Asthma-like symptoms, including chronic persistent cough, are not always specific for classical asthma. In order to investigate whether assessment of extrathoracic airway hyperresponsiveness (EAHR) during methacholine bronchial challenge helped in the evaluation of pediatric patients with asthma-like symptoms such as chronic cough, we examined 133 consecutive, unselected patients (mean age, 10.06 +/- 2.16 years) who had neither established asthma nor bronchial obstruction previously. We recorded the forced mid-inspiratory flow (FIF50) as an index of extrathoracic airway narrowing. In addition, a 25% decrease in FIF50 (PD25FIF50) below the cutoff concentration of less than or equal to 8 mg/mL methacholine was assumed to indicate EAHR. According to the methacholine response, 81 patients had EAHR, and 41 of them had combined EAHR and bronchial hyperresponsiveness (BHR); 39 patients had only BHR. Airway hyperresponsiveness was not demonstrated in 13 patients and not in any of the control children. When patients with cough as the sole presenting symptom (60.9%) were compared with those with cough and wheeze (20.3%), those with cough alone had a significantly greater probability of having EAHR (OR, 4.16; 95% CI, 1.32-13.13) and a lower probability of having BHR (OR, 0.70; CI, 0.25-1.95) than those with cough and wheeze. Patients with cough, wheeze, and dyspnea (18.8%) had a significantly greater chance of having BHR than those with cough alone (OR, 5.08; CI, 1.55-16.64). Patients with cough and wheeze as compared with those with cough, wheeze, and dyspnea had significantly greater probability of having both EAHR and BHR (OR, 4.71; CI, 1.94-11.47). In order to ascertain the clinical relevance of EAHR, we assessed in the second part of the study whether the effects of treatment of the underlying disease would result in relief of airway hyperresponsiveness. Rhinosinusitis and perennial allergic rhinitis accounted for EAHR in 71 patients, and 34 of them also demonstrated BHR. They received specific therapy for their upper airway diseases for 4 weeks. Compared with values before treatment, FIF50 and forced expiratory volume in 1 sec (FEV1) did not change significantly. The dose of methacholine causing a 20% fall in FEV1 (PD20FEV1) and PD25FIF50 values were significantly increased from 2.40 +/- 1.39 to 4.22 +/- 1.13 mg/mL (P< 0.001) and from 1.03 +/- 1.75 to 8.71 +/- 1,21 mg/mL (P < 0,0001), respectively. We conclude that measurements of EAHR and BHR are the most important ways to evaluate children with asthma-like symptoms, including chronic persistent cough when chest X-rays and pulmonary function tests remain within normal limits. Therefore, empirical treatment is not necessary when these investigations are available. Our results suggest that specific treatment of inflammation in the upper airways reversed persistant cough, and may play an important role in modulating lower airways responsiveness in patients with concomitant BHR. (C) 2002 Wiley-Liss, Inc.
