Changes in lung mechanics and histamine responsiveness after sequential canine adenovirus 2 and canine parainfluenza 2 virus infection in beagle puppies

Abstract

We determined the effects of an immediately antecedent viral lower respiratory tract infection (LRI) on the severity of clinical illness, changes in lung function and airway histamine responsiveness produced by a subsequent LRI in 9-12 week old beagle puppies inoculated with canine adenovirus 2, followed in 2 weeks by inoculation with canine parainfluenza 2 virus (CAV2-CP12, n = 7). We compared their acute responses to puppies infected with CP12 alone (n = 5), CAV2 alone (n = 7), and no infection (control, n = 6). Puppies inoculated with either virus alone developed a LRI 3 to 6 days after inoculation which resolved by 12-14 days after inoculation. However, the illness was more severe in the CAV2 group. In the CAV2-CP12 group, CP12 infection following CAV2 infection resulted in a clinical illness nearly comparable to that observed with CAV2 alone. Whereas in control and CP12 puppies, lung resistance (RL) decreased and dynamic lung compliance (Cdyn) increased during the study due to normal growth, RL increased and Cdyn remained unchanged in the CAV2 group. In contrast, RL did not change and Cdyn increased in the CAV2-CP12 group. Airway histamine responsiveness in the CAV2-CP12 group increased during infection with CP12 and was similar to that observed with CAV2 alone. In contrast, infection with CP12 alone produced a small, but non-significant increase in histamine responsiveness. The duration of the increase in histamine responsiveness was not prolonged in the CAV2-CP12 group in comparison to CP12 or CAV2 alone. However, the length of clinical illness was extended in the CAV2-CP12 group in comparison to the other infected groups. These data suggest that an immediately antecedent viral LRI can potentiate the clinical and physiologic effects of a subsequent viral LRI.

A review of canine parainfluenza virus infection in dogs

“…As originally observed in early studies of CITB outbreaks and later confirmed prospectively, [51][52][53][54] CPIV infection results in more severe respiratory disease when complicated by coinfection with other viruses and bacteria. This pathological synergism in CITB is similar to PIV infections in other species, notably BPIV type 3 infection and shipping fever in cattle.…”

“…In human medicine, an area of investigation in the pathogenesis of pediatric PIV infections has been the potential role of these viruses as a risk factor for the development of airway hyperreactivity and chronic airway obstruction later in life. 17 A considerable part of this research has actually been done with CPIV infection in dogs 22,[49][50][51][52][53] and has fortuitously provided greater insights into CPIV-associated pathophysiologic changes in dogs. Experimentally, infection of 2-to 3-monthold laboratory Beagles with CPIV consistently resulted in transient airway hyperresponsiveness to aerosolized histimine.…”

“…22 These responses were more pronounced in the case of dual or sequential infection with CPIV and canine adenovirus type 2 or Bordetella bronchiseptica. [50][51][52][53] Chronic inflammation of airways, including bronchiolitis obliterans, could persist for more than 6 months after infection. 50 Dual infection with CPIV and B bronchiseptica, compared with infection with CPIV or B bronchiseptica alone, also resulted in increased concentrations of the inflammatory mediator and bronchoconstrictor thromboxane A as well as neutrophilia in bronchoalveloar lavage fluid.…”

“…64 There have been numerous attempts to reproduce respiratory disease in dogs with CPIV alone to study viral pathogenesis and test vaccine efficacy by use of parenteral, intranasal, intratracheal, or aerosol delivery, singly or in combination. 7,8,12,18,19,29,[49][50][51][52][53]65 In most cases, clinical signs of respiratory disease were absent or very mild, beginning 7 to 9 days after virus exposure and lasting for 3 to 5 days. There was sometimes serous nasal discharge and mild pharyngitis and tonsillitis.…”

Ragweed sensitization alters pulmonary vascular responses to bronchoprovocation in beagle dogs

“…Pulmonary function. We measured pulmonary function by methods developed and routinely used in our laboratory (20,22,23). Briefly, airflow was measured with a heated pneumotachograph (Fleisch no.…”