No impairment of peripheral deposition in novel asthmatics treated with an MDI corticosteroid with spacer.

Pulmonary distribution and lung functions were evaluated during a 4-month inhaled corticosteroid treatment period in 10 steroid-naïve novel asthmatics with normal or slightly reduced lung functions. Patients were given a total daily dose of 1000 microg of beclomethasone dipropionate aerosol twice a day via a pressured metered dose inhaler with a large-volume chamber device (Volumatic, GlaxoSmith Kline, U.K.). Gamma lung scintigraphy and lung function tests were performed before and after 2 months and 4 months. Inhaled 99mTc-labelled beclomethasone dipropionate liposomes were used to assess lung deposition patterns during inhaled steroid therapy. Serum eosinophil cationic protein (ECP) concentration was used as a surrogate marker of asthmatic inflammation. Following beclomethasone treatment, all lung functions were enhanced, but only FVC values showed significant improvement. The FEV1/FVC ratio remained slightly reduced in spite of inhaled corticosteroid therapy. However, the association between changes in improved FVC values and reduced ECP levels proved to be statistically significant. In lung scintigraphy, no evidence of changes in pulmonary deposition patterns were seen during the follow-up period. We conclude that inhaled corticosteroid therapy can lead to improvements in lung functions and surrogate markers of airway inflammation in novel asthma without affecting the peripheral deposition pattern of aerosols.

Possibilities of formoterol to enhance the peripheral lung deposition of the inhaled liposome corticosteroids.

The pulmonary distribution and clearance of 99m-Tc-labelled beclomethasone dipropionate (Bec)--dilauroylphosphatidylcholine (DLPC) were compared in nine asthmatic patients on inhaled steroids after a 1-week medical treatment period of long-acting beta2-agonist formoterol. The patients were given formoterol 12 microg (OxisTurbuhaler) twice daily in addition to their own regular inhaled corticosteroid therapy. Gamma lung scintigraphy and lung function tests were performed before and after formoterol treatment. The bronchodilating effect ofthe combined therapy was significant: 1-week usage of inhaled formoterol enhanced peripheral lung deposition of beclomethasone liposome and thus diminished central/peripheral deposition ratio (C/P ratio). All measured lung function values except FEV1/FVC% improved after the medication period, although statistically significant levels were not reached. A systemic positive connection was seen between enhanced lung functions and greater lung deposition measured as AUC(0-24h)/24 Beclomethasone liposome formulation maintained its long-lasting effect in connection with formoterol treatment. At the 4-h measurement, 76% of the liposome-entrapped radioactivity still remained in the lungs before and 75% after the medication period.

Regional lung deposition and clearance of 99mTc-labeled beclomethasone-DLPC liposomes in mild and severe asthma.

OBJECTIVE: To compare the distribution and clearance of inhaled beclomethasone dipropionate (Bec)-dilauroylphosphatidylcholine (DLPC) liposomes in patients with mild and severe asthma. DESIGN: A 99mTc-labeled Bec-DLPC suspension was delivered via a nebulizer (Aerotech II). Immediately after inhalation, anterior and posterior views of the lungs and an anterior view of the oropharynx were measured by a large field gamma camera with the patient in a supine position. To evaluate the mucociliary clearance of the inhaled liposomes, anterior and posterior lung scans were repeated 1, 2, 4, and 24 h after the aerosol delivery. PATIENTS: Ten patients with mild asthma (FEV1 >80% of the predicted) and 10 patients with severe asthma (FEV1 <60% of the predicted) were included in an open, parallel group study. RESULTS: Clearance is more rapid among patients with severe asthma (p<0.0001). At the 4-h measurement, a mean of 82% (SD, 5.9) of the total pulmonary dose was detected in the lungs of patients with mild asthma while in those with severe asthma the figure was 69% (SD, 10.9). The ratio between central and peripheral deposition was significantly higher for patients with severe asthma than for those having a mild form of the disease; 1.07 (SD, 0.29) and 0.76 (SD, 0.07), respectively (p=0.008). CONCLUSIONS: Inhaled Bec-DLPC liposomes were deposited more centrally in the lower airways of patients with severe asthma than those having a milder form of the disease. The clearance of Bec-DLPC liposomes is strikingly slow in both groups of asthmatic patients. However, due to the more peripheral penetration of inhaled liposomes in patients with mild asthma, the clearance rate in this group was slower than in those with severe asthma.