Non-Cystic Fibrosis Bronchiectasis: Microbiology, Clinical Outcomes, and Pharmacotherapy Practices.
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ABSTRACT:
SUBMITTER: Montemayor K
PROVIDER: S-EPMC6396858 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundNon-cystic fibrosis bronchiectasis ("bronchiectasis") is a chronic inflammatory lung disease often associated with nontuberculous mycobacteria (NTM) infection. Very little data exist to guide bronchiectasis management decisions. We sought to describe patterns of inhaled corticosteroid (ICS) and antibiotic therapy in the United States.MethodsWe invited 2,000 patients through NTM Info & Research (NTMir) to complete an anonymous electronic survey. We separately queried baseline clinical and laboratory data from the US Bronchiectasis and NTM Research Registry (BRR).ResultsAmong 511 NTMir survey responders with bronchiectasis, whose median age was 67 years, 85 (17%) reported asthma and 99 (19%) reported COPD. History of ICS use was reported by 282 (55%), 171 (61%) of whom were treated 1 year or longer, and 150 (53%) were currently taking ICSs. Fewer reported ever taking azithromycin for non-NTM bronchiectasis (203 responders [40%]) or inhaled tobramycin (78 responders [15%]). The median age of 1,912 BRR patients was 69 years; 528 (28%) had asthma and 360 (19%) had COPD. Among 740 patients (42%) without NTM, 314 were taking ICSs at baseline. Among patients without NTM who were taking ICSs, only 178 (57%) had a concurrent diagnosis of COPD or asthma that could explain ICS use. Fewer were taking suppressive macrolides (96 patients [13%]), and of the 70 patients (10%) taking inhaled suppressive antibiotics, 48 (68%) had chronic Pseudomonas aeruginosa infection.ConclusionsICS use was common in two national samples of patients with bronchiectasis, with relatively few patients taking suppressive antibiotic therapies. Further research is needed to clarify the safety and effectiveness of these therapies in patients with bronchiectasis.
| S-EPMC6026272 | biostudies-literature
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: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: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:Lung clearance index (LCI) is a measure of abnormal ventilation distribution derived from the multiple breath inert gas washout (MBW) technique. We aimed to determine the clinical utility of LCI in non-CF bronchiectasis, and to assess two novel MBW parameters that distinguish between increases in LCI due to specific ventilation inequality (LCIvent) and increased respiratory dead space (LCIds).Forty-three patients with non-CF bronchiectasis and 18 healthy control subjects underwent MBW using the sulphur hexafluoride wash-in technique, and data from 40 adults with CF were re-analysed. LCIvent and LCIds were calculated using a theoretical two-compartment lung model, and represent the proportional increase in LCI above its ideal value due to specific ventilation inequality and increased respiratory dead space, respectively.LCI was significantly raised in patients with non-CF bronchiectasis compared to healthy controls (9.99 versus 7.28, p?<?0.01), and discriminated well between these two groups (area under receiver operating curve?=?0.90, versus 0.83 for forced expiratory volume in one second [% predicted]). LCI, LCIvent and LCIds were repeatable (intraclass correlation coefficient?>?0.75), and correlated significantly with measures of spirometric airflow obstruction.LCI is repeatable, discriminatory, and is associated with spirometric airflow obstruction in patients with non-CF bronchiectasis. LCIvent and LCIds are a practical and repeatable alternative to phase III slope analysis and may allow a further level of mechanistic information to be extracted from the MBW test in patients with severe ventilation heterogeneity.
| S-EPMC4035904 | biostudies-other
Project description:Pseudomonas aeruginosa (Pa), normally a soil commensal, is an important opportunistic pathogen in Cystic Fibrosis (CF) and non-Cystic Fibrosis Bronchiectasis (nCFBR). Persistent infection correlates with accelerated decline in lung function and early mortality. The horizontal transfer of DNA by temperate bacteriophages can add gene function and selective advantages to their bacterial host within the constrained environment of the lower lung. In this study, we chemically induce temperate bacteriophages from clonal cultures of Pa and identify their mixed viral communities employing metagenomic approaches. We compared 92 temperate phage metagenomes stratified from these clinical backgrounds (47 CF and 45 nCFBR Pa isolates) using MG-RAST and GeneWise2. KEGG analysis shows the complexity of temperate phage accessory gene carriage increases with duration and severity of the disease. Furthermore, we identify the presence of Ig-like motifs within phage structural genes linked to bacterial adhesion and carbohydrate binding including Big_2, He_Pig, and Fn3. This study provides the first clinical support to the proposed bacteriophage adherence to mucus (BAM) model and the evolution of phages interacting at these mucosal surfaces over time.
| S-EPMC4332376 | biostudies-literature
Project description:A diverse microbiota exists within the airways of individuals with non-cystic fibrosis bronchiectasis (nCFB). How the lung microbiome evolves over time, and whether changes within the microbiome correlate with future disease progression is not yet known. We assessed the microbial community structure of 133 serial sputa and subsequent disease course of 29 nCFB patients collected over a span of 4-16 years using 16S rRNA paired-end sequencing. Interestingly, no significant shifts in the microbial community of individuals were observed during extended follow-up suggesting the microbiome remains relatively stable over prolonged periods. Samples that were Pseudomonas aeruginosa culture positive displayed markedly different microbial community structures compared to those that were positive for Haemophilus influenzae. Importantly, patients with sputum of lower microbial community diversity were more likely to experience subsequent lung function decline as defined by annual change in ≥-1 FEV1% predicted. Shannon diversity values <1 were more prevalent in patients with FEV1 decline (P = 0.002). However, the relative abundance of particular core microbiota constituents did not associate with risk of decline. Here we present data confirming that the microbiome of nCFB individuals is generally stable, and that microbiome-based measurements may have a prognostic role as biomarkers for nCFB.
| S-EPMC6499777 | biostudies-literature
Project description:BackgroundBoth cystic fibrosis (CF) and non-cystic fibrosis bronchiectasis are characterized by permanent bronchial dilation, impaired mucociliary clearance, and development of chronic colonization and infection. Although the major airway microbiota in both CF and non-CF bronchiectasis may be similar, there are some differences in clinical and microbiologic features. There may also be differences in antibiotic susceptibility patterns between the CF and non-CF populations. Therefore, analysis and comparison of the microbiota and antibiotic susceptibility pattern in CF bronchiectasis versus non-CF bronchiectasis would help to improve the management of both conditions.MethodsTwo authors will independently search the electronic databases PubMed, EMBASE, the Cochrane Library, and LIVIVO, for studies reporting bacterial colonization of the respiratory tract in adults and children diagnosed with bronchiectasis in either CF or non-CF. We will include studies examining any respiratory tract specimen, using conventional bacterial culture or other specialized techniques such as molecular methods. We will also examine the antimicrobial susceptibility patterns in people with CF bronchiectasis versus non-CF bronchiectasis. The authors will independently assess the risk of bias in each included study using the Newcastle Ottawa Scale (NOS). We will present the data with descriptive statistics and provide pooled estimates of outcomes, wherever it is feasible to perform meta-analysis. Heterogeneity in studies will be explored by visual inspection of forest plots as well as using the Higgins and Thompson I2 method. We will contact the corresponding authors of studies where data is/are missing and try to obtain the missing data. We will undertake sensitivity analysis to explore the impact of study quality and subgroup analysis based on pre-set criteria. We will prepare a summary of findings' table and assess the confidence in the evidence using the GRADE methodology.DiscussionTo date, there are no locally applicable evidence-based guidelines for antimicrobial treatment of non-CF bronchiectasis patients. In general, treatment is based on extrapolation of evidence in people with CF bronchiectasis. An insight into the microbiota and antimicrobial susceptibility patterns in the two conditions would facilitate appropriate rather than empiric antimicrobial therapy and hopefully reduce the burden of antimicrobial resistance created by rampant usage of antibiotics.Systematic review registrationThe protocol has been registered in PROSPERO on July 26, 2020 (PROSPERO registration number: CRD42020193859 ).
| S-EPMC7780385 | biostudies-literature