Nathan Yee1, Daniela Markovic2, Russell G Buhr3, Spyridon Fortis4, Mehrdad Arjomandi5, David Couper6, Wayne H Anderson7, Robert Paine8, Prescott G Woodruff5, Meilan K Han9, Fernando J Martinez10, R Graham Barr11, James M Wells12, Victor E Ortega13, Eric A Hoffman14, Victor Kim15, M Bradley Drummond7, Russell P Bowler16, Jeffrey L Curtis17, Christopher B Cooper18, Donald P Tashkin18, Igor Z Barjaktarevic19. 1. 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. 2. Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine at UCLA, Los Angeles, CA. 3. Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA; VA HSR&D Center for the Study of Healthcare Innovation, Implementation, and Policy, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, CA. 4. Center for Access & Delivery Research & Evaluation, Iowa City VA Health Care System, Iowa City, IA; Department of Internal Medicine, Division of Pulmonary, Critical Care and Occupation Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA. 5. Division of Pulmonary Medicine, UCSF, San Francisco, CA. 6. Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, NC. 7. Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC. 8. Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, University of Utah, Salt Lake City, UT; Department of Veterans Affairs Medical Center, Salt Lake City, UT. 9. Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI. 10. Division of Pulmonary and Critical Care, Weill Cornell Medicine, New York, NY. 11. Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY. 12. Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL. 13. Section on Pulmonary, Critical Care, Allergy, and Immunologic Medicine, Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC. 14. Department of Radiology, Division of Physiologic Imaging, University of Iowa, Carver College of Medicine, Iowa City, IA. 15. Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA. 16. Department of Medicine, National Jewish Medical and Research Center, Denver, CO. 17. Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI; Medical Service, VA Ann Arbor Healthcare System, Ann Arbor, MI. 18. Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA. 19. Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA. Electronic address: ibarjaktarevic@mednet.ucla.edu.
Abstract
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 (FEV3/FEV6) 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 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. RESULTS: FEV3/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. INTERPRETATION: FEV3/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 REGISTRATION: ClinicalTrials.gov; No.: NCT01969344; URL: www. CLINICALTRIALS: gov: ClinicalTrials.gov.
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 (FEV3/FEV6) 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 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. RESULTS: FEV3/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. INTERPRETATION: FEV3/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 REGISTRATION: ClinicalTrials.gov; No.: NCT01969344; URL: www. CLINICALTRIALS: gov: ClinicalTrials.gov.
Authors: David Couper; Lisa M LaVange; MeiLan Han; R Graham Barr; Eugene Bleecker; Eric A Hoffman; Richard Kanner; Eric Kleerup; Fernando J Martinez; Prescott G Woodruff; Stephen Rennard Journal: Thorax Date: 2013-09-12 Impact factor: 9.139
Authors: Shawn D Aaron; Wan C Tan; Jean Bourbeau; Don D Sin; Robyn H Loves; Jenna MacNeil; George A Whitmore Journal: Am J Respir Crit Care Med Date: 2017-08-01 Impact factor: 21.405
Authors: Prescott G Woodruff; R Graham Barr; Eugene Bleecker; Stephanie A Christenson; David Couper; Jeffrey L Curtis; Natalia A Gouskova; Nadia N Hansel; Eric A Hoffman; Richard E Kanner; Eric Kleerup; Stephen C Lazarus; Fernando J Martinez; Robert Paine; Stephen Rennard; Donald P Tashkin; MeiLan K Han Journal: N Engl J Med Date: 2016-05-12 Impact factor: 91.245
Authors: Jennifer L Boes; Benjamin A Hoff; Maria Bule; Timothy D Johnson; Alnawaz Rehemtulla; Ryan Chamberlain; Eric A Hoffman; Ella A Kazerooni; Fernando J Martinez; Meilan K Han; Brian D Ross; Craig J Galbán Journal: Acad Radiol Date: 2014-11-04 Impact factor: 3.173
Authors: Carlos H Martinez; Victor Kim; Yahong Chen; Ella A Kazerooni; Susan Murray; Gerard J Criner; Jeffrey L Curtis; Elizabeth A Regan; Emily Wan; Craig P Hersh; Edwin K Silverman; James D Crapo; Fernando J Martinez; Meilan K Han Journal: Respir Med Date: 2013-11-15 Impact factor: 3.415