Isolated small airways obstruction predicts future chronic airflow obstruction: a multinational longitudinal study

Abstract

Background: Chronic airflow obstruction is a key characteristic of chronic obstructive pulmonary disease. We investigated whether isolated small airways obstruction is associated with chronic airflow obstruction later in life.

Methods: We used longitudinal data from 3957 participants of the multinational Burden of Obstructive Lung Disease study. We defined isolated small airways obstruction using the prebronchodilator mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FVC) (FEF_25-75) if a result was less than the lower limit of normal (<LLN) in the presence of a normal forced expiratory volume in 1 s to FVC ratio (FEV₁/FVC). We also used the forced expiratory volume in 3 s to FVC ratio (FEV₃/FVC) to define small airways obstruction. We defined chronic airflow obstruction as post-bronchodilator FEV₁/FVC<LLN. We performed mixed effects regression analyses to model the association between baseline isolated small airways obstruction and chronic airflow obstruction at follow-up. We assessed discriminative and predictive ability by calculating the area under the receiver operating curve (AUC) and Brier score. We replicated our analyses in 26 512 participants of the UK Biobank study.

Results: Median follow-up time was 8.3 years. Chronic airflow obstruction was more likely to develop in participants with isolated small airways obstruction at baseline (FEF_25-75 less than the LLN, OR: 2.95, 95% CI 1.02 to 8.54; FEV₃/FVC less than the LLN, OR: 1.94, 95% CI 1.05 to 3.62). FEF_25-75 was better than the FEV₃/FVC ratio to discriminate future chronic airflow obstruction (AUC: 0.764 vs 0.692). Results were similar among participants of the UK Biobank study.

Conclusion: Measurements of small airways obstruction can be used as early markers of future obstructive lung disease.

Keywords: COPD epidemiology; Lung Physiology.

Figure 1

Incidence rate per 1000 person years for progression from isolated small airways obstruction to chronic airflow obstruction for A) FEF_25-75 and B) FEV₃/FVC ratio.

Figure 2

Receiver operator characteristic curve and area under the curve (AUC) comparing ability of FEF_25-75 and FEV₃/FVC ratio to a model containing age, sex, BMI and smoking history alone to discriminate future chronic airflow obstruction. *P-value less than 0.05 indicates significant difference between models according to X² test.