Evaluation of the onset and duration of response to cold air inhalation challenge in cynomolgus monkeys (Macaca fascicularis).

Cold air inhalation challenge (CAIC) for the evaluation of bronchial reactivity has been proposed as a physical agent alternative to chemical agent challenges (methacholine or histamine), especially suitable for the occupational environment. The present investigation describes and evaluates a method for performing cold air inhalation challenge in Cynomolgus monkeys (Macaca fascicularis), a species shown to be useful in animal modeling studies of occupational asthma. Six adult male anesthetized monkeys were ventilated by changes in external pressure while breathing cold air (-25 degrees C to -30 degrees C). Pulmonary function testing was performed at 10, 25, 40 and 55 min post-challenge. Significant increases (P less than 0.05) in average pulmonary flow resistance (RL) and decreases in dynamic compliance (CL dyn) were observed, with maximum impairment occurring at 25 min post-challenge, with a trend towards a return to baseline values at 55 min post-challenge. Peak expiratory flow rate (PEFR), forced expiratory volume in 0.5 s/forced vital capacity (FEV0.5/FVC) and forced expiratory flow at 50% forced vital capacity (FEF50) showed the same general pattern of reduction as seen with RL; however, these results were not statistically significant, most probably owing to individual monkey variability and the small number of monkeys (N = 6) used. A repeat challenge at 25 min after a primary challenge yielded increased RL in one monkey, suggesting that no absolute refractory period is present from CAIC. Results of these studies demonstrate that CAIC causes bronchoconstriction in monkeys and may be useful in further animal modeling studies designed to determine the asthmogenic/airway irritant potential of occupational toxicants.