Acute canine adenovirus 2 infection increases histamine airway reactivity in beagle puppies

Acute infection with canine adenovirus was studied in 23 specific pathogen-free out-bred beagle puppies (median age = 78 days, range = 67 to 86 days) to determine its effects on pulmonary function and airway responsiveness to aerosolized histamine. The following groups were studied: uninoculated (n = 6, Control); inoculated with canine adenovirus type 2 (CAV2) (n = 11, Infected); and subclinical spontaneous infection with CAV2 (n = 6, Subclinical). While anesthetized with chloralose and mechanically ventilated, lung function and responsiveness to aerosolized histamine were measured 3 days before inoculation (Day -3), the day of inoculation (Day 0), and 3 to 4 (Day 3-4), 6 (Day 6), 8 to 10 (Day 8-10), and 12 to 14 (Day 12-14) days after inoculation. Histamine responsivness was assessed by calculating the provocation concentration of histamine diphosphate to increase lung resistance (RL) to 150% (PC 150% RL), or decrease dynamic lung compliance (Cdyn) to 75% (PC 75% Cdyn) of the response to saline [Rl(sal) and Cdyn(sal), respectively]. Arterial blood gases, functional residual capacity (FRC), specific static lung compliance (spCst), RL, Cdyn, and histamine responsiveness were not significantly different on Day 0 among the groups (p > 0.05). Control and Subclinical puppies remained healthy, had a mean weight gain of 0.7 kg, and did not change their histamine responsivness during the study period. Infected puppies developed moderate to severe clinical illnesses, had poor weight gain, and were histamine hyperresponsive on Days 3-4 and 6. One infected puppy died on Day 3-4, and two died on Day 6 of their illness. Light microscopic examination of their lungs showed severe bronchiolitis and pneumonia. In infected puppies, weight, FRC (n = 4), and arterial oxygen tension (n = 4) decreased by Day 6 from Day 0 values, but returned to normal by Day 12-14. Specific lung conductance (n = 4) and spCst (n = 4) did not change from Day 0 to Day 6. Baseline RL increased during the study in the Infected group, whereas there was a trend for it to decrease in Control and Subclinical puppies. Baseline Cdyn did not change in the Infected group, but increased in the Control and Subclinical puppies. Nevertheless, all puppies were asymptomatic by 14 days after inoculation and histamine responsiveness was not significantly different among groups. These studies suggest that clinical infection with CAV2 produces an increase in histamine responsiveness that parallels the severity and duration of the acute illness in specific pathogen-free beagle puppies.