Small airway function measured using forced expiratory flow between 25% and 75% of vital capacity and its relationship to airflow limitation in symptomatic ever-smokers: a cross-sectional study

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is diagnosed and its severity graded by traditional spirometric parameters (forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) and FEV(1), respectively) but these parameters are considered insensitive for identifying early pathology. Measures of small airway function, including forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75)), may be more valuable in the earliest phases of COPD. This study aimed to determine the prevalence of low FEF(25-75) in ever-smokers with and without airflow limitation (AL) and to determine whether FEF(25-75) relates to AL severity. METHOD: A retrospective analysis of lung function data of 1458 ever-smokers suspected clinically of having COPD. Low FEF(25-75) was defined by z-score<−0.8345 and AL was defined by FEV(1)/FVC z-scores<−1.645. The severity of AL was evaluated using FEV(1) z-scores. Participants were placed into three groups: normal FEF(25-75)/ no AL (normal FEF(25-75)/AL−); low FEF(25-75)/ no AL (low FEF(25-75)/AL−) and low FEF(25-75)/ AL (low FEF(25-75)/AL+). RESULTS: Low FEF(25-75) was present in 99.9% of patients with AL, and 50% of those without AL. Patients in the low FEF(25-75)/AL− group had lower spirometric measures (including FEV(1) FEF(25-75)/FVC and FEV(3)/FVC) than those in the normal FEF(25-75)/AL− group. FEF(25-75) decreased with AL severity. A logistic regression model demonstrated that in the absence of AL, the presence of low FEF(25-75) was associated with lower FEV(1) and FEV(1)/FVC even when smoking history was accounted for. CONCLUSIONS: Low FEF(25-75) is a physiological trait in patients with conventional spirometric AL and likely reflects early evidence of impairment in the small airways when spirometry is within the ‘normal range’. FEF(25-75) likely identifies a group of patients with early evidence of pathological lung damage who warrant careful monitoring and reinforced early intervention to abrogate further lung injury.