Asymptomatic airway hyperresponsiveness: relationships with airway inflammation and remodelling

To study the physiopathology and significance of asymptomatic airway hyperr esponsiveness (AHR), the clinical and bronchial immunohistological paramete rs were evaluated in subjects with asymptomatic and symptomatic AHR. Asymptomatic subjects with AKR (eight females/two males, no respiratory sym ptoms, provocative concentration of methacholine causing a 20% fall in forc ed expiratory volume in one second (PC20) <8 mg.mL(-1) and no treatment) we re compared,vith asthmatic subjects paired for age, sex and PC20, and with nonatopic, nonasthmatic controls paired for age and sex. All three groups w ere evaluated once at baseline, whilst the asymptomatic AHR subjects were r e-evaluated after 1 and 2 yrs. Measurements included spirometry, methacholi ne challenge, serum immunoglobulin (Ig)E, blood eosinophils, and bronchosco py (at baseline and after 2 yrs only). At first evaluation, the mean blood eosinophil count, total serum IgE level , atopic index, baseline forced expiratory volume in one second (FEV1) and the degree of bronchial epithelial desquamation of the asymptomatic AHR sub jects were similar to those of asthmatic subjects. However, they presented focal rather than the continuous bronchial subepithelial fibrosis observed in asthmatics. Their mucosal CD3, CD4, CD25, EG1 and EG2-positive cell coun ts were intermediate between those of the control subjects and asthmatics. At the end of the 2-yr follow-up, four of them had developed asthma symptom s. At this time, bronchial biopsies revealed an increase in the extent of s ubepithelial fibrosis and in the number of CD25 and CD4-positive cells, and a decrease in the number of CD8+ cells, particularly in subjects who devel oped asthma symptoms. These data suggest that asymptomatic airway hyperresponsiveness is associat ed with airway inflammation and remodelling, and that the appearance of ast hma symptoms is associated with an increase in these features, particularly the CD4/CD8 ratio and airway fibrosis. Consequently, this study proposes a n association between asymptomatic airway hyperresponsiveness and airway in flammation, structural changes and asthma although these relationships rema in to be further evaluated.