Bronchial Hyperresponsiveness After Cervical Spinal Cord Injury: Discussion


Patients with transection of the cervical spine (quadriplegia) manifest a unique situation of selective interruption of sympathetic pulmonary innervation with retained intact parasympathetic tone. Although human airways seem to lack tonic sympathetic bronchodilator tone,” it is believed that sympathetic nerves in the lung serve in a neuromodulatory capacity, acting to counteract cholinergic bronchoconstrictor effect. Such unopposed parasympa thetic airway tone most likely explains the hyperresponsiveness to methacholine demonstrated by all of our patients. Selective blockade of sympathetic input to the lung also may account for the prior observation of significant bronchodilator response to inhaled metaproterenol sulfate in a group of otherwise healthy quadriplegic nonsmokers.
A third source of innervation, the nonadrenergic noncholinergic nervous system, exists in human airways. Nonadrenergic inhibitory nerves, which relax airway smooth muscle, have been demonstrated in vitro and in vivo.’29 Since there is no tonic sympathetic influence on human airway smooth muscle, this nonadrenergic inhibitory system serves as the only direct neural bronchodilator pathway Source The effect of transection of the cervical spine on the pulmonary nonadrenergic noncholinergic nervous system is unknown. Whether interruption of nonadrenergic inhibitory nerves in quadriplegia plays a role in the bronchial hyperresponsiveness we have observed remains to be elucidated.
The anticholinergic agent, ipratropium bromide, nonselectively inhibits postganglionic muscarinic receptors of two types: (1) prejunctional М2 receptors, located on cholinergic nerves, which function as feedback inhibitory receptors or autoreceptors, and (2) postjunctional М3 receptors located on airway smooth muscle. The blockade of bronchial hyperresponsiveness to methacholine by pretreatment with ipratropium bromide in our patients supports an М3 receptor-mediated phenomenon.
Despite the uniform presence of airway hyperreactivity among the study group, only two of the subjects reported occasional episodes of dyspnea. However, other patients with cervical spinal cord injury experience respiratory symptoms seemingly out of proportion to their impaired pulmonary function and unexplained by other factors common to this population, such as atelectasis and superimposed infection. The findings of this study may offer an etiologic basis for the heretofore unexplained respiratory symptoms of a subgroup of quadriplegic patients.
In summary, patients with nonacute traumatic quadriplegia demonstrate increased bronchial reactivity to methacholine. This probably reflects the loss of sympathetic airway innervation and resultant unopposed parasympathetic bronchoconstrictor tone which occurs after transection of the cervical spine. Blockade of methacholine hyperresponsiveness by ipratropium bromide suggests a mechanism mediated by airway muscarinic receptors.