An investigation into the mechanisms of virus induced wheezing in an experimental adult model

Episodic wheezing associated with viral infections of the upper respiratory tract (URT) is a common problem in young children but also occurs in adults. This study investigated the mechanisms that underlie 'viral wheeze' by developing an adult model using an experimental infection with human coronavirus (HCoV), the second most prevalent common cold virus. Twenty-four adults with a history of episodic viral wheeze and 19 controls were inoculated with HCoV 229E and monitored for the development of symptoms, changes in airway physiology and inflammatory changes in the URT by nasal lavage and lower respiratory tract (LRT) by induced sputum. Ten subjects also underwent bronchoscopy to collect bronchial biopsies during the cold and to search for evidence of virus infection of the LRT. At baseline, viral wheezers were similar to controls in airway responsiveness, although they had lower forced expiratory volume in one second (FEV1), and in the measured markers of inflammation (nasal lavage cell counts, sputum differential white cell counts, and nasal and sputum interleukin-8 (IL-8), IL-5, interferon- (IFN-), and eosinophilic cationic protein (ECP)). Nineteen viral wheezers and 11 controls developed colds. Viral wheezers with colds reported significantly more URT symptoms than controls. Sixteen viral wheezers and no controls reported LRT symptoms (wheeze, chest tightness and shortness of breath). The viral wheezers with colds had small (3-4%) reductions in FEV, during the illness, but a progressive increase in airway responsiveness from baseline on days 2, 4 and 17 after inoculation, which affected both atopic and non-atopic subjects equally. A modest increase in nasal neutrophil count that correlated with nasal symptom scores was seen in both viral wheezers and controls with colds on day 4. A significant relative increase in sputum differential neutrophil count was seen on day 4 that correlated with LRT symptom scores in the viral wheeze group with a cold but not in controls. Change in sputum differential neutrophil counts for viral wheezers correlated with change in airway responsiveness.