Repeated bronchoconstriction attenuates the cough response to bronchoconstriction in naïve guinea pigs

Repeated bronchoconstriction attenuates the cough response to bronchoconstriction in naïve guinea pigs:

Publication date: Available online 7 October 2019

Source: Allergology International

Author(s): Kenta Yamamura, Johsuke Hara, Tamami Sakai, Noriyuki Ohkura, Miki Abo, Naohiko Ogawa, Akihito Okazaki, Takashi Sone, Hideharu Kimura, Masaki Fujimura, Shinji Nakao, Kazuo Kasahara

Abstract

Background

Cough variant asthma (CVA) is recognized as a precursor of bronchial asthma (BA). However, the cough response to bronchoconstriction differs between these similar diseases. Repeated bronchoconstriction and the resulting imbalance of endogenous lipid mediators may impact the cough response.

Methods

We investigated the influence of repeated bronchoconstriction on the cough response to bronchoconstriction using naïve guinea pigs. Bronchoconstriction was induced for 3 consecutive days and changes in the cough response and lipid mediators, such as PGE₂, PGI₂, and cysteinyl-LTs (Cys-LTs), in BAL fluid (BALF) were assessed. We investigated the effect of endogenous PGI₂ on the cough response by employing a PGI₂ receptor antagonist. In order to investigate the cough response over a longer period, we re-evaluated the cough response 2 weeks after repeated bronchoconstriction.

Results

The number of coughs induced by bronchoconstriction were significantly decreased by repeated bronchoconstriction. The levels of PGE₂, PGI₂, and Cys-LTs, and the ratio of PGI₂/PGE₂ were significantly increased, following repeated bronchoconstriction. This decrease in the cough response was suppressed by pretreatment with a PGI₂ receptor antagonist. Two weeks after repeated bronchoconstriction, the cough response returned to the same level as before repeated bronchoconstriction along with a concomitant return of lipid mediators, such as PGE₂, PGI₂, and Cys-LTs and the ratio of PGI₂/PGE₂.

Conclusions

Our results suggest that repeated bronchoconstriction and the resulting imbalance of endogenous lipid mediators contribute to the difference in cough responses to bronchoconstriction in CVA and BA.