Airway Hyperreactivity in Subjects With Tetraplegia Is Associated With Reduced Baseline Airway Caliber

We administered aerosolized histamine to 32subjects with tetraplegia to determine whether there were differencesin spirometric and/or lung volume parameters between responders andnonresponders. Baseline pulmonary functionparameters revealed mild to moderate restrictive dysfunction. We foundthat 25 subjects (78%) were hyperreactive to histamine (meanprovocative concentration of a substance causing a 20% fall inFEV1 [PC20], 1.77 mg/mL). Responders(PC20, < 8 mg/mL) had significantly lower values forforced expiratory flow between 25% and 75% of the outflow curve(FEF25–75), FEF25–75 percentpredicted, and FEF25–75/FVC ratio. Among all 32subjects, the natural logarithmic transformation performed onPC20 values (lnPC20) correlated withFEF25–75 percent predicted, FEV1 percentpredicted, and FEF25–75/FVC ratio but not with FVC percentpredicted. Responders with PC20 values < 2 mg/mL(n = 13) had significantly reduced values for FVC, FVC percentpredicted, FEV1, and FEV1 percent predictedcompared to those with PC20 values between 2 mg/mL and 8mg/mL. In addition, among responders, there was a significantcorrelation between lnPC20 and FVC percent predicted. Asignificant relationship was found between maximal inspiratory pressure(Pimax) and both FEV1 percent predicted andFEF25–75 percent predicted, but not betweenlnPC20 and either Pimax or maximal expiratorypressure (Pemax). Thesefindings demonstrate that subjects with tetraplegia who exhibit airwayhyperreactivity (AHR) have reduced baseline airway caliber and thatlower values for lnPC20 are associated with parallelreductions in surrogate spirometric indexes of airway size(FEV1 percent predicted and FEF25–75 percentpredicted) and airway size relative to lung size(FEF25–75/FVC ratio). The absence of an associationbetween lnPC20 and FVC percent predicted for the entiregroup or between lnPC20 and either Pimax orPemax indicates that reduced lung volumes secondary torespiratory muscle weakness cannot explain the mechanism(s) underlyingAHR. Among responders, however, a possible role for reduction in lungvolume, as it pertains to increasing AHR, cannot be excluded. Proposedmechanisms for reduced baseline airway caliber relative to lung size insubjects with tetraplegia include unopposed parasympathetic activitysecondary to the loss of sympathetic innervation to the lungs and/orthe inability to stretch airway smooth muscle with deepinhalation.