zithromax and Fibrosis

The efficacy of azithromycin to prevent exacerbation for non-cystic fibrosis bronchiectasis remains controversial. We conduct this meta-analysis to explore the influence of azithromycin versus placebo for the treatment of non-cystic fibrosis bronchiectasis.. We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through July 2019 for randomized controlled trials (RCTs) assessing the efficacy of azithromycin versus placebo for non-cystic fibrosis bronchiectasis. This meta-analysis was performed using the random-effect model.. Four RCTs were included in the meta-analysis. Overall, compared with control group for non-cystic-fibrosis bronchiectasis, azithromycin treatment was associated with improved free of exacerbation (odd ratios [OR] = 3.66; 95% confidence interval [CI] = 1.69-7.93; P = 0.001), reduced pulmonary exacerbations (OR = 0.27; 95% CI 0.13-0.59; P = 0.001) and number of pulmonary exacerbations (standard mean difference [SMD] =  - 0.87; 95% CI - 1.21 to - 0.54; P < 0.00001), but demonstrate no obvious impact on forced expiratory volume in 1 s (FEV1), score on St George's respiratory questionnaire, nausea or vomiting, adverse events.. Azithromycin is effective to prevent exacerbation of non-cystic fibrosis bronchiectasis.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Fibrosis; Forced Expiratory Volume; Humans; Randomized Controlled Trials as Topic

Azithromycin mass drug administration (MDA) could reduce child mortality. However, macrolide resistance, which has generally been reported to develop after whole-community MDA for trachoma control, is a concern, and it has less commonly been studied in the context of treating children to reduce mortality. Here, we report on macrolide resistance after biannual azithromycin MDA at the Malawi site of the MORDOR study.. In the MORDOR cluster-randomised trial in Malawi, 30 communities in Mangochi District were randomly selected. Communities were randomly assigned to receive azithromycin or placebo by simple randomisation without stratification. Children aged 1-59 months were administered azithromycin 20 mg/kg or placebo as an oral suspension biannually for a total of four treatments in 2015-17. 1200 children (40 children per community) were randomly selected for nasopharyngeal swabs at baseline, 12 months (6 months after the second treatment visit), and 24 months (6 months after the fourth treatment visit). Samples were processed to culture. These findings support previous evidence from trachoma MDA programmes and suggest that monitoring of macrolide resistance should remain a key component of azithromycin interventions for reducing child mortality.. Bill & Melinda Gates Foundation.. Our results indicate that non-invasive local LIPUS therapy attenuated heart fibrosis and dysfunction in diabetic mice and the effect could be largely preserved at least 12 weeks after suspending LIPUS stimulation. LIPUS ameliorated diabetic heart fibrosis by inhibiting ACE-mediated NOX4-associated oxidative stress and NLRP3 inflammasome activation in cardiac fibroblasts. Our study may provide a novel therapeutic approach to hamper the progression of diabetic heart fibrosis.

Topics: Acoustics; Adsorption; Angiotensin II; Animals; Anti-Bacterial Agents; Azithromycin; Calcium; Carbon; Charcoal; Child; Chlorides; Copper; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Dopamine; Dopamine Plasma Membrane Transport Proteins; Drug Resistance, Bacterial; Ecosystem; Epigenesis, Genetic; Female; Fibroblasts; Fibrosis; Gallium Radioisotopes; Heterozygote; Hot Temperature; Humans; Hydrogen-Ion Concentration; Inflammasomes; Inflammation; Kinetics; Macrolides; Magnetic Resonance Imaging; Malawi; Male; Mass Drug Administration; Methylene Blue; Mice; Neuroendocrine Tumors; NLR Family, Pyrin Domain-Containing 3 Protein; Octreotide; Organometallic Compounds; Oxidative Stress; Phenotype; Positron-Emission Tomography; Prevalence; Prognosis; Rats; Receptors, Somatostatin; Retrospective Studies; Rivers; Streptococcus pneumoniae; Trachoma; Water Pollutants, Chemical; Zinc Compounds

Non-cystic fibrosis bronchiectasis (NCFB) brought a heavy healthcare burden worldwide. Macrolide maintenance therapy was proved to be helpful in reducing exacerbation of NCFB. However, the optimal dosing regimens of macrolides have not been determined, and its efficacy in Chinese NCFB population has not been validated. This protocol describes a head-to-head clinical trial designed to compare the efficacy of two dosing regimens of azithromycin in Chinese NCFB population.. This prospective, open-label and randomised controlled trial will be conducted in the First People's Hospital of Jiashan, China. Eligible patients with high-resolution CT defined NCFB will be randomly divided into three groups, which will receive either 250 mg daily azithromycin, or 500 mg three-times-weekly azithromycin or no treatment for 6 months. They will be followed up for another 6 months without treatment. The primary outcome is the mean rate of protocol-defined pulmonary exacerbation at 6 months.. Ethical approval was obtained from the First People's Hospital of Jiashan Ethics Committee. The findings will be disseminated in peer-reviewed publications.. ChiCTR2100052906.

Topics: Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Cystic Fibrosis; Fibrosis; Humans; Macrolides; Prospective Studies; Randomized Controlled Trials as Topic

We herein report the case of a 20 year-old-man who developed bronchiolitis obliterans after living-donor renal transplantation. The patient presented with dyspnea on exertion and wheezing two years after renal transplantation, and spirometry showed an obstructive pattern. Surgical lung biopsy revealed subepithelial fibrosis that constricted and obstructed the intrabronchiolar space. Based on these findings, the patient was diagnosed with bronchiolitis obliterans. He was prescribed bronchodilators and azithromycin, and he achieved stable respiratory function for two years. The differential diagnosis of respiratory symptoms after renal transplantation includes opportunistic infection and drug-induced lung injury; however, bronchiolitis obliterans should also be considered.

Topics: Adult; Azithromycin; Bronchiolitis Obliterans; Bronchodilator Agents; Diagnosis, Differential; Fibrosis; Humans; Kidney Transplantation; Living Donors; Lung; Male; Postoperative Complications; Spirometry; Young Adult

Topics: Amoxicillin; Azithromycin; Bronchiectasis; Child; Clavulanic Acid; Double-Blind Method; Fibrosis; Humans

Accumulation of profibrotic myofibroblasts is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF) pathogenesis. TGFB (transforming growth factor β) is one of the major profibrotic cytokines for myofibroblast differentiation and NOX4 (NADPH oxidase 4) has an essential role in TGFB-mediated cell signaling. Azithromycin (AZM), a second-generation antibacterial macrolide, has a pleiotropic effect on cellular processes including proteostasis. Hence, we hypothesized that AZM may regulate NOX4 levels by modulating proteostasis machineries, resulting in inhibition of TGFB-associated lung fibrosis development. Human lung fibroblasts (LF) were used to evaluate TGFB-induced myofibroblast differentiation. With respect to NOX4 regulation via proteostasis, assays for macroautophagy/autophagy, the unfolded protein response (UPR), and proteasome activity were performed. The potential anti-fibrotic property of AZM was examined by using bleomycin (BLM)-induced lung fibrosis mouse models. TGFB-induced NOX4 and myofibroblast differentiation were clearly inhibited by AZM treatment in LF. AZM-mediated NOX4 reduction was restored by treatment with MG132, a proteasome inhibitor. AZM inhibited autophagy and enhanced the UPR. Autophagy inhibition by AZM was linked to ubiquitination of NOX4 via increased protein levels of STUB1 (STIP1 homology and U-box containing protein 1), an E3 ubiquitin ligase. An increased UPR by AZM was associated with enhanced proteasome activity. AZM suppressed lung fibrosis development induced by BLM with concomitantly reduced NOX4 protein levels and enhanced proteasome activation. These results suggest that AZM suppresses NOX4 by promoting proteasomal degradation, resulting in inhibition of TGFB-induced myofibroblast differentiation and lung fibrosis development. AZM may be a candidate for the treatment of the fibrotic lung disease IPF.

Topics: Animals; Azithromycin; Bleomycin; Cell Differentiation; Disease Models, Animal; Fibrosis; Humans; Idiopathic Pulmonary Fibrosis; Lung; Mice, Inbred C57BL; Mitochondria; Models, Biological; Myofibroblasts; NADPH Oxidase 4; Proteasome Endopeptidase Complex; Proteolysis; Reactive Oxygen Species; Transforming Growth Factor beta1; Ubiquitin-Protein Ligases; Ubiquitination; Unfolded Protein Response

Azithromycin has become a standard of care in therapy of bronchiolitis obliterans following lung transplantation. Matrix metalloprotease-9 broncho-alveolar lavage levels increase in airway neutrophilia and bronchiolitis obliterans. Interleukin-17 may play a role in lung allograft rejection, and interleukin-12 is downregulated in bronchiolitis obliterans. Whether these mechanisms can be targeted by azithromycin remains unclear.. Bronchiolitis obliterans was induced by transplantation of Fischer F344 rat left lungs to Wistar Kyoto rats. Allografts with azithromycin therapy from day 1 to 28 or 56 and mono- or combination therapy with the broad-spectrum matrix metalloprotease inhibitor tanomastat from day 1 to 56 were compared to control allografts and isografts. Graft histology was assessed, and tissue cytokine expression studied using Western blotting and immunofluorescence.. The chronic airway rejection score in the azithromycin group did not change between 4 and 8 weeks after transplantation, whereas it significantly worsened in control allografts (P = .041). Azithromycin+tanomastat prevented complete allograft fibrosis, which occurred in 40% of control allografts. Azithromycin reduced interleukin-17 expression (P = .049) and the number of IL-17(+)/CD8(+) lymphocytes at 4 weeks, and active matrix metalloprotease-9 at 8 weeks (P = .017), and increased interleukin-12 expression (P = .025) at 8 weeks following transplantation versus control allografts.. The expression of interleukin-17 and matrix metalloprotease-9 in bronchiolitis obliterans may be attenuated by azithromycin, and the decrease in interleukin-12 expression was prevented by azithromycin. Combination of azithromycin with a matrix metalloprotease inhibitor is worth studying further because it prevented complete allograft fibrosis in this study.

Topics: Animals; Azithromycin; Biphenyl Compounds; Bronchiolitis Obliterans; Disease Models, Animal; Drug Therapy, Combination; Fibrosis; Graft Survival; Interleukin-12; Interleukin-17; Lung; Lung Transplantation; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Phenylbutyrates; Rats, Inbred F344; Rats, Inbred WKY; Time Factors

One of the important causes of failed back surgery is the extensive peridural fibrosis collecting in the surgical field after spinal surgeries. Today we know that inflammatory mechanisms mediated by the immune system of the body plays an important role in generation of fibrosis. Azithromycin, a macrolide antibiotic, has proven immunomodulatory effects in various diseases. This study aims to investigate the effects of azithromycin on peridural fibrosis.. Twenty-four Wistar rats received laminectomies before dividing them into three groups randomly. Animals of the control group received normal saline intraperitoneally while animals in the treatment groups received low (20 mg/kg) and high (80 mg/kg) doses of azithromycin intraperitoneally after surgical interventions. The amount of fibrosis, fibroblast density and inflammatory cell density were analyzed histologically.. Analysis demonstrated significantly reduced fibrosis, fibroblast density and inflammatory cell density in treatment groups compared to the control group. There was no difference between the treatment groups.. Immune system plays critical roles in tissue repair and fibrogenesis. Results of our study demonstrated that azithromycin application reduced formation of peridural fibrosis in experimental laminectomy model in rats. Further studies with different dose regimes and different application routes are required to carry these results to an advanced level.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Disease Models, Animal; Failed Back Surgery Syndrome; Fibrosis; Immunologic Factors; Laminectomy; Rats; Rats, Wistar