Viral lower respiratory infections (LRIs) in children have been implicated as a cause of obstructive airways disease in later life. Acute canine parainfluenza 2 (CPI2) and/or Bordetella bronchiseptica (B.b) infections in Beagle puppies produce LRIs that are pathologically similar to human viral bronchiolitis. Beagle puppies infected acutely with both CPI2 and B.b develop transient airway hyperreactivity that parallels the clinical course in duration and severity. Proposed studies will determine the mechanisms of transient airway hyperreactivity and if single and/or recurrent infections, induction of allergy and/or genetic selection will result in (1) chronic airway hyperreactivity and/or (2) altered lung growth. In outbred Beagle puppies the within- and between dog variability of dynamic compliance and total pulmonary resistance to aerosolized bronchoconstrictor or bronchodilator challenge will be determined. Pre- and post- infection immunologic status and bronchoalveolar lavage fluide (BALF) cytology will be correlated to study the are important determinants of airway hyperreactivity. These studies also will determine if CPI2, Canine Adenovirus 2 or Influenza C infections alter, (1) baseline airway tone as determined by tantalum bronchography, (2) vagal tone, (3) mediator release in plasma and BALF, (4) viral specific immunoglobulins including IgE, (5) adrenergic, cholinergic, histamine or prostaglandin receptor function or number and, (6) alveolar epithelial permeability using 99mTcDTPA uptake techniques. The purpose of these induced by acute viral infection and to investigate several mechanisms that may be responsible or these injuries. Prostaglandin and/or leukotriene inhibitors, ganglionic blockers and atropine will be used to gain insight into the mechanisms of lung injury in viral bronchiolitis. These effects of acute and recurrent viral infections of lung growth will be investigated in longitudinal studies of lung function and with qualitative and quantitative morphometric studies.
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