Search

Background Inflammatory changes such as subepithelial edema and excessive inflammatory cell infiltration have been observed in uvular tissues of obstructive sleep apnea (OSA) subjects. The levels of proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin-6 are elevated in the serum of apneic patients and have been proposed as mediators of muscle weakness. TNF-α has been shown to affect diaphragm contractility in mice and rabbit in vivo . Objectives To assess total and compartmental TNF-α expression in uvular tissues of apneic and nonapneic patients. Methods Uvular tissues were collected from 14 snorers without sleep disorders breathing, 14 subjects with OSA (OSA 1 group) whose body mass index (BMI) was similar to that of snorers, and 12 additional obese OSA subjects (OSA 2 group) who underwent an uvulopalatopharyngoplasty. Sections were examined using immunohistochemistry and Western blot analysis. TNF-α expression was evaluated in the musculus uvulae (MU), epithelial layer, and perimuscular tissues from proximal uvular sections. Results TNF-α was more highly expressed in whole uvular protein extracts of apneic groups than in snorers ([mean ± SEM] snorers, 100.5 ± 3.0%; OSA 1 group, 127.1 ± 6.9%; OSA 2 group, 140.7 ± 11.0%; p = 0.01). In the muscular area, TNF-α levels were higher in the more obese OSA subjects than in the other two groups (snorers, 100.3 ± 3%; OSA 1 group, 107.4 ± 0.7%; OSA 2 group, 124.1 ± 4.2%; p = 0.007). In the muscular area, TNF-α was correlated with BMI, but no relationship was found with the apnea-hypopnea index. Conclusions We conclude that MU is the major TNF-α source in uvular tissue and that TNF-α is more highly expressed in the heaviest OSA patients compared to less obese OSA patients and nonapneic snorers.

Rationale Airway remodeling is believed to be important in the pathophysiology of asthma, and myofibroblasts are increased in the airways of asthmatic individuals 24 h after allergen challenge. Leukotriene receptor antagonists exert antiinflammatory activity in asthma, but it is unknown whether they influence indices of airway remodeling. In the present study, we evaluated the effect of montelukast on airway myofibroblasts following low-dose allergen challenge (LDAC). Methods Stable subjects with mild asthma were included in a two-center, randomized, parallel-group study. A 2-week run-in period was followed by LDAC and endobronchial biopsy. Subjects were then randomized to receive either montelukast, 10 mg/d, or placebo (n = 10 in each group) for 8 weeks in a double-blind manner; at the end of the treatment period, subjects underwent a second LDAC and endobronchial biopsy. The effect of treatment on myofibroblasts, fibroblasts, and inflammatory cells was examined using electron microscopy techniques. Results Treatment with montelukast showed no significant difference by comparison with placebo but did show a significant within-group treatment-related decrease in airway wall myofibroblasts not seen in the placebo group. In addition, the montelukast-treated group also showed a significant within-group reduction in lymphomononuclear cells and increased neutrophils. Conclusions The results suggest that montelukast has an inhibitory effect on airway structural cells that play a key role in airway remodeling in allergic airway inflammation, and that montelukast may be a useful therapy to attenuate airway remodeling in asthma.