Patients with asthma-like symptoms may not have asthma but obstruction of the extrathoracic airway (EA). To evaluate if dysfunction of the EA causes asthma-like symptoms, we assessed bronchial and EA responsiveness to inhaled histamine in 441 patients who presented with at least one of three key symptoms--cough, wheeze, dyspnoea--but had neither documented asthma nor bronchial obstruction. The histamine concentrations causing a 20% fall in forced expiratory volume in 1 s (PC20FEV1) and a 25% fall in maximal mid-inspiratory flow (PC25MIF50) were used as respective thresholds of bronchial and EA responsiveness. Values 8 mg/mL or less indicated bronchial (B-HR) or EA hyper-responsiveness (EA-HR). The influence of concurrent upper respiratory tract diseases, such as post-nasal drip (PND), pharyngitis, laryngitis and sinusitis, was also assessed. We found four response patterns to the histamine challenge: EA-HR in 26.5% of the patients, B-HR in 11.1%, combined EA-HR and B-HR in 40.6%, and no-HR in 21.8%. Cough was reported by 79% of the patients, wheeze by 53%, and dyspnoea by 40%. Patients with cough as the sole presenting symptom (34.2%), as compared with those with wheeze and/or dyspnoea (20%), had significantly greater probability of having EA-HR (OR 5.35, 95% CI 3.25-8.82) and lower probability of having B-HR (OR 0.45, CI 0.28-0.70); patients with cough plus wheeze and/or dyspnoea (45.8%) had significantly greater probability of having both EA-HR and B-HR than either those with cough alone (OR 2.48, CI 1.49-4.13), or those with wheeze and/or dyspnoea but not cough (OR 1.74, CI 1.36-2.22). EA-HR alone or combined with B-HR was strongly associated with EA diseases, particularly pharyngitis and PND. Cough was significantly associated with PND, either when it was the sole symptom (OR 2.16, CI 1.14-4.09) or when it was combined with wheeze and/or dyspnoea (OR 3.53, CI 1.97-6.33). Our results suggest that extrathoracic airway dysfunction may account for asthma-like symptoms, particularly chronic cough. This abnormality seems to be sustained by chronic diseases of the upper respiratory tract.
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