asthma attack child case study

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Case 1 diagnosis: allergy bullying, clinical pearls.

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Case 1: A 12-year-old girl with food allergies and an acute asthma exacerbation

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Lopamudra Das, Michelle GK Ward, Case 1: A 12-year-old girl with food allergies and an acute asthma exacerbation, Paediatrics & Child Health , Volume 19, Issue 2, February 2014, Pages 69–70, https://doi.org/10.1093/pch/19.2.69

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A 12-year-old girl with a history of asthma presented to the emergency department with a three-day history of increased work of breathing, cough and wheezing. She reported no clear trigger for her respiratory symptoms, although she had noted some symptoms of a mild upper respiratory tract infection. With this episode, the patient had been using a short-acting bronchodilator more frequently than she had in the past, without the expected resolution of symptoms.

On the day of presentation, the patient awoke feeling ‘suffocated’ and her mother noted her lips to be blue. In the emergency department, her oxygen saturation was 85% and her respiratory rate was 40 breaths/min. She had significantly increased work of breathing and poor air entry bilaterally to both lung bases, with wheezing in the upper lung zones. She was treated with salbutamol/ipratropium and received intravenous steroids and magnesium sulfate. Her chest x-ray showed hyperinflation and no focal findings.

Her medical history revealed that she was followed by a respirologist for her asthma, had good medication adherence and had not experienced a significant exacerbation for six months. She also had a history of wheezing, dyspnea and pruritis with exposure to peanuts, chickpeas and lentils; she had been prescribed an injectible epinephrine device for this. However, her device had expired at the time of presentation. In the past, her wheezing episodes had been seasonal and related to exposure to grass and pollens; this presentation occurred during the winter. Further history revealed the probable cause of her presentation.

Although reluctant to disclose the information, our patient later revealed that she had been experiencing significant bullying at school, which was primarily related to her food allergies. Three days before her admission, classmates had smeared peanut butter on one of her schoolbooks. She developed pruritis immediately after opening the book and she started wheezing and coughing later that day. This event followed several months of being taunted with peanut products at school. The patient was experiencing low mood and reported new symptoms of anxiety related to school. The review of systems was otherwise negative, with no substance use.

The patient's asthma exacerbation resolved with conventional asthma treatment. Her pulmonary function tests were nonconcerning (forced expiratory volume in 1 s 94% and 99% of predicted) after her recovery. The trigger for her asthma exacerbation was likely multifactorial, related to exposure to the food allergen as well as the upper respiratory infection. A psychologist was consulted to assess the symptoms of anxiety and depression that had occurred as a result of the bullying. During the hospitalization, the medical team contacted the patient's school to provide education on allergy bullying, treatment of severe allergic reactions and its potential for life-threatening reactions with exposure to allergens. The medical team also recommended community resources for further education of students and staff about allergy bullying and its prevention.

Allergy bullying is a form of bullying with potentially severe medical outcomes. In recent years, it has gained increasing notoriety in schools and in the media. Population-based studies have shown that 20% to 35% of children with allergies experience bullying. In many cases (31% in one recent study [ 1 ]), this bullying is related directly to the food allergy. From a medical perspective, there are little published data regarding allergy bullying, and many health care providers may not be aware of the issue.

Allergy bullying can include teasing a child about their allergy, throwing food at a child, or even forcing them to touch or eat allergenic foods. Most episodes of allergy bullying occur at school, and can include episodes perpetrated by teachers and/or staff ( 2 ).

Allergy bullying can lead to allergic reactions, which may be mild or severe (eg, urticaria, wheezing, anaphylaxis), but may also lead to negative emotional consequences (sadness, depression) ( 2 ) and an overall decrease in quality of life measures ( 1 ). Adolescents commonly resist using medical devices, such as injectible epinephrine devices, and bullying may be a contributing factor for this ( 3 ). Attempting to conceal symptoms in a bullying situation may place children at risk for a worse outcome.

Physicians can play a key role in detecting allergy bullying and its health consequences. In many cases, children have not discussed this issue with their parents ( 1 ). Given the prevalence of bullying, its potential to lead to severe harm, including death, and the lack of awareness of this issue, clinicians should specifically ask about bullying in all children and teens with allergies. Physicians can also work with families and schools to support these children, educate their peers and school staff, and help prevent negative health outcomes from allergy bullying.

Online resources

www.anaphylaxis.ca − A national charity that aims to inform, support, educate and advocate for the needs of individuals and families living with anaphylaxis, and to support and participate in research. This website includes education modules for schools and links to local support groups throughout Canada.

www.whyriskit.ca/pages/en/live/bullying.php − A website for teenagers with food allergies; includes a segment that addresses food bullying.

www.foodallergy.org − Contains numerous resources for children and their families, including a significant discussion on bullying and ways to prevent it.

Allergy bullying is common but is often unrecognized as a factor in clinical presentations of allergic reactions.

Physicians should make a point of asking about bullying in patients with allergies and become familiar with resources for dealing with allergy bullying.

Physicians can play roles as advocates, educators and collaborators with the school system to help make the school environment safer for children with allergies who may be at risk for allergy bullying.

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• Volume 6, Issue 1
• Diagnosis and management of asthma in children
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• Joanne Martin 1 , 2 , 3 ,
• Jennifer Townshend 4 ,
• http://orcid.org/0000-0003-4591-8299 Malcolm Brodlie 1 , 4
• 1 Translational and Clinical Research Institute , Newcastle University , Newcastle upon Tyne , UK
• 2 Northern Foundation School , Health Education England North East , Newcastle upon Tyne , UK
• 3 James Cook University Hospital , South Tees NHS Foundation Trust , Middlesbrough , UK
• 4 Paediatric Respiratory Medicine , Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust , Newcastle upon Tyne , UK
• Correspondence to Dr Malcolm Brodlie; malcolm.brodlie{at}newcastle.ac.uk

Asthma is the the most common chronic respiratory condition of childhood worldwide, with around 14% of children and young people affected. Despite the high prevalence, paediatric asthma outcomes are inadequate, and there are several avoidable deaths each year. Characteristic asthma features include wheeze, shortness of breath and cough, which are typically triggered by a number of possible stimuli. There are several diagnostic challenges, and as a result, both overdiagnosis and underdiagnosis of paediatric asthma remain problematic.

Effective asthma management involves a holistic approach addressing both pharmacological and non-pharmacological management, as well as education and self-management aspects. Working in partnership with children and families is key in promoting good outcomes. Education on how to take treatment effectively, trigger avoidance, modifiable risk factors and actions to take during acute attacks via personalised asthma action plans is essential.

This review aimed to provide an overview of good clinical practice in the diagnosis and management of paediatric asthma. We discuss the current diagnostic challenges and predictors of life-threatening attacks. Additionally, we outline the similarities and differences in global paediatric asthma guidelines and highlight potential future developments in care. It is hoped that this review will be useful for healthcare providers working in a range of child health settings.

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This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/ .

https://doi.org/10.1136/bmjpo-2021-001277

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Key messages

Paediatric asthma outcomes are poor and many deaths are preventable.

Diagnosing asthma in childhood can be challenging, and the diagnosis should be reviewed during follow-up to ensure it is correct.

Asthma attacks should be viewed as never events. Postattack reviews are essential to optimise maintenance therapy and prevent future attacks.

Education is key to improving asthma outcomes.

Personalised asthma action plans are essential, and a significant number of children with asthma do not have one.

Introduction

Asthma is a chronic respiratory disease characterised by episodes of wheeze, cough, and shortness of breath. Around 14% of children worldwide have a diagnosis of asthma, making it the most common chronic respiratory disease of childhood. 1

Poor asthma control is associated with a number of negative effects on children and families. For example, they are more likely to be absent from school, have additional educational needs and have lower educational attainment. 2 Caregivers also experience missed work days and financial challenges as a result. 3 Some children will experience severe symptoms and life-threatening attacks. 4

Taking the UK as an example, paediatric asthma outcomes are poor overall with considerable associated morbidity and high rates of emergency hospital admissions, and most pertinently, there are several preventable deaths each year. 5 Alarmingly, the National Review of Asthma Deaths (NRAD) found that in almost all paediatric cases, there were a number of significant avoidable contributing factors and that these deaths may have been preventable. 6

There are several factors that make the diagnosis and management of asthma in children challenging. The aim of this review was to explore these issues and highlight good clinical practice in the diagnosis and management of paediatric asthma.

Presentation of asthma

Children with asthma typically present with a symptom triad of wheeze, shortness of breath and cough. However, ‘asthma’ is an umbrella term used to describe this collection of symptoms and, when present, should prompt practitioners to ask, ‘What type of asthma is this?’ There are a number of asthma subtypes that present and respond to treatment differently. Identification of the features of asthma and modifiable or treatable traits should only be the start of the diagnostic journey. 7 Asthma symptoms are normally intermittent in nature and may not be present at the time of clinical review, making the diagnosis challenging in some cases. 8 Additionally, disease phenotypes are not fixed and may evolve over time, necessitating ongoing review of symptoms and treatment. 9

Wheeze is a key feature of asthma and, if not present, a diagnosis of asthma in a child is unlikely. Wheeze is an expiratory high-pitched whistle that occurs as a result of inflammation and narrowing of the small airways. Parental understanding of wheeze varies, and clarifying what is meant when it is reported is key in making an accurate diagnosis. 10

The prevalence of ‘preschool wheeze’ is an additional challenge when diagnosing asthma in young children. In the first few years of life, many children will experience wheeze, but not all will go on to develop true asthma. The diagnosis of asthma should therefore be reviewed routinely to identify true asthma and alter treatment where necessary. 11 Favourable response to an appropriate trial of asthma treatment is an important confirmatory piece of diagnostic evidence.

Clinical examination may be normal in children and adolescents with asthma if they present during asymptomatic periods. During acute attacks, use of accessory muscles of respiration and widespread wheeze may be present. 12 Chest hyperinflation may be identified in acute and chronic disease settings.

Asthma triggers

Asthma attacks commonly occur following exposure to one or several triggers. Viral respiratory infections remain the leading cause, 13 but there are a number of other known triggers ( box 1 ), including aeroallergens, secondhand smoke exposure, or changes in ambient air temperature or humidity. Identification and documentation of specific asthma triggers should be part of routine care. Education on trigger recognition and avoidance is essential.

Common asthma triggers

Viral respiratory tract infections 6

Exercise 6 59

Weather changes in temperature and humidity 6 59

Domestic pollutants (eg, pests, mould and dust mites) 6

Environmental pollutants (eg, air pollution) 6

Secondhand smoke exposure 13 59

Pets and animals 13

Strong odours 13

Anxiety or strong emotions 59

Drugs (eg, non-steroidal anti-inflammatory drugs and beta blockers) 59

Gastro-oesophageal reflux 59

Risk factors for asthma

There are a number of risk factors that should be explored in the history of children who present with features of asthma. In symptomatic children, a personal or family history of atopic features, including asthma, eczema or rhinitis, supports a diagnosis of asthma. Some additional risk factors are outlined in box 2 . Education on modifiable risk factors, for example, exposure to secondhand smoke or air pollution and obesity, should be delivered routinely during consultations and asthma reviews. A range of social determinants that are linked to poverty impact on outcomes and the health of children with asthma. 14

Asthma risk factors

Personal or family history of atopy: eczema, allergic rhinitis or nasal polyposis 60

Family history of asthma 60

Exposure to secondhand smoke 60

Preterm birth 21

Low birth weight 61

Poor housing quality/mould and dampness 6

Air pollution 63

Paediatric asthma phenotypes

Asthma is a heterogeneous disease in which there are several phenotypes and underlying endotypes. Phenotypes are subtypes of asthma that share clinical characteristics such as symptom triggers, atopic features, disease severity and response to treatment. Endotypes are subtypes of asthma that are characterised by similar underlying biological mechanisms. 15

Key endotypes include ‘type 2-high’ and ‘type 2-low’ asthma. 16 Identifying asthma phenotypes and endotypes can facilitate targeted treatment based on the pathophysiology occurring in a specific individual. 17 For example, allergic or eosinophilic asthma that frequently starts in childhood is type 2-high and is characterised by eosinophilic airway inflammation, raised IgE and fractional exhaled nitric oxide (FeNO) levels. 15 Typically, type 2-high asthma responds well to inhaled corticosteroid (ICS) treatment. 7 A number of biologic agents can be used in the management of asthma, under specialist supervision, and their use varies on asthma endotypes (table 8). 18

Differential diagnoses and diagnostic uncertainty

Misdiagnosis of asthma remains a major problem with rates of both underdiagnosis and overdiagnosis being high. 19 Overdiagnosis is problematic as it exposes children to unnecessary side effects of medications and runs the risk of trivialising asthma. 7

There are several conditions that may be associated with chronic cough, wheeze and/or shortness of breath in children and therefore present similarly to asthma ( table 1 ). Due to the difficulties with diagnosis, especially in young children where objective testing is not possible, the diagnosis of asthma should be reviewed at each clinical presentation and interaction.

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Asthma differentials and clues in medical history

Diagnosing asthma in children

There is no single ‘gold-standard’ test that can be used to accurately diagnose asthma. In practice, a diagnosis should be made based on characteristic symptom patterns, evidence of variability in airflow limitation in the presence of airway inflammation, likelihood of alternative diagnoses and response to treatment. Getting the diagnosis correct is key for optimal management of paediatric asthma.

Lung function tests can be used to aid the diagnosis of asthma in children over the age of 5 years. Peak expiratory flow (PEF) and spirometry are commonly used to assess airflow obstruction and reversibility. PEF can be used to detect diurnal variation, which is a typical feature of asthma. The Global Initiative for Asthma (GINA) specifically recommends the use of either PEF or spirometry in the diagnosis of asthma in children over 5 years. 20 Once a child is old enough to reliably perform lung function testing, it is recommended that this be undertaken if the diagnosis of asthma has not been previously confirmed. In children under 5, lung function testing is rarely practical outside a research setting. This makes diagnosis in this age group additionally challenging. 21 Guidelines vary between countries and regions with regard to diagnostic criteria. An overview of the similarities and differences between these guidelines is displayed in table 2 . Lung function testing is frequently used to monitor progress of children with asthma as part of their care. Objective testing should be repeated if there is poor response to treatment or diagnostic uncertainty.

Summary of paediatric asthma national guidelines: focusing on diagnosis

FeNO is used to detect and quantify eosinophilic airway inflammation with levels elevated in those with eosinophilic asthma. 22 Once staff are trained, and provided equipment is available, FeNO is a practically useful test that is quick to perform in school-aged children. The exact positioning of FeNO testing varies between guidelines worldwide ( table 2 ). FeNO monitoring may also be useful in titrating dosage of ICS in those with an established diagnosis of asthma. 23

Allergy testing (skin prick testing or measurement of specific IgE levels) is not routinely carried out in the diagnostic process; however, it is recommended in a number of clinical guidelines and may identify individual triggers. 24–27

There are several aspects that make paediatric asthma diagnosis challenging. Most diagnoses are made in primary care where there is often limited access to objective testing at present. Despite guideline recommendations, objective testing is frequently only available in secondary or tertiary care settings where equipment and trained staff are available. The COVID-19 pandemic has served to exacerbate these issues and increase backlogs. Various solutions have been proposed, including community diagnostic hubs. 28 In some healthcare systems, the cost of undergoing objective testing is a cause of health inequalities.

Additionally, the symptom onset for most cases of paediatric asthma occurs before the age of 3 years 29 when lung function testing cannot be used to aid diagnosis. In this age group, response to an asthma treatment trial is useful to aid diagnostic decision making and is recommended in a number of national guidelines. 27 30–32

Management of asthma in children

The management of asthma is multifactorial, and to optimise disease control, a number of pharmacological, non-pharmacological and self-management aspects need to be considered.

Pharmacological management

The pharmacological management of asthma involves two key components: maintenance and reliever therapies. Maintenance therapies are the mainstay of asthma management, and the treatment aim is that no reliever therapies are required. Use of reliever therapy suggests asthma control is poor.

An overview of maintenance and reliever therapies is outlined in tables 3 and 4 , respectively. A stepwise approach to asthma management is encouraged, and pharmacological management varies on age, symptom control and the national guideline used. An overview of management approach in a number of national guidelines is summarised in table 5 .

Maintenance therapies

Reliever therapies

Summary of paediatric asthma national guidelines: focusing on management

Biologic agents used in the management of asthma

GINA guidelines recommend dual ICS and short-acting beta-2 agonist (SABA) therapy to children over the age of 5. 20 SABA monotherapy was previously the main management starting point; however, compared with combined treatment, SABA monotherapy has been shown to be associated with asthma mortality. 33 SABA monotherapy is now only recommended by GINA for use in children aged 5 or less. 20 As seen in table 5 , GINA recommends symptom-driven ICS use, compared with daily ICS use, as initial therapy in children over 6 years of age. In comparison to daily ICS use, symptom-driven use has demonstrated a similar exacerbation risk and reduces the risk of ICS adverse effects. 34

Single maintenance and reliever therapy (SMART) inhalers are combined inhalers offering both maintenance and reliever therapy in those with asthma. These inhalers contain a number of maintenance and reliever therapies in different combinations. The use of these inhalers have been shown to reduce the risk of asthma attacks and emergency department (ED) admissions, 35 improve lung function and decrease the need for reliever therapy. 36 There is limited evidence in the effectiveness of SMART inhalers in children, but children over 12 years may be prescribed a SMART inhaler, which acts as both a maintenance and reliever therapy, if symptoms are not well controlled. 37

There are a number of biologic agents ( table 6 ) that may be used in the management of paediatric asthma. These are endotype-specific, targeted therapies that should be used only under the supervision of specialists. Their availability and cost vary between countries and different healthcare systems. Detailed appraisal of the evidence base for their use is provided in the individual management guidelines and has been recently reviewed. 17

Non-pharmacological management

Non-pharmacological aspects of asthma management include providing education on modifiable risk factors and comorbidities to caregivers and conducting annual asthma reviews to assess control and future risk.

Education is key to improving caregiver and child understanding of asthma and its management. Clear information regarding modifiable risk factors, such as smoke exposure, domestic pollutants and obesity, should be given. Short-term educational interventions aimed to improve self-management have been shown to increase medication adherence, 38 improve symptom control and reduce mortality. 39

All young people with asthma should have asthma reviews at least annually. These reviews should focus on current symptom control and management, previous attacks, triggers, modifiable risk factors and personal asthma action plans (PAAPs). Asthma reviews are opportunities to assess child and caregiver understanding of asthma and provide education, if necessary. Annual asthma reviews are also opportunities to assess inhaler technique (including spacer use) and provide education on this if necessary. Poor inhaler technique is common in young people with asthma 40 and associated with poor disease control. 41

Taking time to understand the perceptions of young people and their caregivers in relation to their asthma diagnosis and management is important, and exploring such perceptions may enhance engagement during consultations, subsequently improving outcomes for young people. 42

Self-management

Self-management aspects of paediatric asthma management include asthma education and PAAPs. PAAPs are written documents that are given to young people and/or caregivers that advise them on day-to-day asthma management and what to do in the event of an attack. 43 Action plans should be created with patient/caregiver input, shared with relevant individuals (eg, school teachers) and should be reviewed and updated regularly. PAAPs have been shown to reduce ED attendance and missed school days and to increase caregiver confidence when managing attacks. 44 The 2018 Annual Asthma Survey found that over 50% of children with asthma in the UK had no PAAP, and around 20% of caregivers did not seek medical advice during acute asthma attacks, highlighting large gaps in education. 45

Diet and exercise are additional important self-management aspects within paediatric asthma care. A number of short-term exercise interventions have demonstrated improvements in lung function and symptom control. 46 Healthy eating interventions can help reduce body mass index and improve the quality of life of both young people and their caregivers. 47

Withdrawing management/stepping down

Asthma control should be reviewed at every medical contact. When asthma symptoms are well controlled on pharmacological therapy, stopping or stepping down medication should be considered to protect young people from unnecessary adverse effects.

The GINA 2021 guidelines advise that clinicians should consider stepping down asthma management to the lowest effective treatment regimen when good symptom control has been achieved for at least 3 months. 20 When stepping down treatment, an individualised risk–benefit approach should be taken with focus on the child’s medical history, including frequency of oral corticosteroid use, frequency of asthma attacks, and previous intensive or high-dependency care admissions. 48

When to refer to a specialist

Most paediatric asthma cases are diagnosed in primary care without the input of general paediatricians or paediatric respiratory physicians. 6 However, a number of children with asthma may need to be referred to specialists for diagnostic or management input. Common indications for specialist referral include no or poor response to asthma treatments, inconclusive objective testing, poor symptom control with appropriate treatment, frequent oral corticosteroid use or the occurrence of a severe asthma attack. 20 27 30 31 49 50 A key element of specialist care is a multidisciplinary team consisting of a number of professionals, including specialist nurses, psychologists, physiologists and pharmacists.

Healthcare professionals must consider any safeguarding implications at all paediatric asthma reviews as part of delivering holistic care. Unexplained or frequent ‘do not attend’ appointments or suspicion of poor medical management at home should be flagged and acted on locally.

Predictors of life-threatening attacks

The following features have been shown to increase the likelihood of future severe attacks, and particular attention should be given to these factors during asthma reviews:

Previous attack. The strongest risk factor for a future asthma attack is a personal history of a previous attack. One large systematic review and meta-analysis found that children with a recent history of ED attendance with an asthma attack were up to 5.8 times more likely to have another ED attendance and up to three times more likely to be admitted to the hospital with a future asthma attack. 51

Frequent SABA use and prescription requests. Frequent use of SABA reliever therapy suggests poor control of asthma symptoms. If asthma symptoms are well controlled, no more than two SABA inhalers should be required annually. 52 The UK NRAD found that excess SABA prescription and use were prominent in individuals who died of asthma attacks. For those with data available, around 40% had been prescribed 12 or more SABA inhalers in the 12 months before death. 6

Postattack review

Asthma attacks should be viewed as never events. It is essential that a postattack review is conducted to review asthma maintenance treatment, as this is likely to be suboptimal. Failure to review patients post attack, and to alter treatment where appropriate, is likely to predispose to future attacks, which could be life-threatening. Management of the current attack should be reviewed to ensure treatment is appropriate and symptoms are resolving. Some individuals may require additional courses of oral corticosteroids to settle symptoms. 7

Current NICE quality standards (UK) state that all individuals hospitalised with an asthma attack should receive a follow-up review in primary care within two working days of discharge, 49 to review maintenance management and ensure resolution of symptoms. However, the 2018 National Asthma Survey completed in the UK found that 64% of respondents had no primary care follow-up post attack, and most patients were not aware that this was required. 45

Salbutamol weaning

Salbutamol weaning plans are commonly used by a number of healthcare organisations following discharge after an asthma attack. These plans direct caregivers to provide regular SABA therapy, often in a reducing regime, in the days following discharge. There have been a number of concerns raised with regard to these plans with some believing that providing regular SABA therapy may potentially mask deterioration and could delay care givers seeking medical advice. 53 Healthcare professionals should enquire about salbutamol weaning plans during postattack reviews and urge caregivers to seek medical advice if they have concerns or the effects of SABA are not lasting the 4 hours of duration.

Future developments in care

The management of paediatric asthma is changing over time with, just as two examples, developments in technology and service structure:

Technology. The growing use of technology in asthma care has huge potential to improve clinical outcomes. Smartphone applications can be used to provide medication reminders to users, and this has been shown to increase ICS adherence. 54 Applications can also be used to provide educational content to young people and caregivers, 55 as well as store PAAPs. 56 ‘Smart’ inhalers, not to be confused with SMART inhalers, are devices that can provide audio reminders to users and record when they are used. One paediatric study found that the use of smart inhalers increased treatment adherence to 84%, compared with 30% in the control group. 57

Diagnostic hubs. In the UK, regional diagnostic hubs for asthma care have been recommended in NHS England’s Long Term Plan. 58 Implementation of diagnostic hubs is hoped to result in earlier and more accurate asthma diagnoses by improving access to objective testing and specialised interpretation. Hubs are designed to improve asthma outcomes by enabling most appropriate treatment initiation and monitoring. There is currently no evidence in the literature of the clinical effects of diagnostic hubs being used in the management of paediatric asthma.

Conclusions

Paediatric asthma outcomes are currently poor and many deaths are preventable. The aim should be to avoid asthma attacks occurring with appropriate maintenance therapy, and they should be viewed as never events. In order to improve outcomes, accurate diagnosis and management are essential. Good asthma care extends beyond providing medication and should include education, as well as supported self-management advice. The use of PAAPs remains limited and a significant number of young people with asthma do not have one. Postattack asthma reviews are a key opportunity to review maintenance medication and current symptom control.

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JT and MB contributed equally.

Contributors All authors conceived the ideas for the article. JM wrote the first draft that was then commented on by JT and MB.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests MB received investigator-led research grants from Pfizer and Roche Diagnostics; speaker fees paid to Newcastle University from Novartis, Roche Diagnostics and TEVA; and travel expenses to educational meetings Boehringer Ingelheim and Vertex Pharmaceuticals.

Provenance and peer review Commissioned; externally peer reviewed.

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Protecting Navajo children with asthma: A case study

Joncita Todechine, a mother of four who lives on the Navajo Nation, knows all too well what can trigger asthma symptoms in her daughter Ashley. But she didn’t always. She recalls a time in 2013, living in Phoenix and attending medical assistant school, when she rushed her then-three-year-old to the Indian Medical Center. 

“She was really sick,” Todechine said. “She was fevering, coughing, and had shortness of breath. We had no idea what was wrong.”

Ashley was admitted to the hospital and stayed for an entire week before the doctors could make a diagnosis of asthma. Now a thriving 13-year-old, Ashley loves gaming, social media, and riding on her hoverboard. These days she lives on the Navajo reservation with her family, who moved there shortly after her mother finished school. For the most part, she keeps her asthma under control by taking medication and doing her best to avoid her asthma triggers. 

But that can be challenging.

On the Navajo Nation, there are many asthma triggers. The semi-arid environment is plagued by drought, so on windy days, the gusts kick up ever-present dust and sand into the air. Shuttered coal-fired powerplants dot the landscape and, though they are closed, residual soot still dirties the air. Uranium and other heavy metals contaminate the landscape, and people breathe diesel fumes from the buses that take children to and from school every day. The many dogs and livestock roaming the reservation carry other allergens.

“And that’s just the outdoor pollution,” said Bruce Bender, Ph.D., professor in the pediatrics department at National Jewish Health in Denver, Colorado. “Seventy percent of households heat with indoor stoves that burn wood or charcoal and can leak a lot of smoke into the air.”

Bender would know. He’s co-project leader of an NHLBI-funded project focused on reducing health disparities in children living on the Navajo Nation, and he’s studied some of the factors that make those disparities worse. He’s also looked at the health data overall and found that while Native adults suffer from higher rates of chronic conditions like cardiovascular diseases and diabetes, it’s asthma that remains one of the most common chronic diseases in children. Some 18% of children on the Navajo reservation have it,  compared to 10.2% of children nationwide.

“Asthma can be incredibly scary for children and their families, especially those who cannot get emergency care easily or quickly,” said Michelle Freemer, M.D., M.P.H., director of the asthma program in NHLBI’s Division of Lung Diseases.

The Navajo Nation extends across more than 27,000 square miles, making it the largest Native land area in the U.S. "For families of children with asthma, the distances and travel conditions on the reservation may add challenges,” said Freemer. “The investigators partnered with the community to find solutions that work where they live, not simply provide asthma care that has been shown to work in other places." 

A local solution

Bender and his colleague, Lynn B. Gerald, Ph.D., M.S.P.H., assistant vice chancellor for population health at the University of Illinois-Chicago, started a large-scale effort to teach educators, children, their families, and local medical providers on the Navajo Nation how to identify an asthma attack and what to do in an emergency. (Gerald had worked previously at the University of Arizona and had gained a wealth of knowledge from the university's Native collaborators.) The program rolled out in three Arizona communities on the reservation: Tuba City, Chinle, and Fort Defiance. Combined, these towns represent 43% of the Navajo Nation population and are home to more than 8,000 children with asthma.  

But before they began, the investigators knew they needed to build relationships with the Navajo people – who refer to themselves as Diné – as the community’s prior experiences with non-Native researchers had left them skeptical. The research team began by ensuring the program was tailored to the needs and wishes of the community itself.

“The Navajo Nation human research review board is very careful and thorough,” Bender said. “They’re protecting their population. We had to earn their trust.”

Once the investigators got approval, they hit the ground running, starting in Tuba City. In the hospitals, the research team provided tools for medical professionals, using self-directed online learning and in-person workshops, to increase their use of practices that have been shown to be important in asthma care.

In the schools, the investigators provided education using the American Lung Association’s Asthma Basics and Open Airways for Schools® training, to teach school staff about asthma, its triggers, and what to do when a child is having an attack and to teach Diné children how to manage their asthma. 

Using a “train-the-trainer” model, school staff, community health workers, respiratory therapists, and pharmacists became students and then instructors. This made it possible for the Diné participants to teach additional staff, ensuring the community can sustain the program after the research funding ends.

Still, there was another urgent need that Bender and Gerald realized had not been addressed. “Less than 15% of children with asthma actually have an inhaler at school when they need it,” Gerald said. In response, the team helped start a program in two of the three communities that provided stock inhalers to schools for children who need them. 

A global threat

After starting the program in Tuba City as planned and spending a year there, the research team moved their focus to Chinle. The goal was to be able to compare how well the program worked in each of the three communities. But a global pandemic had other plans.

“The COVID-19 pandemic hit right in the middle of our time in Chinle,” Bender said. “After that, we weren’t allowed on the reservation for two years.”

While the pandemic changed life for all Americans, it devastated many Native communities. Schools closed and medical clinics focused on emergencies. The research team pivoted: they continued some training virtually and were able to keep learning from families about their needs, especially using the Diné members of the research team who were on the reservation.

Taking stock

Today, despite the challenges of the pandemic, all three communities have completed the original program, and 439 Diné members have been trained to identify asthma and its triggers. Yet the work is far from over. The investigators are analyzing the data they collected. “Particularly important is returning the results to the community,” Gerald said. As soon as they are ready, she said, they will be meeting with the school boards and health boards and joining community meetings to share them.

Freemer said that all the materials the researchers developed through their NHLBI funding are available to the community and have also been shared with those at the Indian Health Service leading the Asthma Control in Tribal Communities program.

“The researchers also took the opportunity to build research capacity,” she said. They developed an agreement with Diné College, the only four-year college on the reservation, to provide training through their Summer Research Experience Program. “In that program, students learned about research and were able to readily reach the families who appreciated the interactions with Diné research team members.”

Todechine said knowing that her child will be cared for if the worst happens has given her peace of mind. “Now the school systems have their own asthma alert systems that the employees and even the bus drivers take part in,” she said. “For me, I feel safer for her to be at school without me.”

  Resources:

Learn more about  Asthma in Our Communities  with specific resources for American Indians.

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• v.175(5); 2001 Nov

Evidence-Based Case Review

Childhood asthma, anne morris.

1 The Children's Hospital at Westmead Locked Bag 4001 Westmead NSW 2145 Australia

Craig Mellis

2 Department of Paediatrics and Child Health University of Sydney Australia

A 3-year-old boy presents to the emergency department because for the past 24 hours he has had cough, wheeze, and increasing shortness of breath that began shortly after the onset of a low-grade fever and rhinorrhea. He is agitated and talking in short phrases only, with a respiratory rate of 40 per minute, a heart rate of 130 beats per minute, and oxygen saturation of 89% with the patient breathing room air. Examination of the chest reveals moderate intercostal and subcostal retractions. On auscultation, you note reduced breath sounds throughout the lung fields with widespread expiratory wheeze. Other than a clear nasal discharge, the remainder of the physical examination reveals no abnormalities. You diagnose acute asthma and commence a regimen of nebulized albuterol (Salbutamol) and consider adding ipratropium bromide.

Asthma is the most common chronic condition and the most frequent cause of hospital admission in childhood. Determining a precise definition of asthma has been difficult, particularly in infancy. However, the operational definition proposed in the Third International Pediatric Consensus Statement on the Management of Asthma for Infancy is “Recurrent wheezing and/or persistent coughing in a setting where asthma is likely and other rare conditions have been excluded.” 1 For older children, the National Heart, Lung and Blood Institute's definition describes asthma in terms of airway inflammation with a predominance of eosinophils and mast cells, bronchial hyperresponsiveness, and reversible airflow limitation resulting in recurrent cough and wheeze. 1

Objective evidence indicates increasing rates of asthma in children. 2 Because of the high worldwide burden of childhood asthma, 3 a large body of high-level evidence concerns many aspects of asthma treatment and prevention. Despite this good evidence, considerable mismatching remains between asthma severity and asthma treatment. Consequently, some children continue to be underdiagnosed and undertreated, and others are being overdiagnosed and overtreated.

FORMULATING CLINICAL QUESTIONS

To address the issues of most relevance to the patient described above and to help in searching the literature for the evidence about these, you structure your clinical questions to identify the patient population, the intervention, and the outcomes of interest.

• In children with acute asthma ( population ), does the addition of a nebulized anticholinergic agent (for example, ipratropium bromide) ( intervention ) to a nebulized β-agonist decrease the risk of admission to hospital compared with treatment with β-agonist therapy alone ( outcome )?
• In children with persistent asthma ( population ), does treatment with an inhaled corticosteroid drug ( intervention ) lead to growth impairment ( outcome )?
• In a 3-year-old child with asthma ( population ), is a metered-dose inhaler (MDI) with spacer ( intervention ) an effective means of delivery of inhaled medication ( outcome )?

SEARCH STRATEGY

You start by searching for evidence syntheses in the Cochrane Library using the search terms asthma AND (child OR children) and MEDLINE (Ovid) using the search terms asthma AND (systematic review OR meta- analysis OR meta-analysis) AND (child OR children) , looking specifically for systematic reviews and meta-analyses. Both sources are replete with systematic reviews of many aspects of childhood asthma. When a systematic review is identified, you also search MEDLINE to identify randomized controlled trials (RCTs) published after the publication date of the systematic review.

The search strategy for the Cochrane Library identified systematic reviews addressing all 3 of your questions. The MEDLINE search identified subsequent publications relevant to the last 2 questions.

CRITICAL REVIEW OF THE EVIDENCE

Question 1. pharmacologic management of acute asthma in children: addition of nebulized anticholinergic (ipratropium bromide) to nebulized β-agonist.

A meta-analysis of 13 RCTs involving children between the ages of 18 months and 17 years evaluated the benefit of adding nebulized anticholinergic agents to β-agonists in the treatment of acute asthma in children. 4 The main results were that the addition of a single dose of an anticholinergic drug to a nebulized β-agonist did not reduce the incidence of hospital admission (relative risk [RR], 0.93; 95% confidence interval [95% CI], 0.65-1.32) but that in children with moderate to severe asthma, multiple doses of an anticholinergic agent reduced the admission rate by 25% (RR, 0.75; 95% CI, 0.62-0.89). This means that to avoid 1 admission to the hospital, 12 children (95% CI, 8-32) would need to be treated with multiple doses of an anticholinergic drug in addition to a nebulized β-agonist. However, in children with more severe asthma (forced expiratory volume in 1 second [FEV 1 ] of 55%, or less than predicted), only 7 children (95% CI, 5-20) would need additional treatment with multiple doses of an anticholinergic agent to avoid 1 hospital admission.

The review also found that there was some improvement in lung function, as measured by the change in predicted percentage of FEV 1 following treatment with multiple doses of an anticholinergic drug. The weighted mean difference between the treated and untreated groups was 9.68% (95% CI, 5.70%-13.68%), favoring the use of multiple doses of an additional anticholinergic agent. Treated and untreated children did not differ significantly in the risk of adverse effects.

Overall, the authors of this review concluded that there was no benefit with respect to a reduction in the incidence of hospital admission in treating children with asthma with a single dose of an anticholinergic drug in addition to a β-agonist. The evidence for treating children with mild to moderate asthma with several doses of an anticholinergic drug to reduce the incidence of admission to a hospital is inconclusive; however, multiple doses appear safe and improve lung function. In children with severe asthma, 1 hospital admission would be avoided for every 7 children treated.

Question 2. Effect of corticosteroid drugs on growth of children with persistent asthma

In the Cochrane Library, you find a systematic review of RCTs that address the effect of inhaled beclomethasone dipropionate on linear growth in children with asthma. Three trials were included that involved children with mild to moderate asthma who received beclomethasone, 200 μg twice a day. The final conclusion was that the use of beclomethasone, 400 μg a day, caused a decrease in linear growth of -1.54 cm per year (95% CI, -1.15 to -1.94 cm). Because the maximum duration of follow-up was 54 weeks, no comment on “catch-up” growth or final height was possible. 5

An earlier meta-analysis (published in 1994) included 810 children in 21 studies. 6 The methods of this review differed in several ways from those of the review in the Cochrane Library. It included results from cohort studies rather than RCTs, oral and inhaled steroids, and trials that used as control subjects children who did not have asthma. The conclusion by the authors was that the use of corticosteroid drugs leads to a tendency for decreased linear growth. It remains unclear whether final height is affected. However, treatment with inhaled beclomethasone was associated with normal stature even in children with longer duration of therapy, high doses, and severe asthma.

In assessing the effect of inhaled corticosteroid drugs on growth, a key factor is the choice of the most appropriate outcome measure. Most studies determine short- to medium-term growth by using height velocity (or growth rate) or by comparing with normal centiles or height standard deviation scores. A recently published study examined the effect of long-term treatment with inhaled budesonide on adult height in children with asthma. 7 This study observed a cohort of 142 children with asthma who had received a mean dose of inhaled budesonide of 412 μg daily. The final adult height of children with asthma was compared with that of control patients with asthma who had never received inhaled corticosteroids (18 patients) and healthy siblings of patients in the treatment group (51 siblings). A significant reduction occurred in the mean growth rate of 1 cm during the first year of treatment with budesonide compared with the run-in period ( P <0.001). However, the main result from this study was that no significant difference was found between the final adult height (as predicted from parental heights) and the target adult height for children receiving inhaled budesonide or the control groups. The study did not address the possible effects of the severity of asthma itself on growth rate and did not clearly define how the severity of asthma was determined in enrolled children. However, it has the advantage of a long follow-up of children receiving inhaled steroids for many years.

Question 3. Delivery of inhaled medication

In the Cochrane Library, you find a systematic review that compares the delivery of inhaled bronchodilator medication through an MDI plus spacer device versus nebulizer therapy in children with acute asthma. 8 Patients younger than 2 years with severe asthma were excluded. The outcome measures included the rate of admission to hospital, measures of lung function, duration of stay in the emergency department, and rate of adverse events. The reviewer's conclusion was that in children with acute asthma, no outcome measure was significantly worse with the use of MDI and spacer than with nebulizer. Indeed, the time spent in the emergency department was less, and fewer side effects were noted with the use of the spacer. Thus, the MDI and spacer can be used successfully in children with acute asthma.

An RCT of 90 children aged 5 to 17 years that compared the use of albuterol delivered by MDI and spacer with that delivered by nebulizer published after the most recent amendment to the Cochrane review was identified. 9 All children had mild acute asthma, and the outcome measure was the change in FEV 1 from baseline to 90 minutes after treatment. No statistical difference was found between the groups, and the conclusion was that MDI with spacer is an effective means of delivery of inhaled medication in children with mild asthma.

Although the evidence presented in these studies relates only to children with acute asthma receiving bronchodilator therapy, the principles should be applicable to children receiving inhaled prophylactic therapy.

CONCLUSIONS

We have used explicit evidence-based medicine criteria to answer 3 key questions relating to acute and long-term management of this 3-year-old boy:

• In patients with acute asthma, does the addition of a nebulized anticholinergic agent (ipratropium bromide) to a nebulized β-agonist decrease the risk of admission to hospital?
• In young children with persistent asthma, does inhaled corticosteroid therapy result in growth impairment?
• In 3-year-old children with asthma, is an MDI with spacer an effective means of delivering inhaled medications?

The information obtained from the literature was level 1 evidence (meta-analyses and Cochrane reviews), and the information was appropriate to implement therapy in this 3-year-old boy because the studies were done in a similar population.

The patient was given ipratropium bromide in addition to a β-agonist for treatment of acute asthma. He responds well to management and is seen in your office about 2 weeks after discharge from hospital. Further history reveals that he has had 4 or 5 previous episodes of acute wheezing in the past 18 months. Each episode followed an upper respiratory tract infection, and the episodes seem to be getting progressively worse, both in duration and severity. Also, in the past 2 months he has had frequent interval symptoms, including nocturnal cough, early morning wheezing, and exercise-induced wheezing. The child is, therefore, started on a regimen of a low-dose inhaled corticosteroid drug (for example, beclamethasone, 200 μg per day). His parents are reassured that this should adequately control his asthma without interfering with his growth. The appropriate inhalation device for this 3-year-old boy is an MDI with spacer, rather than a home nebulizer unit. The patient responds well to this treatment, and in view of his good symptomatic control, the dose of inhaled corticosteroid is reduced after several months.

Summary points

• Standardized structuring of the key clinical questions relating to a young boy enabled the development of rapid and effective search strategies
• Level 1 evidence was available to answer the 3 key questions relating to the child's management, namely, Cochrane Library reviews and meta-analyses
• We found many randomized controlled trials on the management of acute and chronic asthma in childhood, and many of these are now well synthesized into secondary publications (systematic reviews or meta-analyses)
• The addition of an anticholinergic agent by inhalation during acute severe asthma offers some advantage over the frequent administration of β-agonists alone, but the effect is predominantly in patients with severe asthma; the routine use of anticholinergic drugs for acute asthma is not recommended
• The issue of whether inhaled corticosteroid drugs impair growth is a complex one; the dose that may impair growth is uncertain, as is whether the newer inhaled corticosteroid drugs, particularly fluticasone proprionate, are less likely to induce changes in linear growth and final height
• Given the strength of the evidence relating to the use of puffers and spacers versus the use of nebulizers, the last will almost certainly become less popular in the near future

An inhaler with spacer is as effective as a nebulizer for mild acute asthma

John Russell/AP

Competing interests: None declared

This article was edited by Elizabeth Elliott of the Department of Paediatrics and Child Health, University of Sydney. Articles in this series are based on chapters from Moyer VA, Elliott EJ, Davis RL, et al. Evidence Based Pediatrics and Child Health . London: BMJ Books; 2000.

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• Volume 73, Issue 9
• At-risk children with asthma (ARC): a systematic review
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• Audrey Buelo 1 ,
• Susannah McLean 1 ,
• Steven Julious 2 ,
• Javier Flores-Kim 1 ,
• Andy Bush 3 ,
• John Henderson 4 ,
• James Y Paton 5 ,
• Aziz Sheikh 1 ,
• Michael Shields 6 ,
• Hilary Pinnock 1
• the ARC Group
• 1 Asthma UK Centre for Applied Research, Usher Institute of Population Health Sciences and Informatics , The University of Edinburgh , Edinburgh , UK
• 2 Medical Statistics Group, ScHARR , University of Sheffield , Sheffield , UK
• 3 Department of Paediatric Respiratory Medicine , Imperial College and Royal Brompton Hospital , London , UK
• 4 Department of Population Health Sciences , Bristol Medical School, University of Bristol , Bristol , UK
• 5 School of Medicine, College of Medical, Veterinary, and Life Sciences , University of Glasgow , Glasgow , UK
• 6 Centre for Experimental Medicine , Queen’s University , Belfast , UK
• Correspondence to Dr Hilary Pinnock, Asthma UK Centre for Applied Research, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh EH8 9AG, Scotland; hilary.pinnock{at}ed.ac.uk

Introduction Asthma attacks are responsible for considerable morbidity and may be fatal. We aimed to identify and weight risk factors for asthma attacks in children (5–12 years) in order to inform and prioritise care.

Methods We systematically searched six databases (May 2016; updated with forward citations January 2017) with no language/date restrictions. Two reviewers independently selected studies for inclusion, assessed study quality and extracted data. Heterogeneity precluded meta-analysis. Weighting was undertaken by an Expert Panel who independently assessed each variable for degree of risk and confidence in the assessment (based on study quality and size, effect sizes, biological plausibility and consistency of results) and then achieved consensus by discussion. Assessments were finally presented, discussed and agreed at a multidisciplinary workshop.

Results From 16 109 records, we included 68 papers (28 cohort; 4 case-control; 36 cross-sectional studies). Previous asthma attacks were associated with greatly increased risk of attack (ORs between 2.0 and 4.1). Persistent symptoms (ORs between 1.4 and 7.8) and poor access to care (ORs between 1.2 and 2.3) were associated with moderately/greatly increased risk. A moderately increased risk was associated with suboptimal drug regimen, comorbid atopic/allergic disease, African-American ethnicity (USA), poverty and vitamin D deficiency. Environmental tobacco smoke exposure, younger age, obesity and low parental education were associated with slightly increased risk.

Discussion Assessment of the clinical and demographic features identified in this review may help clinicians to focus risk reduction management on the high-risk child. Population level factors may be used by health service planners and policymakers to target healthcare initiatives.

Trial registration number CRD42016037464.

• Paediatric asthma

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/thoraxjnl-2017-210939

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Key messages

What is the key question.

What are the factors that could enable clinicians and healthcare services to ‘spot the child’ (5–12 years) with asthma who is at increased risk of a severe asthma attack (requiring systemic steroids or hospital care)?

What is the bottom line?

The ‘at-risk’ picture that emerges is of a child with persistent symptoms who has had previous attacks and is on a suboptimal treatment regimen, especially if they have poor access to healthcare services or other risk factors including comorbid atopic/allergic diseases, vitamin D deficiency, living in poverty and being of African-American ethnicity.

Why read on?

This systematic review identifies risk factors and, based on the consensus view of an Expert Panel, weights the factors to enable parents, clinicians and healthcare services to target evidence-based management on children with asthma at most risk of having a severe attack.

Introduction

Asthma is the most common long-term condition in children, with European prevalence rates among 6–7 year-olds ranging from 5% in Albania to 21% in the UK. 1 Asthma is responsible for substantial morbidity, resulting in 2.8 million school days lost annually in the UK, 2 many involving time off work for parents/carers. 3 In the UK, more than 25 000 children are admitted annually with an asthma attack. 4 Frequent attacks affect the quality of life of children and their parents, are associated with accelerated loss of lung function 5 and may be fatal.

Asthma guidelines recommend that monitoring should include regular assessment both of current symptom control and future risk of an attack. 6 7 Objective assessment of symptoms may be achieved with questionnaires validated in children (eg, Paediatric Asthma Control Questionnaire 8 ; Childhood Asthma Control Test 9 ) or morbidity scores (eg, Royal College of Physicians three questions 10 ) but no evidence-based tools exist for informing assessment of future risk in children.

Guidelines list factors associated with an increased risk of attacks, 6 including a recent history of severe attacks, poor symptom control, allergic sensitisation, comorbid rhinitis, exposure to environmental tobacco smoke (ETS), high use of reliever medication, poor adherence to controller medication, obesity, eosinophilia, elevated FE NO , psychosocial problems and impaired spirometry. The relative contribution of these factors to increased risk, and how they may be used to stratify risk is not clear; clarifying this issue has been identified as a research priority. 7

We were commissioned by Asthma UK to undertake a systematic review to identify factors associated with the risk of attacks in children aged 5–12 years with asthma and, based on the consensus view of a multidisciplinary Expert Panel, to weight their importance and the strength of the underpinning evidence to inform risk stratification.

The systematic review is registered with PROSPERO (CRD42016037464); the protocol is published. 11 We followed Cochrane methodology 12 and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting standards. 13

Search strategy

We searched MEDLINE, EMBASE, CINAHL, AMED, PsycINFO and CENTRAL in May 2016: with no language or date restrictions, identified unpublished and in-progress studies from ClinicalTrials.gov and the ISRCTN registry ( https://www.isrctn.com ), undertook forward and backward citation checks. The search strategy was structured to include terms for ‘Asthma’ and ‘Exacerbations/Attacks’ and ‘Risk factors/Predictors’. 11 (Online supplementary table S1 gives detailed search strategies.) We contacted experts in the field for potentially relevant papers and anticipated risk factors to ensure we captured all likely predictors.

Supplemental material

Selection of studies.

After initial deduplication and sift of obviously irrelevant titles (NT, SM, SMcL, AudB), two reviewers (NT, SM or AudB and SMcL or HP) independently screened titles/abstracts of papers identified. Two reviewers (AudB and SMcL) screened the full text of potentially eligible studies against review criteria. At each stage, disagreements were resolved by team discussion with advice from the study Steering Group (the grant holders and other members of the ARC group).

Inclusion and exclusion criteria

The focus of the review was to identify factors that increased a child’s propensity to asthma attacks. Definitions 6 7 14 and key decisions regarding operationalising the inclusion/exclusion criteria are detailed in table 1 . We used the American Thoracic Society/European Respiratory Society Task Force 14 definition of severe asthma attacks: asthma symptoms and/or airway obstruction outside the normal variation for the patient necessitating a short course of oral corticosteroids and/or hospitalisation/emergency department use. The population included were children aged 5–12 years with a doctor diagnosis of asthma. Studies with a wider range of ages (eg, 3–18 years) were included if children aged 5–12 were reported separately or if more than 50% of the children were within this age range.

• View inline

Criteria for the search strategy and rules devised to operationalise inclusion/exclusion criteria

Quality assessment

We assessed study quality using Newcastle-Ottawa Scale for cohort, case-control and cross-sectional study designs. 15

Data extraction

We extracted details of study design, setting, population, methods, risk factors, definition of asthma and attacks, quality assessment, statistical analyses and results relevant to our objectives using a piloted form, modified from the Cochrane Effective Practice and Organisation of Care data collection form. 16 We contacted authors to clarify unclear or missing data.

Quality assessment and data extraction were conducted by AudB or SMcL and one of eight reviewers (JFK, MW, HB, VD, SS, MP, HKZ or ED) trained to undertake independent duplicate quality assessment and data extraction. Disagreements in quality assessment were independently verified and arbitrated by the principal investigator (HP) who also checked the data presented in the tables.

The results for each risk factor were entered onto a table (online supplementary table S2 ), in order to facilitate weighting. Within each factor, the results were listed from strongest to weakest study design (ie, cohort, case-control, then cross-sectional) and then ranked by study quality (quality assessment score).

Data synthesis: risk factor weighting

We anticipated that clinical and statistical heterogeneity of data would preclude formal meta-analyses. We therefore convened an Expert Panel (selected to provide a range of perspectives from among senior clinical academics of the Asthma UK Centre for Applied Research and the research team) comprising a general practitioner (GP) (HP), three respiratory paediatricians (JYP, JH, MS) and two researchers with a public health background (AudB, JFK), to make weighting decisions by reviewing the ORs and CIs, or other relevant statistics, as presented for each risk factor in online supplementary table S2 . The Panel also had access to the full-text papers. The experts initially worked independently, and then met to reach consensus on weighting. In methodology analogous to the grading of recommendations in which both outcomes and quality of evidence are assessed, there were two decisions to be made:

What is the risk associated with each factor? Following discussion, thresholds for the risk weighting based on the majority of ORs for each factor were agreed (see table 2 ). The risk factor weighting ranged from ‘no’, ‘slightly’, ‘moderately’ or ‘greatly’ increased risk of future attack.

How confident is this estimate of risk? The Expert Panel based the confidence assessment on the following criteria: the number of studies, study design (cohort, case-control and cross-sectional), quality of studies included (Newcastle-Ottawa Scale), consistency of the results and the biological plausibility of the factors’ effect on risk of future attacks to determine the confidence with which the estimates were made. Assessments were rated as ‘highly’, ‘moderately’, ‘slightly’ confident or ‘inconclusive/insufficient evidence’.

Thresholds for weighting risk factors

At the consensus meeting, each factor was considered in turn and all available data taken into account when reaching the decision on risk and confidence. Any subsequent discussion was carried out by email.

Data synthesis: overarching risk

Risk factors for which there was sufficient evidence to reach a consensus decision on weighting and confidence in the assessment based on the decisions reached during Expert Panel discussion were illustrated on a bubble plot. The position of the bubble denotes the weighting of the risk factor and the size of the bubble indicates confidence in the estimate.

End-of-project workshop

An end-of-project videoconference (to allow UK-wide participation) workshop was held in January 2017, in which the researchers and the members of the Expert Panel were joined by a multidisciplinary group (n=18: including medical/nursing professionals from primary and secondary care, health service researchers, patient and public involvement (PPI) members) who reviewed and helped interpret the findings. In addition to the weighting table, data on each factor were presented to the workshop as Forest plots (online supplementary table S3 ) and the bubble plot constructed to visually display the overall results. Each risk factor was discussed, the weighting assessment reviewed and agreed, and the implications considered from the perspective of the different stakeholders.

Patient and public involvement

Two parents of children with asthma (recruited from the Asthma UK Centre for Applied Research PPI Group) were involved throughout the study. In addition, representatives of Asthma UK attended the end-of-project workshop.

Updating prior to publication

In order to update the review prior to publication, we undertook forward citation on all included studies (January 2017). Pursuing references from included studies is an efficient approach to updating systematic reviews as it is unlikely that relevant papers will have been published without citing at least one of the included studies. 17

Search results

The searches yielded 21 963 records. Figure 1 (PRISMA diagram) gives details of the search and selection process. After deduplication and title/abstracts screening, 209 papers remained for full-text review of which 45 were included. Forward and backward citations yielded 23 additional papers; thus, 68 studies were included in the final analysis.

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Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. ATS, American Thoracic Society; ERS, European Respiratory Society.

Characteristics of studies

Of the 68 studies, 28 were cohort, 18–47 4 were case-control 48–51 and 36 were cross-sectional studies. 52–85 Study size varied markedly from 38 participants with severe asthma in a study from the Netherlands 20 to 6.7 million participants in a US census-based study. 77 The studies came from 10 countries: 53 were based in the USA, 18 19 21–24 27 28 30–46 49 51–54 57–61 63 65 66 68 70 71 73 74 76–78 80–84 86 5 in the Netherlands, 20 29 47 48 64 3 in Puerto Rico, 50 55 56 2 in Canada, 26 62 and 1 each in Brazil, 75 Chile, 72 Costa Rica, 69 France, 67 Trinidad 79 and the UK. 25 Publication dates ranged from 1993 74 to 2017. 18

The studies were heterogeneous on most characteristics, including population size, recruitment strategy, definitions of risk factors and attacks, and analytical approaches (confirming our decision that meta-analysis was not appropriate). Figure 2 shows how key variables are illustrated in the Forest plots.

Key variables and key to Forest plots. ED, emergency department.

Study quality varied ( figures 3–6 ; online supplementary table S2 ). Most studies adjusted for at least age and gender, though 10 studies did not report adjusting for any potential confounders, reducing their quality score. 28 45 47 62 67 79 81 83–85

Greatly increased risk: evidence for risk factors and weighting decisions. Note: The scale on all the Forest plots has been curtailed at an OR of 8 to enable comparison between the plots for the different factors. If the CIs are very wide, and the upper limit extends beyond the plot this is indicated with a line with an arrow. (95% CIs are given in online supplementary table S2 if required.) ED, emergency department.

Moderately increased risk: evidence for risk factors and weighting decisions. Note: The scale on all the Forest plots has been curtailed at an OR of 8 to enable comparison between the plots for the different factors. If the CIs are very wide, and the upper limit extends beyond the plot this is indicated with a line with an arrow. (95% CIs are given in online supplementary table S2 if required.) ED, emergency department; ICS, inhaled corticosteroid; LABA, long-acting β 2 agonist.

Slightly increased risk: evidence for risk factors and weighting decisions. Note: The scale on all the Forest plots has been curtailed at an OR of 8 to enable comparison between the plots for the different factors. If the CIs are very wide, and the upper limit extends beyond the plot this is indicated with a line with an arrow. (95% CIs are given in online supplementary table S2 if required.) SABA, short-acting beta 2 agonist.

No increased risk, confounded and inconclusive factors: evidence for weighting decision. Note: The scale on all the Forest plots has been curtailed at an OR of 8 to enable comparison between the plots for the different factors. If the CIs are very wide, and the upper limit extends beyond the plot this is indicated with a line with an arrow. (95% CIs are given in online supplementary table S2 if required).

Overview of results

There were 33 risk factors identified, covering asthma disease status, medication use, allergy/atopy, social context, care and services, environment, and demography. Online supplementary table S2 is the full weighting table containing detailed information about populations studied, definitions used and analyses performed grouped by risk factor. Online supplementary table S3 summarises the data for each risk factor (including Forest plots of ORs where there were sufficient data) and the rationale for the weighting decisions. Figures 3–6 summarise the two detailed supplementary tables including simplified Forest plots. The text below synthesises the findings and weighting for each risk factor.

The overarching risk assessment is illustrated in a bubble plot ( figure 7 ).

Summary of risk factors and weighting. ETS, environmental tobacco smoke; ICS, inhaled corticosteroid; SABA, short-acting beta 2 agonist.

Greatly or moderately/greatly increased risk of attacks (figure 3)

Previous attacks (n=11).

Previous attacks were consistently associated with a greatly increased risk of future attacks (ORs between 2.0 and 4.1). 25 27 29 35–37 43 44 69 81 84 Due to the consistency of findings and quality of the studies the Panel was highly confident in this assessment ( figure 3 ).

Poor control and/or persistent symptoms (n=11)

Ten studies had at least one significant result demonstrating that poor control or persistent symptoms identified a child at moderately/greatly increased risk of future attacks (ORs between 1.4 and 7.8). 20 27 38 41 49 62 65 69 75 85 The exception was a small (n=165), short duration (3 months) cohort study of moderate quality which showed no association. 45 The Panel was highly confident in this assessment. Persistent symptoms of any severity (as opposed to intermittent symptoms) were associated with greater risk. 27 38 45 65 69

Poor access to healthcare (n=5)

Five studies examined access to healthcare defined by insurance status. Four demonstrated that poor access to healthcare was associated with a moderately/greatly increased risk of attacks. 61 65 82 85 A small cohort study of moderate quality demonstrated no increased risk in children with or without Medicaid (a US social welfare programme). 45 The Panel was moderately confident in this assessment. The studies were all US based with participants from deprived inner-city populations: one study controlled for ethnicity and poverty. 65

Moderately increased risk of attacks

Suboptimal drug regimen (n=9).

Five of the seven studies that examined high reliever (short-acting beta 2 agonist (SABA)) use showed a positive association with risk of attacks. 25 36 43 49 54 The increased risk was judged to be slight (ORs between 1.2 and 1.3 in the three larger studies 25 36 49 ), though none of the studies assessed very high levels of SABA use ( figure 4 ).

Paradoxically, controller medication use was associated with an increased risk of attacks, as clinicians followed guideline recommendations and prescribed inhaled corticosteroids to children with poor control and previous exacerbations (‘confounding by indication’). Sixteen studies were included in this category: nine were suggestive of confounding by indication, 25 29 48 50 53 55 56 59 81 four demonstrated fewer exacerbations with controller use 18 35 36 84 and three showed no effect. 31 65 69

The most sensitive marker of moderately increased risk was the ratio of controller-to-total medication. Suboptimal regimens were typically defined (in accordance with Healthcare Effectiveness Data and Information Set criteria 86 ) as a ratio of the number of prescriptions for controller medication to total number of prescriptions for asthma medication <0.5. Six of seven studies that used this marker showed a significant relationship between a suboptimal regimen and asthma attacks (ORs between 1.2 and 2.3 18 24 26 31 53 54 ). In other approaches, two large, high-quality cohort studies showed an association with use of regular medication and fewer attacks. 23 29 Thus, the Panel considered that a suboptimal regimen was associated with moderately increased risk, and were highly confident in their assessment.

Comorbid atopic/allergic diseases (n=6)

Two large, high-quality cohort studies analysed primary care records from the UK 25 and the Netherlands. 29 The UK study found comorbid allergic rhinitis increased the odds of hospitalisation by 2.3 (95% CI 1.4 to 3.9), 25 whereas the Netherlands study found no increased risk of attacks in children with comorbid eczema (RR 0.8, 95% CI 0.4 to 1.4), allergic rhinitis (RR 0.8, 95% CI 0.5 to 1.2) or conjunctivitis (RR 1.4, 95% CI 0.7 to 2.7) compared with no comorbid allergic disease. 29

The remaining four cross-sectional studies all demonstrated at least one positive association between comorbid atopic/allergic conditions and risk of attacks though CIs were wide. 64 70 75 79 The Panel concluded that that there was a moderately increased risk of attacks with comorbid atopic/allergic disease, but they were only slightly confident in this assessment.

African-American ethnicity (n=12)

Twelve US-based studies examined the association between African-American ethnicity/‘race’ and the risk of attacks. 18 22 38 45 52 53 56 61 65 78 81 82 Of the 12 studies, 10 reported at least one significant result demonstrating an increased risk of attacks in African-Americans compared with white or ‘non-black’ children (ORs between 1.6 and 4.1). 18 22 38 52 53 61 65 78 81 82 The exceptions were a study that assessed the impact of African ancestry in a Puerto Rican population, 56 and a small cohort study. 45

Six of these studies demonstrated that the increased risk in African-Americans persisted after controlling for deprivation and/or poverty, 60 65 area of residence, 61 healthcare provision 22 38 53 61 65 or parental education. 52 Two studies compared risk in Black and Hispanic populations 22 52 : the risk was considerably less in Hispanic populations. Overall, the Panel was highly confident that African-American ethnicity was associated with moderately increased risk of asthma attacks.

Vitamin D deficiency (n=4)

Three small studies showed a significant association between vitamin D insufficiency (vitamin D <30 ng/mL) and acute attacks (ORs between 2.2 and 2.8), 50 56 83 though a larger (n=1024) cohort study found only a borderline effect (OR 1.4, 95% CI 1.0 to 1.9). 32 Thus, the Panel was slightly confident that vitamin D deficiency was associated with a moderately increased risk of attacks.

Poverty (n=9)

Nine studies examined the effects of poverty (variously defined as annual family income <US$15 000; <US$20 000; <US$40 000; receiving benefits) on risk of attacks in children with asthma. Seven studies had at least one positive association between risk of attacks and poverty level (ORs between 1.4 and 2.8). 30 49 55 62 65 82 85 The exceptions were two small Puerto Rican studies. 50 56 The Panel was moderately confident that poverty moderately increased risk of attacks.

Slightly increased risk of attacks

Ets exposure (n=8).

Five studies found at least one positive association between ETS exposure and asthma attacks. 42 60 62 74 85 One high-quality cross-sectional study highlighted that the association between cotinine levels and risk of attack was lost when parent report was used to estimate ETS. 60 Of note, the three negative studies relied on parental report. 51 55 82 The Panel was highly confident that ETS exposure was associated with a slightly increased risk of asthma attack ( figure 5 ).

Younger age (n=6)

All six of the studies that examined the effect of age on risk of asthma attacks found that younger children (within the 5–12 age range) were more likely to have an attack. 18 36 39 61 81 82 The ORs ranged from 0.8 to 1.0 (indicating slightly decreased risk as age increased); the Panel was highly confident of this.

Overweight/obesity (n=10)

Four studies (including three very large high-quality studies) showed a significant, though small association between overweight or obesity and increased risk of attacks. 21 30 52 80 The Panel was highly confident that there was a slightly increased risk of an attack in overweight or obese children.

Low parental education (n=4)

All four studies, 49 52 55 62 including one large, high-quality cross-sectional study, 52 showed slightly increased risk of attacks in children of families with low parental education level (ORs between 1.1 and 1.9). The Panel was moderately confident in this assessment.

No effect on risk of attacks

Gender (n=14).

Two studies found girls at an increased risk of attacks, 52 53 and three found boys at increased risk 18 60 65 ; the other nine studies showed no gender difference. 29 36 38 45 61 62 77 81 85 Thus, the Panel was highly confident that the child’s gender had no effect on risk of attacks ( figure 6 ).

Hispanic population (n=9)

Overall, the findings in the US Hispanic population were inconsistent; with the majority of studies demonstrating no increased risk, 38 60 63 or inconsistent risk across the outcome measures used. 52 Four studies showed a small increased risk 18 22 82 (one with very wide CIs 65 ) and one showed a reduced risk of emergency department visits. 53 The Panel thus concluded that overall there was no increased risk, but their confidence in this assessment was only moderate.

Urban residence/proximity to major roads (n=6)

One case-control study showed a small increased risk of attacks in children living very close to a major road. 50 The other five studies 45 53 57 61 73 were negative including two large, high-quality cross-sectional studies, which controlled for a broad range of confounders. 53 57 The Panel was slightly confident in their assessment of no effect.

Confounded by severity

Controller medication use, nebuliser use, ownership of written asthma action plans and routine asthma reviews were all associated with increased risk of attacks and were considered by the panel to be confounded by severity. (For details see online supplementary tables S2 and S3 ).

Insufficient evidence to draw a conclusion

For 12 factors we found inconclusive/insufficient evidence to draw a conclusion. These are listed at the end of figure 6 ; details about why the data were considered to be inconclusive/insufficient are provided in online supplementary table S3 , with full description of all the studies in online supplementary table S2 .

Main findings

This systematic review aimed to identify factors which would identify children aged 5–12 years with asthma who are at increased risk of acute attacks. The child who had a history of previous attacks and persistent asthma symptoms was at greatly increased risk of a future attack, especially if they had poor access to care. Other key markers of moderately increased risk were a suboptimal drug regimen, comorbid atopic/allergic disease, African-American ethnicity, poverty and vitamin D deficiency. Younger age, exposure to ETS, being overweight and low parental education were associated with a slightly increased risk, but gender, urban residence and Hispanic ethnicity were not associated with increased risk.

Strengths and limitations

Despite our wide-ranging search strategies, we may not have identified all significant risk factors. Nevertheless, we identified papers related to almost all the predictors suggested by guidelines and experts in the field, lending face validity to our findings. The main omissions were that preterm delivery and eosinophilia were suggested, but not investigated as risk factors in any of the studies that we identified. That an additional 23 studies were found during forward and backward citations demonstrates the challenge in developing a comprehensive, but manageable, search strategy in such a broad area. There were some factors about which we found very little evidence and were thus unable to reach a conclusion (eg, comorbidities, parental health, FE NO testing); lack of evidence, however, does not mean they are not significant factors. We excluded factors not available in routine clinical practice (eg, novel biomarkers 87 ) which means that our conclusions are immediately transferable to contemporary clinical practice. The overweight of data from the USA (78% of studies included) limits the generalisability of the evidence for some factors (eg, ethnicity, poverty, access to healthcare) which may not be directly transferrable to other healthcare contexts.

The heterogeneity of the studies in terms of definitions of attacks (hospitalisations, emergency department visits, unscheduled GP care, oral steroids courses), thresholds applied to predictors (eg, definitions of persistent/severe symptoms, income levels associated with poverty, objective or reported assessment of ETS), duration of follow-up, provenance of data (collected for research or routine data) as well as study design and analysis precluded meta-analysis. To reduce potential subjectivity, we adopted a rigorous approach to weighting the factors using an Expert Panel’s consensus to define initial weightings and a multidisciplinary end-of-project workshop at which the findings were discussed, refined and agreed. This breadth of internationally recognised professional experience (although all UK based) assisted the interpretation of our findings and lends credibility to our conclusions.

Implications for parents and clinical practice

Our findings suggest that it is possible to identify the ‘high-risk’ child with asthma. The factors associated with moderately or greatly increased risk are easily identifiable in routine practice. For example: a history of acute attacks, persistent troublesome symptoms, frequency of prescription requests and comorbid atopic/allergic conditions are recommended components of regular reviews, 6 7 88 and knowledge of the social context is a core component of family medicine practice. 89 90

Identifying that their child is ‘at-risk’ enables parents to take decisions about modifying risk, such as reducing exposure to ETS, and reconsidering the necessity for controller treatment against their concern about harms of regular medication. 91 Clinicians alerted to the ‘at-risk’ child can target care, specifically instituting evidence-based management (regular controllers 6 7 ; supported self-management 92 ) to reduce risk.

Implications for healthcare systems and policymakers

Poor access to care and living in poverty were important risk factors that should be targeted by policymakers and health service planners to reduce risk of acute attacks in children living in high-risk populations. At a public health level, strategies for reducing smoking 93 and targeting the growing epidemic of obesity in children 21 will also contribute to reducing risk. In the USA, people from African-American communities living in deprived communities are at particular risk.

Implications for future research

Formal prognostic modelling is needed to validate the risk factors identified in this review, 94 and future research should assess whether risk assessment based on these factors improves outcomes when used prospectively in routine clinical practice. Nearly three-quarters of the studies in this review were performed in a US setting. Research is needed to understand the impact of variables such as poverty, urban/rural living, ethnicity and different rates of state/private/no medical insurance in other contexts.

It is possible with the information available in routine clinical practice to identify a child who is at increased risk of an acute attack. Many of the risk factors are potentially modifiable by parents acting to eliminate ETS or adhere to regular controller medication, by clinicians offering evidence-based treatment and self-management support, by healthcare systems ensuring equitable access to care and by policy initiatives addressing social deprivation and the public health challenges of smoking and obesity.

Acknowledgments

We thank Marshall Dozier (Academic Support Librarian) for

help with the search strategy, and Dr John Blakey for practical advice in the early stages.

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Contributors HP led the development of the protocol, securing of funding, study administration, expert panel, workshop and writing of the paper. AS, SJ, AB, JH and MS contributed to the development of the protocol. SJ provided statistical advice. AudB and SMcL undertook the screening, data extraction and presentation of results. HP, JYP, JH, MS, AudB and JFK formed the expert panel. All authors contributed to the interpretation of the findings. AudB wrote the initial draft of the paper with SMcL and HP, to which all the authors contributed. HP is the study guarantor.

Funding This research was supported by Asthma UK (Ref: AUK-SR-2015-01), with contributions from the Asthma UK Centre for Applied Research (AUK-AC-2012-01). AS is supported by the Farr Institute which is funded by a consortium of funders headed by the MRC.

Competing interests None declared.

Patient consent Not required.

Provenance and peer review Not commissioned; externally peer reviewed.

Data sharing statement All data are provided in the manuscript and online supplementary tables.

Collaborators The ARC group members: Helen Benson; Steve Cunningham; Victoria Dalgliesh; Gwyneth Davies; Melissa Goodbourn; Susan Grieve; Jonathan Grigg; Hayley K Zislis; Erin McDonnell; Susan Morrow; Meagan Peterson; Daniel Russell; Jurgen Schwarze; San Selveindran; Nara Tagiyeva; Mike Thomas; Marissa Ware; Andrew Wilson.

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Asthma Case Study

Asthma affects about 6.1 million children in the US under 18 years of age, making it one of the most common chronic childhood disorders (American Lung Association, 2021). Asthma occurs as a result of a stimulus which can range from allergens, cigarette smoke, changes in temperature, stress, or exercise. In this case we’ll experience an asthma attack and subsequent treatment with 16-year-old Ben Mason.

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Ben was also given an additional breathing treatment...

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• Published: 16 October 2014

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

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• 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.

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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.

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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

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

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Circumstances surrounding the deaths of children due to asthma. A case-control study

Affiliation.

• 1 Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver.
• PMID: 2816856
• DOI: 10.1001/archpedi.1989.02150230052022

Features of the courses in 12 children who died of an acute attack of asthma were compared with those in 12 children of comparable age and sex who had a life-threatening attack of asthma but survived. Information obtained by structured interviews with the families and physicians and from the medical records was used to characterize (1) the patient, family, severity, and treatment of asthma primarily in the 6 months before the attack and (2) medical circumstances and patient characteristics present on the day of and/or during the acute episode. Patients in the study (mean age, 14.1 years) and controls (mean age, 13.8 years) were in early to late adolescence, had similar long-term medication use histories and an overall rating of the severity of asthma. For the analysis of the information concerning the 6 months before the attacks, the study patients had a greater frequency of respiratory failure requiring intubation, a decrease in steroid use in the month before the attack, history of family disturbance, abnormal reaction to separation or loss, and expressed hopelessness and despair. For the period more immediately surrounding the acute attack, study patients more often had attacks starting during sleep, but less frequently experienced vomiting during the course of the attacks. Treatment of the attack by the parents was poor (primarily because of delays) in 7 of the 12 children who died, but was also a factor in 6 of the 12 controls. Our data suggest that certain characteristics of asthmatic children may place them at greater risk for death due to their asthma. In addition, we postulate that there may be inherent differences in the mechanisms of the acute attacks between the children who died and those who survived.

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• Statistical interpretation of multiple comparisons and sample size. Anbar RD. Anbar RD. Am J Dis Child. 1990 Jul;144(7):751-2. doi: 10.1001/archpedi.1990.02150310017014. Am J Dis Child. 1990. PMID: 2356791 No abstract available.

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• 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

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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

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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.

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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.

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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

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ORIGINAL RESEARCH article

Ozone exposure and asthma attack in children.

• 1 Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, China
• 2 The First Affiliated Hospital of Xiamen University, Xiamen, China

Background: Increasing evidence indicated that ozone (O 3 ) exposure could trigger asthma attacks in children. However, the effect of O 3 at low concentrations is uncertain.

Purpose: This study aimed to explore the effects of O 3 exposure at low concentrations on asthma attacks in children.

Methods: A total of 3,475 children with asthma attacks from the First Affiliated Hospital of Xiamen University were available for the analyses. Air pollution data and meteorological data in Xiamen during 2016–2019 were also collected. A case-crossover design and conditional logistic regression models were conducted to evaluate the association between asthma attacks and outdoor air pollution with lag structures (from lag 0 to lag 6) in both single and multi-pollutant models. Furthermore, we estimated the influence of various levels of O 3 exposure on an asthma attack in three groups categorized by maximum daily 8-h sliding average ozone (O 3 -8 h) (O 3 -8 h ≥ 100 μg/m 3 , O 3 -8 h: 80–99 μg/m 3 , O 3 -8 h < 80 μg/m 3 ).

Results: For both single-pollutant models and multi-pollutant models, when O 3 -8 h was higher than 80 μg/m 3 , O 3 exposure was increased the risk of acute asthma attacks on each day of lag. The effect of O 3 on children with asthma was significant when O 3 concentration was higher than 100 μg/m 3 .

Conclusion: O 3 concentration above 80 μg/m 3 contributed to an increased risk of asthma attacks in children.

Introduction

Bronchial asthma is a common chronic disease in childhood with shortness of breath, wheezing, and coughing from constriction and mucous-membrane swelling in the bronchi ( 1 ). It is estimated that the prevalence of asthma among children aged 0–14 years in China in 2010 was 3.02% (95% confidence interval (CI): 2.97–3.06%) ( 2 ). Although most children with asthma can be well-controlled through standardized treatment, many children still need rescue medication or hospitalization for acute asthma attacks. Avoiding the risk factors and predisposing factors is essential for the effective management of asthma. The risk factors for acute asthma attacks are complex, including dust mites, fungi, pollen, and infectious factors. In recent years, air pollutants have gradually attracted attention. Ozone (O 3 ), one of the air pollutants, has been repeatedly reported to be associated with respiratory diseases such as asthma ( 3 ) when the ozone concentration is too high.

O 3 exists in the stratosphere and troposphere. When in the stratosphere, it prevents ultraviolet rays from harming the human body. However, when in the troposphere, it adversely affects the human respiratory and cardiovascular system when it reaches high concentrations. Ozone is a strong oxidizing gas, easily soluble in water, and the inhaled ozone can penetrate deeply into the lungs ( 4 ). Some studies found that ozone might cause airway inflammation, worse lung function, airway hyperresponsiveness, and increased sensitivity to allergens ( 5 – 7 ). According to National Ambient Air Quality Standard for Ozone, the daily maximum 8-h average ozone concentration should be less than 150 μg/m 3 , and the World Health Organization believes that the daily maximum 8-h average ozone concentration should be less than 100 μg/m 3 .

Previous studies have suggested that O 3 exposure only affect children with asthma (including increasing respiratory symptoms, asthma medication use, and impaired lung function) in the most polluted areas ( 8 ). Some recent studies have shown that even if it is lower than the standard set by the World Health Organization, O 3 exposure may also cause an acute attack of asthma in children. In a Quebec birth cohort study, the average ozone concentration during the study period was 32.07 ppb (68.76 μg/m 3 ). This study found that ozone exposure was associated with the risk of asthma, with an odds ratio (OR) value of 1.11 (95% CI: 1.10, 1.12) ( 9 ). Short-term increases in low levels (<70 ppb) of ozone are associated with decreased lung function ( 10 ). Children with asthma who use maintenance medications are particularly susceptible to the effects of ozone below the US Environmental Protection Agency (EPA) standard ( 11 ).

Xiamen is a city on the southeast coast of China. During 2016–2019, the average concentration of maximum daily 8-h sliding average ozone (O 3 -8 h) was 81.21 μg/m 3 , the proportion of ozone concentration above ozone level 2 standard (160 μg/m 3 )was 0.62%. In the present study, the effects of increasing ozone levels at low concentrations on acute asthma attacks were investigated.

Study Participants

There were 29 065 cases with the diagnosis code J45 in the emergency department of the First Affiliated Hospital of Xiamen University from 1 January 2016 to 31 December 2019. According to the “Guidelines for the Diagnosis and Treatment of Children’s Bronchial Asthma (2016 Edition),” a total of 3,959 cases were identified as acute asthma attacks. After excluding 221 (5.58%) cases with fever, 15 (0.38%) with acute asthma attacks caused by self-discontinuation within 14 days, 7 cases with allergen exposure, and 2 cases (0.05%) outside of the region, a total of 3,714 cases (93.81%) of acute asthma attacks were eligible for the analyses.

Medical Data

Data were obtained from the Electronic Medical Record for asthma (code J45, International Classification of Diseases, Tenth Revision—ICD-10) among children aged 0-14 years in the First Affiliated Hospital of Xiamen University from 1 January 2016 to 31 December 2019. Combined with the main complaint, current medical history, and time of visit, the date of the first acute onset of asthma in the child was determined, and the recurrent cases were counted as one. The data of non-local residents and cases with fever and a clear diagnosis of asthmatic bronchitis were excluded.

Air Pollution

Ambient monitoring data, including O 3 -8 h concentrations and 24-h average concentrations of carbon monoxide (CO), nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), and particulate matter (PM 10 and PM 2.5 ), were measured at four monitoring stations in Xiamen metropolitan from 1 January 2016 to 31 December 2019. The 8-h average concentration refers to the average concentrations of continuous 8 h, and the daily maximum 8-h average concentration of zone refers to the maximum value of the continuous 8-h average. For example, N1 = average {c1, c2, c3, c8}, N2 = average {c2, c2, c3, c9}, N3 = average {c3, c2, c3, c10}, and so on, N17 = average {c17, c2, c3, c24}. The daily maximum 8-h average concentration = max {N1, N2, N3, N17}. The pollutants concentration was measured by the same method at each monitoring station. O 3 , NO 2 , and SO 2 concentrations were measured by using an open-path deferential optical absorption spectroscopy (DOAS) instrument.

Meteorological Data

Meteorological data, including daily average temperature (in degrees centigrade), relative humidity (as a percentage), wind velocity (in meters per second), and rainfall (in millimeter) were collected from the Xiamen Meteorological Bureau.

Statistical Methods

In this study, the case-crossover method was used to explore the relationship between ozone and asthma exacerbations. Case-crossover design has been widely used in environmental epidemiology to study the impact of short-term environmental exposure on the risk of individuals with rapid onset events. Since each case served as their control and matches all time-varying, unmeasured or unmeasured thematic characteristics, a case-crossover design eliminates time-constant and slowly varying confounders (such as gender, race, age, genetics, personal lifestyle, or behavior). This study was a retrospective analysis and the approaches was “symmetric two-way.” The date of the asthma attack was the case date, and two control dates were the date 1 week before the case date and the other after, avoiding the day of the week effect.

Considering the lag effect of the concentrations of each pollutant, lag0 to lag6 was selected. To control the potential confounding effect of weather, we set the daily relative humidity, average temperature, average wind speed, and rainfall in the same period lag 0–6 days as covariates. Considering the possible interaction between ozone and other pollutants, we also discussed the relationship between acute asthma attacks and other gaseous pollutants (NO 2 , CO, and SO 2 ) and particulate pollutants (PM 10 and PM 2.5 ).

The analysis strategy of each part of the correlation model is as follows:

(1) Single-pollutant model: After adjusting for the meteorological factors, single-pollutant models of O 3 from lag 0 to lag 6 were established.

(2) Multi-pollutant model: After controlling for confounding factors, a multi-pollutant model of O 3 + NO 2 + CO + SO 2 + PM 2.5 + PM 10 was established and the OR with a 95% CI was calculated.

(3) Ozone concentration grouping model: lag structures was categorized into three groups according to the O 3 -8 h concentrations (O 3 -8 h ≥ 100 μg/m 3 , O 3 -8 h: 80–99 μg/m 3 , O 3 -8 h < 80 μg/m 3 ). After adjusting for the lagging meteorological factors, the single-pollutant and multi-pollutant model were established and the effects of pollutants on acute asthma attacks were calculated.

Conditional logistic regression models were used to identify associations between air pollutants and asthma attacks in children, and all results were expressed as OR and 95% CI. All statistical analyses were performed in the R (version 3.6.0).

Characteristics of Acute Asthma Attacks and Participants

The characteristics of acute asthma attacks are presented in Table 1 . Male children accounted for 69.15% of cases, and cases younger than 6 years old accounted for 60.07%. The diagnosis included eight types of J45. Among them, a total of 18 children were hospitalized, and the rest were treated in outpatient clinics and followed up. There were no deaths.

Table 1. Characteristics of acute asthma attacks from 2016 to 2019.

Among the 3,714 cases, there were 3,475 patients, including 2,383 males (68.58%) and 1,092 females (31.42%). Children younger than 6 years old accounted for 61.41%. There were 779 (22.42%) children with a history of eczema, 360 (10.36%) children with rhinitis. There were 784 (22.56%) patients with rhinitis in the family, and 110 (3.17%) patients with a history of asthma, as shown in Table 2 .

Table 2. Characteristics of the study participants.

Characteristics of Air Pollutant Concentrations and Meteorological Variables

As shown in Table 3 , the average concentration of O 3 -8 h in Xiamen during 2016–2019 was 81.21 μg/m 3 , the proportion of ozone concentration above ozone second-level standard (160 μg/m 3 ) was 0.62% and the number of days exceeding ozone first-level standard (100 μg/m 3 ) was 361 days (24.7%). The average concentrations of NO 2 , PM 2.5 , and PM 10 , were 29.02, 12.057, and 44.85 μg/m 3 , respectively, and the proportion of days exceeding the first-level standard was 0.34, 7.94, and 33.26%, respectively. The daily average concentrations of CO and SO 2 did not exceed the first-level standard.

Table 3. Characteristics of daily air pollutants and meteorological variables in Xiamen from 2016 to 2019.

Correlation Analysis of Air Pollutant Concentrations and Meteorological Variables

As shown in Table 4 , there was a positive correlation between ozone and SO 2 , PM 2.5 , PM 10 , air temperature, and wind speed ( P < 0.05), and the correlation coefficients were 0.125, 0.418, 0.418, 0.124, and 0.118, respectively. There was a negative correlation between relative humidity, rainfall, and ozone ( P < 0.05).

Table 4. Correlation analysis between air pollutants and meteorological factors in Xiamen from 2016 to 2019.

Single Pollutant Model

After controlling the confounding factors of daily relative humidity, average temperature, average wind speed, and rainfall, the single pollutant models were established, as shown in Figure 1 .

Figure 1. The correlation of ozone in different lag periods to acute asthma attacks in the single pollutant model.

Multi-Pollutant Model

Under the adjustment of meteorological factors and weekly effects, a multi-pollutant model was constructed to evaluate the effects of pollutants on acute asthma attacks, as shown in Figure 2 .

Figure 2. The correlation of air pollutants in different lag periods to acute asthma attacks in the multi-pollutant model.

Analysis of Ozone Concentration in Different Lag Periods

Figure 3 shows that in the single-pollutant model that adjusts for the lagging meteorological factors, acute asthma attacks were associated with different lag periods and different levels of ozone exposure ( P < 0.001). When O 3 -8 h is greater than or equal to 100 μg/m 3 , every 10 μg/m 3 increase of O 3 -8 h increased 6.33, 7.08, 6.89, 7.11, 7.06, 6.14, and 6.28% of acute asthma attacks from 0 to 6 days lag.

Figure 3. Different O 3 -8 h levels in different lag periods in the single pollutant model.

When O 3 -8 h was between 80 and 99 μg/m 3 , every 10 μg/m 3 increase of O 3 -8 h increased 2.36, 3.08, 2.46, 2.52, 2.15, 2.25, and 2.13% of acute asthma attacks from 0 to 6 days lag.

From lag 0 to lag 6, when O 3 -8 h is less than 80 μg/m 3 , every 10 μg/m 3 increase in O 3 -8 h, the odds ratios is 0.9700, 0.9714, 0.9717, 0.9741, 0.9719, 0.9734, and 0.9743.

As shown in Figures 4 – 6 , the multi-pollutant model with different ozone levels in different lag periods showed that the health effects of ozone on asthma attacks in children was similar to that in the single-pollutant model. Ozone concentration above 80 μg/m 3 contributed to an increased risk of asthma attacks in children. The effect of ozone on children with asthma was significant when ozone concentration was higher than 100 μg/m 3 . When ozone concentration was less than 80 μg/m 3 , the ozone concentration was negatively correlated with asthma attacks in children.

Figure 4. Air pollutants in different lag periods in the multi-pollutant model when O 3 -8 h was higher than 100 μg/m 3 .

Figure 5. Air pollutants in different lag periods in the multi-pollutant model when O 3 -8 h was between 80 and 99 μg/m 3 .

Figure 6. Air pollutants in different lag periods in the multi-pollutant model when O 3 -8 h was less than 80 μg/m 3 .

When O 3 -8 h was higher than 100 μg/m 3 , PM 2.5 (lag0, OR: 1.0503, 95% CI: 1.0277–1.0733; lag2, OR: 1.0437, 95% CI:1.0186–1.0694; lag3 OR: 1.0644, 95% CI: 1.0398–1.0897; lag4, OR: 1.0372, 95% CI: 1.0112–1.0639; lag5, OR: 1.0319, 95% CI: 1.0071–1.0573; lag6, OR: 1.0388, 95% CI: 1.0121–1.0663) was positively correlated with asthma attacks. PM 10 (lag0, lag2, lag3), SO 2 (lag3, lag5, lag6), NO 2 (lag1) were negatively associated with acute asthma attacks ( Figure 4 ).

When O 3 -8 h was between 80 and 99 μg/m 3 , NO 2 (lag4, OR: 1.0186, 95% CI: 1.0065–1.0309) was positively correlated with asthma attacks. SO 2 (lag4, OR: 0.9341, 95% CI: 0.8993–0.9703) was negatively associated with acute asthma attacks ( Figure 5 ).

When O 3 –8 h was less than 80 μg/m 3 , PM 2.5 (lag4, OR: 1.0223, 95% CI: 1.0097–1.0351) and NO 2 (lag0, OR: 1.0216, 95% CI: 1.0140–1.0294; lag1, OR: 1.0210, 95% CI: 1.0134–1.0287; lag2, OR: 1.0242, 95% CI: 1.0164–1.0321; lag3 OR: 1.0186, 95% CI: 1.0111–1.0261; lag4, OR: 1.0241, 95% CI: 1.0165–1.0317; lag5, OR: 1.0210, 95% CI: 1.0132–1.0289; lag6, OR: 1.0283, 95% CI: 1.0206–1.0361) were positively correlated with asthma attacks. PM 10 (lag0, lag1, lag2, lag3), SO 2 (lag0) were negatively associated with acute asthma attacks ( Figure 6 ).

The above correlations were all statistically significant.

Ozone and Asthma

High levels of ozone are a risk factor for childhood asthma attacks. Pulmonary function tests were used to evaluate the prevalence of asthma in children in areas with high and low ozone concentrations, and it was found that ozone pollution would increase the prevalence of asthma ( 12 ). Moreover, high levels of ozone may increase the number of hospitalizations in children with asthma ( 13 ). A study from South Texas that included 902 children who were hospitalized for asthma at least twice found that a higher level of ozone was significantly associated with an increased number of children hospitalized for asthma. A foreign birth cohort study found that long-term exposure to high levels of ozone (>70 ppb) was also associated with hospitalization in children with asthma (OR 1.16–1.68) ( 14 ). In addition, previous epidemiological studies have also reported that children with asthma who take maintenance drugs are particularly susceptible to high concentrations of ozone. The background levels of ozone in this study are O 3 -1 h average 59 ppb (SD: 19 ppb) and O 3 -8 h average 51 ppb (SD: 19 ppb). The study found that in the model of PM 2.5 + O 3 , every 50 ppb increase in O 3 -1 h might increase the risk of wheezing and chest tightness by 35 and 47%, respectively ( 11 ).

Exposure to the high levels of ozone might lead to innate lymphoid cells (ILC2)-mediated type 2 immunity in children with asthma ( 15 ). T and B cells play a role in the adaptive immune. However, an animal study found that the upper respiratory tract changes induced by repeated exposure to ozone were mediated by the second group of ILC2, not T cells and B cells. In addition, surfactant protein D (SP-D) is a product of airway epithelial cells and plays an important role in immune defense mechanisms. SP-D can resist inflammatory changes and has a multimeric structure that is easily oxidized. Inhaled corticosteroids, which could induce the synthesis of SP-D have anti-inflammatory effects on the lungs and can effectively treat asthma ( 16 ). However, an animal study showed that ozone exposure weakened the anti-inflammatory effect of budesonide. Ozone exposure inhibited the release of SP-D in the airway.

As shown in Figures 3 , 5 , this study found that relatively low-level ozone (O 3 -8 h: 80–99 μg/m 3 ) was harmful to acute asthma attacks. Studies have explored the effects of ozone exposure close to or lower than the US EPA standard on infant respiratory system. Previously study found that ozone exposure increased the risk of wheezing and dyspnea in infants whose mothers were diagnosed with asthma. The risk of wheezing and dyspnea increased by 59% (95% CI, 1–154%) and 83% (95% CI, 42–136%) for each additional Inter-quartile range (IQR) respectively ( 17 ). In recent years, some studies have also found the effects of a relatively low ozone environment on children with asthma. A case-crossover study collected the number of emergency department visits ( n = 91 386) for asthma or wheezing in 41 hospitals for children aged 5–17 years. The Poisson generalized linear model found that even at relatively low ozone concentrations (47.3 ppb), ozone was still associated with childhood asthma or wheezing ( 18 ). In a cohort study focused on asthma drug treatment, an electronic drug monitor was installed on a short-acting Beta2 agonist (SABA) metered-dose inhaler to monitor the use of SABA. This study showed that ozone exposure below the US EPA standard was positively correlated with SABA use in both children and adults. Each interquartile range increase in ozone (16.8 ppb) increased the use of SABA in children (11.3%; 95% CI: 7.0–18.2%) than that in adults (8.4%; 95% CI: 6.4–11.0%) ( 19 ). Besides, the low ozone concentrations in the urban area might increase the responsiveness to allergens in patients with atopic asthma ( 20 ).

For both the single-pollutant model and multi-pollutant model ( Figures 3 , 6 ), when ozone concentration was less than 80 μg/m 3 , the ozone concentration was negatively correlated with asthma attacks in children. The potential mechanism of the protective effect of ozone at lower concentrations is still unclear. It might be related to the reactive oxygen species (ROS), produced by ozone, which has a dual influence on cell integrity. ROS are beneficial to cells at low concentrations ( 21 ). After ozone exposure, damage to the bronchiolar cell and airway inflammatory reaction is reversible. The study explored the influence of the interaction between genes and environmental factors on children with asthma observed that children with asthma who carry the TNF-308 GG gene have a significantly lower risk of bronchial symptoms under low ozone exposure (OR: 0.53, 95% CI: 0.31–0.91) ( 22 ). In addition, studies have found that oxidant genes have a protective effect on children living in low-ozone communities. A cohort study found that the effect of HMOX-1 gene variants on the risk of new-onset asthma varies with environmental ozone levels. The shorter HMOX-1 alleles (less than 23 repetitions) have the protective effect (HR, 0.44; 95% CI, 0.23–0.83) in children living in a low-level ozone environment ( 23 ).

In addition, indoor pollution has gradually entered the field of vision, and no association has been found between asthma and indoor ozone. A recent study from Beijing, China evaluated children’s cardiopulmonary response to indoor ozone exposure. During the study period, the average indoor ozone concentration (SD) was 8.7 (6.6) ppb, which was lower than the current guidelines and standards. The results showed low levels of indoor ozone were associated with decreased cardiac autonomic nerve function and increased heart rate in children. For every increase in IQR, cardiac autonomic nerve function decreases by −7.8% (95% CI: −9.9%, −5.6%), and heart rate increases by 2.6% (95% CI: 1.6%, 3.6%), but no significant correlation was found between the effects of airway inflammation and lung function ( 24 ).

Other Pollutants and Asthma

Reports show that air pollution is a risk factor leading to global morbidity and mortality. Pollutants can induce a variety of respiratory symptoms and are closely related to respiratory diseases. Many studies have shown that it was significantly associated with asthma outcomes, such as morbidity, prevalence, hospitalization rate, emergency room visits, mortality, and asthma attacks ( 25 ). This study explores the effects of both gaseous pollutants and particulate pollutants on acute asthma attacks. The results showed the association between acute asthma attacks and PM 2.5 , PM 10 , NO 2 , and SO 2 in the single-pollutant and multi-pollutant models. The results of a meta-analysis which included 22 case-crossover studies showed that all pollutants except SO 2 and PM 10 were significantly related to asthma attacks. The OR of ozone was 1.032 (95% CI: 1.005, 1.060) ( 26 ). A domestic study investigated 4,454 deaths from asthma in China from 2013 to 2018 by using case cross-analysis and conditional logistic regression model. The results showed that PM 2.5 (lag 3; IQR, 47.1 μg/m 3 ), NO 2 (lag 3; IQR, 26.3 μg/m 3 ) and O 3 (lag 3; IQR, 52.9 μg/m 3 ) were positively correlated with asthma mortality, with OR of 1.07 (95% CI): 1.01–1.22), 1.11 (95% CI: 1.01–1.22), and 1.09 (95% CI: 1.01–1.18), indicating that short-term exposure to pollutants may increase asthma mortality ( 27 ). Even exposure early in life may be related to the development of childhood asthma. A foreign prospective birth cohort study, which included 14 126 participants and followed up for 14–16 years found that the increase in PM 2.5 and NO 2 was associated with an increase in the risk of asthma. For every 10 μg/m 3 increase, the OR values were 1.13 (95% CI 1.02–1.25) and 1.29 (1.00–1.66), respectively ( 28 ).

The effects of particulate pollutants on acute asthma attacks are consistent with findings from many previous studies ( 29 , 30 ). We are facing the challenge of the combined effects of the environment and health. In this study, the daily average concentration of PM 2.5 between 2016 and 2019 was 12.057 μg/m 3 , of which 116 days exceeded the first-level standard 35 μg/m 3 (accounting for 7.94%). The average PM 10 was 44.85 μg/m 3 , and the number of days exceeding the standard accounted for 33.26%. The average value of O 3 -8 h was 81.21 μg/m 3 , and the number of days exceeding the standard accounted for 24.7%. Controlling the balance between PM 2.5 and ozone, and reducing the impact of particulate pollutants and ozone on health was still needed to be illustrated in the future. Merely reducing PM will also increase ozone, especially in winter. Merely reducing PM will also increase ozone, especially in winter. By reducing particulate pollutants, reducing the aerosol optical depth by 50% can increase ozone by 25% and also enhance the effect of volatile organic compounds (VOC) ( 31 ).

A study in North China using the Goddard Earth Observation System chemical transport model showed that PM 2.5 might stimulate the production of ozone by slowing down the aerosol deposition of hydroperoxide radicals ( 8 ). The impact of short-term exposure to particulate pollutants and ozone on acute asthma attacks might vary depending on the asthma phenotype, such as whether it was associated with allergic diseases. A time-stratified case-crossover study found that in the two pollutant models with and without allergic diseases, when the 3-day moving average of ozone (lag 0–2) increased by 20 ppb, the OR was 1.08 (95%CI: 1.02, 1.14) and 1.00 (95% CI: 0.95, 1.05), for every 10 μg/m 3 increase in PM 2.5 3-day moving average (lag 0–2), the odds ratio was 1.10 (95% CI: 1.07, 1.13) and 1.05 (95% CI: 1.02, 1.09), suggesting that asthma patients with allergic diseases were more susceptible to PM 2.5 and ozone ( 32 ). In addition, exposure to particulate pollutants may be associated with inflammation of the lower respiratory tract. An animal experimental study found that PM 2.5 (lag by 2 and 3 weeks) per IQR increased the risk of granulocytosis in bronchoalveolar lavage fluid by 11% ( p = 0.04, 95% CI = 1.01–1.22) ( 33 ).

NO 2 also affects children with asthma, such as asthma symptoms, decreased response to bronchodilators, and lung function damage. Studies have shown that asthma has the strongest association with O 3 and NO 2 ( 34 ). A systematic review of short-term exposure to O 3 and NO 2 found that daily short-term exposure to O 3 and NO 2 increased the risk of asthma exacerbation ( 35 ). We found that when O 3 -8 h was between 80 and 99 μg/m 3 , NO 2 (lag 4 days) was positively correlated with the risk of an acute asthma attack. When O 3 -8 h was less than 80 μg/m 3 , NO 2 had a significant positive correlation with the risk of an acute asthma attack after 0–6 days of lag, while ozone shows a negative correlation. Environmental ozone is mainly formed through complex photochemical reactions, and its precursors include nitrogen oxides (NOX: NO and NO 2 ) and volatile organic compounds. The ozone level has a complex non-linear relationship with the concentration of NO 2 , and NO 2 will weaken the photochemical reaction of O 3 to a certain extent. When the NOX concentration is low, the ozone concentration increases with the increase in the NOX concentration and has nothing to do with the VOC concentration. When the NOX concentration is high, reducing NOX will increase ozone ( 31 , 36 ). A study has shown that NO 2 and O 3 are closely related, and there is a long-term time sequence in some periods ( 37 ).

Sulfur dioxide can cause bronchoconstriction ( 5 ). A study in China pointed out that sulfur dioxide is related to the prevalence and symptoms of asthma in children (especially children with atopic allergies) ( 38 ) when the concentration of sulfur dioxide exceeded the World Health Organization’s Clean Air Guidelines. The results of this study showed thatSO 2 (lag 0) was positively correlated with an acute asthma attack (OR: 1.0461, 95% CI: 1.0055–1.0884) when O 3 -8 h was between 80 and 99 μg/m 3 . Ozone is an effective oxidant, while sulfur dioxide is a reducing agent. They may cause asthma symptoms through different mechanisms.

Advantages and Limitations

There are some advantages to this study. First of all, this study analyzed the influence of increasing ozone levels at low concentrations on acute asthma attacks. Secondly, the case-crossover study design is suitable for assessing the transient effects on the risk of the onset of acute events. Moreover, this design allows each patient to serve as his control. Patient-level confounding factors and time-varying variables are readily controlled. Finally, this study used single and multiple pollutant models to examine the relationship between ozone and asthma exacerbations.

The current research has some potential limitations. First, ambient concentration data were from only four monitoring stations of Xiamen. Ambient air monitoring equipment measures air quality at fixed outdoor locations, while asthma children breathe air in several indoor and outdoor environs throughout the day—ultimately do not fully represent children’s exposures. Second, this study did not include pollen exposure in the study. Pollen exposure in the daily environment may also affect lung function. Finally, this study is a single-center study. A multi-center study is needed to verify the reliability of the results.

Our data provided a unique opportunity to examine the influence of ambient ozone on asthma attacks in children. The data indicate that short-term exposure to O 3 , PM 2.5 , PM 10 , NO 2 , and SO 2 may be associated with acute asthma exacerbations. When ozone concentrations are higher than 80 μg/m 3 , children are at significantly increased risk of asthma attacks.

Data Availability Statement

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

Ethics Statement

The studies involving human participants were reviewed and approved by the Ethical Review Board of The First Affiliated Hospital of Xiamen University. Written informed consent from the participants’ legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.

Author Contributions

WH and JW coordinated and supervised the data. WH wrote the manuscript. JW and XL revised the manuscript. All authors contributed to the conception, interpretation of the results, and approved the final manuscript.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Acknowledgments

We thank the Xiamen Meteorological Bureau for providing meteorological data, including ozone. We also thank the Xiamen Department of Environmental Protection for providing air pollutant data. We also thank Yu Zhu, Zhifan Hu, and Xiaoshan Dai, for their contributions to data collection.

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Keywords : asthma attack, ozone, child, case-crossover design, air pollution

Citation: Huang W, Wu J and Lin X (2022) Ozone Exposure and Asthma Attack in Children. Front. Pediatr. 10:830897. doi: 10.3389/fped.2022.830897

Received: 07 December 2021; Accepted: 21 February 2022; Published: 05 April 2022.

Reviewed by:

Copyright © 2022 Huang, Wu and Lin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Jinzhun Wu, [email protected]

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Summer weather and wildfire smoke can trigger allergies and asthma

AMARILLO, Texas (KFDA) - With the latest round of storms and wildfires, there has been an increase in severe allergies and chronic asthma attacks in children.

Thunderstorms, summer weather and wildfire smoke can worsen symptoms for children with allergies or asthma.

“Fine particular matter in the air if you get it down into your lungs can exacerbate any breathing. Chronic respiratory conditions can also worsen other various comorbidities like heart disease, but it’s really just those inheritance within the smoke that can make the breathing more difficult and worse,” said Dr. Sean Anderson, MD, family medicine at Northwest.

Smoke from wildfires can travel thousands of miles, depending on the amount of fire and smoke, as well as the wind patterns which can change daily or weekly.

“That already makes the sensitive to irritants like smoke, like pollen, like allergies that could happen with weather changes, but with smoke with wildfires there’s also fine particular matter that can get down deep in the airways and cause more of this inflammation to get worse and make it harder for them to breathe,” said Dr. Anderson.

Dr. Anderson advises parents to pay close attention to their child’s symptoms, including fatigue, breathing patterns, chest tightness and more.

Copyright 2024 KFDA. All rights reserved.

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