INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Cough is a protective reflex that facilitates the expulsion of mucus from the airways. The proposed mechanism of cough involves stimulation of sensory receptors within the respiratory tract, whose afferent impulses to the brainstem activate a putative cough center (1). Expiratory muscles, which create elevated intrathoracic pressures, are essential for the production of an effective cough. Since these muscles receive their innervation from the first thoracic segment and below, transection of the cervical spinal cord renders expiratory function, and hence cough, severely compromised. As a result, inability to clear secretions, mucus plugging, atelectasis, and respiratory infections are common pulmonary complications among subjects with cervical spinal cord injury (C-SCI). The effects of C-SCI on respiratory muscle strength and pulmonary function have been extensively studied (2). However, to our knowledge, the sensitivity of the cough reflex has not been evaluated previously in this population.

To investigate the effects of C-SCI on cough reflex sensitivity, we performed cough challenge testing with inhaled capsaicin in 12 subjects with tetraplegia. Data from this group were compared to those from a control group of 50 able-bodied volunteers who underwent identical cough challenge testing. The tussive agent capsaicin, a pungent extract of red peppers, has been shown in humans to induce cough in a safe, reproducible, and dose-dependent manner (3).

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Subjects

Twelve male outpatients with chronic mid-to-lower cervical spinal cord injuries were recruited for the study, which was approved by the Institutional Review Board of the Veterans Affairs Medical Center, Bronx, New York. Subjects were nonsmokers without a history of pulmonary disease or recent (within 4 wk) symptoms of respiratory tract infection, seasonal allergies, or postnasal drip syndrome. Subjects denied a history of, and symptoms consistent with, gastroesophageal reflux. None of the subjects were receiving medications known to affect the sensitivity of the cough reflex. Data including subjects' age, level and duration of injury, and baseline FVC are provided in Table 1.

Capsaicin Cough Challenge

Solutions of capsaicin (Sigma Chemical Co., St. Louis, MO) were prepared by dissolving 30.5 mg capsaicin in 1 ml ethanol and 1 ml polyoxyethylenesorbitan (Tween 80) and subsequently dissolved in 8 ml physiologic saline solution to make a stock solution of 0.01 M. This solution was further diluted with saline to make serial doubling concentrations ranging from 0.98 to 1,000 µM. Fresh solutions were prepared on each day of testing.

Subjects inhaled single breaths (from FRC to total lung capacity) of capsaicin aerosol from a compressed air-driven nebulizer (model 646; DeVilbiss Health Care Inc., Somerset, PA) controlled by a dosimeter (KoKo DigiDoser; Pulmonary Data Service Instrumentation, Inc., Louisville, CO). The nebulizer used for these studies was modified by the addition of an inspiratory flow regulator valve (Pulmonary Data Service Instrumentation, Inc.) that limited inspiratory flow rate to 0.5 L/s regardless of inspiratory force, thereby guaranteeing a consistent and reproducible amount of solution delivered with each breath. The duration of aerosol delivery was programmed at 1.2 s, thereby providing 0.02 ml per breath (nebulizer output 1.007 ml/min). Single breaths of capsaicin solution were given in ascending order, with inhalations of saline randomly interspersed to increase challenge blindness, until the concentrations inducing two or more coughs (C₂, cough threshold) and five or more coughs (C₅) were reached. Breaths were delivered at 1-min intervals. The number of coughs in response to each concentration of capsaicin during the 1-min period immediately after each inhalation was recorded by a blinded observer. Subjects were unaware that the end point of the study was the number of coughs induced.

Data Analysis

Mean (± SEM) values for log C₂ and log C₅ were calculated and compared by an unpaired Student's t test for independent samples with those from a control group of 50 able-bodied male nonsmokers who underwent identical cough challenge testing.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

All subjects were able to generate the maximal inspiratory flow rate of 0.5 L/s during each inhalation of capsaicin. The induction of five or more coughs was achieved in all subjects.

Mean (± SEM) log C₂ and log C₅ values for subjects with C-SCI and control subjects are displayed in Figure 1. Cough reflex sensitivity was not significantly different between subjects with C-SCI and the control group, although the groups did differ in terms of age and baseline FVC (Table 2).

View larger version (9K): [in this window] [in a new window]   Figure 1.   Capsaicin cough challenge data in subjects with cervical spinal cord injury (C-SCI) and control subjects. Closed circles represent mean log C5; open circles represent mean log C2. Error bars represent ± SEM.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Our results demonstrate that cough reflex sensitivity is preserved after cervical spinal cord injury. This finding may be explained in light of the neurophysiology of the cough reflex. Experimentally, cough appears to be entirely a vagal phenomenon, being initiated only from structures innervated by the vagus nerve and its branches (1). The mechanism of human cough involves the stimulation of rapidly adapting receptors (RARs) whose thin, myelinated afferent fibers run within the vagus nerves (1). Since transection of the cervical spinal cord does not interrupt vagal pulmonary innervation, the cough reflex would be expected to remain intact. The importance of the vagus nerves to the cough reflex is further supported by the demonstration of enhanced cough reflex sensitivity in the presence of gastroesophageal reflux (4), diminished cough sensitivity in patients after heart-lung transplantation (5), and among those with autonomic neuropathy (6).

As expected, baseline pulmonary function, including vital capacity, was significantly diminished in subjects with C-SCI relative to the control group. Nevertheless, since all subjects were able to generate the maximal inspiratory flow rate of 0.5 L/s during each inhalation of capsaicin, an identical amount of aerosol was delivered by our modified nebulizer to the proximal airway of all subjects, including the control group, with each breath. It is possible, however, that the greater inspiratory vital capacity of the able-bodied control subjects allowed more distal deposition of aerosol within the intrapulmonary airways, where capsaicin may be more effective (7). The mean age of the study subjects being greater than that of the control group is unlikely to be a significant issue, since capsaicin cough threshold has been shown to be similar among different age groups of the same sex (8). Since sex-related differences in cough sensitivity have been demonstrated (9), we used an all-male control group to match the study subjects.

In summary, our data suggest that sensitivity of the cough reflex is preserved in subjects with C-SCI, and that ineffective cough in this population is due primarily to loss of innervation of the respiratory muscles.