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PROVIDER: PRJEB14304 | ENA |
REPOSITORIES: ENA
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Project description:16S rRNA sequencing of sputum from individuals with CF and non-CF bronchiectasis with underlying fungal disease.
| PRJEB33064 | ENA
Project description:Cystic fibrosis (CF) is an inherited, multi-system disease caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a ubiquitous ion channel important for epithelial hydration. A direct consequence of this dysfunction is impaired mucociliary clearance, chronic airway infection and a persistent neutrophilic inflammatory response that results in progressive loss of lung function, development of respiratory failure and premature death. Partial restoration of CFTR function is now possible for most CF patients through mutation specific CFTR modulators. Ivacaftor monotherapy produces significant clinical improvement in CF patients with the G511D mutation. Dual therapy, combining ivacaftor with lumacaftor or tezacaftor, results in modest clinical improvements in patients homozygous for F508del. More recently, triple therapy with elexacaftor/tezacaftor/ivacaftor (ETI) has led to dramatic improvements in lung function and quality of life in patients homozygous and heterozygous for F508del. Sputum proteomics is a powerful research technique capable of identifying important airway disease mechanisms by interrogating the proteome, an entire set of proteins within biological samples. It has confirmed the central role of neutrophilic immune dysregulation in CF and non-CF bronchiectasis, particularly involving the release of antimicrobial proteins and neutrophil-extracellular traps (NETs), and through impaired anti-inflammatory mechanisms. These processes produce distinct molecular signatures within the sputum proteome that become increasingly abnormal with chronic airway infection and progressive lung disease severity. In CF patients, airway and systemic inflammatory cytokines potentially related to these signatures reduce with the various forms of CFTR modulation. To date, no studies of ETI therapy in CF lung disease have assessed large-scale change in protein expression using untargeted proteomics. We hypothesised that ETI therapy would shift the sputum proteome toward health, potentially normalising airway biology in people with CF. The objectives of this study were to investigate changes in the CF sputum proteome with the introduction of ETI, correlate these with changes in clinical markers of disease severity, and make comparisons with the sputum proteome in healthy controls and in repeat samples from CF patients not suitable for ETI therapy. We also explored which molecular pathways associated with CF lung disease did not change with ETI.
2023-11-14 | PXD041950 | Pride
Project description:The PANarray design (GPL13324) contains the genes of eight P. aeruginosa genomes in non-redundant format, thus allowing identification of expression of non-PAO1 and other P. aeruginosa genes. For the series GSE28152, isogenic isolates were sequentially collected from two cystic fibrosis (CF) patients several years apart. The isolates had not been eradicated in the meantime and represent persister strains. One was an Australian Epidemic Strain-1 isolate and the other a non-epidemic strain. Strains were cultured in an artificial sputum medium (ASMDM) closely resembling CF sputum.
2011-07-15 | E-GEOD-28152 | biostudies-arrayexpress
Project description:A longitudinal collection of sputum samples from a non-CF patient
2016-12-02 | MSV000080377 | GNPS
Project description:Dataset for 16S rRNA gene sequencing data for sputum samples 61 COPD patients, generated using PacBio sequencing technology.
| EGAD00001009103 | EGA
Project description:The impact of mono-chronic S. stercoralis infection on the gut microbiome and microbial activities in infected participants was explored. The 16S rRNA gene sequencing of a longitudinal study with 2 sets of human fecal was investigated. Set A, 42 samples were matched, and divided equally into positive (Pos) and negative (Neg) for S. stercoralis diagnoses. Set B, 20 samples of the same participant in before (Ss+PreT) and after (Ss+PostT) treatment was subjected for 16S rRNA sequences and LC-MS/MS to explore the effect of anti-helminthic treatment on microbiome proteomes.
2023-11-07 | PXD037975 | JPOST Repository
Project description:Pseudomonas aeruginosa airway infection is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients. In vitro models that closely mimic CF sputum are needed to improve understanding of the pathobiology of P. aeruginosa in the CF airway. We developed an artificial sputum medium (ASMDM) that more closely resembles the composition of CF sputum than current media. In order to validate the utility of ASMDM, we used GeneChip microarrays to compare expression data of P. aeruginosa UCBPP-PA14 (PA14) in ASMDM with published data for this strain grown under the same conditions in an artificial medium containing 10% (v/v) CF sputum. Thirty-seven of 39 nutrition-related genes were differentially expressed in the same manner in both media. However, 24 quorum-sensing (QS) genes, 23 Type III secretion system and several anaerobic respiration genes were more highly expressed in ASMDM than in sputum-containing medium. When grown to stationary phase in ASMDM, PA14 differentially expressed about 50 biologically significant genes compared to stationary phase growth in Luria Broth; genes involved in iron acquisition (pfeA, fepC) and in assimilatory nitrate reduction (nasC, nirD) were upregulated, while 24 QS genes, including the regulator rhlR, lasA, rsaL, aprADEI and phenazine genes phzC2DD2EG2 were downregulated. Downregulation of QS-regulated virulence genes has been noted in chronic P. aeruginosa infection. ASMDM thus appears highly suitable for studies on gene expression of (i) P. aeruginosa strains from acutely and chronically infected CF patients and (ii) established biofilms that are a hallmark of advanced CF lung disease.
2010-05-31 | GSE18594 | GEO
Project description:Little is known about the lung microbiome dynamics and host-microbiome interactions in relation to chronic obstructive pulmonary disease (COPD) exacerbations and in patient subgroups based on smoking status and disease severity. Here we performed a 16S ribosomal RNA survey on sputum microbiome from 16 healthy and 43 COPD subjects. For COPD subjects, a longitudinal sampling was performed from stable state to exacerbations, at two and six weeks post-exacerbations and at six months from first stable visit. Host sputum transcriptome were characterized for a subset of COPD patient samples.
2021-03-21 | GSE112165 | GEO
Project description:Rationale: We recently demonstrated that the triple combination CFTR modulator therapy elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves lung ventilation and airway mucus plugging determined by multiple-breath washout and magnetic resonance imaging in CF patients with at least one F508del allele. However, effects of ELX/TEZ/IVA on viscoelastic properties of airway mucus, chronic airway infection and inflammation have not been studied. Objectives: To examine the effects of ELX/TEZ/IVA on airway mucus rheology, microbiome and inflammation in CF patients with one or two F508del alleles aged 12 years and older. Methods: In this prospective observational study, we determined sputum rheology, microbiome, inflammation markers and proteome before and 1, 3 and 12 months after initiation of ELX/TEZ/IVA. Measurements and Main Results: CF patients with at least one F508del allele and healthy controls were enrolled in this study. ELX/TEZ/IVA improved the elastic and viscous modulus of CF sputum. Further, ELX/TEZ/IVA improved the microbiome α-diversity and decreased the relative abundance of Pseudomonas aeruginosa (P<0.05) in CF sputum. ELX/TEZ/IVA also reduced IL-8 and free NE activity, and shifted the CF sputum proteome towards healthy. Conclusions: Our data demonstrate that ELX/TEZ/IVA improves sputum viscoelastic properties, chronic airway infection and inflammation in CF patients with at least one F508del allele, however, without reaching levels close to healthy.
2023-06-22 | PXD041844 | Pride
Project description:Cystic Fibrosis lung disease progresses by a combination of accelerated airways inflammation and bacterial colonization and infection. Airways inflammation in CF is predominantly neutrophilic and complicates airway clearance therapies through cellular debris, excessive DNA, excessive and viscous mucous, and high concentrations of neutrophils,Il-8 and related cytokines liberated along the NFkB signaling pathway. We conducted a single site, randomized, double blind, placebo-controlled, proof-of-concept trial in which we evaluated the effects of 28 days of two dose levels (0.05 mg and 0.10 mg daily) of an older cardiac glycoside, digitoxin, as compared with placebo, on inflammatory markers in induced sputum obtained from 24 subjects with mild to moderate CF lung disease. Nasal epithelial cells from 23 subjects were analyzed for microarray analysis. CF patients 18 to 45 years old, any genotype combination, were eligible. The primary objective was to measure the effects of digitoxin on IL-8 and neutrophil counts in induced sputum. Secondary objectives were to measure: 1) the pharmacokinetics of digitoxin in serum in stable CF patients, 2) safety indices, including ECG changes and sputum microbiology, in stable CF patients, 3) the effect of digitoxin on gene expression in nasal epithelial cells of stable CF patients and 4) quality of life scores using the CFQ-R©. As expected, it took several weeks to achieve a detectable serum level of digitoxin in CF. Digitoxin showed a trend towards reduction in sputum free neutrophil elastase and neutrophil counts, but was not associated with a reduction in sputum Il-8. Digitoxin did not dampen sputum inflammation as measured by primary and secondary outcome measures over the 28 day study period. However the patient groups receiving placebo and 50 micro gram digitoxin daily fell into similar patterns which were distinctly different from the patient group taking 100 micro gram digitoxin. The mRNAs encoding chemokine/cytokine or cell surface receptors in immune cells were decreased in nasal epithelial cells at the higher dose, leading to pathway mediated reductions in Il-8, Il-6, lung epithelial inflammation, neutrophil recruitment and mucus hypersecretion. It is possible that a longer treatment period would be necessary to detect a meaningful, dose- dependent change in sputum indices of inflammation in CF. Importantly, there were no safety issues over the course of the study
2017-01-09 | GSE76347 | GEO