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Published ahead of print on May 19, 2004, doi:10.1164/rccm.200308-1100OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 5, September 2004, 541-546

A more recent version of this article appeared on September 1, 2004
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Submitted on August 7, 2003
Accepted on May 15, 2004

Upper Airway Muscle Inflammation and Denervation Changes in Obstructive Sleep Apnea

John H Boyd1, Basil J Petrof2, Qutayba Hamid3, Richard Fraser4, and R John Kimoff2*

1 Respiratory Division and Sleep Laboratory, McGill University Health Center, Montreal, Quebec, Canada, 2 Respiratory Division and Sleep Laboratory, McGill University Health Center, Montreal, Quebec, Canada; Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada, 3 Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada, 4 Department of Pathology, McGill University, Montreal, Quebec, Canada

* To whom correspondence should be addressed. E-mail: john.kimoff{at}muhc.mcgill.ca.

Inflammatory cell infiltration and afferent neuropathy have been shown in the upper airway mucosa of subjects with obstructive sleep apnea (OSA). We hypothesized that inflammatory and denervation changes also involve the muscular layer of the pharynx in OSA. Morphometric analysis was performed on upper airway tissue from non-snoring controls (n=7) and OSA patients (n=11) following palatal surgery. As compared to controls, inflammatory cells were increased in the muscular layer of OSA patients, with CD4+ and activated CD25+ T cells (both increased approximately 3-fold) predominating. Inflammation was also present in upper airway mucosa, but with a different pattern consisting of CD8+ (2.8-fold increase) and activated CD25+ (3.2-fold increase) T cell predominance. As ascertained by immunoreactivity for the pan-neuronal marker PGP9.5, there was a dramatic (5.7-fold) increase in intramuscular nerve fibers in OSA subjects vs. to controls, as well as direct evidence of denervation based on positive immunostaining of the muscle fiber sarcolemmal membrane for neural cell adhesion molecule in OSA patients. These data suggest that inflammatory cell infiltration and denervation changes affect not only the mucosa, but also the upper airway muscle of OSA patients. This may have important implications for the ability to generate adequate muscular dilating forces during sleep.
Key words: N-CAM, Immunohistochemistry, Muscular diseases




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