• Nathan Yee, Daniela Markovic, Russell G Buhr, Spyridon Fortis, Mehrdad Arjomandi, David Couper, Wayne H Anderson, Robert Paine, Prescott G Woodruff, Meilan K Han, Fernando J Martinez, R Graham Barr, James M Wells, Victor E Ortega, Eric A Hoffman, Victor Kim, M Bradley Drummond, Russell P Bowler, Jeffrey L Curtis, Christopher B Cooper, Donald P Tashkin, and Igor Z Barjaktarevic.
• Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA; Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA.
• Chest. 2022 Apr 1; 161 (4): 949959949-959.

BackgroundSmall airways are known to be affected early in the course of COPD; however, traditional spirometric indices may not accurately identify small airways disease.Research QuestionCan forced expiratory volume in 3 s/forced expiratory volume in 6 s (FEV3/FEV6) identify early airflow abnormalities and predict future clinically important respiratory-related outcomes, including development of COPD?Study Design And MethodsThe study included 832 current and former smokers with post-bronchodilator FEV1/FVC ≥ 0.7 from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort. Participants were classified as having a reduced pre-bronchodilator FEV3/FEV6 based on lower limit of normal (LLN) values. Repeatability analysis was performed for FEV3 and FEV6. Regression modeling was used to evaluate the relationship between baseline FEV3/FEV6 and outcome measures, including functional small airways disease, on thoracic imaging and respiratory exacerbations. Interval-censored analysis was used to assess progression to COPD.ResultsFEV3/FEV6 less than the LLN at baseline, defined as reduced compared with FEV3/FEV6 at or above the LLN, was associated with lower FEV1, poorer health status (St. George's Respiratory Questionnaire score), more emphysema, and more functional small airways disease on quantitative imaging. FEV3 and FEV6 showed excellent agreement between repeat measurements. A reduced FEV3/FEV6 was associated with increased odds of a severe respiratory exacerbation within the first year of follow-up and decreased time to first exacerbation. A low FEV3/FEV6 was also associated with development of COPD according to spirometry results (post-bronchodilator FEV1/FVC < 0.7) during study follow-up.InterpretationFEV3/FEV6 is a routinely available and repeatable spirometric index that can be useful in the evaluation of early airflow obstruction in current and former smokers without COPD. A reduced FEV3/FEV6 can identify those at risk for future development of COPD and respiratory exacerbations.Clinical Trial RegistrationClinicalTrials.gov; No.: NCT01969344; URL: www.Clinicaltrialsgov: ClinicalTrials.gov.Copyright © 2021 American College of Chest Physicians. All rights reserved.

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