Airway hyperresponsiveness to cigarette smoke in ovalbumin-sensitized guinea pigs

This study was carried out to determine if the bronchoconstrictive effect o f cigarette smoke (CS) is enhanced when airway hyperresponsiveness is induc ed by ovalbumin (Ova) sensitization, and if so, whether an increase in endo genously released tachykinins is involved. The bronchoconstrictive effects of an acute CS inhalation challenge (15 ml 50% concentration) were compared between guinea pigs sensitized with aerosolized Ova and matching control a nimals (receiving saline aerosol). In Ova-sensitized animals, there were ma rked increases in the numbers of eosinophils and neutrophils in the broncho alveolar ravage fluid (BALF), which was accompanied by an elevated bronchom otor response to acetylcholine (ACh). The baseline lung resistance (RL) and dynamic pulmonary compliance (Cdyn) were not significantly different betwe en the two groups; however, the same CS inhalation challenge evoked a signi ficantly more intense bronchoconstriction in the Ova-sensitized group (cont rol group: Delta RL = 68 +/- 8%, Delta Cdyn = -26 +/- 6%; Ova group: Delta RL = 425 +/- 76%; Delta Cdyn = -47 +/- 8%). The levels of substance P-like immunoreactivity (SP-LI) and calcitonin gene-related peptide-like immunorea ctivity (CGRP-LI) measured in the bronchoalveolar lavage (BAL) collected af ter CS inhalation challenge were also significantly greater in Ova-sensitiz ed animals than in control animals. Furthermore, pretreatment with 5R-48968 , a selective antagonist of neurokinin-2 (NK2) receptor, inhibited more tha n 85% of the enhanced bronchomotor responses to CS challenge, but did not s ignificantly reduce the airway hyperresponsiveness to ACh in Ova-sensitized guinea pigs. These results show that Ova sensitization induces airway hype rresponsiveness to inhaled CS, and that the endogenous tachykinins evoked b y CS-induced activation of lung C fibers play a primary role in this augmen ted response.