Pulmonary sleep function was improved in patients with chronic obstructive pulmonary disease (COPD) when given a triple regimen of budesonide, formoterol, and tiotropium compared with placebo and tiotropium.
Although triple therapy has been shown to improve airway function, reduce COPD worsening, and improve quality of life, a study published in Chronic obstructive pulmonary disease: a journal of the COPD Foundation, was the first to examine the effects of triple therapy on sleep quality in patients with COPD.
According to researchers, patients with COPD often complain of insomnia, difficulty falling asleep, waking up at night, daytime sleepiness and impaired concentration during the day. Poor sleep quality characterized by increased sleep latency, decreased total sleep time, increased arousal index and decreased sleep phase 3 and rapid eye movements sleep associated with poorer quality of life.
In addition, research shows that disturbed sleep is a predictor of worsening COPD and overall survival. The study’s findings suggest that certain drugs may affect sleep in patients with COPD; however, the results show that medications can improve, worsen, or have no effect on sleep.
The current randomized, placebo-controlled study included triple therapy with inhaled corticosteroids (budesonide), a long-acting β-agonist (formoterol), and a long-acting anticholinergic (tiotropium). Twenty-five patients with stage 2 and 3 COPD under the Golden Initiative for Chronic Obstructive Pulmonary Disease and who had bronchodilator regimens were recruited from the Pulmonary Clinic at Temple University Hospital in Philadelphia, Pennsylvania.
Twenty-three patients underwent and completed spirometry, polysomnography, Epworth drowsiness scale (ESS), Pittsburgh sleep quality index, St. John’s respiratory questionnaire. George’s specific for COPD and short form 36 – Survey of medical examination, at the beginning and after 28 days of treatment. Patients had an average age of 55 years, and 48% were male.
After baseline collection, patients were randomized to receive budesonide-formoterol 160 / 4.5 mcg twice daily and tiotropium 18 mcg once daily (n = 10) or placebo twice daily and tiotropium 18 mcg once daily (n = 13). The experimental group was slightly older and had a higher proportion of men compared to the control group.
At the end of the study period, the experimental group had a 1% increase in forced exhalation by 1% (FEV1), from 0.75 to 1.00 L (Str = .031). The placebo group had no significant changes, from 1.20 to 1.15 L (Str = .91).
Similar to FEV1 an improvement in spirometry results was observed for the experimental group but not for the placebo group:
- Experimental group: predicted from 29% to 38% (Str = .039)
- Placebo group: predicted from 46% to 48% (Str = .81)
This finding suggests that budesonide / formoterol / tiotropium therapy has no adverse effect on measurements of sleep quality, nocturnal oxygenation, or diurnal function.
No significant changes in sleep efficiency, total sleep time, or quality of life were observed in either group after 28 days.
Although their time period was similar to other studies evaluating the effects of inhaled bronchodilators in patients with COPD, the researchers noted that a longer period of time would be required to demonstrate improvements in quality of life or quality of sleep.
After 28 days, the control group had a significant increase in ESS results, while the experimental group did not; however, the researchers noted that the underlying difference in ESS scores between the 2 groups may diminish the clinical significance of the increase observed in the placebo group.
The researchers noted that a small group of patients and a short period of study were limited, and that gender differences between the groups may have affected some outcomes.
Krachman SL, Vega ME, Yu D, et al. Effect of triple budesonide-formoterol-tiotropium versus placebo-tiotropium therapy 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