Inhibition of airway hyperreactivity by oxybutynin chloride in subjects with cervical spinal cord injury

Abstract

Objective: To further investigate mechanisms of airway hyperreactivity among subjects with chronic cervical spinal cord injury (SCI), we assessed airway responsiveness to aerosolized methacholine and histamine in subjects receiving chronic oxybutynin chloride therapy, and compared the ®ndings with those not receiving the agent. Methods: Twenty-®ve male subjects with cervical SCI participated in this study; 12 were maintained on oral oxybutynin chloride and 13 served as age-matched controls. Six of the 12 subjects receiving oxybutynin were challenged with aerosolized methacholine, and six with histamine; seven of the 13 control subjects were challenged with aerosolized methacholine and the remaining six with histamine. Results: All 13 control subjects and all six oxybutynin/histamine subjects exhibited a signi®cant bronchoconstrictor response (PC2058 mg/ml), whereas mean PC20 values for the oxybutynin/methacholine group were 525 mg/ml. Conclusion: Our ®nding that the bronchoconstrictor eects of methacholine were blocked by oxybutynin chloride while those of histamine were not suggests that oxybutynin acts primarily through anticholinergic pathways rather than by causing generalized airway smooth muscle relaxation.

Characteristics of sleep apnea syndrome in tetraplegic patients

“…35 This airway hyper-reactivity in tetraplegic patients is discussed in context with autonomic nervous system inbalance, altered mechanical properties of the lungs, and an inadaquate stretch of the airway with deep breathing. 36 It is possible that airway hyperreactivity may be pronounced during the night thus in¯uencing the degree of the obstructive sleep apneas.…”

Biomarkers of inflammation in persons with chronic tetraplegia

“…Autonomic imbalance also provided a plausible explanation for airway hyperrreactivity, or the exaggerated bronchoconstriction we observed following bronchoprovocation with aerosolized methacholine, histamine, or ultrasonically nebulized distilled water [7][8][9]. This neurogenic theory, however, did not explain all our findings [57][58][59], and therefore we postulated that airway inflammation might be involved. When FeNO levels were measured in persons with tetraplegia and compared to a matching asthma cohort, significant elevations were seen in both groups compared to control subjects [22].…”

Cholinergic bronchomotor tone and airway caliber in tetraplegic patients

“…6,7 These same spirometric techniques were used to demonstrate bronchial hyperresponsiveness following inhalation of methacholine, histamine and/or distilled water. 6,7,10,[23][24][25][26][27][28][29] This bronchial hyper-reactivity maybe an additional indirect evidence of pre-existing airway narrowing. Any small further reduction in caliber would produce a large increase in resistance (resistance of laminar gas flow being inversely related to the fourth power of the radius), thus leading to the clinical impression of hyper-reactivity.…”

“…Secondarily, we hoped to clarify the effect of baclofen on the airway tone of these subjects. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33], studied during the same time period. All participants were screened for a history of pulmonary disease or respiratory symptoms, recent respiratory viral or bacterial infection, and asthma or seasonal allergy.…”