A novel technique for measuring the physiological traits causing obstructive sleep apnea

Obstructive sleep apnea (OSA) is a common disorder characterized by pharyngeal obstruction during sleep, which causes hypoxemia, arousals, and surges in sympathetic activation that persist into the daytime and cause hypertension, adverse cardiovascular events, and neurocognitive sequelae. Despite these serious health-related consequences, the diagnosis and management of OSA remains suboptimum. For example, there are no clinically available tests for measuring pharyngeal mechanics or other breathing control metrics. Moreover, the current therapies for OSA are either poorly tolerated or ineffective. Thus, new diagnostic and treatment strategies are needed. The studies described in this manuscript deal directly with these issues. The first study describes a clinically feasible technique for measuring several of the physiological traits causing OSA. Eleven subjects slept on continuous positive airway pressure (CPAP – air pressure at a constant level throughout inspiration and expiration applied through a nasal mask) at various levels, which produced disturbances to the ventilatory control system that could be used to estimate the traits using control-system modeling and parameter estimation methods. The study demonstrated the feasibility of the procedure and confirmed the multifactorial nature of OSA. The second study tested the effectiveness of a drug (acetazolamide) at manipulating one of the pathogenic traits (respiratory control-system loop gain). Diagnosing the abnormal trait(s) in an individual with the above-mentioned procedure is effective from a clinical management perspective only if there are ways to treat the abnormal traits with drugs or devices. This study showed that acetazolamide could lower loop gain by approximately 41%, and that such lowering led to a substantial (51%) improvement in OSA severity. Future studies will test the effectiveness of other drugs at altering the other traits; the ultimate goal is to choose the right combination of drugs in selected individuals to treat OSA without CPAP. The final study describes several important revisions that were made to the original technique for measuring the traits. In particular, the original method had a relatively low success rate of 76% when tested in a larger population. The new procedure is simpler and has a 100% success rate for measuring all traits in the 13 individuals studied to date.