The efficiency of different nebulized steroid dosage regiments in mouse model of chronic asthma

AIM:Inhaled corticosteroids are recommended as a first line treatment for all levelş of persistant asthma. In long term, compliance to the treatment declines according to twice a daily treatment regiments, particularly in children. There is no study demonstrating comparison of the effectiveness and potential side effects of inhaled steroid regiments in asthmatics either twice a day or once a day and every other day in the circumstances of same total cumulative dosage.MATERIAL AND METHOD:Spesific pathogen-free, 6- to 8-week-old, female BALB/c mice, weighting 20 to 25 g, were obtained from Animal Studies Laboratory of Dokuz Eylul University Medical Faculty. They were kept in hygenic macrolene cages and allowed ad libitum in air-conditioned rooms on a 12-hour light/12-hour dark cycle. All experimental procedures complied with the requirements of the Animal Care and Ethics Committee of the Dokuz Eylul University.Thirty-five BALB/c mice were divided into five groups which include seven mice in each; control group (group 1), plasebo group (group 2), 3, 4, and 5. The mice in study groups except control group were sensitized with chicken egg albumin (ovalbumin, grade V, ?98% pure; Sigma, USA) with aluminium intraperitoneally to constitute chronic astma model on 0. and 14. days of the study. After 21th day of the study the mice except controls received aerolized ovalbumine for 8 weeks. Controls received nebulized saline during sensitization period.After sensitization, mice in group 2 treated with saline twice a day, group 3 with budesonide of 250 mcg twice a day, group 4 with budesonide of 500 mcg once a day, and group 5 with budesonide of 1000 mcg every other day in the last 14 days of the challenge period. Animals were sacrificed and lung samples were examined for thicknesses of epithelium, goblet and mast cell counts and subepithelial smooth muscle thickness of lung tissue for examination of effectiveness of different dose regiments of inhaled steroids on lung histology. Bone tissues obtained from proximal tibia were examinated after 6 months of decalsification period for determination of side effects of inhaled streoid on trabecular bone and osteoid matrix.RESULTS:All of the histological parameters of the lung tissue were increased in the placebo group (group 2) than the controls (group 1). The results demonstrate the chronic asthma model was established succesfully.When we compare the histological parameters of lung between group 2 and other groups, all the parameters except goblet cell count was decreased in group 3; basement membrane thickness (p=0.000), subepithelial smooth muscle thickness (p=0.000), epithelial height (p=0.024) were decreased in group 4; and all parameters were sattistically significantly decreased in group 5. When the results of histological parameters of lung were compared between group 3 and 4 basement membrane thickness was decreased in group 4 (p=0.003). In group 5 subepithelial thickness was decreased when compared with either group 3 or group 4 (p=0.008, p=0.008, respectively).When the histological parameters of bone tissue of proximal tibia was compared to demonstrate the side effects of budesonide on bone tissue between group 2 and either the group 3, 4 or 5; all parameters except osteoid bone thickness were statistically significantly higher in group 2 (p<0.05). There was no statistically significant difference found between group 3, 4 and 5 among trabecular count, trabecular thickness and cortex thickness (p>0.05).CONCLUSION:The pulmonary parameters were alimeorated in all groups which received inhaled corticosteroid. Th pulmonary findings were alimeorated more than the other groups in which received budezonide of dose of 1000 mcg every other day. When we compare the side effects of budesonide on bone between the groups, in all groups except placebo group (group 2), a significant trabecular bone and osteoid matrix loss was demonstrated. Unfortunately, there was no significant difference between the groups of 3, 4, and 5 about measured parameters of trabecular bone and osteoid matrix.