title: Airway hyperreactivity in subjects with tetraplegia is associated with reduced baseline airway caliber.
abstract: OBJECTIVE
  We administered aerosolized histamine to 32 subjects with tetraplegia to determine whether there were differences in spirometric and/or lung volume parameters between responders and nonresponders.
  
  
  RESULTS
  Baseline pulmonary function parameters revealed mild to moderate restrictive dysfunction. We found that 25 subjects (78%) were hyperreactive to histamine (mean provocative concentration of a substance causing a 20% fall in FEV(1) [PC(20)], 1.77 mg/mL). Responders (PC(20), < 8 mg/mL) had significantly lower values for forced expiratory flow between 25% and 75% of the outflow curve (FEF(25-75)), FEF(25-75) percent predicted, and FEF(25-75)/FVC ratio. Among all 32 subjects, the natural logarithmic transformation performed on PC(20) values (lnPC(20)) correlated with FEF(25-75) percent predicted, FEV(1) percent predicted, and FEF(25-75)/FVC ratio but not with FVC percent predicted. Responders with PC(20) values < 2 mg/mL (n = 13) had significantly reduced values for FVC, FVC percent predicted, FEV(1), and FEV(1) percent predicted compared to those with PC(20) values between 2 mg/mL and 8 mg/mL. In addition, among responders, there was a significant correlation between lnPC(20) and FVC percent predicted. A significant relationship was found between maximal inspiratory pressure (PImax) and both FEV(1) percent predicted and FEF(25-75) percent predicted, but not between lnPC(20) and either PImax or maximal expiratory pressure (PEmax).
  
  
  CONCLUSIONS
  These findings demonstrate that subjects with tetraplegia who exhibit airway hyperreactivity (AHR) have reduced baseline airway caliber and that lower values for lnPC(20) are associated with parallel reductions in surrogate spirometric indexes of airway size (FEV(1) percent predicted and FEF(25-75) percent predicted) and airway size relative to lung size (FEF(25-75)/FVC ratio). The absence of an association between lnPC(20) and FVC percent predicted for the entire group or between lnPC(20) and either PImax or PEmax indicates that reduced lung volumes secondary to respiratory muscle weakness cannot explain the mechanism(s) underlying AHR. Among responders, however, a possible role for reduction in lung volume, as it pertains to increasing AHR, cannot be excluded. Proposed mechanisms for reduced baseline airway caliber relative to lung size in subjects with tetraplegia include unopposed parasympathetic activity secondary to the loss of sympathetic innervation to the lungs and/or the inability to stretch airway smooth muscle with deep inhalation.
authors.affiliation: Pulmonary/Critical Care Medicine Section, Bronx Veterans Affairs Medical Center, Bronx, NY, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Grimm
authors.forename: D
authors.initials: D
authors.lastname: Chandy
authors.forename: P L
authors.initials: PL
authors.lastname: Almenoff
authors.forename: G
authors.initials: G
authors.lastname: Schilero
authors.forename: M
authors.initials: M
authors.lastname: Lesser
mesh_terms: D000328:Adult; D000336:Aerosols; D000368:Aged; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005541:Forced Expiratory Volume / Q000502:physiology; D006632:Histamine / Q000008:administration & dosage; D006801:Humans; D001239:Inhalation / Q000502:physiology; D016014:Linear Models; D008168:Lung / Q000294:innervation / Q000473:pathology* / Q000503:physiopathology; D008448:Maximal Expiratory Flow Rate / Q000502:physiology; D008450:Maximal Midexpiratory Flow Rate / Q000502:physiology; D008875:Middle Aged; D009130:Muscle, Smooth / Q000503:physiopathology; D011312:Pressure; D012123:Pulmonary Ventilation / Q000502:physiology; D011782:Quadriplegia / Q000503:physiopathology*; D012132:Respiratory Muscles / Q000503:physiopathology; D013147:Spirometry; D014797:Vital Capacity / Q000502:physiology
chemical_list: D000336:Aerosols; D016085:Bronchoconstrictor Agents; D006632:Histamine