Inhaled triple therapy with budesonide-formoterol-tiotropium was superior to tiotropium plus placebo for improving pulmonary function while preserving the quality of sleep in patients with chronic obstructive pulmonary disease (COPD), according to study results published in Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation.

The study included 23 patients (mean age, 55 years) with GOLD stage 2 and 3 COPD who were randomly assigned to either budesonide-formoterol-tiotropium (n=10) or placebo-tiotropium (n=13). Investigators performed spirometry and polysomnography and also administered the Epworth sleepiness scale (ESS), Pittsburgh sleep quality index (PSQI), COPD-specific St. George’s Respiratory Questionnaire (SGRQ-C), and short form 36 (SF-36) at baseline and after 28 days of treatment.

Participants taking the inhaled triple therapy had a significant 29% increase in their bedtime forced expiratory volume in 1 second (FEV1) from baseline to after 28 days (0.75-1.00 L, respectively; P =.031). There was no significant change in the placebo group in terms of the bedtime FEV1 (1.20-1.15 L; P =.91). There was also no change for sleep efficiency in the budesonide-formoterol-tiotropium group (78%- 88%; P =.70) or the placebo-tiotropium group (82%-84%; P =.96).

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The investigators observed a significant increase in the arousal index from baseline to 28 days in the placebo-tiotropium group (11-17 arousals/h, respectively; P =.027). No such change was observed in the budesonide-formoterol-tiotropium arm (9-14 arousals/h; P =.43).

No significant changes were observed for the ESS in either the triple therapy group (6-6; P =.44) or the placebo-tiotropium group (8-10; P =.07). There was, however, a significant difference between the 2 groups in the ESS at 28 days following treatment (6 vs 10; P =.043). Neither group had significant changes in sleep architecture, nocturnal oxygenation, SGRQ-C, PSQI, or SF-36.

Limitations of this study were the small sample size as well as the relatively short duration of the study.

Given the limited duration of the study, the investigators stated that “whether more prolonged use would lead to similar or more substantial effects on sleep quality awaits further investigation.”

Disclosure: This clinical trial was supported by AstraZeneca. Please see the original reference for a full list of authors’ disclosures.


Krachman SL, Vega ME, Yu D, et al. Effect of triple therapy with budesonide-formoterol-tiotropium versus placebo-tiotropium on sleep quality in patients with chronic obstructive pulmonary disease. Chronic Obstr Pulm Dis. Published online February 5, 2021. doi:10.15326/jcopdf.2020.0178