Forced Expiratory Flow at 25%-75% Links COPD Physiology to Emphysema and Disease Severity in the SPIROMICS Cohort

Forced expiratory volume in 1 second (FEV₁) is central to the diagnosis of chronic obstructive pulmonary disease (COPD) but is imprecise in classifying disease burden. We examined the potential of the maximal mid-expiratory flow rate (forced expiratory flow rate between 25% and 75% [FEF_25%-75%]) as an additional tool for characterizing pathophysiology in COPD.

To determine whether FEF_25%-75% helps predict clinical and radiographic abnormalities in COPD.

The SubPopulations and InteRediate Outcome Measures In COPD Study (SPIROMICS) enrolled a prospective cohort of 2978 nonsmokers and ever-smokers, with and without COPD, to identify phenotypes and intermediate markers of disease progression. We used baseline data from 2771 ever-smokers from the SPIROMICS cohort to identify associations between percent predicted FEF_25%-75% (%predFEF_25%-75%) and both clinical markers and computed tomography (CT) findings of smoking-related lung disease.

Lower %predFEF_25-75% was associated with more severe disease, manifested radiographically by increased functional small airways disease, emphysema (most notably with homogeneous distribution), CT-measured residual volume, total lung capacity (TLC), and airway wall thickness, and clinically by increased symptoms, decreased 6-minute walk distance, and increased bronchodilator responsiveness (BDR). A lower %predFEF_25-75% remained significantly associated with increased emphysema, functional small airways disease, TLC, and BDR after adjustment for FEV₁ or forced vital capacity (FVC).

The %predFEF_25-75% provides additional information about disease manifestation beyond FEV₁. These associations may reflect loss of elastic recoil and air trapping from emphysema and intrinsic small airways disease. Thus, %predFEF_25-75% helps link the anatomic pathology and deranged physiology of COPD.