zithromax and montelukast

Inflammation is a major component of the vicious cycle characterizing cystic fibrosis pulmonary disease. If untreated, this inflammatory process irreversibly damages the airways, leading to bronchiectasis and ultimately respiratory failure. Antiinflammatory drugs for cystic fibrosis lung disease appear to have beneficial effects on disease parameters. These agents include oral corticosteroids and ibuprofen, as well as azithromycin, which, in addition to its antimicrobial effects, also possesses antiinflammatory properties. Inhaled corticosteroids, colchicine, methotrexate, montelukast, pentoxifylline, nutritional supplements, and protease replacement have not had a significant impact on the disease. Therapy with oral corticosteroids, ibuprofen, and fish oil is limited by adverse effects. Azithromycin appears to be safe and effective, and is thus the most promising antiinflammatory therapy available for patients with cystic fibrosis. Pharmacologic therapy with antiinflammatory agents should be started early in the disease course, before extensive irreversible lung damage has occurred.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adult; Anti-Inflammatory Agents; Azithromycin; Child; Clinical Trials as Topic; Cyclopropanes; Cystic Fibrosis; Deoxyribonuclease I; Dietary Supplements; Humans; Methotrexate; Pentoxifylline; Quinolines; Sulfides

Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. We hypothesized that inhaled fluticasone, azithromycin, and montelukast (FAM) with a brief steroid pulse could avert progression of new-onset BOS. We tested this in a phase II, single-arm, open-label, multicenter study (NCT01307462). Thirty-six patients were enrolled within 6 months of BOS diagnosis. The primary endpoint was treatment failure, defined as 10% or greater forced expiratory volume in 1 second decline at 3 months. At 3 months, 6% (2 of 36, 95% confidence interval, 1% to 19%) had treatment failure (versus 40% in historical controls, P < .001). FAM was well tolerated. Steroid dose was reduced by 50% or more at 3 months in 48% of patients who could be evaluated (n = 27). Patient-reported outcomes at 3 months were statistically significantly improved for Short-Form 36 social functioning score and mental component score, Functional Assessment of Cancer Therapies emotional well-being, and Lee symptom scores in lung, skin, mouth, and the overall summary score compared to enrollment (n = 24). At 6 months, 36% had treatment failure (95% confidence interval, 21% to 54%, n = 13 of 36, with 6 documented failures, 7 missing pulmonary function tests). Overall survival was 97% (95% confidence interval, 84% to 100%) at 6 months. These data suggest that FAM was well tolerated and that treatment with FAM and steroid pulse may halt pulmonary decline in new-onset BOS in the majority of patients and permit reductions in systemic steroid exposure, which collectively may improve quality of life. However, additional treatments are needed for progressive BOS despite FAM.

Topics: Acetates; Adult; Aged; Anti-Inflammatory Agents; Azithromycin; Bronchiolitis Obliterans; Cyclopropanes; Disease Progression; Fluticasone; Forced Expiratory Volume; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Lung; Male; Middle Aged; Quality of Life; Quinolines; Sulfides; Survival Analysis; Transplantation, Homologous; Treatment Outcome

Clinical trials in children with moderate-to-severe persistent asthma are limited.. We sought to determine whether azithromycin or montelukast are inhaled corticosteroid sparing.. The budesonide dose (with salmeterol [50 microg] twice daily) necessary to achieve control was determined in children 6 to 17 years of age with moderate-to-severe persistent asthma. After a budesonide-stable period of 6 weeks, children were randomized in a double-masked, parallel, multicenter study to receive once-nightly azithromycin, montelukast, or matching placebos plus the established controlling dose of budesonide (minimum, 400 microg twice daily) and salmeterol twice daily. Primary outcome was time from randomization to inadequate asthma control after sequential budesonide dose reduction.. Of 292 children screened, only 55 were randomized. Inadequate adherence to study medication (n = 80) and improved asthma control under close medical supervision (n = 49) were the major reasons for randomization failure. A futility analysis was requested by the Data Safety Monitoring Board. In data available for analyses, no differences were noted for either treatment compared with placebo in time to inadequate control status (median: azithromycin, 8.4 weeks [95% confidence limit, 4.3-17.3]; montelukast, 13.9 weeks [95% confidence limit, 4.7-20.6]; placebo, 19.1 weeks [95% confidence limit, 11.7-infinity]), with no difference between the groups (log-rank test, P = .49). The futility analysis indicated that even if the planned sample size was reached, the results of this negative study were unlikely to be different, and the trial was prematurely terminated.. Based on these results, neither azithromycin nor montelukast is likely to be an effective inhaled corticosteroid-sparing alternative in children with moderate-to-severe persistent asthma.

Topics: Acetates; Adolescent; Albuterol; Anti-Bacterial Agents; Asthma; Azithromycin; Bronchodilator Agents; Budesonide; Child; Cyclopropanes; Double-Blind Method; Female; Glucocorticoids; Humans; Male; Medication Adherence; Quinolines; Salmeterol Xinafoate; Severity of Illness Index; Sulfides; Time Factors

There is an urgent need for effective treatments to prevent or attenuate lung and systemic inflammation, endotheliitis, and thrombosis related to COVID-19. This study aimed to assess the effectiveness of a multidrug-therapy consisting of Ivermectin, Azithromycin, Montelukast, and Acetylsalicylic acid ("TNR4" therapy) to prevent hospitalization and death among ambulatory COVID-19 cases in Tlaxcala, Mexico.. A comparative effectiveness study was performed among 768 confirmed SARS-CoV-2 cases aged 18-80 years, who received ambulatory care at the Ministry of Health of Tlaxcala. A total of 481 cases received the TNR4 therapy, while 287 received another treatment (comparison group). All participants received home visits and/or phone calls for clinical evaluation during the 14 days after enrollment.. Nearly 85% of cases who received the TNR4 recovered within 14 days compared to 59% in the comparison group. The likelihood of recovery within 14 days was 3.4 times greater among the TNR4 group than in the comparison group. Patients treated with TNR4 had a 75% and 81% lower risk of being hospitalized or death, respectively, than the comparison group.. TNR4 therapy improved recovery and prevented the risk of hospitalization and death among ambulatory COVID-19 cases.

Topics: Acetates; Adult; Aged; Aged, 80 and over; Antiviral Agents; Aspirin; Azithromycin; COVID-19 Drug Treatment; Cyclopropanes; Drug Therapy, Combination; Hospitalization; Humans; Ivermectin; Male; Mexico; Middle Aged; Quinolines; SARS-CoV-2; Sulfides; Treatment Outcome; Young Adult

Topics: Acetates; Adrenergic beta-2 Receptor Antagonists; Amoxicillin-Potassium Clavulanate Combination; Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Azithromycin; Betacoronavirus; Budesonide; Convalescence; Coronavirus Infections; COVID-19; Cyclopropanes; Eosinophils; Female; Humans; Hydroxychloroquine; Ipratropium; Male; Middle Aged; Pandemics; Pneumonia, Viral; Quinolines; SARS-CoV-2; Sulfides; Treatment Outcome

Survival after lung transplantation is hampered by chronic lung allograft dysfunction (CLAD). Persistently elevated BAL-neutrophilia is observed in some patients despite treatment with azithromycin, which may be induced by IL-1α. Our aim is to establish an in vitro model, assess mechanistic pathways and test different therapeutic strategies of IL-1α-induced release of IL-8 by human bronchial epithelial cells. Bronchial epithelial cells (16HBE) were stimulated with IL-1α with or without azithromycin or dexamethasone. IL-8 protein was analyzed in cell supernatant. Different MAP kinases (p38, JNK, ERK

Topics: Acetates; Acetylcysteine; Aminopyridines; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Azithromycin; Benzamides; Bronchi; Cell Line; Cyclopropanes; Dapsone; Dexamethasone; Dose-Response Relationship, Drug; Epithelial Cells; Fluoroquinolones; Humans; Interleukin-1alpha; Interleukin-8; MAP Kinase Signaling System; Moxifloxacin; Neutrophils; Phosphorylation; Pyridones; Quinolines; Sulfides; Theophylline; Treatment Outcome

The natural history of lung function in patients with bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplant is poorly characterized. Understanding the trajectory of lung function is necessary for prompt clinical recognition and treatment and also for the rational design of prospective studies.. To describe the longitudinal trajectory of lung function parameters, including FEV. Subjects with BOS defined by National Institutes of Health consensus guidelines criteria from a recent multicenter prospective trial of combination treatment with fluticasone, azithromycin and montelukast and a retrospective cohort from Fred Hutchinson Cancer Research Center were included. Longitudinal change in FEV. The FEV

Topics: Acetates; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Azithromycin; Bronchiolitis Obliterans; Cyclopropanes; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Hematopoietic Stem Cell Transplantation; Humans; Kaplan-Meier Estimate; Linear Models; Lung; Male; Middle Aged; Multivariate Analysis; Postoperative Complications; Prospective Studies; Quinolines; Retrospective Studies; Sulfides; Survival Rate; United States; Young Adult

To discuss the clinical effects of treating secondary asthma attacks of children Mycoplasma pneumoniae with combined therapy of montelukast and azithromycin.. 96 children patients diagnosed with secondary asthma attacks of Mycoplasma pneumonia were enrolled in this study. They were randomly divided into two groups: the control group (n=49) and the observation group (n=47). Patients in the control group received combined therapy using azithromycin and bronchodilators or glucocorticoid, and patients in the observation group received a combined therapy of montelukast, azithromycin and bronchodilators or glucocorticoid. The lung function indexes, T lymphocyte subpopulation, cytokines levels, positive rate of lgG and lgM, asthma control rate and recurrence rate were compared between groups before and after treatment.. The levels of V-T, t-PTEF/t-E, MTIF/MTEF and TEF25/PTEF in both groups increased after treatment, but we observed a more significant improvement in the observation group. The CD4+ and CD4+/CD8+ levels in both groups also increased after the intervention, while the level of CD8+ decreased. The IL-10, IL-17 and TGF-β levels decreased more intensely in the observation group.. The positive rate of lgG and lgM in both groups decreased significantly after the intervention. In the observation group, the asthma control rate was higher while the recurrence rate was lower. Although montelukast had little effect on improving the immune function, it was certainly beneficial for controlling the symptoms of asthma and improving the prognosis.. Using combined therapy of montelukast and azithromycin for treating the secondary asthma attacks of children mycoplasma pneumonia can relieve immunological and inflammatory reactions and improve the lung function.

Topics: Acetates; Asthma; Azithromycin; Child; Cyclopropanes; Humans; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Quinolines; Sulfides

The aims of this work were to study pharmacokinetics of randomly selected drugs in plasma and saliva samples in healthy human volunteers, and to introduce a Salivary Excretion Classification System. Saliva and plasma samples were collected for 3-5 half-life values of sitagliptin, cinacalcet, metformin, montelukast, tolterodine, hydrochlorothiazide (HCT), lornoxicam, azithromycin, diacerhein, rosuvastatin, cloxacillin, losartan and tamsulosin after oral dosing. Saliva and plasma pharmacokinetic parameters were calculated by noncompartmental analysis using the Kinetica program. Effective intestinal permeability (Peff) values were estimated by the Nelder-Mead algorithm of the Parameter Estimation module using the SimCYP program. Peff values were optimized to predict the actual average plasma profile of each drug. All other physicochemical factors were kept constant during the minimization processes. Sitagliptin, cinacalcet, metformin, tolterodine, HCT, azithromycin, rosuvastatin and cloxacillin had salivary excretion with correlation coefficients of 0.59-0.99 between saliva and plasma concentrations. On the other hand, montelukast, lornoxicam, diacerhein, losartan and tamsulosin showed no salivary excretion. Estimated Peff ranged 0.16-44.16 × 10(-4) cm/s, while reported fraction unbound to plasma proteins (fu) ranged 0.01-0.99 for the drugs under investigation. Saliva/plasma concentrations ratios ranged 0.11-13.4, in agreement with drug protein binding and permeability. A Salivary Excretion Classification System (SECS) was suggested based on drug high (H)/low (L) permeability and high (H)/low (L) fraction unbound to plasma proteins, which classifies drugs into 4 classes. Drugs that fall into class I (H/H), II (L/H) or III (H/L) are subjected to salivary excretion, while those falling into class IV (L/L) are not. Additional data from literature was also analyzed, and all results were in agreement with the suggested SECS. Moreover, a polynomial relationship with correlation coefficient of 0.99 is obtained between S* and C*, where S* and C* are saliva and concentration dimensionless numbers respectively. The proposed Salivary Excretion Classification System (SECS) can be used as a guide for drug salivary excretion. Future work is planned to test these initial findings, and demonstrate SECS robustness across a range of carefully selected (based on physicochemical properties) drugs that fall into classes I, II or III.

Topics: Acetates; Anthraquinones; Azithromycin; Benzhydryl Compounds; Cinacalcet; Cloxacillin; Cresols; Cyclopropanes; Female; Fluorobenzenes; Humans; Hydrochlorothiazide; Losartan; Male; Metformin; Naphthalenes; Phenylpropanolamine; Piroxicam; Pyrazines; Pyrimidines; Quinolines; Rosuvastatin Calcium; Saliva; Sitagliptin Phosphate; Sulfides; Sulfonamides; Tamsulosin; Tolterodine Tartrate; Triazoles

Bronchiolitis obliterans syndrome (BOS) is a devastating pulmonary complication affecting long-term survivors of allogeneic hematopoietic cell transplantation. Treatment of BOS with prolonged courses of high dose corticosteroids is often associated with significant morbidity. Reducing the exposure to corticosteroids may reduce treatment-related morbidity. Our institution has recently begun to treat patients with emerging therapies in an effort to diminish corticosteroid exposure. We retrospectively reviewed the 6-month corticosteroid exposure, lung function and failure rates in eight patients with newly diagnosed BOS who were treated with a combination of fluticasone, azithromycin and montelukast (FAM) and a rapid corticosteroid taper. These patients were compared with 14 matched historical patients who received high-dose corticosteroids, followed by a standard taper. The median 6-month prednisone exposure in FAM-treated patients was 1819 mg (0-4036 mg) compared with 7163 mg (6551-7829 mg) in the control group (P=0.002). The median forced expiratory volume in 1 s (FEV(1)) change in FAM-treated patients was 2% (-3 to 4%] compared with 1% (-4 to 5%) in the control group (P=1.0). Prednisone exposure in FAM patients was one quarter that of a retrospective-matched group of patients, with minimal change in median FEV(1), suggesting that BOS may be spared of the morbidities associated with long-term corticosteroid use by using alternative agents with less side effects.

Topics: Acetates; Adrenal Cortex Hormones; Adult; Androstadienes; Azithromycin; Bronchiolitis Obliterans; Cyclopropanes; Female; Fluticasone; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Quinolines; Retrospective Studies; Sulfides; Transplantation, Homologous; Young Adult

Bronchiolitis obliterans syndrome (BOS) remains the major hurdle to improve long-term survival after lung transplantation, as its treatment remains troublesome. In this pilot study, we investigated the effect of montelukast (a leukotriene receptor antagonist) on the FEV(1) decline after diagnosis of BOS and compared this with a control group. In both groups, 11 patients were included with BOS stage <3 and bronchoalveolar lavage (BAL) neutrophilia <15%, already being treated or concurrently being started on azithromycin. Control patients were selected retrospectively. After adding montelukast (10 mg/day) to the immunosuppressive regimen, the FEV(1) decline significantly decreased from 112 ± 26 ml/month before BOS diagnosis to 13 ± 13 ml/month after 6 months of montelukast therapy (P = 0.001). In the control group, there was no significant change in the rate of FEV(1) decline: 103 ± 20 ml/month before BOS diagnosis to 114 ± 27 ml/month (P = 0.55). Adding montelukast may be a promising treatment option in patients with low neutrophilic (<15%) BOS after lung transplantation, already or concurrently being treated with azithromycin.

Topics: Acetates; Azithromycin; Bronchiolitis Obliterans; Cyclopropanes; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Lung Transplantation; Male; Middle Aged; Pilot Projects; Quinolines; Sulfides; Treatment Outcome