Effect of Triple Therapy with Budesonide-Formoterol-Tiotropium Versus Placebo-Tiotropium on Sleep Quality in Patients with Chronic Obstructive Pulmonary Disease

Background: Factors responsible for poor sleep quality in patients with chronic obstructive pulmonary disease (COPD) includes the effects of medications. This study evaluates the effect of the inhaled triple therapy of budesonide-formoterol-tiotropium versus placebo-tiotropium on sleep quality in COPD patients. Methods: Twenty-three patients (11 [48%] males; age 55 [51-60, 48-5] years; body mass index [BMI] 25 [22-30, 18-40] kg/m(2); forced expiratory volume in 1 second [FEV1]1.10 [0.80 - 1.90, 0.60-2.80]L, 42 [31-62, 24-75]% predicted) were studied. Ten patients were randomized to budesonide-formoterol-tiotropium and 13 patients to placebo-tiotropium. At baseline and after 28 days, patients completed spirometry, polysomnography, an Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), COPD-specific St George's Respiratory Questionnaire (SGRQ-C) and short form 36 (SF 36). Results: After 28 days, there was a significant 29% increase in the bedtime FEV1 in the budesonide-formoterol-tiotropium group (from 0.75 [0.55-1.30, 0.50-2.40]L to 1.00 [0.75-1.55, 0.50-3.00]L, p=0.031), with no change in the placebo-tiotropium group (from 1.20 [0.80-1.50, 0.60-1.90]L to 1.15 [0.75-1.55, 0.50-1.80] L, p=0.91). No significant change was found post treatment in sleep efficiency or total sleep time in both the budesonide-formoterol-tiotropium group (from 78 [72-92, 62-98]% to 88 [77-92, 40-98]%, p=0.70 and 290 [268-358, 252-382]min to 342 [303-358, 157-372]min, p=0.77, respectively) and the placebo-tiotropium group (from 82 [75-88, 46-93]% to 84 [77-87, 62-94]%, p=0.96 and 320 [292-350, 180-378]min to 339 [303-349, 241-366]min, p=0.79, respectively). While there was no significant change in the arousal index in the budesonide-formoterol-tiotropium group (9 [5-16, 0-48]arousals/hour to 14 [9-17, 2-36]arousals/hour, p=0.43), a significant increase was seen in the placebo-tiotropium group (11 [4-13, 3-2] arousals/hour to 17 [11-21, 2-33]arousals/hour, p=0.027). Similarly, there was no change in the ESS in the budesonide-formoterol-tiotropium group (6 [3-8, 0-11] to 6 [5-8, 0-1]), p=0.44), but a marginally significant increase in the placebo-tiotropium group (8 [5-12, 2-18] to 10 [7-13, 5-18], p=0.07), with a significant difference in the ESS 28 days post treatment between the 2 groups (6 [5-8, 0-11] versus 10 [7-13, 5-18], p=0.043). There was no significant change in nocturnal oxygenation, sleep architecture, PSQI, SGRQ-C, or SF 36 in both groups. Conclusion: In patients with COPD, inhaled triple therapy with budesonide-formoterol-tiotropium as compared to placebo-tiotropium improves pulmonary function while preserving sleep quality and architecture.