The terms small airway obstruction, small airway dysfunction, and small airway disease are used interchangeably to describe pathophysiology that occurs within airways less than 2 mm in diameter. Beginning around the eighth generation of airway branching, small airways contribute less than 10% to total airway resistance. However, in asthma and chronic obstructive pulmonary disease , the small airways are the predominant site of resistance, and both diseases are associated with acute-on-chronic inflammation, mucus hypersecretion, and small airway remodeling.
In people with asthma, these changes have been associated with poor disease control, increased exacerbations, and decreased quality of life. In people with chronic obstructive pulmonary disease, these changes have been shown to be associated with the perceived effect of the disease on health status and increased gas retention.
Summary
Background
Small airway obstruction is a common feature of obstructive lung diseases. Research on small airway obstruction, its global prevalence, and risk factors is scarce. Our objective was to estimate the prevalence of small airway obstruction, examine associated risk factors, and compare the results of two different spirometry parameters.
Methods
The Burden of Obstructive Lung Disease study is a multinational cross-sectional study of 41 municipalities in 34 countries in all WHO regions. Adults aged 40 years or older who were not living in an institution were eligible to participate. To ensure a representative sample, participants were selected from a random sample of the population according to a predefined site-specific sampling strategy.
We included data from participants in this study if they completed the core study questionnaire and had acceptable spirometry according to predefined quality criteria. Participants with a contraindication to pulmonary function testing were excluded .
Small airway obstruction was defined as a mean forced expiratory flow rate between 25% and 75% of forced vital capacity (FEF 25–75) less than the lower limit of normal or forced expiratory volume in 3 s. forced vital capacity ratio (FEV 3 /FVC ratio) lower than the lower limit of normal. We estimated the prevalence of small airway obstruction pre-bronchodilator (i.e., before administration of 200 μg salbutamol) and post-bronchodilator (i.e., after administration of 200 μg salbutamol) for each site.
To identify risk factors for small airway obstruction, we performed multivariable regression analyzes within each center and pooled estimates using random-effects meta-analysis.
Results
36,618 participants were recruited between January 2, 2003 and December 26, 2016. Data were collected from participants at the time of recruitment. Of the recruited participants, 28,604 participants had acceptable spirometry and completed the study’s core questionnaire.
Data were available for 26,443 participants for FEV 3 /FVC ratio and 25,961 participants for FEF 25–75. Of the 26,443 participants included, 12,490 were men and 13,953 were women.
The prevalence of pre-bronchodilator small airway obstruction ranged from 5% (34 of 624 participants) in Tartu, Estonia, to 34% (189 of 555 participants) in Mysore, India, for FEF 25–75 and FEV 3/ FVC ratio ranged from 5% (31 of 684) in Riyadh, Saudi Arabia, to 31% (287 of 924) in Salzburg, Austria. The prevalence of post-bronchodilator small airway obstruction was universally lower .
Risk factors significantly associated with FEV 3 /FVC ratio below the lower limit of normal included older age, low BMI, active and passive smoking, low level of education, working in a dusty job for more than 10 years, tuberculosis previous and history of chronic obstructive pulmonary disease. Results were similar for FEF 25–75, except for increasing age, which was associated with lower odds of small airway obstruction.
Interpretation
Despite wide geographic variation, small airway obstruction is common and more common than chronic airflow obstruction worldwide.
Small airway obstruction has the same risk factors as chronic airflow obstruction. However, more research is required to investigate whether small airway obstruction is also associated with respiratory symptoms and decreased lung function.
Research in context Evidence before this study We searched PubMed and Web of Science from database inception to July 26, 2022. We used a combination of medical subject headings and text words related to selected spirometry parameters and derivations of the phrase kidney obstruction. small airways. Search terms included: (“FEF 25–75 ” OR “MMEF”, OR “FEV 3 /FVC” OR “FEF 50 ” OR “FEF 75) AND (“small airway obstruction” OR “airway disease airway disease” OR “small airway dysfunction” OR “peripheral airway disease” OR “distal airway obstruction”). We reviewed the titles and abstracts of the search results to identify publications relevant to the objectives of our study. Most population-based studies used mean forced expiratory flow rate between 25% and 75% of forced vital capacity (FEF 25–75) to assess small airway obstruction and there was no agreement with respect to the diagnostic criteria, both with the expected percentage cut-off points and with the lower limit of normal that is being used. Few studies reported the prevalence of small airway obstruction as a primary outcome. Prevalence ranged from 7.5% to 45.9% and varied depending on the choice of spirometry parameter and world region. Prevalence estimates were generally higher for FEF25-75 than forced expiratory volume in 3 s as a ratio of forced vital capacity (FEV 3 /FVC ratio). Only two population-based studies, both in China, provided prevalence estimates and also presented associated risk factors for small airway obstruction. Prevalence estimates were different between these studies (7.5% vs. 43.5%). Risk factors for small airway obstruction reported by these two studies included smoking, low BMI, increasing age, female sex, use of solid fuels for cooking or heating, low level of education , family history of chronic obstructive pulmonary disease and passive smoke exposure. There are no population-based data regarding the prevalence and risk factors of small airway obstruction outside of China. Added value of this study To our knowledge, this is the first study to estimate the prevalence of small airway obstruction in various regions of the world using a standardized protocol. Additionally, we investigated the association of small airway obstruction with several potential risk factors and examined these associations across regions. Our study shows that there is considerable variation in the prevalence of small airway obstruction worldwide, with small airway obstruction generally more common than chronic airflow obstruction (forced expiratory volume in 1 s as a proportion of forced vital capacity less than the lower normal limit). Furthermore, we have shown that prevalence estimates vary depending on the choice of spirometry parameter and world region. We have also identified a strong association between FEF 25-75 and forced vital capacity, which could restrict its use in the evaluation of small airway obstruction compared to the FEV 3 /FVC ratio. We found significant associations of small airway obstruction with active and passive smoking, BMI, age, educational level, working in a dusty job for more than 10 years, family history of chronic obstructive pulmonary disease, and history of tuberculosis. Implications of all available evidence Our study has shown that small airway obstruction is common in the general population. We have corroborated previous findings and identified additional risk factors for small airway obstruction. However, we have identified that prevalence estimates and associations may vary depending on the spirometry parameter used. Although more research is needed, FEF 25-75 is likely not suitable as a binary measure to classify the presence of small airway obstruction, due to its association with forced vital capacity. FEV 3/FVC ratio is an alternative, with fewer limitations. The identification of a significant burden of small airway obstruction in several regions of the world has important implications for global health, especially considering the potential for isolated small airway obstruction to be used as a predictive marker of future obstructive pulmonary disease. . Future research should investigate whether small airway obstruction is associated with accelerated decline in lung function and increased symptom burden , especially in people with normal lung function. |
Funding: National Heart and Lung Institute and Wellcome Trust.
