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)/forced vital capacity (FVC) and FEV, 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), may be more valuable in the earliest phases of COPD. This study aimed to determine the prevalence of low FEF in ever-smokers with and without airflow limitation (AL) and to determine whether FEF relates to AL severity.

Method: A retrospective analysis of lung function data of 1458 ever-smokers suspected clinically of having COPD. Low FEF was defined by z-score<-0.8345 and AL was defined by FEV/FVC z-scores<-1.645. The severity of AL was evaluated using FEV z-scores. Participants were placed into three groups: normal FEF/ no AL (normal FEF/AL-); low FEF/ no AL (low FEF/AL-) and low FEF/ AL (low FEF/AL+).

Results: Low FEF was present in 99.9% of patients with AL, and 50% of those without AL. Patients in the low FEF/AL- group had lower spirometric measures (including FEV FEF/FVC and FEV/FVC) than those in the normal FEF/AL- group. FEF decreased with AL severity. A logistic regression model demonstrated that in the absence of AL, the presence of low FEF was associated with lower FEV and FEV/FVC even when smoking history was accounted for.

Conclusions: Low FEF 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 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.