Environmental exposure to tobacco
smoke contributes to the onset of several
lung diseases, e.g.
chronic bronchitis and
asthma, including an increase in airway reactivity. We have investigated the effect of a new mucoactive compound,
CO 1408, on airway hyperreactivity and
lung inflammation induced in guinea-pigs by passive cigarette
smoke exposure. Animals were exposed to cigarette
smoke in a Plexi-glass box, three times a day for four days. Airway reactivity to
histamine was assessed ex-vivo in lung parenchymal strips. As a measure of
lung inflammation, the number of leucocytes was evaluated in bronchoalveolar lavage (BAL) fluids and histological sections. Passive
smoke exposure potentiated
histamine-induced contraction in lung parenchymal strips, a phenomenon associated with an increase in proinflammatory cells in the BAL fluids and enhanced eosinophil infiltration into parenchymal tissues. Pretreatment with oral
CO 1408 at 400 mg.kg-1 but not 100 mg.kg-1, completely prevented the cigarette
smoke-induced airway hyperreactivity. 400 mg.kg-1
CO 1408 also inhibited the increase in cell numbers in the BAL fluids, but not eosinophil recruitment in parenchymal tissues. The present data indicate the ability of
CO 1408 to modulate
smoke-induced airway hyperreactivity and, to some extent,
lung inflammation, an effect which might be of value in the
therapy of
obstructive pulmonary diseases.