LAMB
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB14304 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To better understand the molecular determinants of lung disease variability among patients with cystic fibrosis (CF), we carried out an epigenome-wide association study (EWAS) in sputum samples from patients with CF. Sputum samples were collected from 50 patients with CF at four time points (visit 1, 2, 3 and 4) over an 18-month follow-up period. We profiled 64 sputum samples collected at visit 1 and 2, using human methylation BeadChips (EPIC). Selected CpG sites were reassessed in independent sputum samples collected at visit 3 and 4, by pyrosequencing. Overall, we provide the first longitudinal assessment of genome-wide DNA methylation in a cohort of patients with CF and identify CpG sites that predict clinical traits of key importance for lung disease. Specifically, we identified (i) differentially methylated CpG sites that correlate with lung function (FEV1pp), (ii) a DNA methylation signature that predicts patients with a pulmonary exacerbation and (iii) CpG sites that split patients with declining lung function from those whose lung function either improved or remained stable.
2026-01-21 | GSE289379 | GEO
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:Sputum airway metagenomics of people with non-CF bronchiectasis
| PRJEB65368 | ENA
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:Several muco-obstructive lung diseases in humans, including cystic fibrosis (CF), feature the chronic recruitment of blood leukocytes and their reprogramming within the lumen of small airways to drive pathological adaptations such as altered immune mediator secretion and defective killing of bacteria. To investigate these mechanisms, we engineered a biomimetic model in which primary human blood monocytes migrate through a human small airway epithelium, andepithelium and differentiate into macrophages upon 4-day exposure to macrophage colony-stimulating factor. We observed that airway-recruited monocytes (ArMos) obtained with the control chemoattractant C-C motif ligand 2 (CCL2) altered their transcriptome and secretome upon transmigration, and further upon differentiation into airway-recruited macrophages (ArMas), as compared to circulating monocytes. We observed specific additional alterations in transcriptomic and secretomic properties of ArMos and ArMas when they were conditioned in CF airway supernatant (derived from cell- and bacteria-free sputum) [CFASN], compared CCL2 conditions. Critically, CF ArMas (but not CF ArMos), showed a much reduced ability to kill P. aeruginosa, a common CF pathogen. These findings extend prior studies on small airway-recruited neutrophils, and identify immune tolerance by macrophages as one underlying cause of bacterial colonization in CF. This biomimetic model support further mechanistic and preclinical investigations of small airway-recruited monocytes and macrophages in CF and other diseases featuring chronic inflammation and infection, like non-CF bronchiectasis, and chronic obstructive pulmonary disease.
2025-12-01 | GSE311629 | GEO