Significance of FEV3/FEV6 in Recognition of Early Airway Disease in Smokers at Risk of Development of COPD

Abstract

Background

Small airways are known to be affected early in the course of chronic obstructive pulmonary disease (COPD); however, traditional spirometric indices may not accurately identify small airways disease.

Research Question

Can FEV₃/FEV₆ identify early airflow abnormalities and predict future clinically important respiratory-related outcomes, including development of COPD?

Study Design and Methods

We included eight hundred thirty-two current and former smokers with post-bronchodilator FEV₁/FVC ≥0.7 from the 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.

Results

FEV₃/FEV₆ 3/FEV₆ ≥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 by spirometry (post-bronchodilator FEV₁/FVC <0.7) during study follow-up.

Interpretation

FEV₃/FEV₆ is a routinely available and repeatable spirometric index which 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.