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

Bonnie E. Ronish, David J. Couper, Igor Z. Barjaktarevic, Christopher B. Cooper, Richard E. Kanner, Cheryl S. Pirozzi, Victor Kim, James M. Wells, Mei Lan K. Han, Prescott G. Woodruff, Victor E. Ortega, Stephen P. Peters, Eric A. Hoffman, Russell G. Buhr, Brett A. Dolezal, Donald P. Tashkin, Theodore G. Liou, Lori A. Bateman, Joyce D. Schroeder, Fernando J. MartinezR. Graham Barr, Nadia N. Hansel, Alejandro P. Comellas, Stephen I. Rennard, Mehrdad Arjomandi, Robert Paine

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Background: 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% [FEF25%-75%]) as an additional tool for characterizing pathophysiology in COPD. Objective: To determine whether FEF25%-75% helps predict clinical and radiographic abnormalities in COPD. Study Design and Methods: 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 FEF25%-75% (%predFEF25%-75%) and both clinical markers and computed tomography (CT) findings of smoking-related lung disease. Results: Lower %predFEF25%-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 %predFEF25%-75% remained significantly associated with increased emphysema, functional small airways disease, TLC, and BDR after adjustment for FEV1 or forced vital capacity (FVC). Interpretation: The %predFEF25%-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, %predFEF25%-75% helps link the anatomic pathology and deranged physiology of COPD.

Original languageEnglish (US)
Pages (from-to)111-121
Number of pages11
JournalChronic Obstructive Pulmonary Diseases
Issue number2
StatePublished - 2022


  • FEF25-75%
  • emphysema
  • functional small airways disease
  • mid-flow rate
  • pulmonary physiology
  • spirometry

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


Dive into the research topics of 'Forced Expiratory Flow at 25%-75% Links COPD Physiology to Emphysema and Disease Severity in the SPIROMICS Cohort'. Together they form a unique fingerprint.

Cite this