Bronchodilators modulate inflammation in chronic obstructive pulmonary disease subjects

Chronic obstructive pulmonary disease (COPD) is characterized by neutrophilic airway inflammation and oxidative stress. Leukotriene B₄ (LTB₄), a potent proinflammatory mediator, is synthesized by 5-lipoxygenase (5-LO), which is activated by the presence of lipid hydroperoxides resulting from oxidative stress on biological membranes. We proposed to evaluate the effect of a four week treatment with two different bronchodilators of common practice in COPD treatment, on the production of reactive oxygen species (ROS), in particular superoxide anions, and of LTB₄ by peripheral blood neutrophils obtained from COPD subjects. 24 subjects among the COPD outpatients were enrolled, and randomized to receive either formoterol (12 μg bid) or tiotropium (18 μg od). Peripheral blood neutrophils were obtained at the start and at the end of the treatment, and production of superoxide anions and of LTB₄ were evaluated as previously published. The results obtained showed a decrease in the unstimulated production of superoxide by isolated neutrophils in both groups, but tiotropium only was effective in modulating the production of LTB₄, while formoterol caused an increased production of superoxide in response to fMLP, when compared to values obtained before treatment. In conclusion, tiotropium showed a better antiinflammatory activity profile when compared to formoterol in a clinical setting, reducing superoxide and LTB₄ production by peripheral neutrophils obtained from COPD subjects.