Increased LTB4 metabolites and PGD2 in BAL fluid after methacholine challenge in asthmatic subjects

The bronchoconstrictor potency of inhaled methacholine is widely used to assess airway responsiveness. However, evidence has accumulated that methacholine inhalation challenge may lead to an inflammatory response in the lower respiratory tract. We therefore compared cellular, leukotriene and prostanoid profiles in bronchoalveolar lavages (BAL) obtained five hours after methacholine challenge to control lavages without prior challenge. Eight subjects with asymptomatic to mild bronchial asthma and nine nonatopic healthy controls were enrolled in the study. Without prior challenge, the percentage of BAL eosinophils was higher in the asthmatic subjects ((mean +/- SD), 1.1 +/- 0.9%) than in the control subjects (0.1 +/- 0.1%. Leukotriene B4 (LTB4), and its omega-oxidation products (20-OH-LTB4 and 20-COOH-LTB4) were the only leukotrienes detectable in the baseline BAL fluids in five of the eight asthmatic patients. After methacholine challenge, no change in BAL cell profile occurred, but in the asthmatic patients, the total amounts of LTB4 and its omega-oxidation products rose from 0.52 +/- 0.50 ng.ml-1 (pre-challenge) to 1.55 +/- 1.32 ng.ml-1 (post-challenge), and prostaglandin D2 (PGD2) rose from 49.1 +/- 15.7 (pre-challenge) to 94.4 +/- 25.4 pg.ml-1 (post-challenge), with no change in 6-keto-PGF1 alpha, thromboxane B2 (TXB2), and prostaglandins F2 alpha and E2 (PGF2 alpha and PGE2). In the healthy controls, no consistent change in BAL cell profile and mediators occurred after methacholine provocation. We conclude that inhaled methacholine stimulates LTB4 and PGD2 release in asthmatics, but not in healthy controls, without affecting the number of inflammatory cells in BAL fluid.