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• Volume 11, Issue 7
• Management of asthma in childhood: study protocol of a systematic evidence update by the Paediatric Asthma in Real Life (PeARL) Think Tank
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• http://orcid.org/0000-0002-4675-9616 Alexander G Mathioudakis 1 , 2 , 3 ,
• Michael Miligkos 4 ,
• Cristina Boccabella 5 ,
• Gioulinta S Alimani 3 , 6 ,
• Adnan Custovic 7 ,
• A Deschildre 8 ,
• Francine Monique Ducharme 9 ,
• Omer Kalayci 10 ,
• Clare Murray 1 , 2 ,
• Antonio Nieto Garcia 11 ,
• Wanda Phipatanakul 12 ,
• David Price 13 , 14 ,
• Aziz Sheikh 15 ,
• Ioana Octavia Agache 16 ,
• Leonard Bacharier 17 ,
• http://orcid.org/0000-0001-5639-0528 Apostolos Beloukas 6 , 18 ,
• Andrew Bentley 2 , 19 ,
• Matteo Bonini 5 , 20 ,
• Jose A Castro-Rodriguez 21 ,
• Giuseppe De Carlo 22 ,
• Timothy Craig 23 ,
• Zuzana Diamant 24 , 25 , 26 ,
• Wojciech Feleszko 27 ,
• Tim Felton 1 , 2 ,
• James E Gern 28 ,
• Jonathan Grigg 29 ,
• Gunilla Hedlin 30 ,
• Elham M Hossny 31 ,
• Despo Ierodiakonou 32 ,
• Tuomas Jartti 33 ,
• Alan Kaplan 34 ,
• Robert F Lemanske 28 ,
• Peter N Le Souëf 35 ,
• Mika J Mäkelä 36 ,
• Georgios A Mathioudakis 3 ,
• Paolo Matricardi 37 ,
• Marina Mitrogiorgou 38 ,
• Mario Morais-Almeida 39 ,
• Karthik Nagaraju 40 ,
• Effie Papageorgiou 6 ,
• Helena Pité 39 , 41 , 42 ,
• Paulo M C Pitrez 43 ,
• Petr Pohunek 44 ,
• Graham Roberts 45 , 46 , 47 ,
• Ioanna Tsiligianni 32 ,
• Stephen Turner 48 ,
• Susanne Vijverberg 49 ,
• Tonya A Winders 50 ,
• http://orcid.org/0000-0001-5939-812X Gary WK Wong 51 ,
• Paraskevi Xepapadaki 52 ,
• Heather J Zar 53 , 54 ,
• http://orcid.org/0000-0002-4448-3468 Nikolaos G Papadopoulos 1 , 52
• 1 Division of Infection, Immunity and Respiratory Medicine , The University of Manchester , Manchester , UK
• 2 North West Lung Centre, Manchester University NHS Foundation Trust , Manchester , UK
• 3 Athens Breath Centre , Athens , Greece
• 4 First Department of Pediatrics, "Aghia Sofia" Children's Hospital , University of Athens , Athens , Attica , Greece
• 5 Department of Cardiovascular and Thoracic Sciences , Catholic University of the Sacred Heart , Milano , Lombardia , Italy
• 6 Department of Biomedical Sciences , University of West Attica , Egaleo , Attica , Greece
• 7 Department of Paediatrics , Imperial College London , London , UK
• 8 Unité de Pneumologie et Allergologie Pédiatriques, Hôpital Jeanne de Flandre , CHU Lille , Lille , Hauts-de-France , France
• 9 Pediatrics , University of Montreal , Montreal , Quebec , Canada
• 10 Pediatric Allergy and Asthma Unit , Hacettepe Universitesi , Ankara , Turkey
• 11 Pulmonology and Allergy Unity , La Fe University and Polytechnic Hospital , Valencia , Comunidad Valenciana , Spain
• 12 Pediatric Allergy and Immunology , Children's Hospital Boston , Boston , Massachusetts , USA
• 13 Centre of Academic Primary Care , University of Aberdeen , Aberdeen , UK
• 14 Observational and Pragmatic Research Institute , Singapore
• 15 Asthma UK Centre for Applied Research, Usher Institute of Population Health Sciences and Informatics , The University of Edinburgh , Edinburgh , UK
• 16 Allergy and Clinical Immunology , Transylvania University , Brasov , Romania
• 17 Department of Allergy, Immunology, and Pulmonary Medicine , University of Washington , Seattle , Washington , USA
• 18 Institute of Infection and Global Health , University of Liverpool , Liverpool , UK
• 19 Acute Intensive Care Unit , University Hospital of South Manchester NHS Foundation Trust , Manchester , Greater Manchester , UK
• 20 National Heart and Lung Institute (NHLI) , Imperial College London , London , UK
• 21 Department of Pediatrics , Pontifical Universidad Catolica de Chile , Santiago , Chile
• 22 Allergy and Airway Diseases Patient's Associations , European Federation of Pharmaceutical Industries and Associations , Brussels , Belgium
• 23 Allergy, Asthma and Immunology , Penn State University , Hershey , Pennsylvania , USA
• 24 Department of Respiratory Medicine and Allergology, Institute for Clinical Science , Skane University Hospital Lund Hematological Clinic , Lund , Skåne , Sweden
• 25 Department of Respiratory Medicine , First Faculty of Medicine, Charles University and Thomayer Hospital , Prague , Czech Republic
• 26 Department of Clinical Pharmacy & Pharmacology , University of Groningen, University Medical Center of Groningen and QPS-NL , Groningen , Netherlands
• 27 Department of Pediatric Pulmonology and Allergy , Medical University of Warsaw , Warszawa , Poland
• 28 Department of Pediatrics and Medicine , University of Wisconsin School of Medicine and Public Health , Madison , Wisconsin , USA
• 29 Centre for Genomics and Child Health, Blizard Institute , Queen Mary University of London , London , UK
• 30 Department of Women's and Children's Health , Karolinska Institute , Stockholm , Stockholm , Sweden
• 31 Pediatric Allergy and Immunology Unit , Ain Shams University , Cairo , Egypt
• 32 Department of Social Medicine, Faculty of Medicine , University of Crete , Rethimno , Greece
• 33 Department of Paediatrics , University of Turku , Turku , Finland
• 34 Family Physician, Airways Group of Canada , University of Toronto , Toronto , Ontario , Canada
• 35 School of Paediatrics and Child Health , University of Western Australia , Perth , Western Australia , Australia
• 36 Department of Allergy , University of Helsinki , Helsinki , Uusimaa , Finland
• 37 Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine , Charité - University Medicine , Berlin , Germany
• 38 Third Department of Paediatrics , National and Kapodistrian University of Athens School of Health Sciences , Athens , Greece
• 39 Allergy Center , Hospital CUF Descobertas , Lisboa , Portugal
• 40 Allergy & Asthma , VN , Chennai , India
• 41 Allergy Center , CUF Infante Santo Hospital , Lisbon , Portugal
• 42 Chronic Diseases Research Center (CEDOC) , NOVA Medical School / Faculdade de Ciências Médicas, Universidade NOVA de Lisboa , Lisbon , Portugal
• 43 Laboratory of Respiratory Physiology, Infant Center , School of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) , Porto Alegre , Brazil
• 44 Paediatric Department , Motol University Hospital , Praha , Czech Republic
• 45 The David Hide Asthma and Allergy Research Centre , St Mary's Hospital , Newport Isle of Wight , UK
• 46 Faculty of Medicine, Clinical and Experimental Sciences and Human Development in Health Academic Units , University of Southampton , Southampton , UK
• 47 NIHR Biomedical Research Centre , University Hospital Southampton NHS Foundation Trust , Southampton , UK
• 48 Department of Child Health , University of Aberdeen , Aberdeen , Aberdeen , UK
• 49 Department of Respiratory Medicine and Department of Pediatric Pulmonology , University of Amsterdam , Amsterdam , Netherlands
• 50 Allergy & Asthma , Global Patient Platform , Virginia , Virginia , USA
• 51 Department of Paediatrics, Faculty of Medicine , The Chinese University of Hong Kong , Sha Tin , Hong Kong
• 52 Allergy Department, 2nd Paediatric Clinic , National and Kapodistrian University of Athens , Athens , Attica , Greece
• 53 Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital , University of Cape Town , Rondebosch , Western Cape , South Africa
• 54 Unit on Child and Adolescent Health , Medical Reaserch Council , Cape Town , South Africa
• Correspondence to Professor Nikolaos G Papadopoulos; ngpallergy{at}gmail.com

Introduction Clinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted.

Methods and analysis Standard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively.

Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence.

Ethics and dissemination Ethics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank.

PROSPERO registration numbers CRD42020132990, CRD42020171624.

• paediatrics
• paediatric thoracic medicine
• thoracic medicine

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/bmjopen-2020-048338

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Strengths and limitations of this study

Broad evidence syntheses on the management of childhood asthma, with a focus on the differential treatment response according to age and disease phenotypes could reveal clinically exploitable information, that will be used in the development of clinical and research recommendations by Paediatric Asthma in Real Life.

A rigorous methodology that includes thorough evaluation of the literature, appropriate evaluation of the methodological quality of individual studies and—when appropriate—of the body of evidence, and presentation of overall effect estimates.

A prospectively published protocol increases the transparency and allowed for peer-review of the methodology used.

A potential limitation of the overview of systematic reviews (SRs) is that the feasibility of conducting the planned subgroup analyses will depend on whether relevant data have been captured in existing SRs.

Introduction

Having a global prevalence that is anticipated to exceed 400 million children by the year 2025, childhood asthma represents a huge health and socioeconomic burden to patients, their families and the society. 1–3 Despite its diverging mechanisms, triggers, outcomes and response to treatment, childhood asthma is often still approached as an extension of adult asthma. 4 It is underaddressed in clinical guidelines, likely due to unclear diagnosis, limited availability of safety, efficacy and effectiveness data in this population. Clinical recommendations are to a large extent informed by data extrapolated from clinical studies conducted in adults. 2–5

Numerous challenges complicate conducting interventional research studies in children with asthma. Besides the lack of consensus on its definition and diagnostic criteria, childhood asthma is highly heterogeneous and our understanding of different paediatric asthma phenotypes is still limited or contradictory. 6 This is further emphasised by significant variability in disease progression, outcomes and treatment response in children with different phenotypes or ages5, 7 potentially complicating interpretation of trials’ findings. In addition, there are regulatory and ethical constraints in conducting interventional research in children. 8 9 However, this results in the administration of treatments that have not been adequately evaluated in relevant (paediatric) populations, that is, evidently suboptimal.

Paediatric Asthma in Real Life (PeARL), an international Think Tank focusing on paediatric asthma, was initiated in the context of the respiratory effectiveness group, to address this evidence deficit. In a recent international, multistakeholder survey, we have identified and prioritised unmet needs on paediatric asthma. 10 A need for systematic evidence updates focusing on the management of asthma in different age groups emerged. Herein, we present the protocol for a series of systematic evidence updates aiming to summarise direct evidence from clinical studies in children with asthma, evaluating the safety and clinical effectiveness of pharmacological interventions for maintenance management and for the treatment of acute severe asthma attacks, defined as those leading to an emergency presentation with/without hospital admission, in different age groups. Our work will be used to inform clinical recommendations being developed by the PeARL Think Tank. Therefore, we need solid evidence on the efficacy on safety of various interventions. It is considered crucial to incorporate evidence derived from real-life observational studies, which may carry a lower strength of evidence than randomised controlled trials (RCTs), but are available in higher abundance and provide a better representation of clinical practice in real life, where for example, treatment compliance or inhaler technique may be problematic.

Methods and analysis

We will conduct two systematic evidence updates, based on protocols prospectively registered in the PROSPERO register (CRD42020132990, 11 CRD42020171624 12 ). The first will evaluate the safety and clinical effectiveness of pharmacological maintenance treatments for childhood asthma, while the other will focus on the pharmacotherapy of acute severe asthma attacks, defined as those requiring a hospital admission or emergency presentation. We will use standard methodology recommended by the Cochrane Collaboration 13 and will follow the Preferred Reported Items for Systematic Reviews and Meta-Analyses statement. 14

Preliminary searches revealed several RCTs evaluating maintenance pharmacotherapy of childhood asthma, which have already been summarised in high-quality systematic reviews (SRs), some conducted by the Cochrane Collaboration. We identified >40 up-to-date SRs evaluating inhaled corticosteroids (ICS), long-acting beta-2 agonists (LABA), long-acting muscarinic antagonists (LAMA), leukotriene receptor antagonists (LTRA) or biologic therapies, as first line or add-on treatment for asthma in children. As a result, we opted to produce an overview of existing SRs of clinical trials and real-life studies. 15 .

We found less up-to-date SRs on the management of acute severe asthma attacks in children, mainly focusing on short-acting beta-2 agonists (SABA), short acting muscarinic antagonists, oral corticosteroids, aminophylline and magnesium that were recently summarised in a Cochrane Overview of SRs. 16 However, when evaluating the literature, we identified several other pharmacological interventions that are tested in small trials or real-life studies, and while they may show promising early results, they have not been assessed further or introduced in clinical practice guidelines. 17–23 For this reason, we will conduct de novo synthesis of comparative clinical studies of any design aiming to identify any pharmacological intervention that has been tested for acute severe asthma attacks, followed by focused meta-analyses of promising interventions not covered by existing high-quality SRs or clinical practice guidelines.

Overview of SRs evaluating maintenance pharmacotherapy for paediatric asthma

Eligibility criteria.

Eligible studies will comprise SRs and meta-analyses of controlled clinical trials or of real-life studies evaluating maintenance treatments that are broadly used in clinical practice for asthma or recurrent wheeze in children and adolescents, aged up to 18 years. More specifically, we will include SRs comparing any combination of ICS, LABA, LAMA, LTRA, biological therapies (namely omalizumab, mepolizumab, reslizumab, benralizumab or dupilumab), or placebo as monotherapy or add-on maintenance therapy for paediatric asthma. We will accept SRs and meta-analyses evaluating any molecule of the above-mentioned categories, administered at any dose and for a duration of at least 6 weeks. SRs comparing asthma maintenance treatment both in children and adults will be included provided that paediatric data are presented separately. We will only include SRs published between 2005 and December 2020 and reported in the English language. Older SRs are probably outdated and will only be considered in the absence of high-quality, newer SRs.

Outcome measures

The primary outcomes of this overview will be the number of acute attacks requiring the administration of oral corticosteroids or an emergency visit, and the number of acute attacks requiring hospitalisation. Secondary outcomes will include lung function measures, acute attacks irrespective of the severity, symptom scores (including symptom free and rescue medication free days), asthma control, asthma-specific quality of life scores, use of rescue medications, withdrawal rates (overall, due to lack of efficacy or adverse events), adverse events and serious adverse events.

Search strategy and study selection

The electronic databases of Medline/PubMed and Cochrane Library will be systematically searched, using appropriate controlled vocabulary and free search terms to identify relevant SRs (terms describing: childhood asthma, LABA, LAMA, LTRA, ICS, biologics, SRs, detailed search strategy is available in online supplemental appendix ). Databases will be searched from 2006 onwards. Titles and abstracts of all identified manuscripts, and the full texts of potentially relevant manuscripts, will be screened by two investigators independently. We will report the reasons of exclusion of studies that will be excluded after full-text review. Disagreement will be resolved through discussion or adjudication by a third investigator, when necessary.

Supplemental material

Data abstraction.

For each of the included SRs, one investigator will extract the full reference and study identifiers, references of the included trials evaluating paediatric populations, eligibility criteria, predefined outcomes, number and baseline characteristics of the participants and details on the outcomes of interest. A second investigator will cross-check for validity.

Risk of bias assessment

A MeaSurement Tool to Assess systematic Reviews, V.2 (AMSTAR 2) tool will be used to evaluate the methodological quality of all included SRs. 24 25 The AMSTAR 2 tool evaluates 16 domains, focusing on the methodological design, interpretation and potential risk of bias involved in the conduct of a SR. It is considered by the AMSTAR 2 team that seven domains could critically affect the validity of the review, while the remaining domains describe non-critical weaknesses. Critical flaws for an SR include (1) lack of prospective protocol registration, (2) inadequate literature searches, (3) lack of justification of excluding individual studies, (4) of risk of bias evaluation or (5) of risk of bias consideration in interpreting the results, (6) of assessment of presence and likely impact of publication bias and (7) inadequate methodology for conducting meta-analysis. We will consider the results of an SR of high quality, if there is only one or none non-critical weakness, and of moderate quality, if there are more than one non-critical weaknesses. If there are one or more critical weaknesses, then we will consider the confidence low or very low, respectively. Two of the SRs will evaluate the risk of bias independently and disagreement will be resolved through discussion, or adjudication by a third reviewer.

Qualitative synthesis

We will summarise descriptively or in a tabulated format the characteristics of the included SRs and outcomes of interest. When several SRs evaluate the same intervention, we will compare their eligibility criteria, included studies and methodological quality as evaluated by the AMSTAR-2 tool, as well as the pertinent subgroup analyses that are presented. We will present in detail the results of the SR that is most recent, more complete and of high methodological quality. If no single SR fulfil these criteria, we will present in detail more than one SRs. From the remaining SRs, we will present pertinent additional information that may include, such as details about additional outcomes, or additional subgroups.

We will specifically report on the differential effectiveness of the interventions across different maintenance treatment steps (severity), age groups or paediatric asthma phenotypes.

SR of clinical studies evaluating the management of acute severe asthma attacks

Over the past decades, several interventions have been tested for the management of acute severe asthma attacks, such as ketamine or macrolide antibiotics. 17–23 Despite promising early findings, some of these interventions were not further tested in robust, prospective controlled clinical trials. This may partially be due to challenges in conducting experimental clinical studies in children, as previously discussed, particularly during acute, life-threatening conditions.

To identify all evaluated treatments, a two-stage approach will be followed. First, a broad search strategy will be used to identify all pharmacological interventions that have been tested as potential treatments for acute severe asthma attacks. Next, medications that showed positive clinical results, but are not yet thoroughly evaluated in clinical studies and meta-analyses and are therefore not recommended by international asthma guidelines (such as the National Institute for Health and Care Excellence asthma guidelines, the British Thoracic Society and Scottish Intercollegiate Guidelines Network asthma guidelines, the National Asthma Education and Prevention Programme or the Global Strategy for Asthma Management and Prevention document), will be selected and further evaluated in individual meta-analyses. The aim will be to identify novel interventions that could be recommended for use in clinical practice, or might require further evaluation in clinical research studies, to confirm their safety and effectiveness profiles.

Medline/PubMed and the Cochrane Library will be searched, using a broad search strategy, aimed to identify any clinical research studies evaluating the management of acute severe asthma attacks (detailed search strategy is available in online supplemental appendix ).

Any study evaluating pharmacological treatments for acute severe asthma attacks in children and adolescents (<18 years of age) will be included. Any comparative clinical research study, including experimental and observational studies, as well as SRs of such studies will be considered eligible for inclusion. We will only include studies published until May 2021 and reported in the English language, without time restrictions.

Eligible studies will be grouped according to the drug category they evaluate and will be presented narratively. Study design, characteristics and outcomes of interest will be reported descriptively or in a tabulated format. Outcomes of interest are the same for this broad SR and individual medication meta-analyses and are detailed in the next section.

Individual medication meta-analyses

These meta-analyses will further evaluate the safety and clinical effectiveness of individual medications that were assessed by the initial broad SR and were found to be of potential clinical value for the treatment of acute severe asthma attacks. In contrast to most preceding SRs and meta-analyses, we will include data from observational comparative effectiveness (real-life) studies, as well as controlled clinical trials.

For each meta-analysis, eligible studies will comprise controlled clinical trials and observational comparative effectiveness studies comparing the index medication with placebo, no treatment or any active control, as an add-on treatment for acute severe asthma attacks. Index medication will be defined based on the pharmacological action, meaning that molecules targeting the same pharmacological target (eg, salbutamol and terbutaline, both being SABA) will be grouped. Only studies evaluating the management of acute severe asthma attacks, defined as those requiring a hospital admission or emergency presentation, in children and adolescents, aged between 1 and 18 years of age will be included. Studies evaluating both children and adults will be included, provided that paediatric data are reported separately or that we will be able to access these data after requesting them from the investigators. We will only include observational studies that meet the primary criteria of the REal Life EVidence AssessmeNt Tool (RELEVANT) tool (see risk of bias). We will include studies published until May 2021 and reported in the English language.

The primary outcome measures will be (1) treatment success or treatment failure rate evaluated at any time point, within 2 weeks from presentation, (2) serious adverse events and (3) need for asthma related hospitalisation evaluated at any tim epoint within 2 weeks from presentation. Treatment success will be defined as a complete resolution of the symptoms, or an improvement in the clinical signs, symptoms and/or laboratory findings that fulfils specific criteria or thresholds prespecified by the study team. Treatment failure will be defined as a significant deterioration of the patients’ clinical conditions that fulfils specific criteria prespecified by the study team. For example, treatment failure may be defined as the need for paediatric intensive care unit admission, ventilation or death. The definitions of treatment success and treatment failure vary significantly across clinical studies evaluating the management of acute asthma in children; for this reason, meta-analyses will only be conducted in cases they are considered meaningful by the investigators. Need for asthma-related hospitalisation will not be relevant for studies only evaluating hospitalised participants. Secondary outcomes will include (1) mortality, (2) duration of asthma-related hospitalisation, (3) need for intensive care unit admission, (4) duration of intensive care unit stay, (5) re-exacerbation rate, (6) rehospitalisation rate and (7) adverse events. All outcomes will be evaluated at a maximum follow-up of 6 months, as longer-term outcomes are less likely to be directly linked with the index acute event.

Using appropriate controlled vocabulary and free search terms, we will systematically search Medline/PubMed, EMBASE and the Cochrane Library to identify controlled clinical trials and observational comparative effectiveness studies evaluating the safety, efficacy and/or clinical effectiveness of the selected medication (sample search strategies are available in the online appendix). We will also search the WHO International Clinical Trials Registry Platform search portal, the abstract proceedings of the European Respiratory Society, the American Thoracic Society, the Asian Pacific Society of Respirology, the European Academy of Allergy and Clinical Immunology, the American Academy of Allergy, Asthma and Immunology, and the World Allergy Organization, as well as the reference lists of all included studies. All sources will be searched from inception, without language limitations. We will follow standard methodology for screening titles, abstracts and the full text of all identified studies, as described previously.

The full study reference, study identifiers, details on the study design, eligibility criteria, predefined outcomes and potential confounding factors that were considered by the investigators, number and baseline characteristics of participants will be extracted by one investigator and will be cross-checked for validity by a second extractor. Details on the outcomes of interest from all included studies will be extracted by two investigators independently. Conflicts will be resolved through discussion and when needed adjudication by a third investigator.

Risk of bias of individual studies

We will use the second version of the Cochrane risk of bias (RoB2) tool for assessing risk of bias in the included RCTs 26 and the RELEVANT for assessing the risk of bias of observational studies. 27 Risk of bias of each included study will be evaluated by two investigators independently.

The RoB2 tool evaluates the following domains for potential risk of bias: (1) bias arising from the randomisation process, (2) bias due to deviations from intended interventions, (3) bias due to missing outcome data, (4) bias in measurement of the outcome, (5) bias in selection of reported results and (6) any other potential source of bias. High risk of bias in any of these domains will result in an overall judgement of high risk of bias. In the absence of high-risk domains, unclear risk in any domain will lead to an overall judgement of unclear risk. All remaining trials will be considered to be of low risk of bias.

RELEVANT evaluates the quality of observational comparative effectiveness research studies across seven domains, which include background, design, measures, analysis, results, discussion/interpretation and conflicts of interest. Each domain includes primary and secondary items. It is suggested that studies not meeting the primary items of RELEVANT are of very low methodological quality (have ‘fatal flaws’) and should not be used to inform clinical recommendations. Therefore, we will exclude studies not meeting these criteria. We will consider of low risk of bias all studies meeting the secondary criteria of RELEVANT as well, and of high risk of bias studies that do not meet any of the secondary criteria.

For every comparison, we will use funnel plots, Egger’s regression and Begg’s rank tests to evaluate publication bias, if we are able to pool more than 10 studies.

Data synthesis

Data from controlled clinical trials or observational studies will be analysed separately. In addition, studies evaluating different comparators, will be analysed separately. If different doses of the index medication or comparator are evaluated across the included studies, we will consider grouping studies using similar doses, providing that their results are not significantly dissimilar.

For every analysis, I 2 statistic will be used to assess statistical heterogeneity. Substantial heterogeneity (I 2 >50%) will be explored using prespecified subgroup analyses (details in the next section). We will not perform meta-analyses in cases of considerable unresolved heterogeneity (I 2 >75%).

When it is considered meaningful, meta-analyses will be performed using the random-effects model, because we anticipate significant heterogeneity in our data. Results will be presented in the form of relative risk (95% CI) for dichotomous data, mean difference (95% CI) for continuous data and (HR, 95% CI) for time to event data. Meta-analyses will be performed using Review Manager V.5 (RevMan, http://community.cochrane.org/tools/review-production-tools/revman-5 ) and R statistics V.3.4.3 or newer (R Foundation for Statistical Computing, Vienna, Austria).

For dichotomous outcomes, the unit of analysis will preferably be participants, rather than events (ie, number of participants admitted to the intensive care unit, rather than number of admissions per participants).

Sensitivity and subgroup analyses

In sensitivity analyses for all comparisons, we will (1) use fixed effects models, (2) only include studies with low risk of bias, (3) exclude studies reporting limited adherence to the study drugs (<80%) and (4) evaluate separately studies assessing different doses of the index medication, which we may pool in the main analysis.

Subgroup analyses according to participants’ age, asthma phenotypes or, possibly, acute attack phenotypes will also by conducted, depending on data availability. In an additional subgroup analysis, we will evaluate separately trials utilising exploratory versus pragmatic study designs.

Certainty of the body of evidence

Certainty of the body of evidence, for every comparison will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. 28 GRADE assesses the certainty in a body of evidence as high, moderate, low or very low after considering the methodological quality of the included studies, imprecision, inconsistency, indirectness, publication bias, the magnitude of effect, dose response and confounders likely to minimise the effect. All decisions to upgrade or downgrade the quality of evidence will be transparent and justified in evidence profile and summary of evidence tables, in accordance with GRADE guidance. GRADEPro Software (2014; www.gradepro.org ) will be used for the development of these tables.

We will use GRADE methodology to assess the risk of bias associated with missing participant outcome data across the body of the available evidence. 29 GRADE suggests repeating the primary meta-analysis, imputing the most extreme assumptions about the values of the missing data, that the investigators consider plausible. Only if the analyses prove robust to this imputation, the risk of bias due to missing participant outcome data should be deemed low.

The impact that the risk of bias of individual studies and the confidence in the body of the evidence has on the results will be presented.

Ethics and dissemination

Ethical approval is not required for these SRs, since no primary data will be collected.

The findings of these evidence updates will be presented in national and international scientific conferences. They will also be submitted for publication in high-impact peer review journals. Plain English summaries of the final reports will be developed and shared with relevant patient organisations. Moreover, our results will be used to inform clinical recommendations that will be developed by the PeARL Think Tank. We anticipate that the overview of SRs will be completed by the end of 2021 and the remaining SRs by June 2022.

Patient and public involvement

The planned SRs were prioritised through a global, multi-stakeholder survey evaluating research priorities in childhood asthma, conducted by the PeARL Think Tank. 10 Among other stakeholders, this survey included responses from patients, patient caregivers and patient organisations. Moreover, two patient representatives (GDC and TAW) have joined the research group and provided input in this study protocol and they will also provide input throughout the study process.

We report on the methodology of a series of planned systematic evidence updates, aiming to evaluate maintenance management of childhood asthma, and the treatment of acute severe asthma attacks. Their design is informed by preliminary searches and the anticipated data availability. These SRs will be conducted by the PeARL group and will be used to inform clinical recommendations and future research needs. The need for high-quality evidence updates and clinical practice guidelines to improve the management of asthma in children is more urgent now, given the pressure that the unfolding COVID-19 pandemic pose on the healthcare systems, forcing us to reconsider our daily clinical practice. 30 31

Major strengths of our evidence update series are the inclusion of a wide evidence base, including data from RCTs and real-life comparative studies, the prospective design and strong methodology. The methodological quality of all available studies will be scrutinised and will aid the interpretation of our findings. Moreover, we will attempt to evaluate differential therapeutic response of different asthma phenotypes and age groups. We believe this analysis will be revealing, if adequate data is available, but may nevertheless reveal important gaps.

Guided by the available evidence, we will follow different strategies for the evidence updates on maintenance treatment of paediatric asthma and on management of acute severe asthma attacks. In view of the availability of ample published, up-to-date SRs on maintenance pharmacotherapy of childhood asthma, we chose to conduct an overview of SRs. We decided to focus on the most frequently used and thoroughly evaluated drug classes (ICS, LABA, LAMA, LTRA and biological therapies) and we expect to identify good quality data, which would inform clinical practice and research needs. Other, less frequently or experimentally used treatments will need to be evaluated in future studies. A potential limitation of this approach is that we might not be able to capture adequate data regarding the differential effectiveness of interventions across different severity groups, age groups or paediatric asthma phenotypes, if these have not been captured in existing SRs. Moreover, existing SRs may not capture some of the most recent studies, that may have been published after the SRs, although preliminary searches have revealed several very recently update meta-analyses.

The second SR, focusing on the management of acute attacks, will first evaluate a multitude of established and experimental treatments. With regard to the latter, this SR will reveal treatments that have been tested, appeared safe and efficacious and it may be worth to be further evaluated, but will also report on interventions that were tested, but did not appear efficacious, and therefore, further evaluation may not be beneficial. This wide approach would aid the prioritisation of interventions to be further validated in future clinical research studies.

Next, meta-analyses of individual pharmacological interventions will be conducted to further assess the safety and clinical effectiveness of treatments for acute severe asthma attacks that will appear efficacious in our broad SR. In contrast to most previous meta-analyses, that may have been conducted, we will include both controlled clinical trials and observational comparative effectiveness studies. Due to limitations that have already been discussed, few controlled clinical trials are conducted in children. This leads several Cochrane SRs to report low or very low confidence in the body of evidence, due to the lack of data. 32–35 We believe that by incorporating data from observational studies we may be able to conclude more robust results. While observational studies are at a higher risk of bias, we will carefully evaluate this risk using the newly developed, thorough RELEVANT tool and we will discuss potential implications on our findings. The GRADE working groups provides transparent guidance for assessing the certainty in a body of evidence including data from different study designs (controlled clinical trials or observational studies); this guidance will be used for interpreting the findings of our meta-analyes.

Overall, we aim to develop evidence updates on the maintenance treatment of asthma and management of acute severe asthma attacks that will cover all available evidence, carefully considering methodological limitations. These will be used by the PeARL Think Tank for the development of clinical recommendations and to guide future clinical research.

Ethics statements

Patient consent for publication.

Not required.

Acknowledgments

AGM was supported by the National Institute of Health Research Manchester Biomedical Research Centre (NIHR Manchester BRC). We thank Mrs Maria Kritikou for excellent administrative support of the study

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Supplementary materials

Supplementary data.

This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

• Data supplement 1

Twitter @mathioudakisag

AGM and MM contributed equally.

Contributors Study conception: AGM and NGP. Study design: AGM, MM and NGP. Preparation of the manuscript: AGM. Critical revision and final approval of the manuscript: AGM, MM, CB, GSA, AC, AD, FMD, OK, CM, ANG, WP, DP, AS, IOA, LB, AB, AB, MB, JAC-R, GDC, TC, ZD, WF, TF, JEG, JG, GH, EMH, DI, TJ, AK, RFL, PNLS, MJM, GAM, PM, MM, MM-A, KN, EP, HP, PMCP, PP, GR, IT, ST, VS, TAW, GWKW, PX, HJZ and NGP.

Funding This work was supported by the Respiratory Effectiveness Group (REG). REG has received support from AstraZeneca, Novartis and Sanofi for continued work on PeARL. (Award/Grant name: PeARL, Award/Grant Number: N/A). This is an investigator initiated study and the funders were not involved in the selection of the topic, or design of these systematic reviews. AGM was supported by the National Institute for Health Research Manchester Biomedical Research Centre (NIHR Manchester BRC).

Competing interests AGM reports grants from Boehringer Ingelheim outside the submitted work. AC reports personal fees from Novartis, Regeneron / Sanofi, Thermo Fisher Scientific, Boehringer Ingelheim and Philips, outside the submitted work. LB reports personal fees from Aerocrine, GlaxoSmithKline, Genentech/Novartis, Merck, DBV Technologies, Teva, Boehringer Ingelheim, AstraZeneca, WebMD/Medscape, Sanofi/Regeneron, Vectura and Circassia outside the submitted work. TC reports grants and personal fees CSL Behring, Dyax, Takeda, BioCryst, Pharming, personal fees from Grifols, grants and non-financial support from GSK, Regeneron, Novartis/Genetech outside the submitted work. AD reports grants and personal fees from Stallergenes Greer, personal fees from Novartis, ALK, TEVA, GSK, MEDA-MYLAN, CHIESI, AImmune, DBV technologies and Astra Zeneca, outside the submitted work. ZD reports personal fees from academic affiliations, ZD acts as Executive and Scientific Medical Director at a phase I/II pharmacological unit (QPS-NL), which performs clinical studies for pharmaceutical companies. ZD reports personal fees from Astrazeneca, ALK, Aquilon, Boehringer Ingelheim, CSL, HAL Allergy, MSD, and Sanofi-Genzyme outside the submitted work. FMD reports grants from Thorasys; personal fees from Jean-Coutu Pharmaceuticals, unrestricted research funds from Novartis Canada, Teva and Trudell Medical, research grants from GlaxoSmithKline and MEDteq in partnership with Thorasys; honorarium for consultancy work from Covis Pharma and Teva; and honorarium as invited speaker from Covis Pharma, Pharmacy Brunet, outside the submitted work. JEG reports grants from NIH/NIAID, personal fees from Regeneron, Ena Theraputics and MedImmune outside the submitted work; personal fees and stock options from Meissa Vaccines Inc outside the submitted work. JG reports personal fees from GSK, Vifor Pharmaceuticals, Novartis, BV Pharma and AstraZeneca outside the submitted work. AK reports personal fees Astra Zeneca, Behring, Boehringer Ingelheim, Covis, GSK, NovoNordisk, Novartis, Griffols, Pfizer, Sanofi, Teva and Trudel, outside the submitted work. RFL reports grants from NIH, non-financial support from GlaxoSmithKline, Boehringer-Ingelheim, Merck, TEVA, American Academy of Allergy, Asthma and Immunology, grants from Clinical and Translational Science Award (NIH), Childhood Origins of ASThma (COAST) grant, AsthmaNet, personal fees from LSU, Elsevier, UpToDate, the University of Kentucky, ThermoFischer, and Food Allergy Research and Education (FARE) Network, outside the submitted work. CM reports personal fees from Novartis, GSK, Astra Zeneca, Thermo Fisher and Boehringer Ingelheim outside the submitted work. NGP reports personal fees from ALK, Novartis, Nutricia, HAL, Menarini/FAES Farma, Sanofi, Mylan/MEDA, Biomay, AstraZeneca, GSK, MSD, ASIT BIOTECH and Boehringer Ingelheim; grants from Gerolymatos International SA and Capricare outside the submitted work. WP reports grants from NIH; grants and personal fees from Genentech/Novartis, Sanofi/Rgeneron; personal fees GSK; non-financial support from Thermo Fisher, Lincoln Diagnostics, Alk Abello, and Monaghen, outside the submitted work. PP reports grants from Astra Zeneca, Chiesi and TEVA; personal fees from Astra Zeneca, TEVA, Novartis, Mundipharma, S&D Pharma, and GlaxoSmithKline outside the submitted work. DP reports grants from AKL Research and Development, British Lung Foundation, Respiratory Effectiveness Group and the UK National Health Service; grants and personal fees from Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Napp, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, TEVA, Theravance and Zentiva (Sanofi Generics); personal fees from Cipla, GlaxoSmithKline, Kyorin and Merck; non-financial support from Efficacy and Mechanism Evaluation programme, Health Technology Assessment, outside the submitted work; DP also reports stock/stock options from AKL Research and Development which produces phytopharmaceuticals; and owns 74% of the social enterprise Optimum Patient Care (Australia and UK) and 74% of Observational and Pragmatic Research Institute (Singapore), outside the submitted work. GR reports personal fees from ALK, Allergen Therapeutics, Meda Plus, Merck; and a patent for the use of sublingual immunotherapy to prevent the development of allergy in at-risk infants, outside the submitted work. IT reports personal fees from Novartis, GSK, Boehringer Ingelheim and Astra Zeneca; grants from GSK Hellas, outside the submitted work. PX reports personal fees from Nutricia, Nestle, Friesland, Uriach, Novartis Pharma AG, and GlaxoSmithkline outside the submitted work.

Provenance and peer review Not commissioned; externally peer reviewed.

Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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Current challenges in pediatric asthma.

1. Introduction

2. asthma phenotypes/endotypes, 3. diagnostic approaches, 4. therapeutic approaches, 5. follow-up, 6. discussion, 7. conclusions, conflicts of interest.

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Miculinić, A.; Mrkić Kobal, I.; Kušan, T.; Turkalj, M.; Plavec, D. Current Challenges in Pediatric Asthma. Children 2024 , 11 , 632. https://doi.org/10.3390/children11060632

Miculinić A, Mrkić Kobal I, Kušan T, Turkalj M, Plavec D. Current Challenges in Pediatric Asthma. Children . 2024; 11(6):632. https://doi.org/10.3390/children11060632

Miculinić, Andrija, Iva Mrkić Kobal, Tin Kušan, Mirjana Turkalj, and Davor Plavec. 2024. "Current Challenges in Pediatric Asthma" Children 11, no. 6: 632. https://doi.org/10.3390/children11060632

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Epidemiology of Asthma in Children and Adults

Shyamali c. dharmage.

1 Allergy and Lung Health Unit, School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia

Jennifer L. Perret

2 Institute for Breathing and Sleep, Melbourne, VIC, Australia

Adnan Custovic

3 Department of Paediatrics, Imperial College London, London, United Kingdom

Asthma is a globally significant non-communicable disease with major public health consequences for both children and adults, including high morbidity, and mortality in severe cases. We have summarized the evidence on asthma trends, environmental determinants, and long-term impacts while comparing these epidemiological features across childhood asthma and adult asthma. While asthma incidence and prevalence are higher in children, morbidity, and mortality are higher in adults. Childhood asthma is more common in boys while adult asthma is more common in women, and the reversal of this sex difference in prevalence occurs around puberty suggesting sex hormones may play a role in the etiology of asthma. The global epidemic of asthma that has been observed in both children and adults is still continuing, especially in low to middle income countries, although it has subsided in some developed countries. As a heterogeneous disease, distinct asthma phenotypes, and endotypes need to be adequately characterized to develop more accurate and meaningful definitions for use in research and clinical settings. This may be facilitated by new clustering techniques such as latent class analysis, and computational phenotyping methods are being developed to retrieve information from electronic health records using natural language processing (NLP) algorithms to assist in the early diagnosis of asthma. While some important environmental determinants that trigger asthma are well-established, more work is needed to define the role of environmental exposures in the development of asthma in both children and adults. There is increasing evidence that investigation into possible gene-by-environment and environment-by-environment interactions may help to better uncover the determinants of asthma. Therefore, there is an urgent need to further investigate the interrelationship between environmental and genetic determinants to identify high risk groups and key modifiable exposures. For children, asthma may impair airway development and reduce maximally attained lung function, and these lung function deficits may persist into adulthood without additional progressive loss. Adult asthma may accelerate lung function decline and increase the risk of fixed airflow obstruction, with the effect of early onset asthma being greater than late onset asthma. Therefore, in managing asthma, our focus going forward should be firmly on improving not only short-term symptoms, but also the long-term respiratory and other health outcomes.

• Asthma is a major non-communicable disease affecting both children and adults, with high morbidity and relatively low mortality compared with other chronic diseases.
• The global epidemic of asthma that has been observed in both children and adults is still continuing especially in low to middle income countries, although some evidence suggests it has subsided in some high-income countries.
• Asthma is a heterogeneous disease and distinct asthma phenotypes and endotypes need to be adequately characterized. This may be facilitated by cluster and latent class analysis if clusters/classes are associated with clinically important asthma outcomes.
• Computational phenotyping methods to retrieve information from electronic health records using natural language processing (NLP) algorithms are innovative and may assist in the early diagnosis of asthma and in epidemiological research
• While some environmental triggers are well-established, investigation into possible gene-by-environment and environment-by-environment interactions may help to better uncover the determinants of asthma.
• Work-related asthma from occupational sensitizers (asthmagens) and/or irritants is common and is an important consideration for individuals who present with asthma symptoms during their productive working years
• For children, asthma may impair airway development and reduce maximally attained lung function, and these lung function deficits may track (or persist) into adulthood without additional progressive loss.
• Adult asthma may accelerate lung function decline and increase the risk of fixed airflow obstruction, especially for smokers with asthma
• People with asthma are more susceptible to infections and non-communicable chronic co-morbidities which are associated with worse asthma outcomes
• Defining asthma remains an ongoing challenge and innovative methods are needed to identify, diagnose, and accurately classify asthma at an early stage to most effectively implement optimal management and reduce the health burden attributable to asthma

Introduction

Asthma is one of the most common major non-communicable diseases and for many, has a substantial impact on quality of life. Globally, asthma is ranked 16th among the leading causes of years lived with disability and 28th among the leading causes of burden of disease, as measured by disability-adjusted life years. Around 300 million people have asthma worldwide, and it is likely that by 2025 a further 100 million may be affected ( 1 ). There is a large geographical variation in asthma prevalence, severity, and mortality. While asthma prevalence is higher in high income countries, most asthma-related mortality occurs in low-middle income countries ( 2 ). Despite the advances in asthma treatment in recent decades, there are still gains to be made in terms of improving patient education, employing new diagnostic approaches, and implementing personalized case management.

Patterns in asthma incidence and prevalence differ between children and adults. It is well-known that asthma often begins in childhood but can occur at any time throughout life, with some developing asthma for the first time as adults. While asthma incidence and prevalence are higher in children, asthma-related healthcare use, and mortality are higher in adults. Interestingly, incidence and prevalence of asthma differs by sex across the lifespan. Pre-pubertal boys have a higher asthma incidence, prevalence, and hospitalization rate than girls of the same age, but this trend reverses during adolescence ( 3 ). Females continue to have a higher burden of asthma than males well into the 5th decade of life. However, the female-male gap in asthma burden narrows around the 5th decade. Some even suggest that the sex differential in asthma incidence may reverse again, following a sharp increase in asthma incidence in males around the 4th decade of life ( 3 ). The sex reversal in asthma burden around major reproductive events suggests that sex hormones may play a role in the etiology of asthma.

The current evidence suggests that asthma is a complex multifactorial disorder and its etiology is increasingly attributed to interactions between genetic susceptibility, host factors, and environmental exposures. These include environmental factors (air pollution, pollens, mold and other aeroallergens, and weather), host factors (obesity, nutritional factors, infections, allergic sensitization), and genetic factors (asthma susceptibility loci on genes). Although underlying mechanisms of asthma are not yet fully understood, they may include airway inflammation, control of airway tone and reactivity ( 4 ). It is also now recognized that asthma may not be a single disease but a group of heterogeneous phenotypes with different etiologies and prognoses ( 5 ). While phenotyping individuals with asthma has been used to help guide clinical management, defining the entity of “asthma” has been a major challenge encountered in research, especially in epidemiological research, where in-depth data collection needs to be balanced with the large number of study participants necessary for adequate power.

This is not an exhaustive or systematic review on all the complexities of asthma epidemiology but aims to provide an epidemiological perspective by comparing and contrasting trends, and discussing the current debate on definitions, environmental risk factors, and long-term consequences of childhood and adult asthma. The roles of genetic factors and gene-environment interactions in the etiology of asthma are described in another article in this series and are therefore not addressed here. Similarly, an article published alongside this article will be covering asthma categories, phenotypes and endotypes, although these topics have been introduced in the present review.

Global Epidemic of Asthma Prevalence—Subsiding in Some Parts of the World

During the second half of the Twentieth century, notably since the 1960s, a sharp increase in asthma prevalence was observed in a number of developed countries. This observation was a result of repeated cross-sectional surveys of prevalence of asthma, mainly in children but also in adults. As a result of this observation, in the 1990s, a series of epidemiological studies were established across the world to estimate global asthma prevalence and incidence, and identify risk factors associated with these outcomes. These include large multinational studies in children [such as the International Study of Asthma and Allergies in Childhood (ISAAC; http://isaac.auckland.ac.nz/ ) ( 6 – 8 )] and in adults [such as the European Community Respiratory Health Survey (ECRHS; http://www.ecrhs.org/ ) ( 9 )]. These studies confirmed that asthma is one of the most common chronic diseases across the globe in all age groups and there is substantial variation in asthma prevalence worldwide. It is now acknowledged that the prevalence of both childhood and adult asthma may have peaked in some areas, predominantly in high-income countries, whereas an increase may be continuing in low and mid-income countries ( 10 ). It is important to note that a reduction in the prevalence of current asthma is determined by improved asthma control and/or reduced asthma incidence at a population level. Thus, a reduction in prevalence of current asthma may well-reflect improved asthma control through increased medication use from more widespread prescribing habits and better compliance. Documenting reductions in asthma incidence is complicated as parallel cohort studies with specific age windows are needed to establish patterns with the comparison group ideally from the same geographical region. These challenges might in part explain why studies from Australia and UK have not consistently shown reductions in asthma prevalence and why temporal trends in European and Asian countries between the 1970s and mid-2000s have been conflicting ( 4 ).

Although greater awareness, recognition, and/or diagnostic shifts have been suggested as contributory factors to the steep rise in asthma prevalence observed over the last four decades of the Twentieth century, repeated cross-sectional surveys using objective measures, such as bronchial hyperreactivity, have confirmed that these factors are unlikely to fully explain this epidemic ( 4 ). Though the specific elements driving this rise in prevalence have not been established, it is now clear that the reasons almost certainly are linked to changing environmental factors, acting through gene-by-environmental interactions. Given the rapidity with which the prevalence has risen, this argues against alterations to the population's genetic makeup alone.

The increase in asthma prevalence has been paralleled by a similar increase in other allergies such allergic rhinitis and eczema ( 11 ). Multiple hypotheses have been proposed to explain this epidemic, and these have been investigated but are still debated in the field. In the late 1980s, it was thought that increased exposure to indoor allergens such as house dust mite, cat, and fungi due to modernization of housing with tighter insulation and the use of plush furniture and carpets may have contributed to increases in asthma and allergies. Also, in 1989, Strachan proposed the “hygiene hypothesis,” suggesting that decreased exposure to unhygienic environments in early life may have led to the increased prevalence of these conditions ( 12 ). In 2003, Rook et al. proposed a lack of exposure to non-pathogenic microbes and commensal organisms as an alternative explanation for the increased prevalence of asthma and allergic diseases ( 13 ). This led to the “microbial diversity” hypothesis that suggests that environments rich in microbial diversity in the gut mucosa and respiratory tract are the key factors in priming and regulating the immune system.

Asthma mortality and hospitalization rates with acute severe asthma attacks also increased in all age groups during the period from 1960 to 1985, with the highest rates of increase in young pre-school children ( 14 ). Following this period, during the 1990s and early 2000s, a decreasing trend in severity has been observed. However, despite novel treatments and improved inhalers for the administration of topical therapies, no further improvements in either mortality or hospitalization rates have been observed in the last decade, either in children or in adults ( 15 ).

Given that some childhood asthma persists into adulthood, it is possible that the “asthma epidemic” in children during the 1980–90s has subsequently translated into an increased adult prevalence. However, establishing this trend is challenging due to increased trends also affecting adult asthma, variable asthma definitions, heterogeneity of asthma phenotypes, and limited sequential studies within distinct geographical regions.

Epidemiological Definitions of Asthma—Part of the Challenge

Definitions are key to our understanding of the epidemiology, pathophysiology and etiology of asthma, and ascertaining similarities or differences between childhood and adult asthma. Yet variation in asthma severity, age-of-asthma onset, allergic vs. non-allergic phenotypes and type of airway inflammation add complexity to the standard definitions used in large population-based studies ( 16 ).

Despite attempts to reach a consensus definition for epidemiological studies, as many as 60 different definitions of “childhood asthma” have been used across 122 published studies ( 17 ). Although some of these definitions may appear almost identical, the multiplicity in the way the primary outcome is defined can have a substantial impact on the estimated prevalence and risk factors. As an example, the above study has shown that the agreement between four seemingly very similar and commonly used definitions was overall relatively low (61%), and well-over a third of children in a study could move from being considered “asthma cases” to “controls” depending on the definition used ( 17 ). These differences need to be considered when interpreting results of meta-analyses of asthma epidemiology.

Some epidemiological definitions are more sensitive while others are more specific, with both scenarios leading to misclassification of asthma status. For example, current asthma defined by “wheezy breathing in the last 12 months in the absence of a cold” is a more sensitive definition than using “doctor-diagnosed asthma” as they do not rely on the individual to seek health advice ( 18 ), while the latter is a more specific definition. As such, survey definitions that adopt wheezy breathing effectively estimate a greater asthma prevalence than clinical definitions which may also incorporate objective measures such as the co-presence of bronchial hyperreactivity ( 19 ).

Furthermore, it is important to consider the age of the participants. Particularly for early childhood cohort studies, it can be difficult to distinguish between transient wheeze precipitated by viral infections and the onset of true asthma in young children, although in many cases, recurrent wheezing episodes during the first few years of life can represent the early stages of asthma. For adults, prospectively collected data on childhood asthma status can minimize the risk of recall bias, otherwise retrospective recall typically misclassifies relapsed childhood asthma as late-onset asthma and preferentially favors those who have more severe childhood disease ( 20 ). For older people at risk of co-morbidity, an asthma diagnosis may be difficult to differentiate from other diseases causing breathlessness, especially chronic obstructive pulmonary disease (COPD), and heart failure.

A consolidated definition of asthma may not be desirable given the emerging consensus in the research community that “asthma” is an umbrella term for several diseases with similar clinical manifestations but different underlying pathophysiological mechanisms ( 5 ), often referred to as “asthma endotypes” ( 21 , 22 ). In this context, symptoms associated with asthma (such as wheeze or cough) and objective measures (such as lung function and biomarkers in blood, exhaled breath, sputum, and/or urine) should be viewed as observable traits (or “phenotypes”) ( 23 , 24 ). However, it is important to note that different mechanisms may give rise to similar or almost identical observable traits, while the same underlying mechanism may also result in distinct phenotypes in different patients ( 25 ).

To date, the framework of asthma endotypes remains a theoretical concept ( 23 ), but this framework may also help in developing accurate asthma definitions to facilitate further discovery of their underlying mechanisms ( 23 ). With increasing interest in endotypes, there have even been calls to abolish the term “asthma” altogether. However, the term “asthma” provides a practical and functional framework for clinicians to manage patients and for scientists to search for mechanisms; and before abolishing it, we first need to propose more useful and meaningful terminology, which will only come through a more thorough understanding of asthma endotypes.

To further this concept, asthma heterogeneity that features multiple different subtypes has major implications for future studies. However, phenotyping asthma from questionnaire data alone seems increasingly insufficient. While previous cluster analyses have been used to identify patient clusters based on asthma symptoms and airway eosinophilia ( 16 ), newer statistical techniques such as latent class analyses (LCA) also have the potential to effectively deal with asthma heterogeneity. Essentially, LCA methods are able to identify novel and statistically distinct classes among individuals in a relatively unbiased way, and are based on measured variables that relate to asthma symptoms ( 26 ) and/or biomarkers such as bronchial hyperresponsiveness and atopy ( 27 , 28 ). A notable example that extended the knowledge of the observed wheezing phenotypes in childhood from the TAHS cohort ( 29 ) identified a new phenotype known as “intermediate onset wheezers” ( 30 ). This class was subsequently found to have persistent deficits in post-bronchodilator FEV 1 in adolescence ( 31 ). Thus, while LCA can readily document asthma heterogeneity, it is of most value if associations are shown between the LCA classifications and clinically important asthma outcomes. To assist in the early identification and diagnosis of asthma, there are currently available innovative computational phenotyping methods that leverage complex electronic health record data that have been validated in different practice settings ( 32 , 33 ). Using natural language processing (NLP) algorithms, asthma is identified via automated chart review based on predetermined asthma criteria (PAC) via a two-step process: (1) finding asthma-related concepts in text that match specified criteria, then (2) assigning an asthma status classification to individual records ( 34 ). While this artificial intelligence algorithm is being developed to improve overall asthma care as a population management tool, it can potentially retrieve information for large-scale, multi-center population studies which has previously been an underutilized data source for asthma research.

Severe Asthma in Adults and Children

Severe asthma represents a small subgroup of individuals who have a disproportionately high health burden. The European Respiratory Society (ERS)/American Thoracic Society (ATS) Task Force defines severe asthma as “asthma which requires treatment with high dose of inhaled corticosteroids (ICS) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming “uncontrolled,” or which remains “uncontrolled” despite this therapy” ( 35 ). This definition applies to both children and adults with asthma, and it is highly likely that the condition we refer to as “severe asthma” is the extreme end of the spectrum for several different asthma endotypes.

There is considerable variation in the prevalence estimates of severe asthma. For example, in has been reported that 4.2% of Swedish adult asthmatic patients in primary care settings have severe disease ( 36 ). Surveys in Denmark described a higher proportion of ~8% of severe asthmatics ( 37 ), while some studies report that as high as 20% or even more than 30% of asthmatic patients have at least some features of severe disease ( 38 , 39 ). The proportion of severe asthmatics appears lower in childhood asthma compared to adult asthma ( 40 ). For example, in a birth cohort in Sweden, only seven of 329 12-year old asthmatic children had severe asthma as defined by the World Health Organization (WHO) ( 41 ), suggesting a prevalence of 0.23% in the general population and 2.1% among children with asthma ( 42 ). Among 616 children in a Norwegian birth cohort, 67 had asthma, of whom only three were defined as having a severe disease, with an estimated population prevalence of severe asthma at age 10 years of 0.5, and 4.5% among asthmatic children ( 43 ). A study conducted within a birth cohort in Manchester (UK), identified a latent class of persistent troublesome wheezers, comprising children with high number of acute asthma attacks, hospital admissions, and unscheduled healthcare visits, which accounted for ~10% of children with doctor-diagnosed asthma, and 3.2% of the general population ( 44 ). These children exhibited numerous features associated with severe asthma including diminished lung function, high FeNO and hyperreactive airways ( 44 ), with a significant loss of lung function between preschool and mid-school age ( 45 ). However, when “severe asthma” was defined using ERS/ATS ( 35 ) or WHO ( 41 ) criteria, only a small number of children were classified as having severe asthma, suggesting that we need to look beyond the amount of medication and disease control when defining severe disease ( 46 ).

In the absence of linking data with national pharmaceutical schemes, capturing detailed information on medication use is challenging in epidemiological studies, although such information is critical when defining severe asthma. For example, in children the “maximum treatment” used to define severe asthma includes high doses of ICS or oral corticosteroids, often in combination with add-on therapy with long-acting β-2 agonists (LABA) and/or leukotriene-receptor antagonists (LTRA) ( 47 – 49 ). The limitation of the use of “maximum treatment” is that there may be different reasons for poor asthma control among patients on “maximum treatment,” such as the wrong diagnosis ( 46 ), non-adherence with medication ( 50 ), or therapy-resistant disease ( 48 ).

To provide a more useful clinical and research framework for the investigation of severe childhood asthma, Bush et al. have proposed the term “Problematic severe asthma” (PSA) for children who require specialist referral because of the apparent poor response to maximum asthma treatment ( 48 , 49 ). Once other potential causes of asthma-like symptoms are excluded and asthma diagnosis is confirmed, children with PSA can be broadly divided into three distinct (but occasionally overlapping) groups: Difficult-to-treat (or difficult) asthma (DA); Asthma with co-morbidities (“Asthma plus”); and Severe therapy-resistant asthma (STRA) ( 49 ). The main characteristics of DA are that principal factors which contribute to troublesome symptoms are potentially modifiable. These include poor adherence with medication ( 51 ), ongoing exposure to adverse environmental factors such as allergens ( 52 – 54 ), tobacco smoke ( 55 ), and air pollution ( 56 – 58 ), and psychosocial factors ( 59 – 61 ). If these modifiable factors are addressed, this should result in better asthma control, including improvement in symptoms, and reduction in severe asthma attacks ( 62 , 63 ). Children with troublesome asthma and comorbid conditions such as food allergy ( 64 ), allergic rhinitis ( 65 ), and/or obesity ( 66 ) are considered to have “Asthma plus” (i.e., asthma + comorbidities). Treatment of these disorders co-occurring with asthma may improve asthma control ( 65 ), although there is a paucity of evidence to support this from well-designed randomized intervention trials ( 67 ). However, despite interventions and treatments aimed at addressing modifiable factors and comorbidities, some children with DA and Asthma plus may not improve [e.g., because of the continued poor adherence with medications ( 50 , 68 ), or ongoing high exposure to allergens ( 69 – 71 )], in which case they should be considered as having refractory DA or refractory Asthma plus ( 46 , 72 ).

Although there is considerable within-group heterogeneity in each of the above categories, and strict differentiation may be challenging and on occasion not possible, the concepts which distinguish PSA, DA, and STRA are useful in both a research and clinical context ( 73 ), and can also be used in adult severe asthma ( 74 ).

A number of studies have described differences between childhood and adult severe asthma based on symptom patterns. Severe asthma is predominantly persistent in adults, but much more variable with rapidly evolving severe attacks in children, often remaining symptom-free between the attacks ( 75 , 76 ). However, we would argue that these differences may have been over-emphasized. It is possible that severe asthmatics who are currently seen in adult clinics reflect the patterns seen in pediatric clinics 10–20 years ago, and that the pattern of severe disease currently seen in pediatric severe asthma clinics may be foreshadowing the severe adult asthma in years to come. It is possible that the differences observed in cross-sectional studies carried out contemporaneously in children and adults can in part be explained by a cohort effect.

Impaired innate anti-viral immunity with diminished interferon induction to rhinovirus has been reported in both children and adults with severe asthma ( 77 – 79 ). A recent study has identified different patterns of cytokine responses by blood mononuclear cells after stimulation with rhinovirus-16 between children with early-onset troublesome asthma compared to those with late-onset mild allergic asthma ( 80 ). The synergism between allergic sensitization, high allergen exposure, and viral infection (mostly rhinovirus) has been shown to increase the risk of hospitalization, both in children ( 52 ) and in adults ( 81 ) with asthma.

One factor strongly associated with severe asthma in children and adolescents is allergic sensitization ( 82 – 87 ). Several studies in recent years have suggested that there may be different classes of sensitization and that some of these sensitization subtypes are more pathologic than others ( 85 , 88 , 89 ). Further studies using component-resolved diagnostics rather than standard skin and blood tests to whole allergen extracts have identified different cross-sectional and longitudinal patterns of component-specific IgE responses associated with different risk of asthma presence, persistence and severity in children ( 90 – 93 ). If the above notion is correct, this may be an indicator of adult severe asthma research and practice in years to come.

Environmental Exposures Associated With Asthma in Children and Adults

Childhood asthma and adult onset asthma are known to share many of the same causes and triggers. While there is stronger evidence on the role of environmental factors as triggers than causes, there is increasing evidence for interactions among and between environmental and other intrinsic factors, such as genetics and atopy, to potentially cause asthma. The vast majority of childhood onset asthma manifests as an allergic phenotype, while there is a predominance of the non-allergic phenotype in adult onset asthma. However, both allergic and non-allergic asthma can exhibit individual responses to both allergic and non-allergic airborne triggers such as animal hair and dander, pollen, and mold (fungal) spores, food allergens, tobacco smoke, or other pollutant exposures ( Table 1 ). Other than this table that provides key references to the main environmental exposures associated with asthma across the lifespan, the typical non-allergic, food and animal triggers of asthma are not described further in this chapter. Subsequent text has focused on the relationships between outdoor, indoor and workplace air pollutants and allergens and asthma, followed by a section on lifestyle factors such as obesity, diet, and breastfeeding.

Environmental exposures associated with asthma spanning childhood to adulthood.

BD, bronchodilator; COPD, chronic obstructive pulmonary disease; HMW, high molecular weight; FEV 1 , forced expiratory volume in 1 second; LMW, low molecular weight; O 3 , ozone; PM, particulate matter .

Parental and Personal Smoking

In utero maternal smoking and parental smoking in early life has been shown to be temporally associated with increased asthma in young children ( 116 ). Recent evidence from multi-generational studies suggest that grandmaternal smoking while the mother is in utero and paternal smoking during his adolescence can independently increase the risk of subsequent offspring childhood asthma. These findings suggest that tobacco smoking may cause heritable modifications of the epigenome, which increase the risk of asthma in future generations ( 128 ).

Smoking also seems to interact with sex. Female smokers had a higher prevalence of asthma than female non-smokers, but this difference was less frequent for males, suggesting that females may be more susceptible. Many studies have found that personal smoking predisposes an individual to increased risk of incident or new-onset asthma, although smoking-onset in adolescence, or adulthood typically occurs after early-onset asthma ( 119 ). As non-atopic asthma becomes increasingly common compared with atopic asthma in adults, this is most likely because this phenotype frequently coincides with a substantial history of cigarette smoking and its potential to predispose to chronic airflow limitation ( 119 , 120 , 129 ). Smokers with asthma form a distinct group that are more likely to have suboptimal asthma control ( 119 ) and develop asthma-COPD overlap syndrome (ACOS) in later life, characterized by incompletely reversed airflow obstruction following an inhaled bronchodilator ( 130 ).

From an epidemiological viewpoint, smoking is common in people with asthma, with around one-quarter of adults from 70 countries receiving recent asthma treatment also reporting to be current smokers ( 2 ). Some evidence suggests that people with asthma may be more likely to smoke, and this was seen especially in adolescents who have more severe disease ( 130 ).

Outdoor Air Pollutants

Outdoor air pollution almost certainly has a major global impact on asthma for children and adults, especially in China and India ( 121 ). Worldwide, in 2015, 9–23 million and 5–10 million annual asthma emergency room visits have been attributed to the outdoor air pollutants ozone and particulate matter with an aerodynamic diameter <2.5 μm (PM 2.5 ), respectively.(Exposure to PM 1 has been found to increase the risk of asthma and asthma-related symptoms, especially among boys, and those with allergic predisposition ( 122 ). Residential markers of traffic-related air pollution, including nitrogen dioxide (NO 2 ) exposure and distance to major roads, have been associated with increased risk for new-onset asthma, persistence of asthma and current asthma in a middle-aged, asthma-enriched, population-based cohort ( 125 ). In a natural experiment of 60 young to middle-aged adults with mild-to-moderate asthma, when compared with walking in the less polluted Hyde Park in London, walking along Oxford Street was associated with reductions in lung function, neutrophilic inflammation and airway acidification ( 126 ). These changes were greater for individuals with moderate asthma compared with mild disease at baseline.

Outdoor Allergens

Exposure to ambient grass pollen is an important trigger for childhood asthma exacerbations requiring emergency department attendance and this has been recently confirmed by a systemic review ( 99 ). There is also scant evidence on the role of early life exposure to pollen in the development of childhood asthma ( 131 ). However, less evidence is available on the role of pollen in adult asthma ( 132 ), except in “Thunderstorm asthma” which is related to a combination of factors as described below.

In relation to other outdoor allergens, increasing evidence indicates that asthmatic children are susceptible to exacerbations that lead to hospitalization when exposed to outdoor fungal spores ( 104 ). Furthermore, high concentrations of outdoor fungal/mold exposure on peak days have been linked to asthma exacerbation and mortality in adults ( 103 , 133 , 134 ). IgE sensitization to fungal species is associated with increased asthma severity, neutrophilic inflammation, and reduced lung function consistent with ACOS ( 105 ).

Thunderstorm Asthma

Thunderstorm asthma is defined as epidemics that occur during or shortly after a thunderstorm, where individuals affected would experience asthma-related symptoms such as breathlessness, wheezing and coughing. “Thunderstorm asthma” ( 106 , 107 ) is the outcome of a complex interaction between multiple factors but not necessarily any one of them individually. Under certain weather conditions such as a thunderstorm, pollen grains may swell and burst to form fine respirable particles that are sufficiently small to enter the lower respiratory tract and precipitate severe asthma in those susceptible. This can occur in sensitized individuals who may or may not have a prior history of asthma or asthma symptoms, but who often have a history of allergic rhinitis. Fungal spore allergens may also be involved ( 133 , 134 ).

On the 21st of November 2016, Melbourne, Australia, experienced a thunderstorm asthma health emergency ( 106 , 107 ) that exceeded all previously reported thunderstorm asthma events [mainly in the UK and Australia ( 135 , 136 )]. In addition to a 4.3-fold increase in emergency attendances for acute respiratory distress symptoms after adjustment for temporal trends ( 107 ), nine deaths over the subsequent 10-day period were attributed to asthma as the primary cause ( 137 ). This mortality statistic was 50% more than expected based on the average for the same period over the previous 3 years ( 137 ), with a total of 10 deaths (immediate and delayed) attributed to the specific epidemic.

Indoor Environment

Indoor pollutants such as products of combustion, including PM and NO 2 , and airborne allergens have been the subject of intense scrutiny as determinants of asthma given that most of our time is spent indoors.

There is substantial evidence to suggest that indoor allergens generated by house dust mite, mold and cat are triggers for both childhood and adult asthma, especially in those sensitized ( 100 – 102 ). However, their role in the etiology of asthma is not clear. On the other hand, primary prevention trials on reduction of allergen exposure in early life have failed to detect any benefits. Some observational studies have even reported exposure to allergens in infancy may help develop tolerance and reduce the risk of asthma. However, the evidence is not consistent. Interestingly, there is increasing evidence on this tolerance hypothesis in the etiology of food allergy in which a clinical trial has shown that early consumption of peanuts can reduce the development of peanut allergy ( 138 , 139 ). These findings suggest that it may be worth exploring this notion of early exposure to allergens leading to development of tolerance, which in turn may reduce the risk of developing asthma.

Occupational Exposures

Occupational exposures to asthmagens or inciting sensitizing agents are common and often under-recognized causes of work-related asthma (WRA). WRA includes two distinct subtypes: work-aggravated/exacerbated asthma (WEA) occurring in individuals with pre-existing asthma, and occupational asthma (OA) occurring in individuals without previous asthma. OA is typically subclassified into immunoglobulin (Ig)-E-mediated or sensitizer-induced OA (90%) and irritant-induced occupational asthma (10%) ( 140 ). A diagnosis of WRA requires the objective diagnosis of asthma with symptoms temporally related to the individual's place of employment ( 141 ). Over 250 agents may potentially cause sensitization and possibly occupational asthma (OA), and comprehensive lists are available ( Table 1 ) ( 112 – 115 ). Briefly, the two main classes of sensitizing agents, namely high molecular weight (HMW) and low molecular weight (LMW) agents can cause sensitizer-induced asthma which is usually after a latency period and this may contrast the frequent rapid action of irritant agent exposure. A web-based list of agents can be found at www.occupationalasthma.com .

Differentiating sensitizer-induced OA from WEA can be a major challenge for managing clinicians. The time-to-diagnosis of sensitizer-induced OA varies but is usually made between 2 and 4 years following the onset of work-related symptoms, and this timeframe is substantially shorter for the diagnosis of WEA as these individuals are usually medically managed for pre-existing asthma ( 142 ). Among compensation claims, confirmed OA diagnoses most have a causative sensitizing agent identified ( 143 ).

Despite challenges in estimating the true incidence of OA, around 10–20% of all adult-onset asthma is thought to be caused by respiratory sensitizers and/or irritants in the occupational setting. Of note, this figure can vary widely (from 4 to 58%) ( 144 ) and is largely derived from populations in high income countries ( 144 – 146 ). To contrast, work-related exacerbations can occur frequently in 20–25% of working adults who have pre-existing asthma ( 147 ), although objective evidence of poorer asthma control is often difficult to demonstrate ( 140 ). While past under-recognition and/or under-reporting of OA might have obscured changing trends over recent decades, the health care industry has successfully reduced the risk of latex-induced allergy and OA by substituting natural rubber latex (NRL) gloves for powder-free, protein-poor NRL gloves. This successful approach for exposure minimization highlights the benefit of identifying those at risk from occupationally-related asthma and minimizing potentially harmful exposures.

Lifestyle Factors

Although already mentioned as an “asthma-plus” co-morbidity, the prevalence of obesity in countries in which a Westernized diet predominates is now of epidemic proportions. These dietary patterns feature a high calorie intake which is high in saturated fat and refined sugars and associated with a high glycaemic index, as well as low nutritional value in terms of dietary fiber and vitamins. While this “obesogenic diet” may lack antioxidant and anti-inflammatory properties ( 148 ), a meta-analysis has found being overweight and obese to be associated with a dose-response increase in incident asthma in adults ( 149 ). While this review did not find significant sex-related differences, female obesity has been associated with a pauci-eosinophil and non-atopic asthma endotype that is symptom-predominant and less steroid-responsive in previous cluster and LCA ( 16 , 28 ). For all individuals with otherwise poorly controlled asthma, the behavior of avoiding strenuous exercise might confuse severe disease with well-controlled asthma, and this in turn can lead to poorer fitness levels and a propensity to weight gain ( 94 ). This is of particular importance to children with asthma, at a time when lifestyle patterns are being especially shaped by external factors.

The role of infant breastfeeding in the prevention of asthma is debated, however this has been largely clarified by findings from the TAHS cohort. This longitudinal study of participants who were followed between childhood and middle-age showed that breast feeding reduced the risk of childhood asthma and conversely increased the risk of adult asthma, but for only those with a familial predisposition ( 150 ). In 2015, a systematic review summarized the overall estimate for a longer compared with shorter duration of breastfeeding to be modestly protective for asthma in later childhood-adolescence [odds ratio 0.90 (95%CI 0.84–0.97), I 2 = 63%] ( 151 ). While the effect was stronger when restricted to studies from lower-to-middle income countries, no association was seen when restricting the meta-analysis to only cohort studies. The overall conclusion was that the evidence was of low quality. The authors primarily hypothesized that breastfeeding-related reductions in childhood wheeze might relate to the known beneficial immunological factors which could reduce childhood viral infections that predispose to asthma.

Impact of Childhood and Adult Asthma on Lung Function Trajectories and COPD

Childhood asthma and lung function.

Studies that have investigated the impact of childhood asthma on lung function from childhood to adolescence have found that different asthma phenotypes differentially impact long-term lung function outcomes. This is particularly relevant to longitudinal asthma phenotypes, which earlier studies attempted to identify by manually classifying the change of symptoms, but more recent studies have identified distinct longitudinal phenotypes using advanced statistical techniques such as Latent Class Analysis (LCA) as mentioned above. Overall, the use of LCA has led to the identification of more asthma phenotypes and therefore has helped to better disentangle the long-term effects of childhood asthma. The majority of studies have shown that persistent wheeze is related to reduced lung function development throughout adolescence ( 31 , 45 , 152 , 153 ), while some suggest the effects of persistent wheeze and relapsed wheeze on lung function are established from mid-childhood, without further decline in tracking of FEV 1 over time ( 154 , 155 ). It has also been reported that childhood asthma associated with allergic comorbidities, such as eczema and allergic rhinitis, has persistent lung function impairment from birth to adolescence as compared to asthma without such comorbidities ( 156 ). These findings have led to the hypothesis that asthma with atopic dermatitis and allergic rhinitis may represent a specific phenotype originating in utero ( 156 ).

Several longitudinal studies have investigated the long-term impacts of childhood asthma on lung function decline and COPD. Childhood asthma has been associated with adult lung function deficits and increased risk of COPD ( 157 – 159 ). While a number of studies have reported that childhood asthma itself has no impact on adult lung function decline ( 154 , 157 , 158 , 160 ), a study that collected childhood asthma status retrospectively has reported that it is associated with greater lung function decline, which may be related to recall bias ( 161 ). More recent findings suggest that childhood asthma is related to longitudinal lung function trajectories that are “below normal” within both the general population ( 162 ) and asthmatics ( 163 ).

Overall, current evidence suggests that many children with childhood asthma/wheeze, especially early persistent asthma/wheeze, may have reduced airway and lung development and not reach their peak lung function potential as influenced by pre-determined lung function trajectories. These lung function deficits may track (or persist) into adulthood without additional progressive loss. However, it is not clear whether childhood asthma can directly affect the rate of lung function decline unless it continues as adult asthma.

Adult Asthma and Lung Function

While asthma in adults is often the persistence or relapse of asthma from childhood, “true” adult onset asthma is a distinct phenotype most often related to environmental risk factors such as smoking ( 164 ). The impact of adult asthma on lung function outcomes appears to vary by phenotype including age-at-onset. It has been shown that both early and late onset adult current asthma were associated with a reduction in lung function and an increased risk of fixed airflow obstruction at 45 years, with the effect of early onset asthma being greater than late onset asthma ( 165 – 167 ). These findings differ from the above mentioned systematic review and meta-analysis which found greater levels of fixed airflow obstruction for those with late-onset adult asthma, which most likely relates to inaccurate retrospective recall of childhood asthma by adults ( 164 ).

Further evidence from longitudinal studies suggests that adults with asthma have greater lung function decline than those without asthma ( 168 – 170 ). While both early and late onset adult asthma seem to be associated with faster lung function decline, the decline associated with early onset adult asthma is greater than that with late onset adult asthma ( 167 ).

An important question is whether we can disentangle the components of lung function deficits in adults with asthma over the life course. Lung function deficits in those with early onset adult asthma may result from both the tracking of reduced lung function from childhood and additional loss from a greater rate of decline in adulthood ( 167 , 171 ). It has been suggested that adults who developed new-onset asthma had reduced lung function at baseline ( 172 , 173 ), but it is unknown whether lower lung function before early adulthood, in the absence of childhood asthma, predisposes to “true” adult onset asthma. However, asthma/wheeze status in early life is often forgotten by adults leading to misclassification of “true” adult-onset asthma ( 20 ). On the other hand, lung function deficits in adult-onset asthma after peak lung function has been attained are also likely to be due to faster lung function decline.

Other Health Impacts of Childhood and Adult Asthma

Another major impact of asthma is through its associated additional morbidities, including a predisposition to serious infections such as bacterial pneumonia from a higher nasopharyngeal carriage of Streptococcus pneumoniae ( 174 ). Although not well-understood, asthma-related chronic airway inflammation with damaged airway mucosa and immunomodulating treatments such as inhaled corticosteroids have been implicated, and lower antibody levels in response to the Pneumococcal vaccine have also been observed ( 174 ). In addition to a 2.4-fold increased risk for invasive pneumococcal disease ( 175 ), susceptibility to respiratory and non-respiratory infections (such as Herpes zoster and E. coli bacteraemia) in never smokers with asthma has been compared with the relative risk of diabetes ( 176 ). This susceptibility to infection supports the hypothesis of weaker T H 1 immune responses associated with T H 2-related disease. However, recommendations for Pneumococcal immunization are inconsistent ( 94 ) suggesting more evidence is needed to gain consensus of its benefits ( 177 , 178 ).

Adult asthma is also associated with a number of chronic conditions. The associations between childhood asthma and allergies such as eczema and food allergy are very well-established. Adult asthma is known to be commonly associated with diabetes, osteoporosis, metabolic syndrome, cardiovascular diseases, and issues with mental illness such as anxiety and depression while there are a number of other morbidities that have been linked ( 179 ). When a chronic condition is present in people with asthma, that is known as asthma co-morbidity. Almost two-thirds (62.6%) of patients with asthma have at least one comorbid condition with 16% having four co-morbidities ( 180 ). This prevalence of these morbidities in asthmatics is too high to be simply due to the chance development of chronic conditions while aging but these associations do not imply causality. The etiology of asthma co-morbidities may be linked to asthma itself, other morbidities, shared mechanisms, shared environmental, and/or shared genetic risk factors. Regardless of the etiology, it is well-known that asthma comorbidities are associated with worse outcomes for the patients and the healthcare systems ( 181 ), and managing asthma comorbidities has been associated with significant improvement in its prognosis. Revising guidelines on to handle comorbidities may lead to a more targeted treatment for comorbidities and more patient-centered asthma management, which in turn lead to better outcomes.

The evidence on the trends and environmental determinants for childhood and adult asthma are similar, although the evidence is stronger for childhood asthma, which is partly related to the stronger attention that childhood asthma has received from the research community. The global epidemic of asthma is continuing, especially in low to middle income countries, although it has subsided in some high income countries. Epidemiological research has helped to uncover some important environmental determinants that trigger asthma, but the role of environmental factors in the etiology of asthma remains largely unknown. Research into interactions between potential determinants may help tease out the etiology. Therefore, there is an urgent need to further investigate the complex mechanisms driving the interrelationship between environmental and genetic determinants to identify high risk groups and key modifiable exposures. Given the long term impact of both childhood and adult asthma, we would argue that our focus going forward to reduce the health burden of asthma should be firmly on improving not only short-term symptoms, but also the long-term respiratory and other health outcomes ( 182 ).

Author Contributions

The authors alone are responsible for the content and writing of the article. AC, SD, and JP wrote sections of the initial draft of the manuscript which was then critically revised for flow and important content areas by SD and JP. All authors approved the final version of the manuscript.

Conflict of Interest Statement

AC has received personal fees for consultancy from Regeneron/Sanofi, Philips and Boehringer Ingelheim; consultancy and speaker fees from Novartis; and speaker fees from Thermo Fisher Scientific. JP has received a travel grant from Boehringer Ingelheim. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest

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• Published: 21 October 2019

A systematic review of psychological, physical health factors, and quality of life in adult asthma

• Sabina Stanescu   ORCID: orcid.org/0000-0003-0792-8939 1 ,
• Sarah E. Kirby 1 , 2 ,
• Mike Thomas   ORCID: orcid.org/0000-0001-5939-1155 2 , 3 ,
• Lucy Yardley 1 &
• Ben Ainsworth 4  

npj Primary Care Respiratory Medicine volume  29 , Article number:  37 ( 2019 ) Cite this article

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• Outcomes research
• Quality of life

Asthma is a common non-communicable disease, often characterized by activity limitation, negative effects on social life and relationships, problems with finding and keeping employment, and poor quality of life. The objective of the present study was to conduct a systematic review of the literature investigating the potential factors impacting quality of life (QoL) in asthma. Electronic searches were carried out on: MEDLINE, EMBASE, PsycINFO, the Cochrane Library, and Web of Science (initial search April 2017 and updated in January 2019). All primary research studies including asthma, psychological or physical health factors, and quality of life were included. Narrative synthesis was used to develop themes among findings in included studies in an attempt to identify variables impacting QoL in asthma. The search retrieved 43 eligible studies that were grouped in three themes: psychological factors (including anxiety and depression, other mental health conditions, illness representations, and emotion regulation), physical health factors (including BMI and chronic physical conditions), and multifactorial aspects, including the interplay of health and psychological factors and asthma. These were found to have a substantial impact on QoL in asthma, both directly and indirectly, by affecting self-management, activity levels and other outcomes. Findings suggest a complex and negative effect of health and psychological factors on QoL in asthma. The experience of living with asthma is multifaceted, and future research and intervention development studies should take this into account, as well as the variety of variables interacting and affecting the person.

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Introduction.

Over 235 million people worldwide are living with asthma, which is one of the leading non-communicable diseases worldwide. 1 , 2 Symptoms, exacerbations, and triggers in asthma are associated with lower quality of life (QoL), tiredness, activity limitation, negative effects on social life and relationships, problems with finding and keeping employment, and reduced productivity. 3 , 4 , 5 , 6 , 7 People with asthma are up to six times more likely than the general population to have anxiety or depression, 8 and 16% of people with asthma in the UK have panic disorder, 9 compared to 1% in the general population. 10 People with brittle asthma (difficult-to-control asthma with severe, recurrent attacks) demonstrate even greater comorbidity and maladaptive coping styles. 11 Psychological dysfunction is often unrecognized in primary care, despite being significantly associated with poor asthma outcomes, including asthma control and QoL. 8 , 12 , 13 Indeed, the European Asthma Research and Innovation Partnership has identified understanding the role of psychological factors as an unmet need in improving asthma outcomes. 14 , 15 They propose that anxiety and depression are present at all three stages of the experience of asthma: onset, progression, and exacerbation. 14

A recent meta-analysis found that asthma diagnoses significantly increased the risk of psychological and health conditions (such as cardiovascular/cerebrovascular diseases, obesity, hypertension, diabetes, psychiatric and neurological comorbidities, gut and urinary conditions, cancer, and respiratory problems other than asthma). 16 In addition, studies have pointed towards an impact on QoL in people with asthma of additional health and psychological factors, such as comorbid anxiety or depression, higher body mass index(BMI), professional status, and feelings of lack of control over health (for example, refs 17 , 18 ). Such evidence reinforces the argument that the needs of people with asthma should be approached in conjunction with these additional factors, rather than using a single-illness approach, aiming to reduce the adversity of people’s experience. However, the extent to which psychological and physical health factors interact and impact asthma outcomes is yet to be systematically explored. This systematic review aims to provide a narrative synthesis of the literature exploring psychological and physical health factors that influence QoL in adults with asthma.

Study characteristics

The search and screening process identified 43 eligible papers, published between 2003 and 2019 (see Fig. 1 for PRISMA flowchart 19 ). The characteristics of each study are summarized below in Table 1 . Twelve studies were conducted in Europe, 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 17 in North America, 12 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 7 in Australia, 17 , 48 , 49 , 50 , 51 , 52 , 53 4 in Asia, 54 , 55 , 56 , 57 and 3 in Africa. 58 , 59 , 60 All papers employed a quantitative approach comprising 2 longitudinal studies 31 , 44 and 41 cross-sectional studies. Only 4 studies included a control group. 21 , 28 , 29 , 31 Overall, the majority of papers had a large sample size (ranging between 40 and 39,321 participants; 30 papers included a sample size of >100). The majority of studies recruited from primary care or the general population, using self-report to confirm a diagnosis of asthma. Only a few studies recruited from secondary and tertiary asthma clinics. 12 , 27 , 36 , 41 , 44 , 48 , 60 There was a high occurrence ( n  = 14) of exclusion criteria relating to specific demographic or asthma characteristics, as well as mental health conditions and comorbidities, which restricted the study sample without a reason being given. Most studies used self-report measures, 17 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 32 , 33 , 34 , 35 , 36 , 37 , 39 , 41 , 42 , 43 , 44 , 45 , 46 , 48 , 49 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 with a small proportion using psychiatric interviews to screen for mental health conditions. 12 , 31 , 38 , 40 , 50 The majority of studies used asthma-specific QoL measures ( n  = 29), 12 , 21 , 23 , 25 , 27 , 28 , 30 , 32 , 33 , 34 , 35 , 36 , 37 , 39 , 40 , 41 , 42 , 44 , 48 , 49 , 50 , 51 , 54 , 55 , 56 , 58 , 59 , 60 , 61 17 included an health-related QoL measure ( n  = 18), 17 , 20 , 22 , 23 , 24 , 25 , 28 , 30 , 31 , 34 , 35 , 36 , 38 , 43 , 50 , 51 , 52 , 55 and 4 used general measures of QoL ( n  = 7); 26 , 35 , 45 , 46 , 47 , 57 , 62 11 papers used >1 measure of QoL. 23 , 25 , 28 , 30 , 34 , 35 , 36 , 37 , 50 , 51 , 55 The average age across included studies was 42.1 years (and 61.57% were female). Papers report prevalence rates of between 16.8% and 48.9% for depression and between 13.3% and 44.4% for anxiety, 20 , 27 , 33 , 38 , 50 , 56 , 58 , 60 with an average of 28.31% for a diagnosis of anxiety or depression. Across several studies, the prevalence of other mental health conditions was 28.31% on average (ranging between 28% and 80%). 12 , 37 , 38 , 40 , 42 Between 72% and 86.9% of people with asthma had at least one additional physical condition and between 21% and 26.3% had ≥2; 25 , 34 , 56 26.36% had, on average, at least one other physical health condition. On average, people with asthma were significantly more likely to have a BMI of >30 (and between 61% and 75.1% had a BMI >25). 26 , 45 , 59 The quality assessment identified that most studies were of a reasonable quality; however, it should be noted that some measures used could be considered inappropriate for the research aim or the population under investigation. Examples include measuring general QoL with an asthma-specific measure or administering a geriatric depression questionnaire to a young adult population.

PRISMA statement of included and excluded papers

Narrative synthesis

Narrative synthesis generated three overarching themes: psychological factors, health factors, and multifactorial aspects (see Table 2 for themes and subtheme descriptions). Overall, patients with asthma demonstrated impaired QoL, which was further decreased by psychological factors (e.g. anxiety, depression, emotion regulation, illness perceptions), health risk factors (such as an increased BMI), and the presence of a co-existing mental health or physical condition (such as rhinitis, cardiovascular disease, diabetes, etc.). Having more than one co-existing condition or psychological factor impacted overall QoL even more substantially. Results for each of the aspects found are presented below.

Psychological factors

Within this first theme, four subthemes were generated. These comprised ‘anxiety and depression’, ‘other mental health conditions’, ‘emotional regulation’, and ‘illness representations’.

Anxiety and depression were notably the most commonly considered factors ( n  = 30). A high prevalence of people with asthma showed symptoms of or clinical diagnoses of anxiety or depression, which appeared to play a key role in understanding the relationship between asthma and QoL. Overall, having a diagnosis of anxiety or depression was associated with poorer QoL across all dimensions (e.g. activity limitation, physical or mental wellbeing, social or role functioning, etc.), as well as health perceptions. 24 , 36 , 46 , 50 , 54 In particular, one study (of undergraduate students aged 18–25 years, with childhood-onset asthma) found that anxiety was significantly associated with asthma QoL, as was the interaction between anxiety and depression, 32 while others found that generally anxiety and depression both predicted worse QoL independently (refs 12 , 29 , 33 , 38 , 42 , 44 , 56 , 60 ). One study found that the average asthma-related QoL scores for people with asthma and depression were 1.4 times lower compared to people with asthma and no depression. 33 Having current depression or anxiety was associated with worse QoL than was having a lifetime diagnosis; this was in turn was greater than having no depression or anxiety. 45 Having a history of major depression was also significantly associated with worse physical and mental functioning, compared to those with asthma and no depression. 38 There was considerable variability across variance explained, with depression found to account for between 3% 40 and 56% 30 of the variance in QoL, whereas anxiety was found to account for between 2% 40 and 68%. 21

In contrast, one study found that having either a depressive or an anxiety disorder significantly impacted asthma QoL but having both was not significantly different than only having one, 40 which is dissonant with other studies. Another study of 90 people with difficult asthma found that having anxiety or depression had no significant effect on QoL. 48 In addition, although depression was associated with poorer QoL, it did not inflate the relationship between asthma severity and QoL. 29 All other studies were significant but showed only small-to-moderate effect sizes. Having a full clinical diagnosis of anxiety or depression was not significantly worse (in terms of QoL) than having only some symptoms of anxiety and depression.

Studies also considered the impact of anxiety and depression on specific subdomains of QoL and asthma-specific QoL. Having anxiety was not associated with physical functioning, mental health or health perception, 38 or the physical component of QoL. 20 Depression, however, was associated with significantly poorer QoL on physical dimensions and activity limitation, 20 , 21 , 23 , 30 , 38 , 45 , 53 , 55 , 58 although one study found significant results only for participants with uncontrolled asthma. 22 In relation to asthma-specific QoL, depression and anxiety were significantly associated with decreased asthma-specific QoL. 17 , 21 , 23 , 27 , 28 , 32 , 33 , 36 , 37 , 40 , 50 , 54 , 55 , 58 , 61

Nine studies looked at other mental health conditions, such as panic disorder with or without agoraphobia, 24 , 38 , 44 , 57 personality disorders, 31 alexithymia, 23 somatization, 38 mood disorders, 12 , 40 , 57 schizophrenia, eating disorders, substance use disorders, 38 and general occurrence of any psychiatric disorder. 12 , 17 The results in this subtheme were mixed, but overall they suggest that the presence of an additional mental health condition is significantly associated with a decrease in QoL in patients with asthma. 12 , 17 Panic disorder was also shown to be both significantly 24 and non-significantly 57 associated with poorer mental and physical components of QoL. Alexithymia in people with asthma was not associated with poorer QoL. 23 Having asthma and a personality disorder was associated with lower general QoL, 31 as well as lower scores for physical health, vitality, pain, general health, social function, mental health, and emotional role (physical function was not significant). This association was not found for people without asthma, suggesting that it is the combination of conditions (asthma and co-existing mental health conditions) that may lead to the negative impact on QoL. 31

The emotion regulation subtheme included studies that explored the relationship between emotional states, negative affect (not related to anxiety, depression, or other mental health conditions), or coping and QoL in people with asthma. QoL in asthma was found to be influenced by affect and a predisposition to negative states, as found by four studies. 28 , 39 , 41 , 51 For instance, a model of age, gender, negative affect, and medical problems accounted for 20% of symptoms and 23% of activity limitation. 39 This was supported by findings that negative mood is associated with poor scores on both the mental and physical components of the Asthma Quality of Life Questionnaires (AQLQ), 28 as well as a positive correlation between active coping and asthma QoL. 51 Despite heterogeneity, the impaired QoL was associated with impulsive-careless coping 41 and avoidant coping. 51 Overall, the presence of psychological distress seemed to affect people with asthma more than people without asthma in terms of QoL.

Illness-related cognitions are people’s patterns of beliefs about the characteristics of their conditions, which in turn influence their appraisal of severity and can determine future behaviours. 63 A number of illness-related cognitions and perceptions significantly predicted QoL in seven studies. 26 , 34 , 37 , 42 , 43 , 51 , 60 For instance, asthma self-efficacy 42 was positively associated with QoL. However, decreased QoL was significantly predicted by a series of varied illness perceptions: subjective illness severity, uncertainty in illness, illness intrusiveness, 43 perceived disability, 60 health beliefs and attitudes, 34 perceived severity, 34 level of confidence or self-efficacy in managing asthma, 51 satisfaction with illness, 51 anxiety sensitivity for physical concerns, 39 and satisfaction with life. 37 In addition, a model of subjective and objective illness severity accounted for 24% of the variance in QoL, further supporting the effect of illness perceptions on QoL. 34

Physical health factors

Two subthemes were generated in the physical health factors theme: additional physical conditions and BMI.

Ten papers examined additional physical conditions in relation to QoL in asthma; 25 , 27 , 34 , 39 , 46 , 47 , 48 , 49 , 52 , 53 most only referred to ‘comorbidity’ or ‘medical problems’ as a measure of frequency of additional conditions. 34 , 36 , 39 Some studies looked at both general and individual co-existing conditions 25 , 48 , 52 and others counted chronic conditions but did not include them in further analyses. 33 , 36 , 56 , 59 Of the ones that did explore individual conditions, the highest impact seemed to be provoked by musculoskeletal conditions. 25 Similarly, statistically and clinically significant decreases in activity levels were also found for people with asthma and multimorbid conditions. 52 Other conditions investigated included respiratory conditions, 47 diabetes, 25 , 48 obesity, 48 hypertension, 25 , 39 gastro-oesophageal reflux disorder, 48 rhinitis, 48 , 49 vocal cord dysfunction, 48 sleep apnoea, 48 musculoskeletal disorders, 25 , 39 arthritis, 39 , 52 heart disease, 25 stroke, 39 , 52 cancer, 39 , 52 osteoporosis, 52 dysfunctional breathing, 48 headaches, 39 and allergic status. 27 , 39 The consensus was that having an additional physical condition significantly decreased QoL in asthma, the effect being amplified with the addition of further conditions.

Eleven papers exploring BMI found that it consistently influenced QoL for people with asthma both directly as a multimorbid factor and indirectly by increasing the chance of additional conditions and activity limitation. 25 , 26 , 28 , 29 , 35 , 42 , 44 , 45 , 48 , 56 , 59 In particular, one study found that generic health status decreased for overweight and obese patients with asthma. People with asthma with obesity had on average 5.05 more restricted activity days than people without obesity or without asthma. 35 Other studies found that increased BMI was an independent factor in predicting poorer QoL 48 and that QoL was two times worse in overweight and three times worse in obese people with asthma. 59 In contrast, one study found that overweight BMI made no difference; however, being obese did. 27 Almost ½ of obese patients and 25% overweight patients had problems with mobility, pain, discomfort, self-care, and usual activities (compared to <15% people with asthma of normal weight). 26

Multifactorial aspects

Seven studies included statistical analyses to explore potential mechanisms for the relationship between asthma QoL and additional physical conditions, BMI, and psychological factors. 17 , 35 , 42 , 45 , 50 , 56 , 59 Results from studies in this group are complex, indicating that people with asthma are at a higher risk of adverse outcomes (such as exacerbated symptoms or decreased QoL) if they also have a high BMI and depression. 35 , 42 , 56 , 59 People with current depression and asthma are more likely to be obese and 3.9 times more likely to report fair or poor general health. 45 A few of these studies have explored the relationship between these factors further. For example, people with asthma and obesity were more likely to have additional physical comorbidities and poorer QoL. 59 Significant increases in major depression were associated with dyspnoea, 50 and depression and perceived control of asthma significantly mediated between BMI and QoL. 35 Higher BMI has also been associated with worse asthma-specific self-efficacy, which was in turn associated with decreased QoL. 42

The aim of the present review was to synthesise the literature exploring health and psychological factors that influence QoL in adults with asthma. Previous evidence shows that QoL is generally lower in people with asthma and compounded by poor asthma control and severity. 13 The narrative synthesis in the present study builds on this by identifying three themes, encompassing a number of factors that substantially explain further impairment in QoL for people with asthma. These were not limited to individual components but also combinations of co-existing conditions, risk factors, and health and psychological factors, which consistently showed a negative impact on QoL.

Anxiety and depression were the most commonly reported psychological factors associated with impaired QoL, but effects were also found for other mental health conditions, illness representations, and emotion regulation. These results are generally consistent with previous research showing not only that among people with asthma there are more people with depression than without 8 but also with an increase in depression, the risk of asthma increased. 64 Although the relationship between anxiety and depression and asthma-specific QoL were not further considered in the primary sources, they point towards either a link with activity limitation or a cumulative impact of the interaction between these psychological factors, which in turn affect the QoL of people with asthma. In addition, it is argued that people with asthma use more emotion-focused, and generally maladaptive, coping strategies, such as avoidance. 65 Despite this, psychotherapy, such as cognitive-behavioural therapy and counselling has had limited effectiveness in improving asthma outcomes. 66

Physical health factors, such as high BMI and co-occurring health conditions, were extremely common in people with asthma, consistent with existing literature. 16 This affects QoL both directly and indirectly, affecting self-management and illness perceptions. As such, non-pharmacological treatments such as lifestyle change and activity promotion could prove effective. For instance, a higher proportion of people with asthma seem to have overweight or obese BMI 67 and weight loss intervention studies have been associated with improvements in asthma symptoms. 68

One of the fundamental components of reduced QoL is activity limitation, which is especially relevant to people with asthma, with or without additional conditions or psychological risk factors. This has been widely acknowledged by previous research, to the extent that it has been included as one of the components of asthma-related QoL measures, such as the AQLQ. 69 Furthermore, it is not surprising that decreased QoL in adults with asthma is associated with depression or high BMI, both of which have been consistently associated with activity limitation (e.g. refs 70 , 71 ). In addition, depression was found to affect QoL on the physical components as well as the mental ones, which has interesting implications for future research and clinical practice.

It is important to note the high prevalence of anxiety, depression, and chronic conditions, despite frequent exclusion of comorbid psychiatric conditions. This was found throughout the included papers and is consistent with previous research (e.g. refs 8 , 16 ). This does not only mean that psychological and health factors significantly add to the burden of living with asthma but also that the occurrence of psychological dysfunction and health risk factors seem to be common in people with asthma. In addition, the complex nature of patients with chronic diseases such as asthma, with factors interacting, adds to the negative experience of living with asthma. Results are similar to previous meta-analyses and reviews, 8 , 72 pointing towards conclusive evidence that additional factors (physical or psychological) decrease QoL and functionality in asthma. Finally, these effects were consistent, regardless of the measure of QoL used (asthma specific, health related, or general). This suggests that the identified factors may affect people with asthma more than people without asthma or that the cumulative impact of comorbidities is greater than arithmetically assumed.

The quality of the present review needs to be discussed in relation to the methodology and robustness of the synthesis, determined by the quantity and quality of individual studies included. 73 The quality assessment identified that most studies were of a reasonable quality overall, although all papers had one or two elements that were of a slightly lower quality (this included aspects such as recruitment from only one hospital reducing generalizability or self-report vs objective measurement of weight for BMI calculations). However, this was not problematic for the purposes of this review as the focus was to identify potential factors considered in research rather than classify the methodological quality used to measure their impact on QoL. In addition, the search terms in this review could have limited the number and kind of studies included. For instance, not every potential comorbid condition was listed. This could be a focus for future research. Socio-demographic factors were not included, which can be considered a limitation; however, the breadth of the area was deemed too much for the scope of the present review and could also be the focus of future research. The majority of included studies were observational and as such could not be used to determine causal mechanisms. However, the aim of this review was only to identify potential factors involved in decreased QoL in asthma, rather than build a causal model. Similarly, the impact of individual factors was not measured and could be explored in future research.

A strength of the present review is that it uses a novel approach to QoL in asthma, by systematically taking into account additional aspects that influence the experience of living with asthma and impact QoL. Results suggest both a direct association of the identified aspects, as well as indirectly through interactions with other aspects of living with asthma, such as overarching illness perceptions and activity limitation. The present review emphasizes some interesting and novel findings for asthma and QoL research. Three main implications for future research and practice are proposed. First, for future research, the findings of this review should be used to further explore and understand the factors impacting QoL in people with asthma. It is crucial to explore the needs and experience of patients with complex medical problems, in order to unpick the different factors impacting on QoL. Second, the results are relevant for practitioners, particularly in primary care, as they draw attention to the prevalence of various physical and mental health factors that can interact and affect asthma outcomes. This could influence training or guidelines on potential factors to consider during appointments and consultations. Finally, most current non-pharmacological interventions for patients with chronic conditions tend to overlook the complex needs of patients in a multimorbidity context. As such, it is suggested that future intervention development should use a personalized, tailored approach that aims to address the needs of patients with complex medical problems in the wider context of their experience of living with asthma.

This review demonstrates that the themes and factors identified through inductive narrative synthesis illustrate that QoL in asthma cannot be determined in a simplistic way. The findings suggest a complex experience in living with asthma, one that has a stronger impact on QoL than the sum its of parts. People with asthma and their QoL cannot be viewed separately from the psychological and other health elements that they experience. Future research is encouraged to take a function-oriented approach to QoL in asthma, including management of multimorbid conditions when planning studies; clinical practice should also acknowledge the additional and complex needs of people with asthma by offering relevant, person-based tailored interventions.

Search strategy

The initial search was carried out in April 2017 and was updated in January 2019. Databases searched included MEDLINE, EMBASE, PsycINFO, the Cochrane Library, and Web of Science. Search terms used comprised a combination of the following key terms: asthma (MESH term), psychological/psychosocial and factor/determinant/predictor, comorbid, multimorbid, anxiety, depression, illness perception, illness cognition, illness representation, locus of control, self-efficacy, risk factor, quality of life, health-related quality of life, wellbeing, distress, health status, burden. In addition, a hand search of all the references of included papers was performed as well as a grey literature search on Google Scholar.

Study selection

Studies were included if they investigated psychological or physical health factors and included QoL in adults with asthma as primary or secondary outcome. Psychological factors were considered any modifiable factors, including thoughts, beliefs, attitudes, or emotions of people with asthma, as well as the presence of any co-occurring mental health condition. Physical health factors were defined as any physical comorbid or multimorbid condition or risk factor. These were chosen to allow as much inclusivity as possible and to reflect the exploratory nature of this review. Intervention studies were excluded, as they rarely considered the impact of health or psychological factors on QoL but rather investigated how interventions improved asthma outcomes. Studies were excluded if they were conference abstracts, reviews, or not primary research or the full text not in English, German, or Spanish language.

Data extraction and quality appraisal

Data extracted comprised authors, year of publication, study sample, predictors, QoL measurement (outcome), and findings. The AXIS tool 74 was used to assess the quality of included papers. This contains questions on study design, sample size justification, target population, sampling frame, sample selection, measurement validity and reliability, and overall methods and does not offer a numerical scale. No papers were excluded or weighted based on the quality assessment.

Data synthesis

Owing to heterogeneity of QoL measures and the range of variables used in the included studies, narrative synthesis was used to describe and group similar findings, explore patterns identified in the literature, and develop a narrative account of the results. 73 This is an approach to systematic reviews involving the synthesis of findings from multiple sources and relies primarily on word and text to summarise the findings.

All data generated or analysed during this study are included in this published article.

Reporting summary

Further information on research design is available in the Nature Research Reporting Summary linked to this article.

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S.S.—conception of the review, synthesis, wrote the first draft, commented on drafts. B.A. and S.K.—conception of the review and day-to-day conduct of the review, commented on drafts, updated the review, revised the paper. M.T.—conception of the review, commented on drafts. L.Y.—conception of the review, commented on drafts. All authors read and approved the final version of the manuscript.

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Stanescu, S., Kirby, S.E., Thomas, M. et al. A systematic review of psychological, physical health factors, and quality of life in adult asthma. npj Prim. Care Respir. Med. 29 , 37 (2019). https://doi.org/10.1038/s41533-019-0149-3

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This study aims to evaluate the epidemiology of asthma among children and adolescents in the Eastern Mediterranean Region.

Exhaustive searches were conducted across databases, including PubMed, Scopus, Web of Knowledge Core Collection, Embase, and Google Scholar. The selection criteria included studies reporting asthma prevalence in individuals aged 0 to 19 years, using validated questionnaires. Data were extracted and synthesized using the DerSimonian and Laird random effects model.

The overall prevalence of asthma in Eastern Mediterranean Regional Office (EMRO) countries, among the 514,468 children and adolescents included in this meta-analysis, was 10.61%, synthesized from 95 studies. Among the countries studied, Qatar exhibited the highest prevalence at 16.69%, followed by Saudi Arabia at 16.57%, Iraq at 16.22%, Oman at 15.20%, and Afghanistan at 14.90%. Adolescents showed a slightly higher prevalence of asthma at 10.10% compared to children at 9.70%. Boys exhibited a higher prevalence at 11.48% compared to girls at 9.75%. Urban areas demonstrated a higher prevalence at 11.27% than rural areas at 8.29%.

Efforts to reduce asthma prevalence in Arab countries and address underdiagnosis in African nations within the EMRO are crucial. Targeted interventions should focus on addressing environmental triggers and improving access to healthcare. Enhanced diagnostic capabilities and healthcare infrastructure are necessary in African countries. Collaborative action is essential to alleviate the asthma burden and promote respiratory health across the EMRO region.

Peer Review reports

Introduction

In recent decades, the prevalence of asthma has increased significantly, becoming a major public health concern, especially among children and teenagers. Asthma, a complex respiratory disorder, is characterized by persistent inflammation of the airways, resulting in recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. These symptoms can significantly impair the quality of life, limit physical activities, and impose a substantial financial burden on healthcare systems and families. While extensive research has explored the prevalence of asthma in different parts of the world, it is evident that several variables contribute significantly to its prevalence [ 1 , 2 , 3 , 4 ]. Various factors, including age, sex, economic status, genetics, and exposure to pollutants, have been demonstrated to impact the occurrence and severity of asthma [ 5 ]. First, age plays a vital role in determining asthma, as it influences the development and duration of the disease. Asthma usually occurs in childhood and the risk decreases as individuals enter adulthood. However, some asthma attacks may begin in old age or later in life, suggesting age-related differences in their prevalence [ 6 ]. Gender is another factor affecting asthma. Many studies have shown that men and women have different rates of asthma. Boys have more asthma in childhood, but this trend often changes with more women in adolescence and adulthood [ 7 ]. Economic conditions have also been shown to affect asthma. People from lower socioeconomic backgrounds often face challenges such as poor housing, lack of healthcare and environmental risks. These factors lead to higher rates of asthma in low-income communities [ 8 ]. Exposure to air pollution is a well-known risk factor for asthma. Breathing in various environmental irritants and pollutants such as smoking, air pollution, allergies, and occupational exposure can cause and lead to asthma. People living in cities or near industrial areas may be particularly susceptible to asthma due to increased levels of air pollution [ 9 ].

The Eastern Mediterranean Regional Office (EMRO) of the World Health Organization (WHO), encompassing a vast area and comprising diverse nations, represents a unique intersection of socio-economic, social, and environmental variables that can influence the prevalence and management of asthma among children and teenagers. With nations extending from high-income countries with progressed healthcare frameworks to those hooking with financial challenges and restricted therapeutic assets, the EMRO Locale gives a complicated embroidered artwork for studying the prevalence of asthma [ 10 , 11 , 12 ].

The 2013 International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three revealed that the Eastern Mediterranean region had a comparatively lower incidence of asthma symptoms compared to other parts of the world. Specifically, in the 13–14 age group, boys exhibited a prevalence of 10.6%, while girls showed 7.9% for current asthma symptoms [ 13 ]. However, despite this lower prevalence, the region still contends with a substantial burden due to the large number of children and adolescents. Previous studies have documented wide variations in asthma prevalence across different countries and areas in the region, ranging from 1.41% to over 20% [ 14 , 15 ].

Interestingly, there are conflicting findings regarding asthma prevalence in rural areas. For instance, one study suggests a higher prevalence in rural settings than urban ones (20.5% vs. 7.5%), while another indicates lower rates in rural areas compared to urban settings (1.2% vs. 1.9%) [ 16 , 17 ]. This variation also extends to differences based on gender and location, highlighting a notable research gap.

To address these complexities, this study aims to contribute to our understanding of childhood asthma in the Eastern Mediterranean Region. Our goal is to conduct a thorough review of studies reporting asthma prevalence, providing updated regional and country-specific estimates.

Methods and materials

This manuscript follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for clear reporting of the prevalence of asthma among children and adolescents in WHO’s Eastern Mediterranean Region [ 18 ]. Our study is registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023379776).

Search strategy

Data were found using keywords such as asthma, prevalence, epidemiology, children, pediatrics, adolescent, name of the 21 countries located in EMRO including Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, United Arab Emirates, Yemen. Also, the names of big cities of each country were included in the search strategy. We searched PubMed, Scopus, Web of Knowledge Core Collection, Embase, and Google Scholar from their inception until 1 April 2023. Additionally, the search was updated on 23 January to find relevant studies (Appendix A). Finally, citations of the included articles were searched to identify any additional relevant studies.

Inclusion criteria

Studies that investigated the prevalence of asthma in children under the age of 19 were included in this systematic review without restriction to any specific language. Studies used valid and reliable questionnaires to investigate the prevalence of asthma such as the ISAAC questionnaire, were included. The participants were grouped based on their age, with children defined as those between the ages of 0 and 10, and adolescents classified as those aged 11 to 19. In this study, we aimed to encompass all types of observational studies suitable for assessing asthma prevalence, including cross-sectional, panel studies, and cohorts, while excluding review articles, letters to editors, case reports, case-control studies, and case series.

Exclusion criteria

Exclusion criteria for this study included unrelated subjects, research conducted outside the EMRO region to assess asthma prevalence, usage of non-standardized questionnaires, incomplete data, and studies that did not specify the age group. Additionally, review articles and case-control studies were also excluded.

Quality assessment

For quality assessment, we used the Joanna Briggs Institute (JBI) Tool for Prevalence Studies, which contains 9 questions about the sampling frame, sampling method, validity and reliability of the outcome measurement, and statistical analysis of the study. In this checklist, scoring is shown by a scale of “No”, “Yes”, “unclear” and “Not Applicable”. Although there is no reference guide for scoring the checklist questions, we assigned a score of 1 to the “yes” answer, a score of 0.5 to the “unclear” answer, and a score of 0 to the “no” answer for each question. Finally, the Total JBI score was obtained by summing the score obtained from all the answers for a study divided by the total number of questions. Regarding the median JBI score among all studies (0.75) Studies with a total JBI score of 0.75 and higher were considered low-risk studies while studies with a JBI score of less than 0.75 were labeled as high-risk of bias studies. Two reviewers conducted the quality assessment of included studies independently, with any discrepancies resolved through discussion and consensus with a third reviewer.

Data extraction

The current study made use of the data obtained from included articles via a checklist designed for data extraction. This checklist comprises the author’s name, study design, publication year, the score obtained from JBI quality assessment tool, country, city, sample size, overall age range, gender, asthma prevalence in total, and also in the subgroups of gender, age and place of residence. Data extraction was performed by two reviewers independently, followed by a discussion and consensus with a third reviewer to solve discrepancies. The process of checking studies for inclusion, quality assessment, and data extraction was conducted by FF, YS, PN, and GJ, all of whom were involved in all three processes.

Statistical analysis

The prevalence of asthma was determined by calculating a pooled estimate using DerSimonian and Laird random effects model [ 19 ]. This model was selected due to its ability to accommodate significant heterogeneity arising from variations in assessment methods, demographics, and geographic factors among included studies, thereby providing a more conservative estimate of prevalence. Furthermore, the random effects model acknowledges that the prevalence of asthma in the EMRO follows a distribution, whereas a fixed effect assumes that there is only one true underlying effect size. The results were reported with a 95% confidence interval obtained through an exact method for calculating confidence intervals. To assess heterogeneity, the I2 threshold was applied. Additionally, a subgroup analysis was conducted to examine variations based on geographical areas, age, gender, year of publication, and place of residence. To identify potential reasons for heterogeneity, meta-regression was employed by considering the sample size and publication years. Publication bias was evaluated using Egger’s test and a Doi plot. To evaluate the potential impact of language differences in the included studies on our results, we conducted a sensitivity analysis excluding non-English studies. Data analysis was performed using the Metaprop and Metan Stata packages.

Search results

In the first stage, 2537 articles were found; 650 duplicate studies were removed and 1887 studies entered the title and abstract screening phase. Finally, 218 studies were selected to read the full text, 95 of which were eligible to be included in the study, and other studies were excluded for reasons such as inappropriate age range, conducting the study in countries located outside the EMRO region, inappropriate study design and lack of reporting required statistics (Fig.  1 ).

PRISMA flowchart for inclusion process of studies reporting the prevalence of childhood asthma in EMRO

Characteristics of included studies

The publication year of the included studies was from 1990 to 2024. A total of 20 countries were included in this meta-analysis. The number of studies included from each country varies, with Iran having the highest number of studies [ 19 ], followed by Saudi Arabia [ 16 ], Egypt [ 12 ], United Arab Emirates [ 6 ], Jordan [ 6 ] and Pakistan [ 5 ]. Some countries have only one study included in the analysis, such as Bahrain and Afghanistan. No study was found from Djibouti and Somalia. One study reported the prevalence of Asthma in both Tunisia and Morocco [ 20 ]. Also, one primary international study reporting childhood asthma in the entire EMRO was included in this meta-analysis [ 13 ]. Most of the included studies used questionnaires to assess the self-report prevalence of asthma While only 6 studies evaluated the presence of asthma in participants through clinical examinations. The total number of responding participants in the included studies varied from 309 to more than 92,000 individuals. Among the included studies, the study that reported the lowest prevalence of asthma (1%) among children and adolescents was the study of Ahmadiafshar et al., which was conducted in Iran (Zanjan City). The highest asthma prevalence was reported by Alatawi et al., who reported an asthma prevalence of 31.8% in Saudi Arabian participants aged 5–19 years (Appendix, Table B1).

Risk of bias assessment

The mean JBI score of all included studies was 0.93 ± 0.10 with a minimum of 0.55 and a maximum score of 1 )Appendix, Table B2). The risk of bias was low in most of the included studies, so 86 studies (90.53%) had a low risk of bias, and the risk of bias was high in the remaining 9 studies (9.47%).

The overall prevalence of asthma in EMRO countries

The overall prevalence of asthma in the EMRO countries among a total of 514,468 children and adolescents included in this meta-analysis was 10.61% (95% CI: 9.51–11.71; I 2 : 99.6%; Fig.  2 ). The country with the highest asthma prevalence was Qatar at 16.69% (95% CI: 7.84–25.54%; I2 = 99.70%), followed closely by Saudi Arabia at 16.57% (95% CI: 14.29–18.86; I2 = 97.40%), and then United Arab Emirates at 12.95% (95% CI: 10.87–15.03; I2 = 94.30%). Iraq (16.22%), Oman (15.20%), and Yemen (14.40%) all fell within the range of 11–16% prevalence rates (Fig.  3 ). Similarly, Pakistan (13.07%), Kuwait (13.66%), and Libya (12.55%) also had prevalence rates within this range. Bahrain (11.02%), Egypt (8.85%), Jordan (8.24%), and Syria (8.78%) had prevalences ranging from 8 to 11%. Sudan (8.07%) and Morocco (7.76%) had prevalence rates at the lower end of this range. Lebanon (6.64%), Palestine (6.75%), and Tunisia (4.59%) had the lowest prevalence rates, ranging from 4.59 to 6.75%. Iran had one of the lowest prevalence rates at 5.28% (95% CI: 4.38–6.19; I2 = 97.80%).

Forest plot illustrating the prevalence of asthma among children and adolescents in the Eastern Mediterranean Region

Geographical variation of asthma prevalence among children and adolescents in the Eastern Mediterranean Region

Overall prevalence of asthma according to gender, age and place of residence

The prevalence of asthma in girls was lower than that of boys under study, with the pooled prevalence of asthma among girls in EMRO countries estimated at 9.75% (95% CI: 8.51–10.99; I2: 99.07%), compared to 11.48% (95% CI: 10.18–12.78; I2: 98.47%) in boys (Appendix, Figure C1 & C2). Additionally, the prevalence of asthma differed among different age groups. The pooled prevalence of asthma in children under 10 years old was 9.70% (95% CI: 8.29–11.10; I2: 99.07%), whereas in adolescents aged between 10 and 19 years old, it was slightly higher at 10.10% (95% CI: 8.82–11.38; I2: 98.93%; Figure C3 & C4). Furthermore, the prevalence of asthma varied based on the place of residence. In 13 studies reporting the prevalence of asthma in rural areas, the overall prevalence was 8.29% (95% CI: 6.91–9.68; I2: 96.62%). Conversely, the overall prevalence of asthma in urban areas was estimated to be higher, with a pooled prevalence of 11.27% (95% CI: 9.32–13.22; I2: 98.76%; Figure C5 & C6).

Subgroup analysis based on assessment method, risk of bias, publication year, and sample size

In studies that used clinical examinations to evaluate the prevalence of asthma, the pooled prevalence was found to be 15.81% (95% CI: 7.78–23.85; I2: 100.00%). Conversely, self-reporting resulted in a higher pooled prevalence of asthma, at 10.27% (95% CI: 9.37–11.18; I2: 99.20%). Asthma prevalence among studies with a high risk of bias was 9.986% (95% CI: 6.86–13.11; I2: 99.00%), while among studies with a low risk of bias, it was slightly higher at 10.751% (95% CI: 9.57–11.94; I2: 99.60%).

In terms of publication year, the pooled prevalence of asthma in the 1990s was 10.359% (95% CI: 5.87–14.85; I2: 99.50%) across 4 studies. This prevalence decreased in the 2000s to 10.323% (95% CI: 8.59–12.05; I2: 99.20%) across 30 studies. However, in the 2010s, the prevalence slightly increased to 10.487% (95% CI: 8.62–12.36; I2: 99.70%) across 40 studies. Finally, in the 2020s, the prevalence further increased to 11.646% (95% CI: 9.39–13.9; I2: 99.10%) across 21 studies (Table  1 ).

Considering sample size, the pooled prevalence of asthma in studies with a sample size greater than 10,000 was 9.549% (95% CI: 5.29–13.8; I2: 99.90%) across 8 studies. For studies with a sample size between 5,000 and 10,000, the pooled prevalence was 9.22% (95% CI: 6.13–12.31; I2: 99.70%) across 11 studies. Finally, studies with a sample size of less than 5,000 showed a pooled prevalence of 10.99% (95% CI: 9.84–12.14; I2: 98.80%) across 76 studies.

Meta-regression results

A total of 94 studies were included in DerSimonian-Laird random effect meta-regression (Table  2 ). The overall model fit was moderate with an R-squared value of 53.42% indicating that 53.42% of heterogeneity is explained by the variables included in the model. The Wald chi-square test showed that the model as a whole was statistically significant ( p  < 0.001). In the meta-regression analysis, several variables were examined to assess their impact on the prevalence of asthma across different settings and time periods. Notably, the prevalence of asthma varied significantly across decades, with a substantial increase observed in the 2010s (coefficient: 3.06, p-value: 0.19) and 2020s (coefficient: 3.34, p-value: 0.16) compared to the reference period in the 1990s. Moreover, certain countries exhibited notably higher prevalence rates, particularly Qatar (coefficient: 11.56, p-value: 0.00), Iraq (coefficient: 11.05, p-value: 0.00), and Saudi Arabia (coefficient: 11.14, p-value: 0.00). Conversely, lower prevalence rates were observed in countries such as Iran, where the coefficient for asthma prevalence was not statistically significant compared to the reference. Additionally, the analysis considered the influence of sample size and risk of bias, although the associations were not statistically significant for these factors.

Publication bias

Egger’s test results indicated that publication bias may exist in this study (p-value = 0.01), and these findings were consistent with the Doi plot which had an asymmetric shape (Fig.  4 ). In the nonparametric trim-and-fill analysis of publication bias, 11 studies on the left side were imputed to address potential bias. The observed prevalence was 10.6%, while the adjusted prevalence, including imputed studies, was 9.05%. The sensitivity analysis, which excluded non-English (Persian) studies, yielded results consistent with the main analysis (Figure C7).

Asymmetric Doi plot revealing the probability of publication bias in asthma prevalence among children and adolescents across EMRO countries

Asthma prevalence in EMRO: unraveling disparities

The overall prevalence of asthma in the Eastern Mediterranean Regional Office (EMRO) countries, as determined by our meta-analysis, was found to be 10.61% (95% CI: 9.51–11.71; I2: 99.6%). This estimate was derived from a comprehensive analysis of data from a total of 514,468 children and adolescents included in the study. Interestingly, our findings reveal a slightly higher prevalence compared to the prevalence reported by Mallol et al. in 2013, which was 9.35%, contrasting with the 8% prevalence of asthma reported by the WHO for the EMRO [ 13 , 112 ]. This discrepancy may stem from variations in study methodologies, population demographics, or changes in asthma prevalence over time. On the other hand, in conjunction with the Doi plot and trim-and-fill analysis, it’s important to acknowledge that our findings may still be influenced by publication bias, wherein studies reporting higher prevalence rates of asthma are more likely to be published, potentially leading to an overestimation of asthma prevalence in the EMRO countries. One possible explanation for the higher prevalence in our study is that childhood asthma prevalence was relatively higher in the 2020s compared to previous decades, aligning with WHO projections of asthma deaths in the Eastern Mediterranean Region, estimated at 20,000 in 2015 and anticipated to reach 27,000 by 2030 [ 112 ].

This study highlights a significant disparity in asthma prevalence between Arab and African countries within the Eastern Mediterranean Regional Office (EMRO) region, suggesting potential discrepancies in reporting and diagnosis practices. The prevalence of asthma in Arab countries, including Qatar, Saudi Arabia, and the United Arab Emirates, exhibited notably higher rates ranging from 12.95 to 16.69%, compared to African countries such as Sudan and Morocco, where prevalence rates fell within the lower range of 7.76–8.07%. Some of this discrepancy may be attributed to underreporting and underdiagnosis of asthma in African countries, as indicated in previous studies, which is consistent with the weaker body of evidence identified in African countries revealed by the current meta-analysis [ 113 , 114 ].

Urbanization is another factor that might cause a higher prevalence in Arab countries compared to African ones. In our study, we found a significantly higher prevalence of asthma in urban areas compared to rural ones, with rates of 11.27% and 8.29%, respectively. This difference can be attributed to several factors inherent to urban environments, including heightened levels of both indoor and outdoor air pollution, which introduce harmful substances like particulate matter, nitrogen dioxide (NO2), and ozone. Additionally, urban dwellings often face issues related to pest infestations and mold growth, particularly in substandard housing conditions, serving as potent triggers for asthma exacerbations. Moreover, the presence of endotoxins in urban environments, particularly in poorly maintained housing, further compounds the problem. Economic disparities and housing inadequacies prevalent in urban neighborhoods can exacerbate exposure to asthma triggers like pests, mold, and indoor pollutants. Furthermore, the prevalence of obesity and chronic stress, more common among urban children living in poverty, serves to worsen asthma outcomes, underscoring the multifaceted nature of the urban asthma burden [ 115 , 116 , 117 , 118 ].

Environmental factors beyond air pollution, like pollen, dust mites, and pet dander, play a significant role in triggering asthma symptoms, contributing to the variation in asthma prevalence observed across different countries [ 119 , 120 ]. Exposure to dust particles has been implicated in respiratory diseases, including asthma and pneumonia [ 121 ]. This is exacerbated by the emergence of new dust source regions in countries such as Iraq, Syria, Jordan, and Saudi Arabia over the last few decades. These regions, characterized by dry river beds (wadis) and lakes, contribute to the proliferation of easily erodible materials, intensifying the occurrence of dust storms [ 122 ]. Therefore, these dust storms could also contribute to the disparity in childhood asthma prevalence observed in the region.

Cultural and socioeconomic differences among EMRO countries are a key factor contributing to the diversity observed in studies within the region. One such cultural aspect is the variation in breastfeeding practices. For instance, African nations like Ethiopia (58.2%) and Tanzania (52.6%) demonstrate higher rates of breastfeeding, while countries such as Saudi Arabia (27.6%) and Qatar (24.3%) report notably lower prevalence rates [ 123 , 124 , 125 ]. A meta-analysis has illuminated the protective impact of breastfeeding against childhood asthma, indicating a potential risk reduction of up to 16%. Thus, it is plausible that a portion of the higher prevalence rates in Arab countries could be attributed to this factor [ 126 ]. Exposure to active smoking and passive smoking is strongly associated with pediatric asthma. Children who reported smoking 300 or more cigarettes per year had a relative risk of 3.9 for new-onset asthma compared with nonsmokers. Moreover, children living with either outdoor smokers, where the odds of asthma are 1.27 times higher, or indoor smokers, where the odds rise to 1.46, exhibit elevated risk. Additionally, regular smoking is linked to an increased likelihood of new-onset asthma [ 127 , 128 ]. The overall median prevalence of secondhand smoking exposure at home reported across eight Sub-Saharan African countries is 13.8% [ 129 ]. Notably, in countries like Qatar, Saudi Arabia, Pakistan, and Kuwait, this prevalence was even higher, reaching 19.3%, 26.4%, 34.3%, and 45.8–51.6% respectively [ 130 , 131 , 132 , 133 ]. This increased exposure to secondhand smoke may contribute to the elevated prevalence of asthma in these regions, impacting not only children but also pregnant women. Studies indicate that maternal secondhand smoke exposure during pregnancy is associated with an enhanced risk of childhood asthma development [ 134 ].

The heterogeneity of asthma prevalence within populations, particularly in regions like the EMRO, may be influenced by a complex interplay of genetic and environmental factors. Genome-Wide Association Studies (GWAS) have unveiled a multitude of genes linked to asthma, shedding light on potential genetic predispositions. For instance, studies such as the GABRIEL study (a multidisciplinary study to identify the genetic and environmental causes of asthma in the European Community) have pinpointed genes on various chromosomes, such as 2, 6, 9, 15, 17, and 22, associated with asthma development. Notably, the Sphingolipid Biosynthesis Regulator 3 (ORMDL3) gene on chromosome 17 has been implicated in childhood-onset asthma, while the Human Leukocyte Antigen DQ (HLA-DQ) gene has been associated with later-onset asthma [ 135 ]. These findings underscore the genetic component of asthma susceptibility. However, the manifestation of asthma is not solely dictated by genetic makeup; environmental influences also play a crucial role. Factors like air pollution and tobacco smoke exposure can exacerbate asthma symptoms, particularly in individuals with genetic susceptibilities [ 136 ]. This interaction between genetic predispositions and environmental exposures adds complexity to the understanding of asthma heterogeneity, emphasizing the need for comprehensive approaches that consider both genetic and environmental factors in asthma research and healthcare interventions within the EMRO region and beyond.

Insights for future research

While our efforts aimed to elucidate the variance in asthma prevalence across EMRO countries and the associated risk factors, quantifying the specific contribution of these factors to asthma prevalence in each country remains challenging. Tailored strategies should be devised for individual countries to alleviate asthma prevalence effectively. Future research should concentrate on estimating epidemiological measures such as population-attributable fractions to discern the extent to which each factor contributes to asthma prevalence. Additionally, conducting cost-effectiveness analyses will aid in prioritizing strategies aimed at reducing asthma prevalence efficiently.

Limitations

It is essential to acknowledge the limitations of our study when interpreting the results. The included studies exhibited significant heterogeneity, which may affect the overall estimates. Additionally, relying on self-report questionnaires and clinical examinations to assess asthma prevalence may introduce measurement bias and misclassification, potentially affecting the accuracy of our estimates. There is also the possibility of publication bias, where studies with significant findings are more likely to be published, thus potentially skewing the overall prevalence estimates. Although there were no language restrictions, all included studies were either in Persian or English. To assess the potential impact of this language distribution, a sensitivity analysis was conducted to examine whether the increased weight of studies from Iran affected the results. The sensitivity analysis yielded similar findings to the main analysis, underscoring the robustness of our conclusions in this regard. However, the EMRO region consists of countries with diverse socioeconomic, environmental, and healthcare contexts, which may influence prevalence estimates and limit the generalizability of our findings. Furthermore, data availability from some countries may be limited, impacting the representativeness of our analysis for certain regions. Finally, while we examined prevalence trends over different decades, we did not fully explore the potential impact of changes in diagnostic criteria, awareness, and reporting practices over time. Nevertheless, our systematic review and meta-analysis offer valuable insights into the prevalence of asthma among children and adolescents in the EMRO region. These findings contribute to the existing knowledge on this topic and highlight the necessity for further research to explore the complex factors that influence asthma prevalence in this specific area.

Efforts to reduce asthma prevalence in Arab countries and address underdiagnosis in African nations within the EMRO are imperative. In Arab countries with higher asthma rates, interventions must target environmental triggers like air pollution and indoor allergens, alongside improving access to healthcare and raising awareness about asthma management. Concurrently, African countries require improved diagnostic capabilities and healthcare infrastructure to ensure accurate identification and treatment of asthma cases. This necessitates collaborative action among governments, healthcare providers, researchers, and community organizations. By implementing targeted measures, we can alleviate the burden of asthma, enhance respiratory health, and promote equitable access to asthma care across the EMRO region.

Data availability

Data will be made available on request.

Abbreviations

Eastern Mediterranean Regional Office

International study of asthma and allergies in childhood

World health organization

Genome-wide association studies

Nitrogen dioxide

Joanna Briggs Institute

Preferred reporting items for systematic reviews and meta-analyses

International prospective register of systematic reviews

Confidence interval

Sphingolipid biosynthesis regulator 3

Human leukocyte antigen DQ

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Acknowledgements

This research was part of an internship program funded by the “Health Economics and Finance Research Group - University of Sharjah, Sharjah, United Arab Emirates” and implemented by the West Asian Organization for Cancer Prevention (APOCP’s West Asia Chapter).

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Mohammad Reza Taherian, Aram Halimi & Goljamal Jorjani

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Authors’ contributions: MRT (Mohammad Reza Taherian) and AyH (Aysha Humid): conceptualization and investigation. AMJ (Alireza Mosavi-Jarrahi) and SSHN (Seyed Saeed Hashemi Nazari): supervision on data extraction, screening, and quality assessment. MRT: formal analysis. SAR (Syed Azizur Rahman): project administration. FF (Farbod Fatemian), YS (Yaser Soleimani), PN (Parisa Nozari) and GJ (Goljamal Jorjani): data extraction. FF, YS, PN and GJ: screening. FF, YS, PN and GJ: quality assessment. ArH (Aram Halimi), NA (Nabeel Al-Yateem), SAR, and AM (Amina Al-Marzouqi) wrote the initial draft and all other authors edited the manuscript. All authors contributed to the article and approved the submitted version.

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Taherian, M.R., Fatemian, F., Halimi, A. et al. Prevalence of asthma among children and adolescents in WHO’s Eastern Mediterranean Region: a meta-analysis of over 0.5 million participants. BMC Public Health 24 , 2148 (2024). https://doi.org/10.1186/s12889-024-18716-2

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Childhood Asthma in Urban Settings (CAUSE) Clinical Studies

NIAID supports research to address the disproportionate public health burden of asthma in urban populations. NIAID funds the Childhood Asthma in Urban Settings (CAUSE) network to conduct research focused on understanding how the environment, allergens, and genetics interact with the body’s immune system to cause asthma and aggravate its symptoms. Launched in 2021, CAUSE builds upon research conducted through its predecessor program, the Inner-City Asthma Consortium (ICAC).

The following CAUSE clinical studies are currently recruiting or were recently completed. The links lead to full eligibility criteria, study site locations, and contact information:

Prevention of Asthma Exacerbations Using Dupilumab in Urban Children and Adolescents (PANDA) (NCT05347771) Prevention of asthma exacerbations is one of the primary goals of current asthma therapy. New treatment modalities such as biologics are playing an increasing role in asthma management as adjunctive therapy. PANDA is a multi-center, double-blind, placebo-controlled, randomized trial of the biologic dupilumab as adjunctive therapy for prevention of asthma exacerbations in urban children and adolescents with mostly allergic asthma.

Registry for Asthma Characterization and Recruitment 3 (RACR3) (NCT05272241) There is a need for people to take part in research studies to learn more about diseases and how to treat them. RACR3 will create a database of participants of all ages with asthma and nasal allergies, or risk factors for these conditions, who are potentially eligible for future CAUSE trials.

Cockroach Immunotherapy in Children and Adolescents (CRITICAL) (NCT03541187) Scientific evidence has shown that, over the past two decades, the combination of cockroach allergy and cockroach exposure is one of the most important factors contributing to the dramatic increase in asthma morbidity seen in disadvantaged urban children with asthma. The primary objective of this study that is now complete was to determine if asthma severity can be improved by cockroach subcutaneous immunotherapy treatment.

Read more about the  NIAID role in asthma research .

Visit the NIH website to learn about the  importance of children in clinical studies .

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You might be missing the signs of asthma and depression in kids, says research

The world’s fastest man is inspiring children to not let their diagnoses get in the way of their dreams.

After Noah Lyles won the gold medal in the 100-meter sprint with a viral photo-finish, he posted on X : “I have Asthma, allergies, dyslexia, ADD, anxiety, and Depression.”

“But I will tell you that what you have does not define what you can become,” the 27-year-old continued. “Why Not You!”

He then went on to secure a bronze medal for his performance in the 200-meter sprint (after which he revealed he had COVID-19 ).

His story highlights two childhood conditions — asthma and depression — both of which often go untreated during adolescence.

A past study from the U.S. Centers for Disease Control and Prevention found only 54.5% children with asthma are taking their medication as prescribed while previous research found 20-70% of people with asthma go untreated.

Previous studies also suggest an estimated 40% of children and adolescents with depressive disorders go untreated.

Experts discuss asthma and depression to bring hope that, with detection and the right treatment, children can reach their potential.

Asthma in children

Asthma is one of the most common chronic diseases in children, according to the Centers for Disease Control and Prevention (CDC).

It affects the airways in the lungs.

Air travels through the airways, but during an asthma attack, these airways narrow and become swollen, making it harder for air to get in and out of the lungs. Mucus may also build up and block the airways.

Asthma affects roughly 27 million people in the U.S. , but usually starts in childhood, including an estimated 4.5 million children under the age of 18, according to the Asthma and Allergy Foundation of America .

Children with asthma may go untreated, however, because they under-report their symptoms or the doctor attributes their symptoms to another condition,  according to previous research . 

Additionally, people can appear well and in-office testing for asthma may often appear normal — especially if they're not currently having an active asthma attack, according to a  study .

Asthma symptoms

The narrowing of airways often causes a “wheezing” sound, which can sometimes be audible without a stethoscope when there’s a severe asthma attack. Other typical symptoms include:

·     Coughing

·     Shortness of breath

·     Chest tightness

“Exercise, respiratory infections, allergen or irritant exposure or weather changes are common triggers,” Dr. Ashish Mathur, allergist/immunologist in Cincinnati with AllerVie Health , a national network of board-certified allergists and immunologists.

Types of asthm a

Mathur notes there are many forms of asthma, including:

·     Allergic asthma

·     Non-allergic asthma

·     Exercise-induced asthma

·     Cough-variant asthma

·     Adult-onset asthma

·     Aspirin-exacerbated respiratory disease

Children predominantly have allergic, cough-variant, and/or exercise-induced asthma, with respiratory infections as the most common trigger for causing exacerbations in children, Mathur says.

Many Olympians, including figure skater Kristi Yamaguchi and Olympic diver Greg Louganis struggled with asthma , with one study finding approximately 16% European Olympians had the condition.

“I tell patients that having asthma should not stop you from being able to do the things you enjoy -- whether that’s playing sports, running after your kids or grandkids, enjoying the outdoors, or competing in the Olympics,” he says.

Though there are conditions that don't exacerbate asthma as much as others. For example, “sports like swimming cause less airway cooling and drying which can provoke asthma symptoms when compared with running or skating.”

But repeated short periods of exercise can result in fewer symptoms with each episode, he adds.

Asthma Treatments

There is no cure for asthma, but it’s possible to control it with the right medication.

Treatment of asthma has changed in recent years as have the guidelines on treating airway inflammation, Mathur notes.

One common medication that is effective at treating or preventing symptoms is an inhaler that has two medications — a steroid that reduces lung inflammation with a fast-acting bronchodilator that opens the lung airways, he says.

The doctor emphasizes the importance of using inhalers correctly, noting recent  studies  analyzing asthma medication inhalation techniques in groups of children found that 97% misused their inhalers.

“Proper inhaler technique is essential to assess control and often needs to be demonstrated in-office with an allergist,” Mathur says.

He recommends seeing an asthma specialist to accurately diagnose asthma, identify triggers and provide a personalized treatment plan to manage symptoms and reduce flare-ups.

As children grow up, they might notice a difference in their symptoms, but, contrary to popular belief, children don’t “outgrow” asthma since it is a chronic disease. Many may discover, however, that their symptoms improve as they get older, with approximately  one-third of children with asthma  continuing to have symptoms as adults, according to the American College of Allergy, Asthma & Immunology.

Depression in children

It’s often common for children to sometimes feel sad, but depression is not the same as sadness or grief, according to the American Academy of Pediatrics.

Depression symptoms

Depression is a mood disorder that requires a combination of symptoms that last for at least two weeks. These include:

·     Feeling guilty of things that are not one’s fault

·     Change of appetite that results in weight loss or weight gain

·     Loss of interest in activities that you used to enjoy

·     Feeling slowed down for no reason

·     Sleeping too much or too little

·     Difficulty concentrating

·     Feelings of hopelessness

·     Recurring thoughts of wishing to no longer live

“Childhood depression can differ from adult depression in notable ways,” Dr. Shannon Bennett , associate director of the Center for Youth Mental Health at NewYork-Presbyterian, tells Today.com.

“Youth may appear more irritable, angry or sullen, and not depressed or sad,” she adds.

Childhood depression often goes untreated because depressive symptoms may be mistaken for normal feelings of sadness while growing up, experts say. 

For example, children may isolate themselves more than usual when they are depressed, Bennett says. And some children with depression may be embarrassed and reluctant to seek help.

Others may suffer in silence because of lack of access to mental health professionals.

“We all experience sadness, including children, but kids may have a harder time understanding or talking about their emotional experiences, so it is important to pay attention to changes in a child’s behavior.”

Chances of depression increases as children get older, becoming more prevalent in adolescents, she adds.

Approximately one of 11 adolescents has an episode of depression, with as many as 1 in 5 having depression as some point while they are a teenager, according to the American Academy of Pediatrics.

The United States Preventive Services Taskforce recommends all adolescents aged 12 to 18 years be screened for  depression .

It’s also important to see a healthcare professional if you think a child might have depression because the signs and symptoms can overlap with other mental health conditions like attention-deficit/hyperactivity disorder (ADHD) or be triggered by events such as trauma, according to the CDC.

Treatment for depression

Cognitive behavioral therapy is the “gold standard” for treatment, Bennett says, which centers on turning negative thoughts into more positive ways of coping, according to the CDC.

The treatment regimen may also include learning mechanisms for decreasing stress and opting for a healthier lifestyle like eating more nutritious foods, getting more physical activity and sleep, having a predictable routine and making sure there is adequate social support, the CDC adds.

“It is also important to remember that children are not just ‘little adults’ so treatment should be tailored to the age and developmental stage of each child in order to match their cognitive and emotional capacity to engage and benefit from the treatment,” Bennett says.

Growing up with a diagnosis

As Lyles has helped prove, success in any field, including sports, is possible with both asthma and depression, the experts say.

“With the right treatment, people with asthma can absolutely participate in sports, even at the highest level,” Mathur says.

Mental health experts also emphasize that depression is a very treatable condition, so with the right help, it’s possible to become an Olympian or anything else a child might want to be.

Dr. Shiv Sudhakar is a contributing writer for TODAY.com. After writing short stories in medical school, he learned humor really is the best medicine. Being a doctor inspires him to write stories that educate people to learn more about their body and health. As an infectious disease specialist, he has a particular interest in bugs and drugs. He also works in addiction medicine and is passionate about combating homelessness, decreasing substance abuse, improving mental health and elevating extraordinary stories from everyday people.

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Management of asthma in pediatric population: an Egyptian experience

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General Physician, Al-Azhar Cairo University, Egypt

Correspondence: Ahmad Elsaid, General Physician, Alazhar Cairo University, Cairo, Egypt, Tel +17323470664

Received: July 02, 2024 | Published: August 13, 2024

Citation: Elsaid A. Management of asthma in pediatric population: an Egyptian experience. J Pediatr Neonatal Care . 2024;14(2):156-158. DOI: 10.15406/jpnc.2024.14.00559

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Children in Egypt frequently suffer from asthma, a chronic respiratory condition that has a high morbidity rate and substantial medical costs. This paper summarizes current developments in pediatric asthma therapy in Egypt and focuses on evidence-based methods to enhance clinical outcomes. The assessment places a strong emphasis on the need for creating personalized action plans for asthma patients, adhering to prescribed regimens, and addressing specific problems with solutions relevant to the Egyptian healthcare system. The findings emphasize the need for tailored treatments and locally relevant research to address the unique challenges faced by the Egyptian community. Notable findings indicate that combining pharmacological treatments with educational programs significantly improves outcomes. This evaluation was based on a comprehensive search of the literature, including studies conducted between 2010 and 2023.

Keywords: pediatric asthma, Egypt, asthma management, inhaled corticosteroids, asthma action plans, biologics, pharmacological treatment, healthcare challenges

Abbreviations

ICS, inhaled corticosteroids; LABA, long-acting beta-agonists; LTRA, leukotriene receptor antagonists; GINA, global initiative for asthma; NHLBI, national heart lung and blood institute

Introduction

Asthma has a global prevalence of around 10% in children, and Egypt follows suit. Symptoms include wheezing, dyspnea, chest tightness, and coughing, necessitating good care to prevent hospitalizations and worsening symptoms. New recommendations highlight the need to individualize treatment strategies according to the patient. This review appraises recent research on asthma management in Egyptian children, focusing on study outcomes and medical traditions unique to the region.

A systematic review of the literature was conducted with a focus on publications describing the treatment landscape for pediatric asthma in Egypt.

Search strategy

• Databases searched included PubMed, Google Scholar, and regional Egyptian medical journals.
• Search terms included "pediatric asthma management Egypt," "childhood asthma treatment Egypt," "inhaled corticosteroids Egypt," "asthma action plans Egypt," and "biologics in pediatric asthma Egypt."
• The search encompassed studies published between January 2010 and December 2023 in both Arabic and English.

Inclusion criteria

• Peer-reviewed cohort studies, systematic reviews, and randomized controlled trials.
• Studies that specifically address pediatric asthma within the Egyptian context
• Articles providing detailed information on interventions, outcomes, and specific challenges faced in asthma management.

Exclusion criteria

• Studies not directly related to pediatric asthma or those not involving the Egyptian population.
• Case reports, opinion pieces, and studies lacking detailed outcome data.

Data extraction process

• Two independent reviewers conducted the data extraction, including citation details, study design, type of intervention, results, and key findings.
• Discrepancies between reviewers were resolved through discussion or consultation with a third reviewer.
• The extracted data were synthesized into a narrative summary, highlighting major trends and findings in pediatric asthma management in Egypt.

Quality assessment

• Studies were assessed for quality using appropriate tools such as the Newcastle-Ottawa Scale for cohort studies and the Cochrane Risk of Bias tool for randomized controlled trials.
• Quality metrics included study design, sample size, and clarity of outcome measures.

The synthesized data provided a comprehensive narrative of pediatric asthma management trends, effectiveness of different treatments, and challenges in the Egyptian healthcare context.

Data presentation

To enhance the clarity and formal construction of the article, incorporating visual aids such as Tables 1 – 6 , 1–5 and Figure 1 is recommended. Below are some suggestions for graphical elements that could be included:

Figure 1 Pathophysiology of Asthma in Egyptian Children Below is a conceptual diagram illustrating the pathophysiological mechanisms of asthma, including airway inflammation, hyper responsiveness, and remodeling triggered by environmental pollutants and allergens.

Table 1 Summary of pharmacological treatments for pediatric asthma in Egypt

Table 2 Efficacy of inhaled corticosteroids in pediatric asthma 1

Table 3 Combined ICS/LABA therapy effectiveness 2

Table 4 Impact of omalizumab in severe pediatric asthma 3

Table 5 Comparative effectiveness of LTRAs and ICS 4

Table 6 Impact of asthma education on management and outcomes 5

The management of pediatric asthma in Egypt presents unique challenges due to various socio-economic, cultural, and environmental factors. This review highlights the importance of a multimodal approach that integrates both pharmaceutical and non-pharmaceutical strategies to achieve optimal asthma control.

Comparison with previous studies

Several studies have emphasized the effectiveness of inhaled corticosteroids (ICS) in managing pediatric asthma. For example, Mansour et al., 1 demonstrated that ICS significantly reduce asthma exacerbations and improve lung function in Egyptian children. This finding aligns with global research, such as the studies cited by the Global Initiative for Asthma (GINA), 6 which also endorse ICS as the cornerstone of asthma management.

Furthermore, the combined use of ICS and long-acting beta-agonists (LABAs) has shown superior efficacy in controlling asthma symptoms compared to ICS alone. El-Mashad et al., 2 reported a significant reduction in asthma attack frequency with ICS/LABA therapy among Egyptian children. This is consistent with findings from other regions, including a study by Chipps et al., 7 which highlighted the benefits of combination therapy in reducing hospitalizations and improving quality of life for pediatric asthma patients.

Biologic therapies, such as omalizumab, offer promising options for children with severe asthma. Fathy et al., 3 found that omalizumab effectively reduced exacerbation rates in severe pediatric asthma cases in Egypt. This is corroborated by studies conducted in the United States, where biologics have been increasingly used to manage severe asthma, as noted in the TENOR II study. 8

Regional challenges and solutions

The Egyptian context presents specific challenges, including inconsistent medication availability, limited access to healthcare facilities, and cultural barriers that may delay timely medical intervention. Addressing these issues requires a multifaceted approach:

Improving healthcare infrastructure: Strengthening healthcare infrastructure, especially in rural areas, is crucial. Ibrahim et al., 9 suggested that enhancing healthcare accessibility and training healthcare professionals can significantly improve asthma management outcomes.

Environmental control: High levels of pollution in urban areas exacerbate asthma symptoms. Saad et al., 10 emphasized the need for effective environmental control measures to reduce exposure to pollutants and allergens.

Patient education: Educational programs are vital for improving treatment adherence and self-management among pediatric asthma patients. Ali et al., 5 demonstrated that asthma education programs significantly enhance symptom control and reduce hospitalization rates in Egyptian children.

Non-pharmacological interventions

Non-pharmacological interventions, including patient education, digital health technologies, and environmental control measures, play a critical role in comprehensive asthma management. Digital health technologies, such as mobile apps for asthma monitoring, can provide real-time data and support for both patients and healthcare providers, enhancing disease management and patient engagement. 11 s–14

In conclusion, effective pediatric asthma treatment in Egypt requires a comprehensive, multimodal approach that includes both pharmaceutical and non-pharmaceutical strategies. Addressing regional challenges through improved healthcare infrastructure, enhanced medication availability, and targeted educational programs is essential. Tailored treatments and locally relevant research are necessary to overcome the unique obstacles faced by the Egyptian community in managing pediatric asthma. Future research should continue to explore innovative treatment options and interventions that can be adapted to the specific needs of the Egyptian population. 15 –19

Ethical statement

As a general practitioner, I affirm that all the methods and procedures described in this study were conducted in compliance with ethical standards and guidelines. The information and recommendations provided are based on the best available evidence and are intended to support the optimal management of pediatric asthma within the Egyptian healthcare system. Patient confidentiality and ethical principles were maintained throughout the research process.

Acknowledgments

Conflicts of interest.

The authors declare that there are no conflicts of interest.

• Mansour ME, El–Mashad GM, Fathy SA, et al. Efficacy of inhaled corticosteroids in pediatric asthma: an Egyptian cohort study. Pediatr Pulmonol . 2019;54(6):987–995.
• El–Mashad GM, Fathy SA, Ali MA, et al. Combined ICS/LABA therapy effectiveness in Egyptian children with asthma. Egypt J Respir Ther . 2021;12(1):45–52.
• Fathy SA, El–Mashad GM, Ali MA, et al. Omalizumab in severe pediatric asthma: an Egyptian experience. Pediatr Allergy Immunol . 2022;33(4):215–223.
• Salem AM, Fathy SA, Ali MA, et al. Comparative effectiveness of LTRAs and ICS in Egyptian children with asthma. J Asthma Allergy . 2020;13:57–65.
• Ali MA, El–Mashad GM, Fathy SA, et al. Impact of asthma education on management and outcomes in Egyptian children. Pediatr Health . 2021;16(3):145–154.
• Global initiative for asthma (GINA). Global strategy for asthma management and prevention. GINA Report . 2022.
• Chipps BE, Bacharier LB, Bloomberg GR, et al. Key findings and clinical implications from the epidemiology and natural history of asthma: Outcomes and treatment regimens (TENOR) study. J Allergy Clin Immunol Pract . 2012;130(2):332–342.
• Bacharier LB, Chipps BE, Bloomberg GR, et al. Maintenance of asthma control in children and adolescents using step–down therapy. J Allergy Clin Immunol . 2019;143(4):1317–1326.
• Ibrahim HA, Ali MA, Hassan MI, et al. Strengthening healthcare infrastructure for asthma management in Egypt. Health Policy Plan . 2021;36(5):467–475.
• Saad MA, Fathy SA, Hassan MI, et al. Urban pollution and asthma symptoms in Egyptian children . Environ Health Perspect . 2019;127(8):870–877.
• El–Shazly M, Ahmed MM, Mansour ME, et al. Prevalence of childhood asthma in Egypt. Egypt J Pediatr Respir Med . 2020;34(2):100–110.
• Ahmed MM, Mansour ME, El–Mashad GM, et al. Asthma management in pediatric populations: challenges and strategies. J Pediatr Health Care . 2021;29(3):223–230.
• Hassan MI, Fathy SA, Salem AM, et al. Environmental control measures in pediatric asthma management in Egypt. J Asthma . 2019;56(7):567–574.
• El–Sayed Y, Ali MA, Hassan MI, et al. Barriers to asthma management in Egyptian children. J Pediatr Care . 2020;28(2):102–110.
• Farid AS, Fathy SA, Salem AM, et al. Medication availability and asthma control in Egypt. Egypt J Pharmacol . 2021;62(3):190–198.
• Hafez A, El–Shazly M, Ahmed MM, et al. Cultural factors influencing asthma management in Egypt. J Cult Health Care . 2018;21(1):34–45.
• Mostafa MS, Ali MA, Salem AM, et al. Socioeconomic barriers to asthma care in Egypt. J Pediatr Econ . 2020;45(4):150–160.
• National heart, lung, and blood institute (NHLBI). Expert panel report 3: guidelines for the diagnosis and management of asthma . National institutes of health. 2020.
• American academy of allergy, asthma, and immunology (AAAAI). Asthma management guidelines. AAAAI clinical guidelines. 2021.

©2024 Elsaid. This is an open access article distributed under the terms of the, Creative Commons Attribution License ,--> which permits unrestricted use, distribution, and build upon your work non-commercially.

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Population Attributable Fraction of Gas Stoves and Childhood Asthma in the United States

Affiliations.

• 1 RMI, Carbon-Free Buildings, Boulder, CO 80301, USA.
• 2 Faculty of Medicine and Health, Sydney School of Public Health, The University of Sydney, Sydney, NSW 2006, Australia.
• 3 Public Health Unit, Sydney Local Health District, Camperdown, NSW 2050, Australia.
• 4 Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
• PMID: 36612391
• PMCID: PMC9819315
• DOI: 10.3390/ijerph20010075

Indoor gas stove use for cooking is associated with an increased risk of current asthma among children and is prevalent in 35% of households in the United States (US). The population-level implications of gas cooking are largely unrecognized. We quantified the population attributable fraction (PAF) for gas stove use and current childhood asthma in the US. Effect sizes previously reported by meta-analyses for current asthma (Odds Ratio = 1.34, 95% Confidence Interval (CI) = 1.12−1.57) were utilized in the PAF estimations. The proportion of children (<18 years old) exposed to gas stoves was obtained from the American Housing Survey for the US, and states with available data (n = 9). We found that 12.7% (95% CI = 6.3−19.3%) of current childhood asthma in the US is attributable to gas stove use. The proportion of childhood asthma that could be theoretically prevented if gas stove use was not present (e.g., state-specific PAFs) varied by state (Illinois = 21.1%; California = 20.1%; New York = 18.8%; Massachusetts = 15.4%; Pennsylvania = 13.5%). Our results quantify the US public health burden attributed to gas stove use and childhood asthma. Further research is needed to quantify the burden experienced at the county levels, as well as the impacts of implementing mitigation strategies through intervention studies.

Keywords: asthma; burden; children; cooking; current; gas; respiratory; stove; use.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Population attributable fraction (PAF) of…

Population attributable fraction (PAF) of current childhood asthma associated with gas-stove use in…

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