study, and provide management strategies for treating this common, yet complex disorder in children and adults. Data sources: Selected clinical guidelines, clinical articles, and research studies. Conclusions: Asthma is a chronic inflammatory airway disorder with acute exacerbations that currently affects approximately 14 million ...
Patient views on asthma diagnosis and how a clinical decision support
We received 53 expressions of interest within the study period and using purposive sampling, 27 individuals were invited to take part. 17 participants contributed to interviews, including 14 individuals with asthma and 3 parents of children with asthma (Table 1). All participants had been diagnosed with asthma before the COVID‐19 pandemic.
Long-Term Outcomes of Combination Biologic Therapy in ...
Our aim is to add our experience to the limited body of evidence supporting combination biologic therapies. Case study. Here we present the case of a 68-year-old nonsmoker female, with an allergic and eosinophilic corticosteroid-dependent severe asthma. She displayed well controlled comorbidities and good adherence to the inhaled therapy.
Case-control study of severe life threatening asthma (SLTA) in adults
BACKGROUND Severe life threatening asthma (SLTA) is important in its own right and as a proxy for asthma death. In order to target hospital based intervention strategies to those most likely to benefit, risk factors for SLTA among those admitted to hospital need to be identified. A case-control study was undertaken to determine whether, in comparison with patients admitted to hospital with ...
PDF Learning the Asthma Guidelines by Case Studies
Quick-Relief Medication for All Patients: SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals as needed. Short course of systemic oral corticosteroids may be needed. Caution: Increasing of b-agonist or use >2x/week for symptoms control indicates.
Asthma Essay With Conclusions
Conclusion. In conclusion asthma can be described as a chronic respiratory condition which can be identified by breathing difficulty, wheezing, cough and chest tightness. ... Case study on diabetes management. The following reflection is based on my experience of observing the care of MJ, a diabetic patient, using the model proposed by Boud ...
How do you diagnose asthma? A multiple case study design to understand
There was limited use of National Institute for Health and Care Excellence (NICE) 2017 guidelines. Barriers to guideline recommended diagnostic asthma care included: lack of acceptability, financial costs and disempowerment of nursing staff. Conclusion: The findings from this study replicate and reinforce the findings of previous work. It is ...
Asthma: A Case Study, Review of Pathophysiology, and Management
To review the pathophysiology of asthma, present a case study, and provide management strategies for treating this common, yet complex disorder in children and adults. ... Selected clinical guidelines, clinical articles, and research studies. Conclusions. Asthma is a chronic inflammatory airway disorder with acute exacerbations that currently ...
A case study of asthma care in school age children using nurse
Introduction: Despite symptoms control being the primary focus of asthma management according to guidelines, uncontrolled asthma is still an issue worldwide, leading to huge costs and asthma ...
A case of uncontrolled asthma
A 48-year-old female patient with uncontrolled severe asthma was referred to our hospital for anti-IgE therapy. She was suffering with persistent wheezing and dyspnea after a severe asthma attack that had taken place 5 months previously. Her asthma had not been controlled with adequate asthma treatment, including budesonide at 320 μg ...
Validation of adult asthma case definitions for primary care sentinel
Most asthma diagnoses and patient care take place in primary care settings. Electronic medical records (EMRs) offer an opportunity to utilize technology to improve asthma diagnosis and care. The purpose of this study was to create and validate separate case definitions for suspected and confirmed asthma in primary care EMRs, to enable surveillance, benchmarking, and quality improvement in ...
Clinical case study
Clinical case study - asthma . 2019 . Clinical Case Study - Asthma. pdf. Clinical Case Study - Asthma. 6.34 MB. Resource information. Respiratory conditions. Asthma; Respiratory topics. Disease management; Diagnosis; Type of resource. Presentation . Author(s) Jaime Correia de Sousa Ioanna Tsiligianni Miguel Román Rodriguez
PDF Asthma Right Care case studies
Primary Care Respiratory Update. The uncomfortable outputs of the NRAD1 report - why overuse of SABA can be indicative of poor asthma control. Understanding the signs and symptoms of asthma and early recognition of increasing symptoms - effective self-monitor-ing. Use of the Asthma Control Test and understanding of the scores.
Asthma: A descriptive case study
The fullowing case is a descriptive study of the positive effects of spinal manipulation on spinal dysfunction in a patient with a long history of asth- ma. Case Report Mrs T, a 33-year-old mother of a 2 year-old-chikt. had sufl:emd from asthma since the age of five years. However, since the birth of her child, which had been protracted ...
Prediction of the number of asthma patients using environmental factors
Background Air pollution, weather, pollen, and influenza are typical aggravating factors for asthma. Previous studies have identified risk factors using regression-based and ensemble models. However, studies that consider complex relationships and interactions among these factors have yet to be conducted. Although deep learning algorithms can address this problem, further research on modeling ...
Asthma
Case Example. A 32-year-old female smoker presents with a seven-day history of "bronchitis." ... bronchial inhalation challenge tests, blood and sputum studies, chest x-ray examination, or a combination of these procedures.2, 3. ... Conclusion. Asthma is an important chronic disease resulting in clinically significant morbidity, missed days ...
Gas stoves linked to childhood asthma cases, study finds
A 2022 study similarly found that 13% of childhood asthma cases in the U.S. were attributable to gas stoves. On average, the new study found, gas or propane stoves account for a yearly exposure to ...
Full article: Effectiveness of the Assessment of Burden of Chronic
The primary aim of the current study was to assess the effectiveness of using the ABCC-tool in patients with COPD, asthma, type 2 diabetes, or heart failure (or a combination of these) on the perceived quality of care, as measured by the Patient Assessment of Chronic Illness Care (PACIC), after 18 months as compared to usual care.
Case Study: 60-Year-Old Female Presenting With Shortness of Breath
Case Presentation. The patient is a 60-year-old white female presenting to the emergency department with acute onset shortness of breath. Symptoms began approximately 2 days before and had progressively worsened with no associated, aggravating, or relieving factors noted. She had similar symptoms approximately 1 year ago with an acute, chronic ...
Gas Stove Pollution Risk Is Greatest in Smaller Homes, Study Finds
A new study from researchers at ... study estimated that long-term exposure to nitrogen dioxide from stoves was likely causing up to 50,000 cases of asthma in children. ... Guest Essays; Op-Docs ...

Case Study: Managing Severe Asthma in an Adult

More On This Topic

A woman with asthma: a whole systems approach to supporting self-management

Similar content being viewed by others

Barriers to implementing asthma self-management in Malaysian primary care: qualitative study exploring the perspectives of healthcare professionals

The self-management abilities test (SMAT): a tool to identify the self-management abilities of adults with bronchiectasis

Improving primary care management of asthma: do we know what really works?

What do we know about asthma self-management? The academic perspective

Personalised asthma action plans

Supported self-management

The challenge of implementation

The solution will need a whole systems approach

Box 1: What self-management help should this lady expect from her general practitioner or asthma nurse? The patient’s perspective

What are the clinical challenges for the healthcare professional in providing self-management support?

What are the challenges for the healthcare organisation in providing self-management support?

The case study continues...

Author information

Corresponding author

Ethics declarations

Rights and permissions

About this article

Share this article

Quick links

Pediatric severe asthma: a case series report and perspectives on anti-IgE treatment

Case presentation

Conclusions

Case presentations

Discussion and conclusions

Abbreviations

Acknowledgements

Availability of data and materials

Author information

Contributions

Corresponding author

Ethics declarations

Consent for publication

Competing interests

Publisher’s Note

Rights and permissions

About this article

Share this article

BMC Pediatrics

Log in using your username and password

You are here

Statistics from Altmetric.com

Matched hospital control group

Community comparison group

QUESTIONNAIRE

STATISTICAL ANALYSIS

Acknowledgments

Read the full text or download the PDF:

How do you diagnose asthma? A multiple case study design to understand and explain current use of national guidelines by primary care clinicians

Validation of adult asthma case definitions for primary care sentinel surveillance

Study design

Chart abstraction and data collection

Asthma classification definition

Case definition development

Statistical analysis

Sample characteristics

Case definition results

Limitations

Availability of data and materials

Abbreviations

Acknowledgements

Author information

Contributions

Corresponding author

Ethics declarations

Consent for publication

Additional information

Supplementary Information

Rights and permissions

About this article

Share this article

Allergy, Asthma & Clinical Immunology

Working locally in primary care and collaborating globally to improve respiratory health

Prediction of the number of asthma patients using environmental factors based on deep learning algorithms

Data collection

Prediction of patients with asthma using environmental factors based on deep learning algorithms

Comparison with conventional modeling methods