Asthma diagnosis in children: more evidence needed
Authors: Philipp Latzin, Oliver Fuchs
Journal: The Lancet Child & Adolescent Health (2017)

With about 1–18% of the population worldwide being affected, wheeze and asthma are the most prevalent chronic respiratory diseases during childhood and adulthood.1Global Initiative for Asthma (GINA)Global strategy for asthma management and prevention.http://ginasthma.org/Date: 2017Google Scholar As such, many children each day will enter an outpatient clinic or a paediatrician's office needing diagnostic tests for suspected asthma. If it were only that simple. Individuals with suspected asthma symptoms vary substantially in their complaints and clinical manifestations despite common pathophysiological factors that lead to the final common pathway of (sometimes only partly) variable airway obstruction due to a range of triggers, which results in symptoms such as wheeze, difficulty breathing, chest tightness, and cough.2Martinez FD Vercelli D Asthma.Lancet. 2013; 382: 1360-1372Summary Full Text Full Text PDF PubMed Scopus (406) Google Scholar, 3Fuchs O Bahmer T Rabe KF von Mutius E Asthma transition from childhood into adulthood.Lancet Respir Med. 2017; 5: 224-234Summary Full Text Full Text PDF PubMed Scopus (125) Google Scholar What is the best way then to diagnose asthma during childhood? Importantly, no single test exists for the diagnosis of asthma in adults, and especially not in children. In diagnostic investigation of patients of all ages, clinical observations (ie, suggestive symptoms) need to be complemented by objective measurements. These tests aim to rule in asthma and to rule out important differential diagnoses by identifying variable airway obstruction or airway inflammation. In mathematical terms, asthma diagnosis depends on the patient's pretest probability of having a diagnosis (suggestive symptoms and history) in combination with both sensitivity and specificity of further corroborating objective tests such as lung function. Beyond the individual symptom level, this includes the precision of used tests (ie, both their positive and negative predictive values). Therefore, asthma diagnosis is a common clinical task that needs to be taken seriously, and the importance of such diagnosis is reflected by a range of recommendations.1Global Initiative for Asthma (GINA)Global strategy for asthma management and prevention.http://ginasthma.org/Date: 2017Google Scholar, 4British Thoracic Society (BTS)Scottish Intercollegiate Guidelines Network (SIGN)British guideline on the management of asthma.https://www.brit-thoracic.org.uk/standards-of-care/guidelines/btssign-british-guideline-on-the-management-of-asthma/Date: 2016Google Scholar, 5National Heart, Lung, and Blood InstituteNational Asthma Education and Prevention ProgramExpert panel report 3: guidelines for the diagnosis and management of asthma.https://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines/full-reportDate: 2007Google Scholar The present asthma management guidelines by the British Thoracic Society/Scottish Intercollegiate Guidelines Network allude to the fact that the diagnosis of asthma is primarily a clinical one.4British Thoracic Society (BTS)Scottish Intercollegiate Guidelines Network (SIGN)British guideline on the management of asthma.https://www.brit-thoracic.org.uk/standards-of-care/guidelines/btssign-british-guideline-on-the-management-of-asthma/Date: 2016Google Scholar To prevent misdiagnosis, the UK National Institute for Health and Care Excellence (NICE) developed additional guidance for asthma diagnosis incorporating objective tests in addition to suggestive clinical observations.6National Institute for Health and Care ExcellenceAsthma: diagnosis and monitoring of asthma in adults, children and young people. Clinical guideline, methods, evidence and recommendations.https://www.nice.org.uk/guidance/gid-cgwave0640/documents/asthma-diagnosis-and-monitoring-draft-nice-guideline2Date: 2015Google Scholar Although the NICE guidance is mainly based on data extrapolated from adults and yet to be effected in the UK, it proposes an algorithm with a predefined sequence of four lung function measurements for use in the paediatric context.6National Institute for Health and Care ExcellenceAsthma: diagnosis and monitoring of asthma in adults, children and young people. Clinical guideline, methods, evidence and recommendations.https://www.nice.org.uk/guidance/gid-cgwave0640/documents/asthma-diagnosis-and-monitoring-draft-nice-guideline2Date: 2015Google Scholar The algorithm starts with spirometry as a first-line measure, followed by a bronchodilator reversibility test, measurement of exhaled nitric oxide as a marker of allergic airway inflammation, and, if needed, recording of peak expiratory flow variability over 2–4 weeks.6National Institute for Health and Care ExcellenceAsthma: diagnosis and monitoring of asthma in adults, children and young people. Clinical guideline, methods, evidence and recommendations.https://www.nice.org.uk/guidance/gid-cgwave0640/documents/asthma-diagnosis-and-monitoring-draft-nice-guideline2Date: 2015Google Scholar However, the dilemma is that although the clinical symptoms themselves are already poor predictors for asthma, test results can vary over time, as a result of both the variable nature of the underlying pathophysiology and the resulting asthma symptoms.4British Thoracic Society (BTS)Scottish Intercollegiate Guidelines Network (SIGN)British guideline on the management of asthma.https://www.brit-thoracic.org.uk/standards-of-care/guidelines/btssign-british-guideline-on-the-management-of-asthma/Date: 2016Google Scholar Moreover, lung function criteria are limited in their usability, especially during childhood if more or less fixed cutoffs irrespective of age are used.7Stanojevic S Quanjer P Miller MR Stocks J The Global Lung Function Initiative: dispelling some myths of lung function test interpretation.Breathe. 2013; 9: 463-474Crossref Scopus (37) Google Scholar In addition, many difficulties exist with regards to peak expiratory flow recordings or the so far absent universal definition of bronchodilator reversibility in children. These issues have immense implications on the combination of the aforementioned pretest probabilities for asthma diagnosis and on further objective tests and their precision. The issue of applying guidelines in children that originate from studies in adults becomes evident in the study by Clare Murray and colleagues8Murray C Foden P Lowe L Durrington H Custovic A Simpson A Diagnosis of asthma in symptomatic children based on measures of lung function: an analysis of data from a population-based birth cohort study.Lancet Child Adolesc Health. 2017; (published online July 12, 2017.)http://dx.doi.org/10.1016/S2352-4642(17)30008-1Summary Full Text Full Text PDF PubMed Scopus (50) Google Scholar in The Lancet Child & Adolescent Health. The authors assessed the usefulness of the newly proposed NICE diagnostic algorithm for asthma diagnosis in children aged 13–16 years during regular follow-up visits as part of a well established population-based birth cohort, the Manchester Asthma and Allergy Study (MAAS).9Custovic A Simpson BM Murray CS Lowe L Woodcock A The national asthma campaign Manchester Asthma and Allergy Study.Pediatr Allergy Immunol. 2002; 13: 32-37Crossref PubMed Scopus (125) Google Scholar To simulate asthma assessment in the primary care setting, Murray and colleagues did their analyses in a subgroup of study participants with recent asthma symptoms who were not already on regular treatment with inhaled corticosteroids.8Murray C Foden P Lowe L Durrington H Custovic A Simpson A Diagnosis of asthma in symptomatic children based on measures of lung function: an analysis of data from a population-based birth cohort study.Lancet Child Adolesc Health. 2017; (published online July 12, 2017.)http://dx.doi.org/10.1016/S2352-4642(17)30008-1Summary Full Text Full Text PDF PubMed Scopus (50) Google Scholar Unsurprisingly, the authors found only poor agreement between the proposed NICE algorithm and their definition of asthma in children aged 13–16 years, which is questionnaire-based and follows widely used epidemiological classifications.8Murray C Foden P Lowe L Durrington H Custovic A Simpson A Diagnosis of asthma in symptomatic children based on measures of lung function: an analysis of data from a population-based birth cohort study.Lancet Child Adolesc Health. 2017; (published online July 12, 2017.)http://dx.doi.org/10.1016/S2352-4642(17)30008-1Summary Full Text Full Text PDF PubMed Scopus (50) Google Scholar Only two of 89 symptomatic children met the algorithm's definition of asthma, but neither met the epidemiological definition. Although adherence to the NICE algorithm under real-life settings resulted in a substantial number of false-positives, many children diagnosed with asthma by the MAAS criteria would not have been identified if the proposed NICE algorithm was followed.8Murray C Foden P Lowe L Durrington H Custovic A Simpson A Diagnosis of asthma in symptomatic children based on measures of lung function: an analysis of data from a population-based birth cohort study.Lancet Child Adolesc Health. 2017; (published online July 12, 2017.)http://dx.doi.org/10.1016/S2352-4642(17)30008-1Summary Full Text Full Text PDF PubMed Scopus (50) Google Scholar In view of the scarcity of available population-based data on lung function in acutely symptomatic children who are not on controller medication, Murray and colleagues used the data they had already at hand. As they acknowledge in their discussion,8Murray C Foden P Lowe L Durrington H Custovic A Simpson A Diagnosis of asthma in symptomatic children based on measures of lung function: an analysis of data from a population-based birth cohort study.Lancet Child Adolesc Health. 2017; (published online July 12, 2017.)http://dx.doi.org/10.1016/S2352-4642(17)30008-1Summary Full Text Full Text PDF PubMed Scopus (50) Google Scholar this subgroup of the MAAS birth cohort (ie, adolescents not on regular controller treatment) is unlikely to be a valuable proxy for children with asthma symptoms in real-life settings. In mathematical terms, this issue translates to the problem of whether the patients with asthma used for the analyses by Murray and colleagues have a similar distribution of pretest probability for asthma diagnoses, in combination with the precision of further objective tests as proposed by the NICE algorithm, to that of children with newly presenting asthma symptoms. Nevertheless, the study by Murray and colleagues8Murray C Foden P Lowe L Durrington H Custovic A Simpson A Diagnosis of asthma in symptomatic children based on measures of lung function: an analysis of data from a population-based birth cohort study.Lancet Child Adolesc Health. 2017; (published online July 12, 2017.)http://dx.doi.org/10.1016/S2352-4642(17)30008-1Summary Full Text Full Text PDF PubMed Scopus (50) Google Scholar is essential and, despite its limitations, the clinical message of the Article is an important one: algorithms to diagnose disease based on data extrapolated from adults should not be used in children and especially not without a proper reflection of their limitations. As such, until data have been collected in a setting that resembles the real-life situation in everyday practice, these data are the best we can get for now. Ideally, data would be gathered in children with new-onset symptoms and therefore at an early stage of disease, who did all the diagnostic tests while being acutely symptomatic, and were not yet on regular treatment with inhaled corticosteroids. However, although we may wish for these ideal data and perfect guidelines for asthma diagnosis in children, better evidence is unlikely to become available, at least not in the near future. We declare no competing interests. Diagnosis of asthma in symptomatic children based on measures of lung function: an analysis of data from a population-based birth cohort studyOur findings challenge the proposed cutoff values for spirometry, the order in which the lung function tests are done, and the position of bronchodilator reversibility within the algorithm sequence. Until better evidence is available, the proposed NICE algorithm on asthma diagnosis should not be implemented in children. Full-Text PDF Open Access