Significance of FEV/FEV in Recognition of Early Airway Disease in Smokers at Risk of Development of COPD: Analysis of the SPIROMICS Cohort.

BACKGROUND: Small airways are known to be affected early in the course of COPD; however, traditional spirometric indices may not accurately identify small airways disease.RESEARCH QUESTION: Can forced expiratory volume in 3 s/forced expiratory volume in 6 s (FEV/FEV) identify early airflow abnormalities and predict future clinically important respiratory-related outcomes, including development of COPD?STUDY DESIGN AND METHODS: The study included 832 current and former smokers with post-bronchodilator FEV/FVC ≥ 0.7 from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort. Participants were classified as having a reduced pre-bronchodilator FEV/FEV based on lower limit of normal (LLN) values. Repeatability analysis was performed for FEV and FEV. Regression modeling was used to evaluate the relationship between baseline FEV/FEV and outcome measures, including functional small airways disease, on thoracic imaging and respiratory exacerbations. Interval-censored analysis was used to assess progression to COPD.RESULTS: FEV/FEV less than the LLN at baseline, defined as reduced compared with FEV/FEV at or above the LLN, was associated with lower FEV, poorer health status (St. George's Respiratory Questionnaire score), more emphysema, and more functional small airways disease on quantitative imaging. FEV and FEV showed excellent agreement between repeat measurements. A reduced FEV/FEV 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 FEV/FEV was also associated with development of COPD according to spirometry results (post-bronchodilator FEV/FVC < 0.7) during study follow-up.INTERPRETATION: FEV/FEV 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 FEV/FEV can identify those at risk for future development of COPD and respiratory exacerbations.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT01969344; URL: www.CLINICALTRIALS: gov: ClinicalTrials.gov.