DELIVERY OF NEBULIZED BUDESONIDE LIPOSOMES TO THE RESPIRATORY-TRACT OF ALLERGIC SHEEP

Inhaled budesonide has been shown to be an effective therapy for asthm a. In a previous study in a sheep model, acute treatment with budesoni de delivered by pressurized metered dose inhaler (pMDI) modified the l ate bronchoconstrictor response to inhaled antigen. In the present stu dy, 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 detecta ble 24 hours after challenge. In a crossover trial, six conscious intu bated sheep were pretreated with 1 mg of budesonide/dilauroyl phosphat idylcholine (DLPC), or DLPC alone, 16 hours and again 1 hour prior to the administration of aerosolized Ascarissuum antigen. Using esophagea l and tracheal pressure measurements and plethysmography, specific lun g resistance (sR(L)) was measured over an 8-hour period following admi nistration of the antigen. In addition, airway responsiveness to carba chol (as assessed by potential difference [PD] 400, the dose required to induce a 400% increase in sR(L)) was measured 24 hours pre- and pos tantigen administration. Bronchoalveolar lavage (BAL) was performed be fore and after the antigen was administered, and BAL fluid was assayed for total cell count and differential. The results showed that compar ed with control liposomes, budesonide inhibited late onset bronchocons triction. With budesonide pretreatment, the mean (+/-standard deviatio n (SDI) increase in baseline sR(L) postantigen administration was 35% +/- 37. Without budesonide pretreatment, the mean (+/-SD) increase in baseline sR(L) was 206% +/- 70, (P < 0.05). Early onset bronchoconstri ction was not significantly affected: the increase in baseline sR(L) p ostantigen administration with budesonide was 281% +/- 169; without bu desonide, it was 303% +/- 157, (P = not significant [NS]). The degree of hyperresponsiveness that occurred after the antigen was administere d was significantly less with budesonide pretreatment compared with th at in control studies (PD 400, 9.5 +/- 2.9 breath units [control studi es] 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 b y aerosolized liposomes, significantly modifies the late asthmatic res ponse and the associated hyperresponsiveness in allergic sheep and tha t this mode of delivery may merit further study as a potentially usefu l therapeutic option for clinical asthma.