Effect of inhaled low molecular weight heparin on methacholine-induced bronchoconstriction

Objectives: Recent studies have shown that inhaled standard heparin exhibit s protection towards various bronchoconstrictor stimuli in asthma including methacholine. Low molecular weight hepatins (LMWH) (4000 - 5000 daltons) h ave higher bioavailability than standard heparins (12,000 - 16,000 daltons) . It is possible that the anti-asthmatic activity of heparin may be molecul ar weight-dependent. The purpose of the present investigation was to study the effect of LMWH on methacholine-induced bronchoconstriction and to compa re the effect of LMWH with that of standard heparin. Subjects: Fifteen subj ects (7 male, 8 female, mean age: 33 +/- 13 years, range. 20 - 65) with mil d asthma were studied. Method: Methacholine bronchial provocation tests wer e performed in a single-blind, crossover, randomized order and repeated 45 minutes after placebo or aerosolized standard heparin(1.000 U/kg) or aeroso lized LMWH (Enoksaparin, Clexane, 0.8 mg/kg). Results: There was no signifi cant difference in baseline FEV I values between study days. The standard h eparin and enoksaparin inhibited bronchoconstriction induced by methacholin e. The geometric mean log PD20 values after placebo, standard heparin, and enoksaparin were 0.24 +/- 0.57 (1.74) mg/ml, 0.79 +/- 0.59 (6.17 mg/ml), 0. 76 +/- 6.57 (5.7 mg/ml), respectively (p < 0.0009). Three subjects in stand ard heparin group and two subjects in enoksaparin group showed increased hy perreactivity, the others showed decreased bronchial hyperreactivity. The d egree of protection offered by standard heparin and enoksaparin did not sho w any statistical difference. Conclusions: These data suggest that both inh aled LMWH and inhaled standard heparin play inhibitory roles in methacholin e-induced bronchoconstriction.