Although atopic asthma symptoms often seem to disappear around puberty, subjects in this age group may experience unexpected, often severe, asthma attacks. This may be related to persistence of untreated airway hyperresponsiveness/inflammation in a life period characterized by low perceptiveness of disease-related symptoms. This study was designed to evaluate the prevalence and the severity of bronchial hyperreactivity and the exhaled nitric oxide (FENO) levels in a group of steroid-naive asthmatic adolescents. Fifty-two patients with mild-intermittent asthma were studied, ages 12 to 16, sensitized to house dust mites; 22 age-matched controls, were also studied. Asthma patients showed FEV1, FEF25-75%, and FVC values not significantly different from controls, (p > 0.05, each comparison). By contrast, although none of the control subjects showed bronchial hyperreactivity, increased airway responsiveness to methacholine (MCh) was demonstrated in the majority of the patients and found to be severe in 36.5% (MCh PD20 > or = 400 microg or accumulative dose < or = 1220 microg) and moderate in 32.7% (MCh PD20 400-1400 microg or accumulative dose 1220-4620 microg). In addition, FENO concentrations were significantly higher in asthmatics, as compared with controls (20.4 +/- 5.3 ppb and 4.4 +/- 0.7 ppb, respectively; p < 0.01) and 83% of the patients had FENO levels higher than 8.9 ppb (i.e., > 2 standard deviations of the mean in control subjects). A positive, statistically significant correlation was found between FEF25-75% values and MCh PD20 (r = 0.358; p < 0.01) or MCh accumulative dose (r = 0.355; p < 0.05). No correlations were demonstrated between MCh responsiveness and FVC or FEV1 values or FENO levels and between FENO levels and pulmonary function parameters (p > 0.05). The high incidence of bronchial hyperresponsiveness to MCh and of airway inflammation (as demonstrated by the elevated FENO levels) in adolescents with mild asthma suggests the need for more accurate evaluation and, possibly, for early intervention with antiinflammatory drugs in a significant proportion of patients in this age group.