Daily versus three-times-weekly azithromycin in Chinese patients with non-cystic fibrosis bronchiectasis: protocol for a prospective, open-label and randomised controlled trial.
Ontology highlight
ABSTRACT: Introduction
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.Methods and analysis
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.Ethics and dissemination
Ethical approval was obtained from the First People's Hospital of Jiashan Ethics Committee. The findings will be disseminated in peer-reviewed publications.Trial registration number
ChiCTR2100052906.
SUBMITTER: Mao Y
PROVIDER: S-EPMC9272127 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Bronchiectasis is usually classified as cystic fibrosis (CF) related or CF unrelated (non-CF); the latter is not considered an orphan disease any more, even in developed countries. Irrespective of the underlying etiology, bronchiectasis is the result of interaction between host, pathogens, and environment. Vitamin D is known to be involved in a wide spectrum of significant immunomodulatory effects such as down-regulation of pro-inflammatory cytokines and chemokines. Respiratory epithelial cells constitutively express 1?-hydroxylase leading to the local transformation of the inactive 25(OH)-vitamin D to the active 1,25(OH)2-vitamin D. The latter through its autocrine and paracrine functions up-regulates vitamin D dependent genes with important consequences in the local immunity of lungs. Despite the scarcity of direct evidence on the involvement of vitamin D deficiency states in the development of bronchiectasis in either CF or non-CF patients, it is reasonable to postulate that vitamin D may play some role in the pathogenesis of lung diseases and especially bronchiectasis. The potential contribution of vitamin D deficiency in the process of bronchiectasis is of particular clinical importance, taking into consideration the increasing prevalence of vitamin D deficiency worldwide and the significant morbidity of bronchiectasis. Given the well-established association of vitamin D deficiency with increased inflammation, and the indicative evidence for harmful consequences in lungs, it is intriguing to speculate that the administration of vitamin D supplementation could be a reasonable and cost effective supplementary therapeutic approach for children with non-CF bronchiectasis. Regarding CF patients, maybe in the future as more data become available, we have to re-evaluate our policy on the most appropriate dosage scheme for vitamin D.
| S-EPMC5547424 | biostudies-other
Project description:BackgroundThe prevalence of fungal disease in cystic fibrosis (CF) and non-CF bronchiectasis is increasing and the clinical spectrum is widening. Poor sensitivity and a lack of standard diagnostic criteria renders interpretation of culture results challenging. In order to develop effective management strategies, a more accurate and comprehensive understanding of the airways fungal microbiome is required. The study aimed to use DNA sequences from sputum to assess the load and diversity of fungi in adults with CF and non-CF bronchiectasis.MethodsNext generation sequencing of the ITS2 region was used to examine fungal community composition (n = 176) by disease and underlying clinical subgroups including allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, non-tuberculous mycobacteria, and fungal bronchitis. Patients with no known active fungal disease were included as disease controls.ResultsITS2 sequencing greatly increased the detection of fungi from sputum. In patients with CF fungal diversity was lower, while burden was higher than those with non-CF bronchiectasis. The most common operational taxonomic unit (OTU) in patients with CF was Candida parapsilosis (20.4%), whereas in non-CF bronchiectasis sputum Candida albicans (21.8%) was most common. CF patients with overt fungal bronchitis were dominated by Aspergillus spp., Exophiala spp., Candida parapsilosis or Scedosporium spp.ConclusionThis study provides a framework to more accurately characterize the extended spectrum of fungal airways diseases in adult suppurative lung diseases.
| S-EPMC8048771 | biostudies-literature
Project description:BackgroundBronchiectasis is associated with morbidity, low exercise capacity and poor quality of life. There is a paucity of data on exercise capacity using cardiopulmonary exercise test (CPET) in non-cystic fibrosis (CF) bronchiectasis. Our aim was to compare exercise capacity using CPET in CF and non-CF bronchiectasis patients.MethodsCross-sectional retrospective/prospective controlled study assessing CPET using cycle ergometer. Exercise parameters and computed tomography (CT) findings were compared. Results: Hundred two patients with bronchiectasis and 88 controls were evaluated; 49 CF (age 19.7 ± 9.7 y/o, FEV1%predicted 70.9 ± 20.5%) and 53 non-CF (18.6 ± 10.6 y/o, FEV1%predicted 68.7 ± 21.5%). Peak oxygen uptake (peak [Formula: see text]) was similar and relatively preserved in both groups (CF 1915.5±702.0; non-CF 1740±568; control 2111.0±748.3 mL/min). Breathing limitation was found in the two groups vs. control; low breathing reserve (49% in CF; 43% non-CF; 5% control) and increased [Formula: see text] (CF 31.4±4.1, non-CF 31.7±4.1 and control 27.2 ± 2.8). Oxygen pulse was lower in the non-CF; whereas a linear relationship between peak [Formula: see text] vs. FEV1 and vs. FVC was found only for CF. CT score correlated with [Formula: see text] and negatively correlated with [Formula: see text] and post exercise oxygen saturation (SpO2).ConclusionsCPET parameters may differ between CF and non-CF bronchiectasis. However, normal exercise capacity may be found unrelated to the etiology of the bronchiectasis. Anatomical changes in CT are associated with functional finding of increased [Formula: see text] and decreased SpO2. Larger longitudinal studies including cardiac assessment are needed to better study exercise capacity in different etiologies of non-CF bronchiectasis.Trial registrationClinicalTrials.gov, registration number: NCT03147651.
| S-EPMC6563963 | biostudies-literature
Project description:Non-cystic fibrosis (non-CF) bronchiectasis is a condition characterized by an airway inflammatory response to bacterial pathogens. Frequent exacerbations have a major influence on the quality of life. Macrolide antibiotics have not only antibacterial but also immune-regulation effects. It is proved that macrolides have a benefit in preventing exacerbations. However, it is still uncertain whether azithromycin or erythromycin is more effective and safe. The purpose of this study was to answer the following question: Which kind of macrolide antibiotic is more effective and safe in preventing non-CF bronchiectasis exacerbation? We conducted a systematic review to identify randomized clinical trials published up to May 2017 that reported on macrolides for non-CF bronchiectasis and an adjusted indirect treatment comparison (AITC) between macrolides to evaluate their efficacy and safety. The direct comparison meta-analysis found that macrolides decreased the rate of exacerbation of non-CF bronchiectasis (risk ratio (RR) = 0.45; 95% confidence interval (CI) 0.36-0.55) with heterogeneity ( I2 = 63.7%, p = 0.064). The AITC showed that azithromycin had a significantly lower bronchiectasis exacerbation rate than erythromycin (RR = 0.35; 95% CI: 0.403-0.947). Azithromycin increased the risk of diarrhea and abnormal pain. This meta-analysis suggested that long-term treatment with macrolides significantly reduced the incidence of non-CF bronchiectasis exacerbation. Moreover, azithromycin is more efficient than roxithromycin and erythromycin in preventing exacerbation.
| S-EPMC6302979 | biostudies-other
Project description:OBJECTIVE:To determine whether total exposure to penicillin V can be reduced while maintaining adequate clinical efficacy when treating pharyngotonsillitis caused by group A streptococci. DESIGN:Open label, randomised controlled non-inferiority study. SETTING:17 primary healthcare centres in Sweden between September 2015 and February 2018. PARTICIPANTS:Patients aged 6 years and over with pharyngotonsillitis caused by group A streptococci and three or four Centor criteria (fever ?38.5°C, tender lymph nodes, coatings of the tonsils, and absence of cough). INTERVENTIONS:Penicillin V 800 mg four times daily for five days (total 16 g) compared with the current recommended dose of 1000 mg three times daily for 10 days (total 30 g). MAIN OUTCOME MEASURES:Primary outcome was clinical cure five to seven days after the end of antibiotic treatment. The non-inferiority margin was prespecified to 10 percentage points. Secondary outcomes were bacteriological eradication, time to relief of symptoms, frequency of relapses, complications and new tonsillitis, and patterns of adverse events. RESULTS:Patients (n=433) were randomly allocated to the five day (n=215) or 10 day (n=218) regimen. Clinical cure in the per protocol population was 89.6% (n=181/202) in the five day group and 93.3% (n=182/195) in the 10 day group (95% confidence interval -9.7 to 2.2). Bacteriological eradication was 80.4% (n=156/194) in the five day group and 90.7% (n=165/182) in the 10 day group. Eight and seven patients had relapses, no patients and four patients had complications, and six and 13 patients had new tonsillitis in the five day and 10 day groups, respectively. Time to relief of symptoms was shorter in the five day group. Adverse events were mainly diarrhoea, nausea, and vulvovaginal disorders; the 10 day group had higher incidence and longer duration of adverse events. CONCLUSIONS:Penicillin V four times daily for five days was non-inferior in clinical outcome to penicillin V three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci. The number of relapses and complications did not differ between the two intervention groups. Five day treatment with penicillin V four times daily might be an alternative to the currently recommended 10 day regimen. TRIAL REGISTRATION:EudraCT 2015-001752-30; ClinicalTrials.gov NCT02712307.
| S-EPMC6776830 | biostudies-literature
Project description:This phase II, randomised, double-blind, multicentre study (NCT00930982) investigated the safety and efficacy of ciprofloxacin dry powder for inhalation (DPI) in patients with non-cystic fibrosis bronchiectasis. Adults who were culture positive for pre-defined potential respiratory pathogens (including Pseudomonas aeruginosa and Haemophilus influenzae) were randomised to ciprofloxacin DPI 32.5 mg or placebo administered twice daily for 28 days (with 56 days of follow-up). Bacterial density in sputum (primary end-point), pulmonary function tests, health-related quality of life and safety were monitored throughout the study. 60 subjects received ciprofloxacin DPI 32.5 mg and 64 received placebo. Subjects on ciprofloxacin DPI had a significant reduction (p<0.001) in total sputum bacterial load at the end of treatment (-3.62 log10 CFU·g(-1) (range -9.78-5.02 log10 CFU·g(-1))) compared with placebo (-0.27 log10 CFU·g(-1) (range -7.96-5.25 log10 CFU·g(-1))); the counts increased thereafter. In the ciprofloxacin DPI group, 14 (35%) out of 40 subjects reported pathogen eradication at end of treatment versus four (8%) out of 49 in the placebo group (p=0.001). No abnormal safety results were reported and rates of bronchospasm were low. Ciprofloxacin DPI 32.5 mg twice daily for 28 days was well tolerated and achieved significant reductions in total bacterial load compared with placebo in subjects with non-cystic fibrosis bronchiectasis.
| S-EPMC3640146 | biostudies-literature
Project description:Rationale: Non-cystic fibrosis bronchiectasis is characterized by airway mucus accumulation and sputum production, but the role of mucus concentration in the pathogenesis of these abnormalities has not been characterized.Objectives: This study was designed to: 1) measure mucus concentration and biophysical properties of bronchiectasis mucus; 2) identify the secreted mucins contained in bronchiectasis mucus; 3) relate mucus properties to airway epithelial mucin RNA/protein expression; and 4) explore relationships between mucus hyperconcentration and disease severity.Methods: Sputum samples were collected from subjects with bronchiectasis, with and without chronic erythromycin administration, and healthy control subjects. Sputum percent solid concentrations, total and individual mucin concentrations, osmotic pressures, rheological properties, and inflammatory mediators were measured. Intracellular mucins were measured in endobronchial biopsies by immunohistochemistry and gene expression. MUC5B (mucin 5B) polymorphisms were identified by quantitative PCR. In a replication bronchiectasis cohort, spontaneously expectorated and hypertonic saline-induced sputa were collected, and mucus/mucin concentrations were measured.Measurements and Main Results: Bronchiectasis sputum exhibited increased percent solids, total and individual (MUC5B and MUC5AC) mucin concentrations, osmotic pressure, and elastic and viscous moduli compared with healthy sputum. Within subjects with bronchiectasis, sputum percent solids correlated inversely with FEV1 and positively with bronchiectasis extent, as measured by high-resolution computed tomography, and inflammatory mediators. No difference was detected in MUC5B rs35705950 SNP allele frequency between bronchiectasis and healthy individuals. Hypertonic saline inhalation acutely reduced non-cystic fibrosis bronchiectasis mucus concentration by 5%.Conclusions: Hyperconcentrated airway mucus is characteristic of subjects with bronchiectasis, likely contributes to disease pathophysiology, and may be a target for pharmacotherapy.
| S-EPMC7068838 | biostudies-literature
Project description:As no specific pharmacological treatment has been validated for use in coronavirus disease 2019 (COVID-19), we aimed to assess the effectiveness of azithromycin (AZM) in these patients at a referral centre in Iran. An open-label, randomised controlled trial was conducted on patients with laboratory-confirmed COVID-19. A total of 55 patients in the control group receiving hydroxychloroquine (HCQ) and lopinavir/ritonavir (LPV/r) were compared with 56 patients in the case group who in addition to the same regimen also received AZM. Patients with prior cardiac disease were excluded from the study. Furthermore, patients from the case group were assessed for cardiac arrythmia risk based on the American College of Cardiology (ACC) risk assessment for use of AZM and HCQ. The main outcome measures were vital signs, SpO2 levels, duration of hospitalisation, need for and length of intensive care unit admission, mortality rate and results of 30-day follow-up after discharge. Initially, there was no significant difference between the general conditions and vital signs of the two groups. The SpO2 levels at discharge were significantly higher, the respiratory rate was lower and the duration of admission was shorter in the case group. There was no significant difference in the mortality rate between the two groups. Patients who received AZM in addition to HCQ and LPV/r had a better general condition. HCQ+AZM combination may be beneficial for individuals who are known to have a very low underlying risk for cardiac arrhythmia based on the ACC criteria.
| S-EPMC7445147 | biostudies-literature
Project description:Bronchiectasis are often encountered in clinical practice, and are characterized by abnormal airway dilatation and distortion associated with impaired mucociliary clearance and mucous plugging, which are frequently associated with recurrent infections. Numerous etiologies can underlie the development of bronchiectasis, but the most important distinction in research and clinical practice is between bronchiectasis due to cystic fibrosis (CF) and bronchiectasis due to all other reasons (non-CF bronchiectasis). The causes of non-CF bronchiectasis are varied and often unclear. Patients disease severity and phenotypes of non-CF bronchiectasis also varied, which can influence disease trajectory, frequency of exacerbations and mortality. This article reviews the published evidence and suggests interventions to enhance airways clearance in patients with non-CF bronchiectasis, which are key components of an individualized therapeutic program in order to achieve symptomatic relief and prevention of exacerbations and functional decline.
| S-EPMC6830171 | biostudies-literature
Project description:BackgroundAzithromycin is commonly prescribed drug for individuals with cystic fibrosis (CF), with demonstrated benefits in reducing lung function decline, exacerbation occurrence and improving nutrition. As azithromycin has antimicrobial activity against components of the uncultured microbiome and increasingly the CF microbiome is implicated in disease pathogenesis - we postulated azithromycin may act through its manipulation. Herein we sought to determine if the CF microbiome changed following azithromycin use and if clinical benefit observed during azithromycin use associated with baseline community structure.ResultsDrawing from a prospectively collected biobank we identified patients with sputum samples prior to, during and after initiating azithromycin and determined the composition of the CF microbial community by sequencing the V3-V4 region of the 16S rRNA gene. We categorized patients as responders if their rate of lung function decline improved after azithromycin initiation. Thirty-eight adults comprised our cohort, nine who had not utilized azithromycin in at least 3 years, and 29 who were completely naïve. We did not observe a major impact in the microbial community structure of CF sputum in the 2 years following azithromycin usage in either alpha or beta-diversity metrics. Seventeen patients (45%) were classified as Responders - demonstrating reduced lung function decline after azithromycin. Responders who were naïve to azithromycin had a modest clustering effect distinguishing them from those who were non-Responders, and had communities enriched with several organisms including Stenotrophomonas, but not Pseudomonas.ConclusionsAzithromycin treatment did not associate with subsequent large changes in the CF microbiome structure. However, we found that baseline community structure associated with subsequent azithromycin response in CF adults.
| S-EPMC8008652 | biostudies-literature