Molecular and physiologic basis of obstructive sleep apnea.

Obstructive sleep apnea-hypopnea syndrome occurs because of various combinations of anatomic, mechanical, and neurologic anomalies that jeopardize ventilation only when normal state-dependent reductions in drive to upper airway respiratory muscles and pump muscles occur. A well thought out and carefully described infrastructure of the normal and abnormal physiology in persons with OSAHS has been developed over the past few decades, which enables the development of innovative and largely effective therapies. The most recent data complement the infrastructure with the neurochemical changes underlying the state-dependent respiratory disorder and observations that the disease process itself can impair muscles, neural inputs, and soft tissue in a manner that has the potential to worsen disease. Oxidative and nitrosative stress from the repeated oxyhemoglobin desaturations and re-oxygenations is implicated in the injury to these tissues. An improved understanding of the mechanisms through which OSAHS progresses may lead to alternative therapies and aid in the identification of persons at risk for disease progression.