Contribution of Upper Airways to Antigen-induced Late Airway Obstructive Responses in Guinea Pigs

The pathogenesis of the late asthmatic response has been of interest due to the fact that its development has been associated with airway obstruction, airway inflammation, and airway hyperresponsiveness: all features of chronic asthma. In order to study more precisely late responses, a number of animal models have been developed. Previous reports have described alterations in airway mechanics at both 3 to 6 and 17 h after antigen challenge in sensitized guinea pigs. In these experiments, however, animals were challenged through the nose with aerosolized antigen, and airway conductance was measured using whole body plethysmography while the animals breathed through the upper airways. In rats similarly challenged, the predominant immediate change in resistance occurs in the upper airways. The purpose of this study, therefore, was to evaluate the contribution made by both the upper and lower airways to late changes after allergen challenge in guinea pigs. Outbred female Hartley guinea pigs were actively or passively sensitized (IgG1 antibody response) to three different antigens and challenged either by direct tracheal insufflation (sheep gamma globulin [SGG] or oxazolone-human serum albumin [OX-HSA]) or by aerosolization (ovalbumin [OA]). Lung resistance (Rl) and dynamic compliance (Cdyn) were measured in anesthetized guinea pigs through a tracheostomy tube, and specific airway conductance (SGaw) was measured in unanesthetized, nose-breathing guinea pigs using a whole body plethysmograph. Late responses were defined as a Rl greater than the mean + 2 SD Rl or as a decrease in SGaw from baseline greater than 2 SD from the placebo-challenged (bovine serum albumin) group. In guinea pigs challenged through the lower airways (SGG or OX-HSA), and in which Rl was evaluated 6 to 23 h later through a tracheostomy, no late responses were observed despite vigorous immediate responses. In guinea pigs challenged through the upper airways (aerosolized OA), and in which Rl was measured through a tracheostomy 18 to 24 h later, late responses were observed in 2 of 20 animals (10%). When guinea pigs were challenged through the upper airways (aerosolized OA), and in which measurements of SGaw included the upper airways, 5 of 18 (28%) had a late response. There was no correlation between the magnitude of the immediate response and the propensity to develop late responses. We conclude that late responses after allergen challenge in guinea pigs are composed of both an upper and lower airway component and that the contribution of the upper airways to the pattern of pulmonary response observed is significant and therefore should not be overlooked.