Upper airway muscle inflammation and denervation changes in obstructive sleep apnea.
Inflammatory cell infiltration and afferent neuropathy have been shown in the upper airway (UA) 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 UA tissue from nonsnoring control subjects (n = 7) and patients with OSA (n = 11) following palatal surgery. As compared with control subjects, inflammatory cells were increased in the muscular layer of patients with OSA, with CD4+ and activated CD25+ T cells (both increased approximately threefold) predominating. Inflammation was also present in UA 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 panneuronal marker PGP9.5, there was a dramatic (5.7-fold) increase in intramuscular nerve fibers in OSA patients compared with control subjects, as well as direct evidence of denervation based on positive immunostaining of the muscle fiber sarcolemmal membrane for the neural cell adhesion molecule in patients with OSA. These data suggest that inflammatory cell infiltration and denervation changes affect not only the mucosa, but also the UA muscle of patients with OSA. This may have important implications for the ability to generate adequate muscular dilating forces during sleep.
Boyd
John H
JH
Respiratory Diivsion and Sleep Laboratory, McGill University Health Center, Montreal, PQ, Canada H3A 1A1.
Petrof
Basil J
BJ
Hamid
Qutayba
Q
Fraser
Richard
R
Kimoff
R John
RJ
D001369:Axons / Q000473:pathology; D016022:Case-Control Studies; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D010156:Palatal Muscles / Q000294:innervation / Q000378:metabolism / Q000473:pathology*; D010160:Palate, Soft / Q000294:innervation / Q000378:metabolism / Q000473:pathology*; D014066:Palatine Tonsil / Q000294:innervation / Q000378:metabolism / Q000473:pathology*; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology*; D020181:Sleep Apnea, Obstructive / Q000378:metabolism / Q000473:pathology*
D019006:Neural Cell Adhesion Molecules