A TIME-COURSE STUDY OF AIRWAY HYPERRESPONSIVENESS IN CONSCIOUS PARAINFLUENZA VIRUS TYPE 3-INFECTED GUINEA-PIGS

The study of virus-induced airway hyperresponsiveness may provide insi ght into mechanisms that contribute to respiratory diseases such as as thma. We examined changes induced by parainfluenza virus type 3 (PI-3) in lung lesions, tissue weights, and airway responsiveness to aerosol s of histamine, methacholine, or citric acid in conscious guinea pigs, using modified whole body plethysmography. During the first week afte r inoculation, infected lung tissue had peribronchiolitis and airway h yperresponsiveness to various agents when dyspnea and significant resp iratory events were measured; these effects persisted throughout posti noculation weeks 2 and 3. Airway hyperresponsiveness was defined by re ductions in the onset of dyspnea or significant respiratory events. Th roughout the course of the study, PI-3 infected animals had resting re spiratory patterns that reflected labored breathing and may have been related to the edema indicated by increased lung weights. Furthermore, increased numbers of inflammatory cells were, observed in lung tissue as well as bronchoalveolar lavage fluid of infected animals at these times. Unlike PI-3 infection., exposure to gram-negative endotoxin res ulted primarily in airway hyporesponsiveness to histamine aerosol. Hen ce, we have shown PI-3 infection in guinea pigs causes time-dependent alterations in airway responsiveness to diverse bronchoactive agents a s well as in normal breathing patterns, which may persist up to severa l weeks after inoculation in animals that may otherwise appear normal.