Diversity of cystic fibrosis chronic rhinosinusitis microbiota correlates with different pathogen dominance.
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ABSTRACT:
SUBMITTER: Lucas SK
PROVIDER: S-EPMC8403624 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
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Diversity of cystic fibrosis chronic rhinosinusitis microbiota correlates with different pathogen dominance.
Lucas Sarah K SK Feddema Erin E Boyer Holly C HC Hunter Ryan C RC
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 20210427 4
Chronic rhinosinusitis (CRS) affects nearly all individuals with cystic fibrosis (CF) and is thought to serve as a reservoir for microbiota that subsequently colonize the lung. To better understand the microbial ecology of CRS, we generated a 16S rRNA gene sequencing profile of sinus mucus from CF-CRS patients. We show that CF-CRS sinuses harbor bacterial diversity not entirely captured by clinical culture. Culture data consistently identified the dominant organism in most patients, though lower ...[more]
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Project description:BackgroundChronic rhinosinusitis (CRS) is a significant manifestation of cystic fibrosis (CF) with wide-ranging symptom and disease severity. The goal of the study was to determine clinical variables that correlate with outcome measures of disease severity.MethodsA prospective, longitudinal, observational study of 33 adults with symptomatic CRS treated in a CF-focused otolaryngology clinic was performed. Symptom severity, the presence of rhinosinusitis exacerbations, and endoscopic appearance were assessed, and regression analysis was used to determine clinical predictors of disease outcome.ResultsThirty-three adults with CF-CRS were included in the study and followed for a mean of 15 months. Rhinosinusitis exacerbations occurred in 61% of participants during the study, and female sex increased the odds of presenting with an exacerbation visit. Sinus disease exacerbations were associated with an odds ratio of 2.07 for presenting with a pulmonary exacerbation at the next visit. CF-related diabetes was found to be associated with worse symptoms and endoscopic appearance. Infection with Staphylococcus aureus predicted worsening of symptoms, whereas infections with Pseudomonas aeruginosa improved over time. Allergic rhinitis was associated with worse endoscopic appearance, and nasal steroid use was associated with improved endoscopic appearance.ConclusionSex, CF-related diabetes, sinonasal infection status, allergic rhinitis, and nasal steroid use may all modulate severity of CF-CRS in adults. Sinusitis exacerbation may be a precursor to pulmonary exacerbation.
| S-EPMC6715283 | biostudies-literature
Project description:BackgroundChronic rhinosinusitis frequently occurs in people with cystic fibrosis. Several medical interventions are available for treating chronic rhinosinusitis in people with cystic fibrosis; for example, different concentrations of nasal saline irrigations, topical or oral corticosteroids, antibiotics - including nebulized antibiotics - dornase alfa and modulators of the cystic fibrosis transmembrane conductance regulator (CFTR) (such as lumacaftor, ivacaftor or tezacaftor). However, the efficacy of these interventions is unclear. This is an update of a previously published review.ObjectivesThe objective of this review is to compare the effects of different medical interventions in people diagnosed with cystic fibrosis and chronic rhinosinusitis.Search methodsWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search of trials register: 09 September 2021. We also searched ongoing trials databases, other medical databases and the reference lists of relevant articles and reviews. Date of latest additional searches: 22 November 2021.Selection criteriaRandomized and quasi-randomized trials of different medical interventions compared to each other or to no intervention or to placebo.Data collection and analysisTwo review authors independently assessed trials identified for potential inclusion in the review. We planned to conduct data collection and analysis in accordance with Cochrane methods and to independently rate the quality of the evidence for each outcome using the GRADE guidelines.Main resultsWe identified no trials that met the pre-defined inclusion criteria. The most recent searches identified 44 new references, none of which were eligible for inclusion in the current version of this review; 12 studies are listed as excluded and one as ongoing.Authors' conclusionsWe identified no eligible trials assessing the medical interventions in people with cystic fibrosis and chronic rhinosinusitis. High-quality trials are needed which should assess the efficacy of different treatment options detailed above for managing chronic rhinosinusitis, preventing pulmonary exacerbations and improving quality of life in people with cystic fibrosis.
| S-EPMC8989145 | biostudies-literature
Project description:BackgroundChronic rhinosinusitis frequently occurs in people with cystic fibrosis. Several medical interventions are available for treating chronic rhinosinusitis in people with cystic fibrosis; for example, different concentrations of nasal saline irrigations, topical or oral corticosteroids, antibiotics - including nebulized antibiotics, dornase alfa and modulators of the cystic fibrosis transmembrane conductance regulator (CFTR) (such as lumacaftor, ivacaftor or tezacaftor). However, the efficacy of these interventions is unclear.ObjectivesThe objective of this review is to compare the effects of different medical interventions in people diagnosed with cystic fibrosis and chronic rhinosinusitis.Search methodsWe searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search of trials register: 22 May 2019.We also searched ongoing trials databases, other medical databases and the reference lists of relevant articles and reviews. Date of latest additional searches: 20 May 2019.Selection criteriaRandomized and quasi-randomized trials of different medical interventions compared to each other or to no intervention or to placebo.Data collection and analysisTwo review authors independently assessed trials identified for potential inclusion in the review. We planned to conduct data collection and analysis in accordance with Cochrane methods and to independently rate the quality of the evidence for each outcome using the GRADE guidelines.Main resultsWe identified no trials that met the pre-defined inclusion criteria. The searches identified 47 trials, none of which were eligible for inclusion in the current version of this review.Authors' conclusionsWe identified no eligible trials assessing the medical interventions in people with cystic fibrosis and chronic rhinosinusitis. High-quality trials are needed which should assess the efficacy of different treatment options detailed above for managing chronic rhinosinusitis, preventing pulmonary exacerbations and improving quality of life in people with cystic fibrosis.
| S-EPMC6805252 | biostudies-literature
Project description:BackgroundChronic infection and concomitant airway inflammation is the leading cause of morbidity and mortality for people living with cystic fibrosis (CF). Although chronic infection in CF is undeniably polymicrobial, involving a lung microbiota, infection surveillance and control approaches remain underpinned by classical aerobic culture-based microbiology. How to use microbiomics to direct clinical management of CF airway infections remains a crucial challenge. A pivotal step towards leveraging microbiome approaches in CF clinical care is to understand the ecology of the CF lung microbiome and identify ecological patterns of CF microbiota across a wide spectrum of lung disease. Assessing sputum samples from 299 patients attending 13 CF centres in Europe and the USA, we determined whether the emerging relationship of decreasing microbiota diversity with worsening lung function could be considered a generalised pattern of CF lung microbiota and explored its potential as an informative indicator of lung disease state in CF.ResultsWe tested and found decreasing microbiota diversity with a reduction in lung function to be a significant ecological pattern. Moreover, the loss of diversity was accompanied by an increase in microbiota dominance. Subsequently, we stratified patients into lung disease categories of increasing disease severity to further investigate relationships between microbiota characteristics and lung function, and the factors contributing to microbiota variance. Core taxa group composition became highly conserved within the severe disease category, while the rarer satellite taxa underpinned the high variability observed in the microbiota diversity. Further, the lung microbiota of individual patient were increasingly dominated by recognised CF pathogens as lung function decreased. Conversely, other bacteria, especially obligate anaerobes, increasingly dominated in those with better lung function. Ordination analyses revealed lung function and antibiotics to be main explanators of compositional variance in the microbiota and the core and satellite taxa. Biogeography was found to influence acquisition of the rarer satellite taxa.ConclusionsOur findings demonstrate that microbiota diversity and dominance, as well as the identity of the dominant bacterial species, in combination with measures of lung function, can be used as informative indicators of disease state in CF. Video Abstract.
| S-EPMC7114784 | biostudies-literature
Project description:BackgroundCystic fibrosis is a debilitating, autosomal recessive disease which results in chronic upper and lower airway infection and inflammation. In this study, four adult patients presenting with cystic fibrosis and chronic rhinosinusitis were recruited. Culture and molecular techniques were employed to evaluate changes in microbial profiles, host gene expression and antimicrobial resistance (AMR) in the upper respiratory tract over time.MethodsSwab samples from the sinonasal cavity were collected at the time of surgery and at follow-up clinics at regular time intervals for up to 18 months. Nucleic acids were extracted, and DNA amplicon sequencing was applied to describe bacterial and fungal composition. In parallel, RNA was used to evaluate the expression of 17 AMR genes and two inflammatory markers (interleukins 6 and 8) using custom qPCR array cards. Molecular results were compared with routine sinus and sputum culture reports within each patient.ResultsBacterial amplicon sequencing and swab culture reports from the sinonasal cavity were mostly congruent and relatively stable for each patient across time. The predominant species detected in patients P02 and P04 were Pseudomonas aeruginosa, Staphylococcus aureus in patient P03, and a mixture of Enterobacter and S. aureus in patient P01. Fungal profiles were variable and less subject specific than bacterial communities. Increased expressions of interleukins 6 and 8 were observed in all patients throughout the sampling period compared with other measured genes. The most prevalent AMR gene detected was ampC. However, the prevalence of AMR gene expression was low in all patient samples across varying time-points.ConclusionsWe observed a surprising degree of stability of sinonasal microbial composition, and inflammatory and AMR gene expression across all patients post sinus surgery.
| S-EPMC8045235 | biostudies-literature
Project description:Bacterial communities in the airways of cystic fibrosis (CF) patients are, as in other ecological niches, influenced by autogenic and allogenic factors. However, our understanding of microbial colonization in younger versus older CF airways and the association with pulmonary function is rudimentary at best. Using a phylogenetic microarray, we examine the airway microbiota in age stratified CF patients ranging from neonates (9 months) to adults (72 years). From a cohort of clinically stable patients, we demonstrate that older CF patients who exhibit poorer pulmonary function possess more uneven, phylogenetically-clustered airway communities, compared to younger patients. Using longitudinal samples collected form a subset of these patients a pattern of initial bacterial community diversification was observed in younger patients compared with a progressive loss of diversity over time in older patients. We describe in detail the distinct bacterial community profiles associated with young and old CF patients with a particular focus on the differences between respective "early" and "late" colonizing organisms. Finally we assess the influence of Cystic Fibrosis Transmembrane Regulator (CFTR) mutation on bacterial abundance and identify genotype-specific communities involving members of the Pseudomonadaceae, Xanthomonadaceae, Moraxellaceae and Enterobacteriaceae amongst others. Data presented here provides insights into the CF airway microbiota, including initial diversification events in younger patients and establishment of specialized communities of pathogens associated with poor pulmonary function in older patient populations.
| S-EPMC2890402 | biostudies-literature
Project description:Our data demonstrates an increased number of submucosal glands in the sinus mucosa of pediatric patients with chronic rhinosinusitis (CRS). Additionally, data in the literature indicates differentially altered expression of innate markers of immunity and of inflammatory mediators in the sinus mucosa of adult patients with cystic fibrosis, non-CF controls, and controls. Experiment Overall Design: Analyses will focus on inflammatory/immune response genes to identify genes in CRS or CF patients that are involved in pathways that impact on pathogenesis in these diseases. Analysis will also focus on genes in developmental pathways to identify mediators implicated in the development of submucosal glandular hyperplasia in pediatric patients with CRS.
2008-04-09 | E-GEOD-10406 | biostudies-arrayexpress
Project description:Secretory cells in submucosal glands (SMGs) secrete antibacterial proteins and mucin glycoproteins into the apical lumen of the respiratory tract, and these are critical for innate immune mucosal integrity. Glandular hyperplasia is manifested in diseases with obstructive respiratory pathologies associated with mucous hypersecretion, and is predominant in the sinus mucosa of patients with chronic rhinosinusitis (CRS), cystic fibrosis (CF), and clinical symptoms of CRS. To gain insights into the molecular basis of SMG hyperplasia in CRS, gene expression microarray analyses were performed to identify the differences in global and specific gene expression in the sinus mucosa of control, CRS, and CRS/CF patients. A marked up-regulation of 11 glandular-associated genes in CRS and CRS/CF sinus mucosa was evident. The RNA and protein expressions of the four most highly up-regulated genes (DSG3, KRT14, PTHLH, and OTX2) were evaluated. An increased expression of DSG3, KRT14, and PTHLH was demonstrated at the mRNA and protein levels in both CRS and CRS/CF sinus mucosa, whereas the increased expression of OTX2 was evident only for CRS/CF sinus mucosa, implicating OTX2 as a CF-specific gene. Immunofluorescence analysis localized DSG3, PTHLH, and OTX2 to serous cells, and KRT14 to myoepithelial cells, in SMGs. Because glandular hyperplasia is a central histologic feature of CRS, the identification of overexpressed glandular genes in the sinus mucosa lays the groundwork for future studies of glandular hyperplasia, and may ultimately lead to the development of novel treatments for mucous hypersecretion in patients with CRS.
| S-EPMC3175585 | biostudies-literature
Project description:ObjectiveGiven the recent dramatic changes in medical therapy for cystic fibrosis (CF), this study aims to describe temporal changes in chronic rhinosinusitis (CRS) and endoscopic sinus surgery (ESS) rates.MethodsNational Inpatient Sample (2004-2019; weighted estimates for 119,067 pediatric and 202,407 adult patients) was used to analyze adult (age ≥18 years) and pediatric patients with CF with pulmonary manifestations. Comorbid CRS, ESS rates, and extended length of stay (LOS, ≥75th percentile) were analyzed.ResultsThe rate of CRS in both pediatric (14.1% vs 21.1%, P < .001) and adult (16.5% vs 40.9%, P < .001) patients increased. Rate of ESS in pediatric patients with CRS decreased from 25.3% to 3.4% (P < .001). A similar decline occurred in adults with CRS (12.3% vs 3.6%, P < .001). In multivariate analysis from 2015 to 2019, ESS and extended LOS were associated with admission in the Western United States (P < .001). CRS (OR 1.14, P = .002) and ESS (OR 1.78, P = .002) were independent predictors of extended LOS. Elective admission, primary insurance, race, and hospital teaching/location were significantly associated with ESS and extended LOS (P < .05).ConclusionDespite the increased prevalence of CRS in adults and pediatric patients with CF, rates of inpatient ESS have declined from 2004 to 2019. Patient and hospital factors affect undergoing ESS in 2015 to 2019. CRS and ESS are associated with extended LOS in recent years.
| S-EPMC11840695 | biostudies-literature
Project description:The role of phagocytes of children with cystic fibrosis (CF) associated with different phenotypes of chronic rhinosinusitis (CRS) is unclear. The aim of this study was to evaluate the phagocytic capacity of blood neutrophils and monocytes and production of superoxide anion by phagocytes in patients with CF with or without chronic rhinosinusitis and with or without nasal polyps (NP). This cross-sectional study was established in 2015-2017 in a tertiary reference center to the CF treatment, Brasilia, Brazil. Sample included 30 children volunteers with CRS related to CF (n = 16) and control subjects (n = 14). Epidemiological and clinical data were compared. Collection of 15 mL of peripheral blood and nasal endoscopy to identify the presence or absence of nasal polyps (NP) were performed. Phagocytosis of Saccharomyces cerevisiae by pathogen-associated molecular pattern receptors and opsonin receptors was assessed. Superoxide anion production was evaluated. The control group showed a higher phagocytic index to monocytes and neutrophils than to the CF or CF+CRS with NP groups [Kruskal-Wallis p = 0.0025] when phagocytosis were evaluated by pathogen-associated molecular pattern receptors (5 yeasts/cell). The phagocytic index of the CF+CRS without NP group was higher than in the CF+CRS with NP group (Kruskal-Wallis p = 0.0168). In the control group, the percentage of phagocytes involved in phagocytosis and superoxide anion production (74.0 ± 9.6%) were higher in all CF groups (p < 0,0001). The innate immune response, represented by phagocytic activity and superoxide anion production by monocytes and neutrophils was more impaired in patients with CF related or not related to CRS than in the control group. However, the phagocytic function of patients without NP showed less impairment.
| S-EPMC9075614 | biostudies-literature