Secondhand smoke alters arachidonic acid metabolism in infants and children with cystic fibrosis
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PROVIDER: PRJNA421681 | ENA |
REPOSITORIES: ENA
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Project description:Children ages 0-10 years old with CF were recruited from 2012-2015 at the outpatient CF clinic, and classified according to age (infants <1 year old, vs. children 1-10 years old). The diagnosis of CF was defined as two disease-causing mutations or a sweat chloride test ≥ 60 mmol/L. Hair and blood samples were collected from each subject. Hair nicotine concentrations were determined and considered as the primary objective measure of SHSe. Hair nicotine provides a long-term measure of SHSe as nicotine is integrated into the growing hair shaft over multiple months. (15) For each subject, 30-40 shafts of hair of approximately 2-3 cm in length were cut at the hair root from the occipital skull. Hair samples were refrigerated at 4° for storage, washed before analyses to remove ambient nicotine (15) and batch-tested at a contract research facility (Environmental Health Sciences, Johns Hopkins School of Public Health). Samples were processed by reverse-phase high-performance liquid chromatography with electrochemical detection as described. (15) Hair nicotine concentrations were expressed as ng/mg of hair and the assay limit of detection was 0.087 ng/mg.
2020-12-01 | GSE107846 | GEO
Project description:BackgroundMechanisms that facilitate early infection and inflammation in cystic fibrosis (CF) are unclear. We previously demonstrated that children with CF and parental-reported secondhand smoke exposure (SHSe) have increased susceptibility to bacterial infections. SHSe hinders arachidonic acid (AA) metabolites that mediate immune function in patients without CF, and may influence CF immune dysfunction. We aimed to define SHSe's impact on inflammation mediators and infection in children with CF.MethodsSeventy-seven children with CF <10 years of age (35 infants <1 year; 42 children 1-10 years) were enrolled and hair nicotine concentrations measured as an objective surrogate of SHSe. AA signalling by serum and macrophage lipidomics, inflammation using blood transcriptional profiles and in vitro macrophage responses to bacterial infection after SHSe were assessed.ResultsHair nicotine concentrations were elevated in 63% of patients. Of the AA metabolites measured by plasma lipidomics, prostaglandin D2 (PGD2) concentrations were decreased in children with CF exposed to SHSe, and associated with more frequent hospitalisations (p=0.007) and worsened weight z scores (p=0.008). Children with CF exposed to SHSe demonstrated decreased expression of the prostaglandin genes PTGES3 and PTGR2 and overexpression of inflammatory pathways. These findings were confirmed using an in vitro model, where SHSe was associated with a dose-dependent decrease in PGD2 and increased methicillin-resistant Staphylococcus aureus survival in human CF macrophages.ConclusionsInfants and young children with CF and SHSe have altered AA metabolism and dysregulated inflammatory gene expression resulting in impaired bacterial clearance. Our findings identified potential therapeutic targets to halt early disease progression associated with SHSe in the young population with CF.
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Project description:The link between human gut microbiota (a complex group of microorganisms including not only bacteria but also fungi, viruses, etc.,) and the physiological state is nowadays unquestionable. Metaproteomic has emerged as a useful technique to characterize this microbial community, not just taxonomically, but also focusing on specific biological processes carried out by gut microbiota that may have an effect in the host health or pathological state. Cystic fibrosis is a genetic disease in which the microbiota of the respiratory tract determines the patient's survival and differences in composition of gut microbiota of cystic fibrosis patients respect to healthy infants have been reported. In order to characterize this host-microbiota inter-relation, we carried out the metaproteomic study of 30 stool samples from infants with cystic fibrosis.
2022-10-11 | PXD029284 | Pride
Project description:Secondhand smoke exposure (SHSe) is a common environmental factor known to increase asthma severity and respiratory infections in children, as well disrupt metabolic signals and host immune responses in patients with cystic fibrosis (CF). This study defines biomarkers and metabolic profiles of SHSe (includes ENDS exposure) in the young CF population and determines how SHSe impacts regulation of infection, inflammation, and respiratory health.
2018-10-10 | ST001079 | MetabolomicsWorkbench
Project description:The goal of this project is to identify novel genes that contribute to inflammation in cigarette smoke induced chronic obstructive pulmonary disease (COPD). Our lab is interested in a class of RNA genes called Long noncoding RNAs (lncRNAs). There are over 16,000 lncRNAs in the human genome and less than 3% have defined functions. Here we aim to identify inflammatory specific lncRNAs that are dysregulated following cigarette smoke exposure in macrophages.
2023-06-23 | GSE184571 | GEO
Project description:Cigarette smoke is the most relevant risk factor for the development of lung cancer and chronic obstructive pulmonary disease. Many of its more than 4500 chemicals are highly reactive, thereby altering protein structure and function. Here, we used subcellular fractionation coupled to label-free quantitative MS to globally assess alterations in the proteome of different compartments of lung epithelial cells upon exposure to cigarette smoke extract. Proteomic profiling of the human alveolar derived cell line A549 revealed the most pronounced changes within the cellular secretome with preferential downregulation of proteins involved in wound healing and extracellular matrix organization. In particular, secretion of secreted protein acidic and rich in cysteine, a matricellular protein that functions in tissue response to injury, was consistently diminished by cigarette smoke extract in various pulmonary epithelial cell lines and primary cells of human and mouse origin as well as in mouse ex vivo lung tissue cultures. Our study reveals a previously unrecognized acute response of lung epithelial cells to cigarette smoke that includes altered secretion of proteins involved in extracellular matrix organization and wound healing. This may contribute to sustained alterations in tissue remodeling as observed in lung cancer and chronic obstructive pulmonary disease.
2019-01-08 | PXD007180 | Pride
Project description:Circular RNAs, once thought to be a result of splicing errors, have been found to be involved in various molecular processes and in pathology of various diseases, including cancer and neurodegenerative disease. Additionally, circRNA expression was found to be altered by lifestyle habits, such as smoking cigarettes. Past studies have revealed that the rate of smoking remains high in the HIV-positive population. In this study, we isolated total RNA from uninfected T-cells that have been exposed to cigarette smoke and compared the expression levels of circRNAs to those of T-cells that were not exposed to cigarette smoke. We identified certain circRNAs that were upregulated or downregulated in T-cells when exposed to cigarette smoke. These data indicate that the study of circRNAs is warranted within the context of HIV infection.
2023-04-05 | GSE228979 | GEO
Project description:Mass spectrometry-based proteomics was carried out on Naso- and oropharyngeal swabs collected from infants and children presenting to hospital with both mild and severe respiratory illnesses as well as age-matched control children who were well and sampled from home.
2018-04-04 | MSV000082238 | MassIVE
Project description:To investigate the effect of cigarette smoke exposure on gene expression in airway epithelial cells of Canton S Drosophila melanogaster larvae, we isolated the airways of cigarette smoke exposed larvae and air controls. We then performed gene expression profiling analysis using data obtained from RNA-seq of smoke-exposed males, smoke-exposed females, air-control males and air-control females. For each group 4 biological replicates were prepared, representing 40-50 larval airways.
2022-09-30 | GSE205093 | GEO
Project description:We procured peripheral whole blood from ten healthy preterm infants and ten preterm infants with bronchopulmonary dysplasia
2024-10-27 | E-MTAB-14506 | biostudies-arrayexpress