TY - JOUR
T1 - Bronchodilators in Tobacco-Exposed Persons with Symptoms and Preserved Lung Function
AU - RETHINC Study Group
AU - Han, Mei Lan K.
AU - Ye, Wen
AU - Wang, Di
AU - White, Emily
AU - Arjomandi, Mehrdad
AU - Barjaktarevic, Igor Z.
AU - Brown, Stacey Ann
AU - Buhr, Russell G.
AU - Comellas, Alejandro P.
AU - Cooper, Christopher B.
AU - Criner, Gerard J.
AU - Dransfield, Mark T.
AU - Drescher, Frank
AU - Folz, Rodney J.
AU - Hansel, Nadia N.
AU - Kalhan, Ravi
AU - Kaner, Robert J.
AU - Kanner, Richard E.
AU - Krishnan, Jerry A.
AU - Lazarus, Stephen C.
AU - Maddipati, Veeranna
AU - Martinez, Fernando J.
AU - Mathews, Anne
AU - Meldrum, Catherine
AU - McEvoy, Charlene
AU - Nyunoya, Toru
AU - Rogers, Linda
AU - Stringer, William W.
AU - Wendt, Christine H.
AU - Wise, Robert A.
AU - Wisniewski, Stephen R.
AU - Sciurba, Frank C.
AU - Woodruff, Prescott G.
N1 - Funding Information:
Supported by grants from the National Heart, Lung, and Blood Institute (HL128952, HL128954, HL137880, K24HL138188, K24HL137013, and K24HL140108) and the National Center for Advancing Translational Sciences (KL2TR001882) and by Sunovion Pharmaceuticals (financial support to the clinical centers for costs of conducting the trial through the COPD Foundation ). Novartis Pharmaceuticals donated the trial medication and placebo.
Publisher Copyright:
Copyright © 2022 Massachusetts Medical Society.
PY - 2022/9/29
Y1 - 2022/9/29
N2 - BACKGROUND Many persons with a history of smoking tobacco have clinically significant respiratory symptoms despite an absence of airflow obstruction as assessed by spirometry. They are often treated with medications for chronic obstructive pulmonary disease (COPD), but supporting evidence for this treatment is lacking. METHODS We randomly assigned persons who had a tobacco-smoking history of at least 10 pack-years, respiratory symptoms as defined by a COPD Assessment Test score of at least 10 (scores range from 0 to 40, with higher scores indicating worse symptoms), and preserved lung function on spirometry (ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] ≥0.70 and FVC ≥70% of the predicted value after bronchodilator use) to receive either indacaterol (27.5 μg) plus glycopyrrolate (15.6 μg) or placebo twice daily for 12 weeks. The primary outcome was at least a 4-point decrease (i.e., improvement) in the St. George's Respiratory Questionnaire (SGRQ) score (scores range from 0 to 100, with higher scores indicating worse health status) after 12 weeks without treatment failure (defined as an increase in lower respiratory symptoms treated with a long-acting inhaled bronchodilator, glucocorticoid, or antibiotic agent). RESULTS A total of 535 participants underwent randomization. In the modified intentionto-treat population (471 participants), 128 of 227 participants (56.4%) in the treatment group and 144 of 244 (59.0%) in the placebo group had at least a 4-point decrease in the SGRQ score (difference, -2.6 percentage points; 95% confidence interval [CI], -11.6 to 6.3; adjusted odds ratio, 0.91; 95% CI, 0.60 to 1.37; P = 0.65). The mean change in the percent of predicted FEV1 was 2.48 percentage points (95% CI, 1.49 to 3.47) in the treatment group and -0.09 percentage points (95% CI, -1.06 to 0.89) in the placebo group, and the mean change in the inspiratory capacity was 0.12 liters (95% CI, 0.07 to 0.18) in the treatment group and 0.02 liters (95% CI, -0.03 to 0.08) in the placebo group. Four serious adverse events occurred in the treatment group, and 11 occurred in the placebo group; none were deemed potentially related to the treatment or placebo. CONCLUSIONS Inhaled dual bronchodilator therapy did not decrease respiratory symptoms in symptomatic, tobacco-exposed persons with preserved lung function as assessed by spirometry.
AB - BACKGROUND Many persons with a history of smoking tobacco have clinically significant respiratory symptoms despite an absence of airflow obstruction as assessed by spirometry. They are often treated with medications for chronic obstructive pulmonary disease (COPD), but supporting evidence for this treatment is lacking. METHODS We randomly assigned persons who had a tobacco-smoking history of at least 10 pack-years, respiratory symptoms as defined by a COPD Assessment Test score of at least 10 (scores range from 0 to 40, with higher scores indicating worse symptoms), and preserved lung function on spirometry (ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] ≥0.70 and FVC ≥70% of the predicted value after bronchodilator use) to receive either indacaterol (27.5 μg) plus glycopyrrolate (15.6 μg) or placebo twice daily for 12 weeks. The primary outcome was at least a 4-point decrease (i.e., improvement) in the St. George's Respiratory Questionnaire (SGRQ) score (scores range from 0 to 100, with higher scores indicating worse health status) after 12 weeks without treatment failure (defined as an increase in lower respiratory symptoms treated with a long-acting inhaled bronchodilator, glucocorticoid, or antibiotic agent). RESULTS A total of 535 participants underwent randomization. In the modified intentionto-treat population (471 participants), 128 of 227 participants (56.4%) in the treatment group and 144 of 244 (59.0%) in the placebo group had at least a 4-point decrease in the SGRQ score (difference, -2.6 percentage points; 95% confidence interval [CI], -11.6 to 6.3; adjusted odds ratio, 0.91; 95% CI, 0.60 to 1.37; P = 0.65). The mean change in the percent of predicted FEV1 was 2.48 percentage points (95% CI, 1.49 to 3.47) in the treatment group and -0.09 percentage points (95% CI, -1.06 to 0.89) in the placebo group, and the mean change in the inspiratory capacity was 0.12 liters (95% CI, 0.07 to 0.18) in the treatment group and 0.02 liters (95% CI, -0.03 to 0.08) in the placebo group. Four serious adverse events occurred in the treatment group, and 11 occurred in the placebo group; none were deemed potentially related to the treatment or placebo. CONCLUSIONS Inhaled dual bronchodilator therapy did not decrease respiratory symptoms in symptomatic, tobacco-exposed persons with preserved lung function as assessed by spirometry.
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U2 - 10.1056/NEJMoa2204752
DO - 10.1056/NEJMoa2204752
M3 - Article
C2 - 36066078
AN - SCOPUS:85139375980
SN - 0028-4793
VL - 387
SP - 1173
EP - 1184
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 13
ER -