BackgroundObstructive sleep apnea (OSA) is associated with obesity, insulin resistance (IR) and diabetes. Continuous positive airway pressure (CPAP) rapidly mitigates OSA in obese subjects but its metabolic effects are not well-characterized. We postulated that CPAP will decrease IR, ghrelin and resistin and increase adiponectin levels in this setting.MethodsIn a pre- and post-treatment, within-subject design, insulin and appetite-regulating hormones were assayed in 20 obese subjects with OSA before and after 6 months of CPAP use. Primary outcome measures included glucose, insulin, and IR levels. Other measures included ghrelin, leptin, adiponectin and resistin levels. Body weight change were recorded and used to examine the relationship between glucose regulation and appetite-regulating hormones.ResultsCPAP effectively improved hypoxia. However, subjects had increased insulin and IR. Fasting ghrelin decreased significantly while leptin, adiponectin and resistin remained unchanged. Forty percent of patients gained weight significantly. Changes in body weight directly correlated with changes in insulin and IR. Ghrelin changes inversely correlated with changes in IR but did not change as a function of weight.ConclusionsWeight change rather than elimination of hypoxia modulated alterations in IR in obese patients with OSA during the first six months of CPAP therapy.

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Rationale: Improvement in FEV 1 is a main endpoint in clinical trials assessing the efficacy of bronchodilators. However, the effect of bronchodilators on maximal expiratory flow may be confounded by thoracic gas compression (TGC). Objective: To determine whether TGC confounds effect of albuterol on FEV 1 . Methods: We evaluated the response to albuterol inhalation in 10 healthy subjects, 9 subjects with asthma, and 15 subjects with chronic obstructive pulmonary disease (COPD) with mean (SD) age in years of 38 (SD, 11), 45 (SD, 11), and 64 (SD, 8), respectively. Lung mechanics were measured at baseline and 20 minutes after inhalation of 180 g of albuterol. We then applied a novel method to calculate FEV 1 corrected for the effect of TGC (NFEV 1 ). Results: Prior to albuterol administration, NFEV 1 was significantly higher than FEV 1 . However, post-albuterol inhalation, FEV 1 increased more than NFEV 1 because of reduced TGC. In multiple regression analysis, the changes in TGC, inspiratory lung resistance, and ratio of residual volume to total lung capacity postalbuterol predicted more than 75% of FEV 1 improvement in patients with COPD. Conclusion: Improvements in FEV 1 after albuterol in patients with COPD are due to reduction of lung resistance, hyperinflation, and TGC. The latter is negligible during tidal breathing. Thus, although reduction of lung resistance and hyperinflation may result in improved dyspnea with a bronchodilator, the contribution of TGC reduction to improvement of FEV 1 may not exert any meaningful clinical effect during tidal breathing. This fact has to be taken into consideration when assessing the efficacy of new bronchodilators. Keywords: FEV 1 ; chronic obstructive pulmonary disease; asthma; lung mechanics; albuterol Expiratory airflow limitation is the hallmark of physiologic abnormality in asthma and chronic obstructive pulmonary disease (COPD) (1-3). Bronchodilators improve expiratory airflow, thus improving exercise capacity and relieving symptoms in patients suffering from these diseases. Clinical trials assessing the effect of bronchodilators use the improvement in FEV 1 as the main efficacy endpoint. However, FEV 1 improvement does not correlate very well with improvement in symptoms and exercise capacity (4).

Chronic obstructive pulmonary disease (COPD) is a prevalent progressive condition that adversely affects quality of life and sleep. Patients with COPD suffer from variety of sleep disorders including insomnia, sleep disordered breathing and restless leg syndrome. The sleep disorders in COPD patients may stem from poor control of primary disease or due to side effects of pharmacotherapy. Thus, optimization of COPD therapy is the main step in treating insomnia in these patients. Further, pharmacotherapy of sleep disorders may result in respiratory depression and related complications. Therefore, clear understanding of respiratory physiology during transition from wakefulness to sleep and during various stages of sleep plays an important role in therapies that are recommended in patients with significant airway obstruction. In this publication, we review respiratory physiology as it relates to sleep and discuss sleep disorders and their management in patients with COPD.

Obstructive sleep apnea (OSA) is associated with serious comorbid illnesses and diminished quality of life. At this time, continuous positive airway pressure (CPAP) therapy is the treatment of choice. However, only half of those individuals who accept CPAP are still using it at the end of one year. Furthermore, efficacy for improving self-reported sleepiness appears to be greater for patients with severe sleep apnea and severe sleepiness than other patient groups. Some patients, notwithstanding optimized therapy and therapeutic adherence continue experiencing excessive daytime somnolence. Consequently, other treatment modalities have developed, including oral appliances, surgery and pharmacotherapy. It is widely believed, albeit not empirically demonstrated, that an effective medication to treat OSA would elicit better acceptance and adherence than having to use a machine for many hours on a nightly basis. Nonetheless, paucity of data (i.e. lack of large-scale randomized controlled trials), variability of perceived and actual benefits, and adverse side-effects of the drugs thus far tested have prevented the use of pharmacotherapy until now. In this paper we review the outcome data from published trials designed to evaluate efficacy and safety of various medications proposed for treating obstructive sleep apnea.