Anita L Oh1, Richard A Mularski2, Igor Barjaktarevic3, R Graham Barr4, Russell P Bowler5, Alejandro P Comellas6, Christopher B Cooper3, Gerard J Criner7, MeiLan K Han8, Nadia N Hansel9, Eric A Hoffman10, Richard E Kanner11, Jerry A Krishnan12, Robert Paine11, Trisha M Parekh13, Stephen P Peters14, Stephanie A Christenson1, Prescott G Woodruff1. 1. Division of Pulmonary, Critical Care, and Sleep Medicine, University of California San Francisco, San Francisco, California. 2. The Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon. 3. Divison of Pulmonary and Critical Care, David Geffen School of Medicine, University of California, Los Angeles, California. 4. Department of Medicine and Epidemiology, Columbia University Medical Center, New York, New York. 5. Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health, Denver, Colorado. 6. Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa. 7. Division of Thoracic Medicine and Surgery, Temple University, Philadelphia, Pennsylvania. 8. Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan. 9. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland. 10. Department of Radiology, University of Iowa, Iowa City, Iowa. 11. Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine, University of Utah, Salt Lake City, Utah. 12. Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, University of Illinois at Chicago, Chicago, Illinois. 13. Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and. 14. Pulmonary, Critical Care, Allergy, and Immunologic Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Abstract
Rationale: Diagnosis of chronic obstructive pulmonary disease (COPD) relies on abnormal spirometry. However, spirometry may underestimate the effects of smoking, missing smokers with respiratory disease who have minimal or no airflow obstruction. Objectives: To develop a multidimensional definition of a lung-related "resilient smoker" that is useful in research studies and then identify a resilient smoker subgroup in the SPIROMICS (SubPopulations and InteRmediate Outcome Measures In COPD Study) cohort using this definition. Methods: We performed a three-round modified Delphi survey among a panel of COPD experts to identify and reach a consensus on clinical and radiographic domains to be included in a lung-related resilient smoker definition. Consensus on domains of resilience was defined as ⩾80% of experts voting "agree" or "strongly agree" on a 5-point Likert scale. The Delphi-derived definition of resilience was applied to SPIROMICS to identify resilient smokers, whom we then characterized using known biomarkers of COPD. Results: Consensus was achieved on 6 of 12 diagnostic items, which include cough and sputum production, dyspnea, radiographic measures of emphysema and small airways disease, exacerbations, and decline in forced expiratory volume in 1 second. Although 892 SPIROMICS participants were classified as smokers with preserved lung function by spirometry, only 149 participants (16.7%) qualified as resilient smokers by our definition. Blood biomarker expression of CRP (C-reactive protein) and sTNFRSF1A (soluble tumor necrosis receptor factor1A) was lower in resilient than nonresilient smokers (P = 0.02 and P = 0.03). Conclusions: A Delphi-derived consensus definition of resilient smoker identified 83.3% of smokers with preserved spirometry as "nonresilient" based on the presence of adverse effects of smoking on the lung. Resilient smokers were biologically distinct from nonresilient smokers based on CRP measurements. Clinical trial registered with ClinicalTrials.gov (NCT01969344).
Rationale: Diagnosis of chronic obstructive pulmonary disease (COPD) relies on abnormal spirometry. However, spirometry may underestimate the effects of smoking, missing smokers with respiratory disease who have minimal or no airflow obstruction. Objectives: To develop a multidimensional definition of a lung-related "resilient smoker" that is useful in research studies and then identify a resilient smoker subgroup in the SPIROMICS (SubPopulations and InteRmediate Outcome Measures In COPD Study) cohort using this definition. Methods: We performed a three-round modified Delphi survey among a panel of COPD experts to identify and reach a consensus on clinical and radiographic domains to be included in a lung-related resilient smoker definition. Consensus on domains of resilience was defined as ⩾80% of experts voting "agree" or "strongly agree" on a 5-point Likert scale. The Delphi-derived definition of resilience was applied to SPIROMICS to identify resilient smokers, whom we then characterized using known biomarkers of COPD. Results: Consensus was achieved on 6 of 12 diagnostic items, which include cough and sputum production, dyspnea, radiographic measures of emphysema and small airways disease, exacerbations, and decline in forced expiratory volume in 1 second. Although 892 SPIROMICS participants were classified as smokers with preserved lung function by spirometry, only 149 participants (16.7%) qualified as resilient smokers by our definition. Blood biomarker expression of CRP (C-reactive protein) and sTNFRSF1A (soluble tumor necrosis receptor factor1A) was lower in resilient than nonresilient smokers (P = 0.02 and P = 0.03). Conclusions: A Delphi-derived consensus definition of resilient smoker identified 83.3% of smokers with preserved spirometry as "nonresilient" based on the presence of adverse effects of smoking on the lung. Resilient smokers were biologically distinct from nonresilient smokers based on CRP measurements. Clinical trial registered with ClinicalTrials.gov (NCT01969344).
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