Study Objective: Animal data suggest that Δ⁹-TetraHydroCannabinol (Δ⁹THC) stabilizes autonomic output during sleep, reduces spontaneous sleep-disordered breathing, and blocks serotonin-induced exacerbation of sleep apnea. On this basis, we examined the safety, tolerability, and efficacy of dronabinol (Δ⁹THC), an exogenous Cannabinoid type 1 and type 2 (CB1 and CB2) receptor agonist in patients with Obstructive Sleep Apnea (OSA). Design and Setting: Proof of concept; single-center dose-escalation study of dronabinol. Participants: Seventeen adults with a baseline Apnea Hypopnea Index (AHI) ≥15/h. Baseline polysomnography (PSG) was performed after a 7-day washout of Continuous Positive Airway Pressure treatment. Intervention: Dronabinol was administered after baseline PSG, starting at 2.5 mg once daily. The dose was increased weekly, as tolerated, to 5 mg and finally to 10 mg once daily. Measurements and Results: Repeat PSG assessments were performed on nights 7, 14, and 21 of dronabinol treatment. Change in AHI (ΔAHI, mean ± SD) was significant from baseline to night 21 (−14.1 ± 17.5; p = 0.007). No degradation of sleep architecture or serious adverse events was noted. Conclusion: Dronabinol treatment is safe and well-tolerated in OSA patients at doses of 2.5–10 mg daily and significantly reduces AHI in the short-term. These findings should be confirmed in a larger study in order to identify sub-populations with OSA that may benefit from cannabimimetic pharmacologic therapy.

Obstructive sleep apnea (OSA) and asthma are highly prevalent chronic respiratory disorders. Beyond their frequent coexistence arising from their high prevalence and shared risk factors, these disorders feature a reciprocal interaction whereby each disease impacts the severity of the other. Emerging evidence implicates airway and systemic inflammation, neuroimmune interactions, and effects of asthma-controlling medications (corticosteroids) as factors that predispose patients with asthma to OSA. Conversely, undiagnosed or inadequately treated OSA adversely affects asthma control, partly via effects of intermittent hypoxia on airway inflammation and tissue remodeling. In this article, we review multiple lines of recently published evidence supporting this interaction. We provide a set of recommendations for clinicians involved in the care of adults with asthma, and identify critical gaps in our knowledge about this overlap.

There remains an important and unmet need for fully effective and acceptable treatments in obstructive sleep apnea (OSA). At present, there are no approved drug treatments. Dronabinol has shown promise for OSA pharmacotherapy in a small dose-escalation pilot study. Here, we present initial findings of the Phase II PACE (Pharmacotherapy of Apnea by Cannabimimetic Enhancement) trial, a fully blinded parallel groups, placebo-controlled randomized trial of dronabinol in people with moderate or severe OSA. By random assignment, 73 adults with moderate or severe OSA received either placebo (N = 25), 2.5 mg dronabinol (N = 21), or 10 mg dronabinol (N = 27) daily, 1 hour before bedtime for up to 6 weeks. At baseline, overall apnea–hypopnea index (AHI) was 25.9 ± 11.3, Epworth Sleepiness Scale (ESS) score was 11.45 ± 3.8, maintenance of wakefulness test (MWT) mean latency was 19.2 ± 11.8 minutes, body mass index was 33.4 ± 5.4 kg/m², and age was 53.6 ± 9.0 years. The number and severity of adverse events, and treatment adherence (0.3 ± 0.6 missed doses/week) were equivalent among all treatment groups. Participants receiving 10 mg/day of dronabinol expressed the highest overall satisfaction with treatment (p = .04). In comparison to placebo, dronabinol dose-dependently reduced AHI by 10.7 ± 4.4 (p = .02) and 12.9 ± 4.3 (p = .003) events/hour at doses of 2.5 and 10 mg/day, respectively. Dronabinol at 10 mg/day reduced ESS score by −3.8 ± 0.8 points from baseline (p < .0001) and by −2.3 ± 1.2 points in comparison to placebo (p = .05). MWT sleep latencies, gross sleep architecture, and overnight oxygenation parameters were unchanged from baseline in any treatment group. These findings support the therapeutic potential of cannabinoids in people with OSA. In comparison to placebo, dronabinol was associated with lower AHI, improved self-reported sleepiness, and greater overall treatment satisfaction. Larger scale clinical trials will be necessary to clarify the best potential approach(es) to cannabinoid therapy in OSA.

Rationale: Approximately 20% of patients hospitalized for COPD exacerbations in the United States will be readmitted within 30 days. The Centers for Medicare and Medicaid Services has recently proposed to revise the Hospital Readmissions Reduction Program to financially penalize hospitals with high all-cause 30-day rehospitalization rates after a hospitalization for COPD exacerbation on or after October 1, 2014. Objectives: To report the results of a systematic review of randomized clinical trials evaluating interventions to reduce the rehospitalizations after COPD exacerbations. Methods: Multiple electronic databases were systematically searched to identify relevant studies published between January 1966 and June 2013. Titles, abstracts, and, subsequently, full-text articles were assessed for eligibility. Each study was appraised using predefined criteria. Measurements and Main Results: Among 913 titles and abstracts screened, 5 studies (1,393 participants) met eligibility criteria. All studies had a primary outcome of rehospitalization at 6 or 12 months. No study examined 30-day rehospitalization as the primary outcome. Each study tested a different set of interventions. Two studies (one conducted in Canada and one conducted in Spain and Belgium) showed a decrease in all-cause rehospitalization over 12 months in the intervention group versus comparator group (mean number of hospitalizations per patient, 1.0 vs. 1.8; P = 0.01; percent hospitalized, 45 vs. 67%; P = 0.028; respectively). The only study conducted in the United States found a greater than twofold higher risk of mortality in the intervention group (17 vs. 7%, P = 0.003) but no significant difference in rehospitalizations. It was unclear which set of interventions was effective or harmful. Conclusions: The evidence base is inadequate to recommend specific interventions to reduce rehospitalizations in this population and does not justify penalizing hospitals for high 30-day rehospitalization rates after COPD exacerbations.

Home-based diagnosis of obstructive sleep apnea (OSA) with portable monitoring (PM) is increasingly utilized, but remains understudied in underserved and minority populations. We tested the feasibility of home PM in an urban population at risk for OSA compared to in-laboratory polysomnography (PSG) and examined patient preference with respect to home PM versus PSG. Randomized crossover study of home PM (WatchPAT200) and in-laboratory simultaneous PSG and PM in 75 urban African Americans with high pre-test probability of OSA, identified with the Berlin questionnaire. Fifty-seven of 75 participants were women, average age 45 ± 11 years (mean ± SD), 35% with ≤ high school education, and 76% with annual household income < $50,000. Technical failure rates were 5.3% for home vs. 3.1% for in-laboratory PM. There was good agreement between apnea hypopnea index on PSG; AHIPSG and AHI on home PM (mean ± 2 SD of the differences = 0.64 ± 46.5 and intraclass correlation coefficient; ICC = 0.73). The areas under the curve for the receiver-operator characteristic curves for home PM were 0.90 for AHIPSG ≥ 5, 0.95 for AHIPSG ≥ 10, and 0.92 for AHIPSG ≥ 15. 62/75 (82%) participants preferred home over in-laboratory testing. Home PM for diagnosis of OSA in a high risk urban population is feasible, accurate, and preferred by patients. As home PM may improve access to care, the cost-effectiveness of this diagnostic strategy for OSA should be examined in underserved urban and rural populations. ClinicalTrials.gov, identifier: NCT01997723.