Postmortem studies have shown that airway wall thickening is present in asthmatic patients and may play a pathophysiologic role. We investigated the presence and characteristics of airway wall thickening in patients with asthma, using helical computed tomography. Eighty-one asthmatic patients and 28 healthy control subjects were studied cross-sectionally. Airway wall thickness was assessed by a validated method on the basis of wall area (WA), WA corrected by body surface area (WA/BSA), and WA%, defined as (WA/total area) x 100 at the apical bronchus of the right upper lobe. Airway luminal area (Ai) and Ai/BSA were also examined. Asthma duration and severity, pulmonary function, and serum eosinophil cationic protein levels were evaluated. Intraobserver and interobserver reproducibility of WA, WA%, and Ai measurements were good. As compared with control, WA, WA/BSA, and WA% were significantly increased in patients with mild (n = 13), moderate (39), and severe persistent (22) asthma but not in patients with intermittent asthma (7). Comparison of the four asthmatic subgroups demonstrated thicker airways in more severe disease, but no difference in Ai or Ai/BSA. When all asthmatic patients were analyzed together, WA and WA/BSA correlated with the duration, although weakly, and severity of asthma. WA and WA/BSA negatively correlated with FEV(1) (percentage of predicted), FEV(1)/FVC (%), and FEF(25-75%) (percentage of predicted), whereas WA% negatively correlated with only FEV(1). We conclude that airway wall thickening occurs in patients with asthma and is not limited to those with severe disease. The degree of airway wall thickening may relate to the duration and severity of disease and the degree of airflow obstruction.
Transient receptor potential vanniloid-1 (TRPV-1) mediates the cough response induced by the pepper extract capsaicin and is expressed in sensory nerves that innervate the airway wall. We determined the expression of TRPV-1 in the airways of patients with chronic persistent cough of diverse causes and with an enhanced capsaicin cough response. We obtained airway mucosal biopsies by fiberoptic bronchoscopy in 29 patients with chronic cough and 16 healthy volunteers without a cough. Immunostaining for nerve profiles with anti-protein gene product (PGP)-9.5 antibody showed no increase in nerve profiles in the airway epithelium of patients with chronic cough; however, with an anti-TRPV-1 antibody, there was a fivefold increase of TRPV-1 staining nerve profiles (p < 0.001). There was a significant correlation between capsaicin tussive response and the number of TRPV-1-positive nerves within the patients with cough. Our findings indicate that TRPV-1 receptors may contribute to an enhanced cough reflex and the cough response in chronic persistent cough of diverse causes.
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