Pirfenidone, an antifibrotic drug with anti-inflammatory and
antioxidant effects, delays
fibrosis in
idiopathic pulmonary fibrosis (IPF). Patients with IPF have a greater
cough reflex sensitivity to inhaled
capsaicin than healthy people, and
cough is an independent predictor of IPF
disease progression; however, the effects of
pirfenidone on
cough reflex sensitivity are unknown. After challenge with an aerosolized
antigen in actively sensitized guinea pigs,
pirfenidone was administered intraperitoneally, and the
cough reflex sensitivity was measured at 48 h after the challenge. Bronchoalveolar lavage (BAL) was performed, and the tracheal tissue was collected.
Pirfenidone suppressed the
capsaicin-induced increase in
cough reflex sensitivity in a dose-dependent manner. Additionally, increased levels of
prostaglandin E2,
substance P, and
leukotriene B4, but not
histamine, in the BAL fluid were dose dependently suppressed by
pirfenidone. The decrease in
neutral endopeptidase activity in the tracheal tissue was also alleviated by
pirfenidone treatment. The total number of cells and components in the BAL fluid was not influenced. These results suggest that
pirfenidone ameliorates isolated
cough based on increased
cough reflex sensitivity associated with allergic airway diseases, and potentially relieve
chronic cough in IPF patients who often have increased
cough reflex sensitivity. Prospective studies on
cough-relieving effects of
pirfenidone in patients with IPF are therefore warranted.