The pathogenesis of obstructive sleep apnea (OSA), a disorder characterized by increased upper airway collapsibility, is largely unknown. Currently, two major hypotheses exist to account for the increase in upper airway collapsibility in OSA: the structural hypothesis and the neuromuscular hypothesis. Under the structural hypothesis, the pathogenesis of OSA is due to a defect in the structural properties of the pharynx. In contrast, under the neuromuscular hypothesis, OSA is caused by a defect in upper airway reflexes. While both likely contribute to the pathogenesis of the disease, we believe that obesity confers primarily a neuromuscular defect. We hypothesize that obesity is associated with progressive defects in reflex control mechanisms that lead to the development of upper airway obstruction. The Starling resistor is an ideal model to study the pathogenesis of OSA given its ability to characterize a range of upper airway obstruction, from health to disease. This model will allow us to characterize how reflex response to upper airway obstruction differ in individuals with and without OSA, and how increasing obesity affects the reflex response.
In Specific Aim #1, we will demonstrate that reflex responses to upper airway obstruction are reduced in OSA patients versus normal subjects matched on age, gender, and weight. In, Specific Aim #2, we will test the hypothesis that the reflex response to upper airway obstruction is reduced in obese individuals relative to age- and gender-matched individuals of normal weight. This proposal combines state-of-the-art polysomnographic, physiologic, and epidemiologic methods to build a mechanistic understanding of the role of adiposity in the pathogenesis of OSA.
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| Schneider, H; Patil, S P; Canisius, S et al. (2003) Hypercapnic duty cycle is an intermediate physiological phenotype linked to mouse chromosome 5. J Appl Physiol 95:11-9 |
| Patil, Susheel P; Krishnan, Jerry A; Lechtzin, Noah et al. (2003) In-hospital mortality following acute exacerbations of chronic obstructive pulmonary disease. Arch Intern Med 163:1180-6 |
