Delivery of nebulized budesonide liposomes to the respiratory tract of allergic sheep

Inhaled budesonide has been shown to be an effective therapy for asthma. In a previous study in a sheep model, acute treatment with budesonide delivered by pressurized metered dose inhaler (pMDI) modified the late bronchoconstrictor response to inhaled antigen. In the present study, we utilized the same sheep model to assess whether the delivery of budesonide in a liposome preparation would modify the late asthmatic response and the associated airway hyperresponsiveness that is detectable 24 hours after challenge. In a crossover trial, six conscious intubated sheep were pretreated with 1 mg of budesonide/dilauroyl phosphatidylcholine (DLPC), or DLPC alone, 16 hours and again 1 hour prior to the administration of aerosolized Ascaris suum antigen. Using esophageal and tracheal pressure measurements and plethysmography, specific lung resistance (sR(L)) was measured over an 8-hour period following administration of the antigen. In addition, airway responsiveness to carbachol (as assessed by potential difference [PD] 400, the dose required to induce a 400% increase in sR(L)) was measured 24 hours pre- and postantigen administration. Bronchoalveolar lavage (BAL) was performed before and after the antigen was administered, and BAL fluid was assayed for total cell count and differential. The results showed that compared with control liposomes, budesonide inhibited late onset bronchoconstriction. With budesonide pretreatment, the mean (±standard deviation [SD]) increase in baseline sR(L) postantigen administration was 35% ± 37. Without budesonide pretreatment, the mean (±ISD) increase in baseline SRL was 206% ± 70, (P < 0.05). Early onset bronchoconstriction was not significantly affected: the increase in baseline sR(L) postantigen administration with budesonide was 281% ± 169; without budesonide, it was 303% ± 157, (P = not significant [NS]). The degree of hyperresponsiveness that occurred after the antigen was administered was significantly less with budesonide pretreatment compared with that in control studies (PD 400, 9.5 ± 2.9 breath units [control studies] versus 21.5 ± 3.7 breath units [budesonide studies)], (P < 0.05). Total cell count and differential in BAL fluid were not affected by budesonide pretreatment. We conclude that budesonide, when delivered by aerosolized liposomes, significantly modifies the late asthmatic response and the associated hyperresponsiveness in allergic sheep and that this mode of delivery may merit further study as a potentially useful therapeutic option for clinical asthma.