zithromax and Pulmonary-Fibrosis

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pulmonary condition, characterized by diffuse proliferation of neuroendocrine cells in the respiratory epithelium. DIPNECH lesions are less than 5 mm in size and are limited to the basement membrane with no invasion. There is limited information regarding epidemiology, natural history of disease progression, or the management of this rare entity. We present the experience of a center with extensive expertise in neuroendocrine disease.. A cohort of patients (N = 13) with DIPNECH treated and followed at our institution was identified. We describe the our approach to their care, our disease management and also provide a review of DIPNECH pathophysiology.. Our patient cohort consisted of twelve females and one male with a mean age of 63 years at the time of diagnosis. Dyspnea on exertion and dry cough were the most common presenting symptoms. Two patients were under surveillance without treatment; three patients were treated with a short-acting somatostatin analog; three patients were treated with azithromycin alone; four were treated with a combination of long-acting monthly somatostatin analogs and azithromycin; one patient received a combination of long-acting somatostatin analog and everolimus. Five patients had concomitant bronchial carcinoids.. DIPNECH is a rare pathology that can profoundly affect a patient's quality of life. Paroxysmal coughing episodes can be difficult to treat. Our limited single center experience shows encouraging response to use of somatostatin analogs, azithromycin, and everolimus in the management of debilitating DIPNECH associated symptoms.

Topics: Aged; Anti-Bacterial Agents; Antineoplastic Agents, Hormonal; Azithromycin; Bronchial Neoplasms; Carcinoid Tumor; Cough; Dyspnea; Everolimus; Female; Humans; Hyperplasia; Immunosuppressive Agents; Lung Diseases; Male; Middle Aged; Multiple Pulmonary Nodules; Neuroendocrine Cells; Octreotide; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Quality of Life; Respiratory Mucosa

Bronchiolitis obliterans syndrome remains the leading cause of morbidity and mortality in the pulmonary transplant population. Previous studies show that macrolide antibiotics may be efficacious in the treatment of panbronchiolitis and cystic fibrosis. In the latter, azithromycin decreases the number of respiratory exacerbations, improves FEV1, and improves quality of life. We hypothesized that oral azithromycin therapy may improve lung function in patients with bronchiolitis obliterans syndrome. To test this hypothesis, we conducted an open-label pilot trial using maintenance azithromycin therapy in six lung transplant recipients (250 mg orally three times per week for a mean of 13.7 weeks). In this study, five of these six individuals demonstrated significant improvement in pulmonary function, as assessed by FEV1, as compared with their baseline values at the start of azithromycin therapy. The mean increase in the percentage of predicted FEV1 values in these individuals was 17.1% (p

Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Azithromycin; Bronchiectasis; Bronchiolitis Obliterans; Cystic Fibrosis; Drug Administration Schedule; Follow-Up Studies; Forced Expiratory Volume; Humans; Immunosuppressive Agents; Lung Transplantation; Middle Aged; Pilot Projects; Pulmonary Fibrosis; Quality of Life; Severity of Illness Index; Syndrome; Time Factors; Treatment Outcome

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the Paracoccidioides genus. Most of the patients with chronic form present sequelae, like pulmonary fibrosis, with no effective treatment, leading to impaired lung functions. In the present study, we aimed to investigate the antifibrotic activity of three compounds: pentoxifylline (PTX), azithromycin (AZT), and thalidomide (Thal) in a murine model of pulmonary PCM treated with itraconazole (ITC) or cotrimoxazole (CMX). BALB/c mice were inoculated with P. brasiliensis (Pb) by the intratracheal route and after 8 weeks, they were submitted to one of the following six treatments: PTX/ITC, PTX/CMX, AZT/ITC, AZT/CMX, Thal/ITC, and Thal/CMX. After 8 weeks of treatment, the lungs were collected for determination of fungal burden, production of OH-proline, deposition of reticulin fibers, and pulmonary concentrations of cytokines and growth factors. Pb-infected mice treated with PTX/ITC presented a reduction in the pulmonary concentrations of OH-proline, associated with lower concentrations of interleukin (IL)-6, IL-17, and transforming growth factor (TGF)-β1 and higher concentrations of IL-10 compared to the controls. The Pb-infected mice treated with AZT/CMX exhibited decreased pulmonary concentrations of OH-proline associated with lower levels of TGF-β1, and higher levels of IL-10 compared controls. The mice treated with ITC/Thal and CMX/Thal showed intense weight loss, increased deposition of reticulin fibers, high pulmonary concentrations of CCL3, IFN-γ and VEGF, and decreased concentrations of IL-6, IL-1β, IL-17, and TGF-β1. In conclusion, our findings reinforce the antifibrotic role of PTX only when associated with ITC, and AZT only when associated with CMX, but Thal did not show any action upon addition.

Topics: Animals; Antifungal Agents; Azithromycin; Cytokines; Disease Models, Animal; Drug Therapy, Combination; Immunosuppressive Agents; Intercellular Signaling Peptides and Proteins; Itraconazole; Male; Mice; Mice, Inbred BALB C; Paracoccidioides; Paracoccidioidomycosis; Pentoxifylline; Pulmonary Fibrosis; Random Allocation; Thalidomide; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Azathioprine; Azithromycin; Fatal Outcome; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Prednisolone; Pulmonary Fibrosis; Respiratory Function Tests; Thoracoscopy; Tomography, X-Ray Computed

To study the role of Th1/Th2 balance in the pathogenesis of pulmonary fibrosis and to investigate the therapeutic mechanisms of azithromycin.. Male wistar rats were randomly divided into three experimental groups: the bleomycin A(5) (BLM) group (BLM group), the azithromycin (AZI) group (AZI group) and the control group. Quantitative analysis of the histopathologic changes was performed by computer gray scan. The expression of IL-10 mRNA and IFN-gamma mRNA was examined by RNase protection assay (RPA).. (1) In the BLM group, up-regulation of IL-10 mRNA was stronger than that of IFN-gamma mRNA, resulting in the inversion of the IL-10/IFN-gamma mRNA ratio, a shift from the Th1-like response of IFN-gamma predominance in the control group to the Th2-like response of IL-10 predominance in the BLM group. (2) The oral administration of AZI inhibited the expression of IL-10 and IFN-gamma mRNA; reversed the Th2-like response in the BLM group to the Th1-like response on day 7; and decreased the exudation of inflammatory cells as well as the degree of fibrosis.. (1) At the early stage of fibrosing alveolitis, Th2 domination and the lack of IFN-gamma in the presence of alveolar epithelial and basement membrane injury may promote the development of fibrosis. (2) Azithromycin can inhibit the expression of IL-10 and IFN-gamma, and reverse the Th2-like response in the BLM group to a Th1-like response, and as a result, decrease the inflammatory injury as well as the degree of BLM-induced lung injury in rats.

Topics: Animals; Azithromycin; Bleomycin; Lung; Lung Injury; Pulmonary Fibrosis; Rats; RNA, Messenger