Airway hyperresponsiveness to methacholine in subjects with spinal cord injury

Previously, we found that never-smokers with quadriplegia were hyperresponsive to aerosolized methacholine. To further explore the phenomenon, we compared responsiveness to methacholine in never-smokers with that of smokers and ex-smokers. We also evaluated responsiveness in subjects with high paraplegia (lesions at T-1 to T-6) or low paraplegia (lesions at T-7 and below). We found that smokers and ex-smokers with quadriplegia were hyperresponsive to methacholine (provocative concentration causing a 20% fall in FEV1 = 1.9 mg/mL), and that the response was comparable to that found in never-smokers, revealing that hyperresponsiveness among never-smokers cannot be attributed to preinjury airway hyperreactivity that precluded cigarette use. In contrast, subjects with low paraplegia were not hyperresponsive to methacholine. Among subjects with high paraplegia, the three subjects demonstrating airway hyperresponsiveness had significantly lower FEV1 (percent predicted). The findings support the hypothesis that airway hyperresponsiveness in subjects with quadriplegia represents loss of sympathetic innervation of the lung, thereby leaving intact unopposed bronchoconstrictor cholinergic activity. However, reduced lung volumes in these subjects also suggest the possibility that airway hyperresponsiveness is due to loss of ability to stretch airway smooth muscle by deep breathing.