Small airway abnormalities as a marker of early lung injury: challenges ahead

Abstract

In The Lancet Global Health, Ben Knox-Brown and colleagues1Ben KB Jaymini P James P et al.Prevalence of small airways obstruction and its risk factors in the multinational Burden of Obstructive Lung Disease (BOLD) study.Lancet Glob Health. 2023; 11: e69-e82Google Scholar reported the prevalence and risk factors of small airways obstruction across several world regions using data from Burden of Obstructive Lung Disease (BOLD) study. Small airways obstruction was defined as either mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FEF25–75) less than the lower limit of normal (LLN) or forced expiratory volume in 3 s to forced vital capacity ratio (FEV3/FVC ratio) less than the LLN. Consistent with the China Pulmonary Health (CPH) study,2Xiao D Chen Z Wu S et al.Prevalence and risk factors of small airway dysfunction, and association with smoking, in China: findings from a national cross-sectional study.Lancet Respir Med. 2020; 8: 1081-1093Summary Full Text Full Text PDF PubMed Scopus (40) Google Scholar small airways obstruction was categorised into pre-bronchodilator small airways obstruction and post-bronchodilator small airways obstruction. Knox-Brown and colleagues1Ben KB Jaymini P James P et al.Prevalence of small airways obstruction and its risk factors in the multinational Burden of Obstructive Lung Disease (BOLD) study.Lancet Glob Health. 2023; 11: e69-e82Google Scholar reported that, although the prevalence varies across the world, small airways obstruction is common in the general population. The overall prevalence of pre-bronchodilator small airways obstruction ranged from 5% to 34% for FEF25–75 less than the LLN and ranged from 5% to 31% for FEV3/FVC ratio less than the LLN. For post-bronchodilator small airways obstruction, the prevalence ranged from 3% to 33% for FEF25–75 less than the LLN and ranged from 2% to 22% for FEV3/FVC ratio less than the LLN. Notably, this study estimated the prevalence of small airways obstruction to be 18% for the BOLD study site of Guangzhou, whereas in the CPH study,2Xiao D Chen Z Wu S et al.Prevalence and risk factors of small airway dysfunction, and association with smoking, in China: findings from a national cross-sectional study.Lancet Respir Med. 2020; 8: 1081-1093Summary Full Text Full Text PDF PubMed Scopus (40) Google Scholar the prevalence was 42·7% in the central south region of China. This disagreement is likely to be explained by different diagnostic criteria, sample size, study procedures, and study time. Additionally, Knox-Brown and colleagues1Ben KB Jaymini P James P et al.Prevalence of small airways obstruction and its risk factors in the multinational Burden of Obstructive Lung Disease (BOLD) study.Lancet Glob Health. 2023; 11: e69-e82Google Scholar once again identified cigarette smoking as one of the most important risk factors for small airways obstruction, emphasising the importance of comprehensive tobacco control, particularly smoking cessation,3Verbanck S Schuermans D Paiva M et al.Small airway function improvement after smoking cessation in smokers without airway obstruction.Am J Respir Crit Care Med. 2006; 174: 853-857Crossref PubMed Scopus (79) Google Scholar for early lung care. A key issue in this topic is how to name this condition. Numerous names have been used for small airway abnormalities, such as small airways obstruction, dysfunction, impairment, disorder, disease, and syndrome. Small airway abnormalities include functional and structural changes across different stages, which are important considerations for these terms to be correctly used to encompass the various features and different stages of small airway abnormalities. Identifying small airway abnormalities is particularly important. In 1850, William Gairdner discussed the effect of changes to distal airways and association with emphysema, giving the basis for our understanding of the relationship between small airway and chronic respiratory diseases.4Gairdner WT On the pathological states of the lung connected with bronchitis and bronchial obstruction.Mon J Med Sci. 1850; 2: 122-138Google Scholar Increasing evidence suggests that small airway dysfunction could be a biomarker of the risk of development of chronic multimorbidity.5Papi A Morandi L Fabbri L Small airway dysfunction: not so silent after all?.Lancet Respir Med. 2020; 8: 1062-1063Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar The CPH study showed that the presence of chronic obstructive pulmonary disease or asthma was associated with about a two times higher odds ratio for small airway dysfunction,2Xiao D Chen Z Wu S et al.Prevalence and risk factors of small airway dysfunction, and association with smoking, in China: findings from a national cross-sectional study.Lancet Respir Med. 2020; 8: 1081-1093Summary Full Text Full Text PDF PubMed Scopus (40) Google Scholar and Kraft and colleagues showed that asthmatic small airway disease predicted asthma control and exacerbations.6Kraft M Richardson M Hallmark B et al.The role of small airway dysfunction in asthma control and exacerbations: a longitudinal, observational analysis using data from the ATLANTIS study.Lancet Respir Med. 2022; 10: 661-668Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar Kraft and colleagues also indicated that damage to the small airways occurred early in the disease process.6Kraft M Richardson M Hallmark B et al.The role of small airway dysfunction in asthma control and exacerbations: a longitudinal, observational analysis using data from the ATLANTIS study.Lancet Respir Med. 2022; 10: 661-668Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar Despite their importance, the small airways are difficult to study, partly due to their small size and inaccessibility for biopsy. No gold-standard criteria have been suggested.7McNulty W Usmani OS Techniques of assessing small airways dysfunction.Eur Clin Respir J. 2014; 125898Crossref PubMed Google Scholar Taking spirometric measurements is the most feasible and practical approach for epidemiological studies. Knox-Brown and colleagues1Ben KB Jaymini P James P et al.Prevalence of small airways obstruction and its risk factors in the multinational Burden of Obstructive Lung Disease (BOLD) study.Lancet Glob Health. 2023; 11: e69-e82Google Scholar defined small airways obstruction by FEF25–75 and FEV3/FVC. FEF25–75 is one of the most used measures. However, FEF25–75 is dependent on the forced vital capacity and, if FEF25–75 is not adjusted for lung volume, there is poor reproducibility. FEV3/FVC was suggested by a previous study8Morris ZQ Coz A Starosta D An isolated reduction of the FEV3/FVC ratio is an indicator of mild lung injury.Chest. 2013; 144: 1117-1123Summary Full Text Full Text PDF PubMed Scopus (27) Google Scholar as an indicator of mild lung injury. Furthermore, Knox-Brown and colleagues applied the LLN as reference, because it is more appropriate than using arbitrary percent predicted cutoffs. Further studies could consider establishing a well accepted gold standard for testing small airway abnormalities, which would also be beneficial for comparing results across different populations and regions. Additionally, establishing a grading system for the severity of small airway abnormalities is needed. The Assessment of Small Airways Involvement in Asthma (ATLANTIS) study9Postma DS Brightling C Baldi S et al.Exploring the relevance and extent of small airways dysfunction in asthma (ATLANTIS): baseline data from a prospective cohort study.Lancet Respir Med. 2019; 7: 402-416Summary Full Text Full Text PDF PubMed Scopus (141) Google Scholar proposed a small airway score that reflects the degree of physiological impairment of small airways. Future work should elucidate whether this system or other grading systems are reliable and applicable to a broad population. Other challenges include how to treat small airway abnormalities and whether treatment of small airway abnormalities could contribute to the treatment of chronic respiratory diseases. In summary, Knox-Brown and colleagues,1Ben KB Jaymini P James P et al.Prevalence of small airways obstruction and its risk factors in the multinational Burden of Obstructive Lung Disease (BOLD) study.Lancet Glob Health. 2023; 11: e69-e82Google Scholar along with previous studies,2Xiao D Chen Z Wu S et al.Prevalence and risk factors of small airway dysfunction, and association with smoking, in China: findings from a national cross-sectional study.Lancet Respir Med. 2020; 8: 1081-1093Summary Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 6Kraft M Richardson M Hallmark B et al.The role of small airway dysfunction in asthma control and exacerbations: a longitudinal, observational analysis using data from the ATLANTIS study.Lancet Respir Med. 2022; 10: 661-668Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar, 8Morris ZQ Coz A Starosta D An isolated reduction of the FEV3/FVC ratio is an indicator of mild lung injury.Chest. 2013; 144: 1117-1123Summary Full Text Full Text PDF PubMed Scopus (27) Google Scholar have shown that small airway abnormalities are prevalent in the general population. More importantly, the small airways are frequently involved early in the course of lung disease, and the early identification of small airway abnormalities is important because they could represent a modifiable precursor of future obstructive lung disease. Given that small airway abnormalities have been neglected as an important health issue globally, we call for a global joint effort on the research, prevention, detection, treatment, and management of this condition as a way of preventing early lung injury. We declare no competing interests. Small airways obstruction and its risk factors in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional studyDespite the wide geographical variation, small airways obstruction is common and more prevalent than chronic airflow obstruction worldwide. Small airways obstruction shows the same risk factors as chronic airflow obstruction. However, further research is required to investigate whether small airways obstruction is also associated with respiratory symptoms and lung function decline. Full-Text PDF Open Access

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