zithromax and Bronchial-Hyperreactivity

The effect of azithromycin on bronchial hyperresponsiveness was measured in a group of 11 patients with mild asthma. Azithromycin 250 mg orally was administered intermittently to all the patients twice a week for eight weeks. The only other treatment was inhaled beta2 agonist, when required. A histamine inhalation test was performed at the beginning and at the fourth and the eighth week of the study. The mean PC20 values increased significantly over the initial value at the eighth week after the administration of azithromycin (p < 0.05) but mean values for FEV1 and FEV1 percent predicted did not differ significantly. These results suggested that eight weeks of intermittent, low-dose administration of azithromycin in patients with mild asthma might reduce the severity of bronchial hyperresponsiveness.

Topics: Adult; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchial Hyperreactivity; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Severity of Illness Index

We investigated the effect of long-term treatment with azithromycin on the pathogenesis of chronic asthma with airway remodeling.. Six-week-old-BALB/c mice were sensitized with ovalbumin (OVA) combined with lipopolysaccharide (LPS) for 1 month, then challenged with OVA for 3 months. Azithromycin at 75 mg/kg was administered via oral gavage five times a week during the challenge period. Inflammatory cells, T helper 2 cytokines in bronchoalveolar lavage fluid (BAL) fluid, and airway hyperresponsiveness (AHR) were measured. Parameters related to airway remodeling were evaluated. The levels of neutrophil elastase, Interleukin (IL)-8, and BRP-39 (human homologue YKL-40) were assessed. The expression of MAPK and NF-κB signaling were investigated.. Long-term treatment with azithromycin improved AHR and airway inflammation compared with the OVA and the OVA/LPS groups. The concentrations of IL-5 and IL-13 in the OVA/LPS group decreased significantly after azithromycin administration. The levels of neutrophil elastase and IL-8, as surrogate markers of neutrophil activation, were reduced in the azithromycin group compared with the OVA/LPS group. Goblet cell hyperplasia and the smooth muscle thickening of airway remodeling were attenuated after azithromycin treatment. The expression of MAPK/NF-kappaB signal and the level of BRP-39 in the lung decreased remarkably in the OVA/LPS with azithromycin-treated group.. This study suggests that in a murine model of chronic asthma, long-term azithromycin treatment ameliorates not only airway inflammation but also airway remodeling by influencing on neutrophilc-related mediators, BRP-39 and MAPK/NF-κB signal pathways. Macrolide therapy might be an effective adjuvant therapy in a chronic, severe asthma with remodeling airway.

Topics: Animals; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Female; Interleukins; Leukocyte Elastase; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; Ovalbumin; Pneumonia; T-Lymphocytes, Helper-Inducer

Definitive conclusions regarding the antiinflammatory effects of macrolide antibiotics for treatment of asthma are difficult to formulate since their beneficial effects may be related to their antimicrobial action. We hypothesized that azithromycin possesses distinct antiinflammatory properties and tested this assumption in a noninfectious mouse model of allergic asthma.. To induce allergic airway inflammation, 7-week-old BALB/cJ mice underwent intraperitoneal ovalbumin sensitization on days 0 and 7 followed by an intranasal challenge on day 14. Mice were treated with azithromycin or phosphate-buffered saline (PBS) solution on days 13 through 16. On day 17, airway inflammation was assessed by quantifying leukocytes in the airway, expression of multiple inflammatory mediators in the BAL fluid, and mucous cell metaplasia. In a separate set of experiments, azithromycin or PBS solution treatment were initiated after the ovalbumin challenge. Each experiment was repeated 3 times (a total of 9 to 11 mice in each group).. Compared to treatment with PBS solution, azithromycin attenuated the ovalbumin-dependent airway inflammation. We observed a decrease in total leukocytes in the lung tissue and BAL fluid. In addition, azithromycin attenuated the expression of cytokines (eg, interleukin [IL]-13 and IL-5) and chemokines (eg, CCL2, CCL3, and CCL4) in the BAL fluid and abrogated the extent of mucous cell metaplasia. Similar antiinflammatory effects were observed when azithromycin treatment was initiated after the ovalbumin challenge.. In this noninfectious mouse model of allergic asthma, azithromycin attenuated allergic airway inflammation. These findings demonstrate an antiinflammatory effect of azithromycin and suggest azithromycin may have beneficial effects in treating noninfectious airway inflammatory diseases, including asthma.

Topics: Animals; Asthma; Azithromycin; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Female; Immunoglobulin E; Inflammation; Inflammation Mediators; Leukocyte Count; Lung; Mice; Mice, Inbred BALB C; Mucous Membrane; Ovalbumin; Random Allocation; Reference Values; Risk Factors; Sensitivity and Specificity