24hr Effects of Tiotropium Bromide in Tetraplegia

In addition to a restrictive ventilatory defect stemming for respiratory muscle paralysis, cervical SCI (tetraplegia) is associated with obstructive airway physiology similar to that associated with asthma. The investigators hypothesize that these aspects of obstructive physiology stem from unopposed increases in cholinergic airway tone as a result of autonomic imbalance; where vagal innervation (cholinergic neurotransmission) to the lungs is intact, and the bronchodilating adrenergic influences of sympathetic pathways are interrupted. The investigators demonstrated using spirometric criteria, significant bronchodilator responses in approximately 50% of subjects with tetraplegia following inhalation of short acting beta-2 agonists (albuterol sulfate) and anticholinergic agents (ipratropium bromide). When specific airway conductance (sGaw), a more sensitive indicator of bronchodilation, was assessed via whole body plethysmography, significant bronchodilation and restoration of normal airway caliber was noted in all subjects.

Intuitively, one might expect that through bronchodilation susceptible individuals with tetraplegia who already have compromised respiratory muscle strength and weakened cough might benefit from better airway clearance, and via increases in lung volumes improve the length-tension relationship of residual expiratory muscles for initiation of more forceful coughs. Based upon a comparative study of the bronchodilator effects of ipratropium bromide versus albuterol in persons with tetraplegia (in publication), it appears that ipratropium bromide elicited greater bronchodilation, perhaps because of the specificity of action in blocking acetylcholine binding to the muscarinic-3 (M3) airway smooth muscle receptor. The investigators purpose in this preliminary study is to assess whether salutary effects upon pulmonary function, cough strength, and airway inflammation are observed across a twenty-four hour period following inhalation of a single dose of tiotropium bromide 18 mcg inhalational capsule versus placebo utilizing a double-blind crossover design in persons with chronic stable tetraplegia.

Inclusion criteria

• Chronic Spinal Cord Injury (>1 year post-injury)
• Stable tetraplegia (level of injury C3-C8, non-ventilator dependent)
• Male or female between the ages 18-65

Exclusion criteria

• Smoking, active or history of smoking during last 6 months;
• Ventilator dependent;
• Known history of asthma, COPD or inflammatory disease during lifetime;
• Active or recent (within 3 months) respiratory infection;
• Use of medications known to affect the respiratory system;
• Use of medications known to alter airway caliber
• Uncontrolled hypertension;
• Glaucoma or cataracts;
• History of milk protein allergy
• Pregnant or trying to become pregnant
• Lack of mental capacity to give informed consent