Formaldehyde-induced airway hyperreactivity in vivo and ex vivo in guinea pigs

Human exposure to formaldehyde is extensive, in both the indoor and the outdoor environment. The airways are clearly an important site of action of formaldehyde. Although many previous studies have examined the effect of formaldehyde in the upper respiratory tract, it remains controversial whether this compound can affect the lower respiratory tract. To determine whether formaldehyde induces airway hyperreactivity, guinea pigs were exposed to formaldehyde or filtered air (sham control) for 2 or 8 hr. Airway smooth muscle responsiveness was evaluated in vivo and ex vivo. Specific pulmonary resistance and airway reactivity (to infused acetylcholine) increased with formaldehyde exposure. Formaldehyde exposure caused bronchoconstriction and hyperreactivity at lower concentrations when exposure duration was extended from 2 to 8 hr. Exposure to > or = 0.3 ppm formaldehyde for 8 hr was sufficient to produce a significant increase in airway reactivity, while similar effects only occurred after > 9 ppm formaldehyde for 2 hr. Formaldehyde exposure also heightens airway smooth muscle responsiveness to acetylcholine (or carbachol) ex vivo. These effects occurred with no evidence of epithelial damage or inflammation up to 4 days after formaldehyde exposure. Thus, at concentrations relevant to environmental exposure, formaldehyde, a common indoor air pollutant, alters airway smooth muscle reactivity in guinea pigs. These findings suggest that the duration of exposure is important to the induction of airway hyperreactivity and that prolonged, low-level exposures may generate abnormal physiological responses in the airways not detectable after acute exposures.