Thomas Keller1, Laura J Spece2, Lucas M Donovan2, Edmunds Udris3, Scott S Coggeshall3, Matthew Griffith2, Alexander D Bryant4, Richard Casaburi5, J Allen Cooper6, Gerard J Criner7, Philip T Diaz8, Anne L Fuhlbrigge9, Steven E Gay10, Richard E Kanner11, Fernando J Martinez12, Ralph J Panos13, David Shade14, Alice Sternberg14, Thomas Stibolt15, James K Stoller16, James Tonascia14, Robert Wise17, Roger D Yusen18, David H Au2, Laura C Feemster2. 1. Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA. Electronic address: tlk33@uw.edu. 2. Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA; Health Services Research & Development Center of Innovation for Veteran-centered and Value-driven Care, VA Puget Sound Healthcare System, Seattle, WA. 3. Health Services Research & Development Center of Innovation for Veteran-centered and Value-driven Care, VA Puget Sound Healthcare System, Seattle, WA. 4. Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, WA. 5. Los Angeles Biomedical Research Institute at Harbor - UCLA Medical Center, Torrance, CA. 6. Birmingham VA Medical Center and the Lung Health Center, University of Alabama Birmingham, Birmingham, AL. 7. Temple University School of Medicine, Philadelphia, PA. 8. 201 Heart Lung Institute, Ohio State University School of Medicine, Columbus, OH. 9. University of Colorado School of Medicine, Aurora, CO. 10. University of Michigan School of Medicine, Ann Arbor, MI. 11. University of Utah Health Sciences Center, Salt Lake City, UT. 12. Weill Cornell Medical College, New York, NY. 13. Cincinnati VA Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH. 14. Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD. 15. Kaiser Permanente Center for Health Research, Portland, OR. 16. Cleveland Clinic Foundation, Cleveland, OH. 17. Johns Hopkins University School of Medicine, Baltimore, MD. 18. Washington University School of Medicine, Saint Louis, MO.
Abstract
BACKGROUND: Although inhaled therapy reduces exacerbations among patients with COPD, the effectiveness of providing inhaled treatment per risk stratification models remains unclear. RESEARCH QUESTION: Are inhaled regimens that align with the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy associated with clinically important outcomes? STUDY DESIGN AND METHODS: We conducted secondary analyses of Long-term Oxygen Treatment Trial (LOTT) data. The trial enrolled patients with COPD with moderate resting or exertional hypoxemia between 2009 and 2015. Our exposure was the patient-reported inhaled regimen at enrollment, categorized as either aligning with, undertreating, or potentially overtreating per the 2017 GOLD strategy. Our primary composite outcome was time to death or first hospitalization for COPD. Additional outcomes included individual components of the composite outcome and time to first exacerbation. We generated multivariable Cox proportional hazard models across strata of GOLD-predicted exacerbation risk (high vs low) to estimate between-group hazard ratios for time to event outcomes. We adjusted models a priori for potential confounders, clustered by site. RESULTS: The trial enrolled 738 patients (73.4% men; mean age, 68.8 years). Of the patients, 571 (77.4%) were low risk for future exacerbations. Of the patients, 233 (31.6%) reported regimens aligning with GOLD recommendations; most regimens (54.1%) potentially overtreated. During a 2.3-year median follow-up, 332 patients (44.9%) experienced the composite outcome. We found no difference in time to composite outcome or death among patients reporting regimens aligning with recommendations compared with undertreated patients. Among patients at low risk, potential overtreatment was associated with higher exacerbation risk (hazard ratio, 1.42; 95% CI, 1.09-1.87), whereas inhaled corticosteroid treatment was associated with 64% higher risk of pneumonia (incidence rate ratio, 1.64; 95% CI, 1.01-2.66). INTERPRETATION: Among patients with COPD with moderate hypoxemia, we found no difference in clinical outcomes between inhaled regimens aligning with the 2017 GOLD strategy compared with those that were undertreated. These findings suggest the need to reevaluate the effectiveness of risk stratification model-based inhaled treatment strategies.
RCT Entities:
BACKGROUND: Although inhaled therapy reduces exacerbations among patients with COPD, the effectiveness of providing inhaled treatment per risk stratification models remains unclear. RESEARCH QUESTION: Are inhaled regimens that align with the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy associated with clinically important outcomes? STUDY DESIGN AND METHODS: We conducted secondary analyses of Long-term Oxygen Treatment Trial (LOTT) data. The trial enrolled patients with COPD with moderate resting or exertional hypoxemia between 2009 and 2015. Our exposure was the patient-reported inhaled regimen at enrollment, categorized as either aligning with, undertreating, or potentially overtreating per the 2017 GOLD strategy. Our primary composite outcome was time to death or first hospitalization for COPD. Additional outcomes included individual components of the composite outcome and time to first exacerbation. We generated multivariable Cox proportional hazard models across strata of GOLD-predicted exacerbation risk (high vs low) to estimate between-group hazard ratios for time to event outcomes. We adjusted models a priori for potential confounders, clustered by site. RESULTS: The trial enrolled 738 patients (73.4% men; mean age, 68.8 years). Of the patients, 571 (77.4%) were low risk for future exacerbations. Of the patients, 233 (31.6%) reported regimens aligning with GOLD recommendations; most regimens (54.1%) potentially overtreated. During a 2.3-year median follow-up, 332 patients (44.9%) experienced the composite outcome. We found no difference in time to composite outcome or death among patients reporting regimens aligning with recommendations compared with undertreated patients. Among patients at low risk, potential overtreatment was associated with higher exacerbation risk (hazard ratio, 1.42; 95% CI, 1.09-1.87), whereas inhaled corticosteroid treatment was associated with 64% higher risk of pneumonia (incidence rate ratio, 1.64; 95% CI, 1.01-2.66). INTERPRETATION: Among patients with COPD with moderate hypoxemia, we found no difference in clinical outcomes between inhaled regimens aligning with the 2017 GOLD strategy compared with those that were undertreated. These findings suggest the need to reevaluate the effectiveness of risk stratification model-based inhaled treatment strategies.
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