TY - JOUR
T1 - Association of Guideline-Recommended COPD Inhaler Regimens With Mortality, Respiratory Exacerbations, and Quality of Life
T2 - A Secondary Analysis of the Long-Term Oxygen Treatment Trial
AU - Keller, Thomas
AU - Spece, Laura J.
AU - Donovan, Lucas M.
AU - Udris, Edmunds
AU - Coggeshall, Scott S.
AU - Griffith, Matthew
AU - Bryant, Alexander D.
AU - Casaburi, Richard
AU - Cooper, J. Allen
AU - Criner, Gerard J.
AU - Diaz, Philip T.
AU - Fuhlbrigge, Anne L.
AU - Gay, Steven E.
AU - Kanner, Richard E.
AU - Martinez, Fernando J.
AU - Panos, Ralph J.
AU - Shade, David
AU - Sternberg, Alice
AU - Stibolt, Thomas
AU - Stoller, James K.
AU - Tonascia, James
AU - Wise, Robert
AU - Yusen, Roger D.
AU - Au, David H.
AU - Feemster, Laura C.
N1 - Funding Information:
FUNDING/SUPPORT: The Long-term Oxygen Treatment Trial was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH) and Department of Health and Human Services [Contracts HHSN268200736183C , HHSN268200736184C , HHSN268200736185C , HHSN268200736186C , HHSN268200736187C , HHSN268200736188C , HHSN268200736189C , HHSN268200736190C , HHSN268200736191C , HHSN268200736192C , HHSN268200736193C , HHSN268200736194C , HHSN268200736195C , HHSN268200736196C , HHSN268200736197C , Y1-HR-7019-01 , Y1-HR-8076-01 ], in cooperation with the Centers for Medicare and Medicaid Services , Department of Health and Human Services . Additional funding support was provided by Dr Laura Feemster’s NIH NHLBI K23 award [Grant HL 111116] and an NIH institutional training grant [Grant T32 HL 007287].
Publisher Copyright:
© 2020 American College of Chest Physicians
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
KW - COPD
KW - guidelines
KW - inhaled corticosteroids
KW - pharmacotherapy
UR - http://www.scopus.com/inward/record.url?scp=85088393326&partnerID=8YFLogxK
U2 - 10.1016/j.chest.2020.02.073
DO - 10.1016/j.chest.2020.02.073
M3 - Article
C2 - 32278779
AN - SCOPUS:85088393326
SN - 0012-3692
VL - 158
SP - 529
EP - 538
JO - CHEST
JF - CHEST
IS - 2
ER -