Pulmonary reactivity to vanadium pentoxide following subchronic inhalation exposure in a non‐human primate animal model

Abstract

Abstract An experimental study was conducted to evaluate changes in pulmonary reactivity resulting from repeated vanadium pentoxide (V 2 O 5 ) dust inhalation. The study assessed pulmonary reactivity to V 2 O 5 through the use of provocation challenges, and compared V 2 O 5 reactivity before and after subchronic V 2 O 5 exposure. A total of 24 adult, male cynomolgus monkeys ( Macaca fascicularis ) were exposed by inhalation for 6 h per day, 5 days per week, for 26 weeks. Two V 2 O 5 ‐exposed groups ( n =8 each) received equal weekly V 2 O 5 exposures (concentration x time) with different exposure profiles. One V 2 O 5 ‐exposed group received 0.1 mg V 2 O 5 m −3 on Mondays, Wednesdays and Fridays, with a twice‐weekly peak exposure of 1.1 mg V 2 O 5 m −3 on Tuesdays and Thursdays, and was included to investigate the influence of an exposure regimen with peaks on the development of pulmonary hyper‐reactivity. The other V 2 O 5 ‐exposed group received a constant daily concentration of 0.5 mg V 2 O 5 m −3 . A control group ( n ‐8) received filtered, conditioned air. Pre‐exposure challenges with V 2 O 5 produced a concentration‐dependent impairment in pulmonary function, characterized by airway obstructive changes (increased resistance and decreased flow). Analysis of respiratory cells recovered from the lung by bronchoalveolar lavage demonstrated that airway obstruction was accompanied by a significant influx of inflammatory cells into the lung. Subchronic V 2 O 5 inhalation did not produce an increase in V 2 O 5 reactivity in comparison to the control group, and cytological, immunological and skin test results indicate the absence of allergic sensitization. Instead, a trend toward decreased pulmonary reactivity was found following subchronic V 2 O 5 inhalation. Pulmonary reactivity to V 2 O 5 (both functional and cellular responses) was affected, as well as non‐specific reactivity to methacholine. This finding suggests that the absence of increased pulmonary reactivity to V 2 O 5 following subchronic inhalation may be related to the induction of tolerance under the exposure conditions used in the study.