Evaluating Differences in the Disease Experiences of Minority Adults With Cystic Fibrosis.
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SUBMITTER: Hutchins K
PROVIDER: S-EPMC9289912 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:RationaleAdults with cystic fibrosis (CF) possess multiple potential risk factors for chronic kidney disease, including CF-related diabetes (CFRD) and lifetime nephrotoxic drug exposure.ObjectivesTo determine whether cumulative intravenous (IV) aminoglycoside exposure and CFRD increase the risk of chronic kidney disease in adults with CF.MethodsThis was a cohort study using adults (≥ 18 yr) in the CF Foundation registry from 2001-2008. Chronic kidney disease (stage 3 or greater) was defined by an estimated glomerular filtration rate of less than 60 ml/min/1.73 m(2). Time-dependent multivariable Cox proportional hazards models were used to determine whether cumulative number of acute pulmonary exacerbations (surrogate for IV aminoglycoside exposure) and CFRD requiring insulin increase the risk of chronic kidney disease, adjusting for confounders.Measurements and main resultsThe study cohort included 11,912 adults with a median follow-up of 4 years. During the study period, 204 subjects had chronic kidney disease, with an annual disease prevalence of 2.3%. Disease prevalence doubled with every 10-year increase in age. CFRD requiring insulin therapy substantially increased the risk of chronic kidney disease (1-4 yr of CFRD requiring insulin vs. no CFRD, hazard ratio [HR] = 2.40, 95% confidence interval [CI] 1.74-3.32; ≥ 5 yr, HR = 4.56, 95% CI 2.84-7.31). Pulmonary exacerbations did not significantly increase the risk of chronic kidney disease (one to five exacerbations vs. none, HR = 0.79, 95% CI 0.56-1.11; six to nine exacerbations, HR = 0.92, 95% CI 0.58-1.46; ≥ 10 exacerbations, HR = 1.16, 95% CI 0.75-1.81).ConclusionsCF-related diabetes is a significant risk factor for chronic kidney disease in adults with CF, but additional studies examining IV aminoglycoside exposure directly are required.
| S-EPMC3262023 | biostudies-literature
Project description:This multi-center study will compare multi-target DNA and quantitative FIT stool-based testing to colonoscopy in individuals with Cystic Fibrosis (CF) undergoing colon cancer screening with colonoscopy. The primary endpoint is detection of any adenomas, including advanced adenomas and colorectal cancer (CRC).
| 2726863 | ecrin-mdr-crc
Project description:Cystic Fibrosis is a life limiting disease due to mutations in the Cystic Fibrosis Conductance Gene Regulator (CFTR). This is associated with a multiorgan disease combining pancreatic insufficiency, chronic infected bronchopathy and production of a salty sweat. Increased survival of patients leads to observation of new complications, including proximal tubule transport dysfunctions with increased output of glucose, amino acids, phosphate, calcium, uric acid, and low Molecular Weight proteins, which ultimately triggers tubulo-interstitial injury and chronic kidney disease. (Jouret et al. 2007) Exosomes are membrane vesicles stemming from Multi-Vesicular Bodies. They reflect the biological state of the cell they stem from because they incorporate various bioactive molecules from their cell of origin, which can be transferred to target cells. They are therefore ideal biomarkers for early diagnosis, prediction of disease progression or response to treatment. Urinary exosomes have been largely investigated in kidney or urothelial diseases and exosomal proteins proved to be biomarkers reflecting renal cellular biology. We hypothetized that urinary exosomal proteins might be differentially expressed, according to the presence of the mutation in the CFTR gene and its correction. We analyzed urinary exosomes of patients with CF and healthy controls based on their protein content determined by high resolution mass spectrometry, in combination with Gene Set Enrichment Analysis. These results were compared to those obtained in exosomes collected in patients treated with CFTR modulators.
2021-03-29 | PXD018537 | Pride
Project description:BackgroundLittle is known about the impact of COVID-19 and the United Kingdom's (UK) national shielding advice on people with cystic fibrosis (CF) and their families. This study explored the experiences and support needs of children and young adults (CYAs) with CF, and parents who have a child with CF, during the COVID-19 pandemic.MethodsCYAs with CF and parents of CYAs with CF completed a UK wide online survey with open and closed questions exploring experiences, information and support needs and decision-making processes. Qualitative thematic content analysis and descriptive quantitative analyses were undertaken.ResultsCYAs aged 10-30 years (n = 99) and parents of CYAs aged 0-34 years (n = 145) responded. Parents (72.7%) and CYAs (50.0%) worried about the virus, and both were vigilant for virus symptoms (82.7% and 79.7%). Over three-quarters of CYAs were worried about their own health if they caught the virus. CYAs worried about feeling more isolated during the virus (64.9%). Qualitative findings reported the following themes: (1) Disruption-caused by isolation, (2) impact on psychological wellbeing, (3) safety of shielding, and (4) healthcare and treatment provision-changes to care, access and support.ConclusionsThe impact of COVID-19 and UK shielding advice to have no contact with anyone outside the household caused disruption to the lives and routines of individuals in relation to work, education, social lives, relationships, CF management routines and support. Parents and CYAs highlighted the need for clear, up-to-date and tailored advice on individualized risks and shielding.
| S-EPMC8441823 | biostudies-literature
Project description:Airway inflammation is central to cystic fibrosis (CF) pathophysiology. Pre-clinical models have shown that phosphodiesterase inhibitors (PDEi) like sildenafil have anti-inflammatory activity. PDEi have not been studied in CF subjects.We evaluated the pharmacokinetics, tolerability, and safety of sildenafil in subjects with CF. Sputum biomarkers were used to explore efficacy.An open-label pilot study of oral sildenafil administration was conducted in adults with mild to moderate CF lung disease. Subjects received oral sildenafil 20 or 40 mg p.o. t.i.d. for 6 weeks.Twenty subjects completed the study. Estimated elimination rate constants were statistically different in subjects with CF compared to previously published non-CF subjects. Side effects were generally mild. There were no drug-related serious adverse events. Sputum neutrophil elastase activity decreased.Subjects with CF may eliminate sildenafil at a faster rate than non-CF subjects. Sildenafil administration was safe in subjects with CF and decreased sputum elastase activity. Sildenafil warrants further study as an anti-inflammatory in CF.
| S-EPMC4355330 | biostudies-literature
Project description:Background: Patients with cystic fibrosis (CF) have an elevated lifetime risk of infection and disease caused by nontuberculous mycobacteria (NTM). Currently, there is no method to predict whether patients with cystic fibrosis will develop disease related to non-tuberculous mycobacteria. In non cystic fibrosis populations, several genetic susceptibility factors have been described. In this study, we examined whether patients with cystic fibrosis demonstrate a similar pattern of genetic susceptibility and explored host immune-related biomarkers predictive of NTM pulmonary disease (NTM-PD). Methods: We evaluated whole blood gene expression using bulk RNA-seq in a cohort of CF patients at the time of first isolation of NTM. Differential gene expression was compared in patients who did (n = 12) vs. did not (n= 30) develop NTM-PD following first NTM growth. Results: No differences in demographics or composition of white blood cell sample populations at the time of sample collection were identified between groups. There were no significant differences in the expression of genes previously reported to confer susceptibility to NTM-PD in non-CF populations. However, CF patients who went on to develop NTM-PD had higher expression of genes involved in the interferon ( and ), tumor necrosis factor, and IL6 STAT3 JAK pathways. Conclusion: Patients with CF who develop NTM-PD have increased expression of genes involved in innate immunity, in contrast to non-CF populations where these responses seem to be suppressed.
2022-12-14 | GSE205161 | GEO
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:BackgroundPhysical activity (PA) is a well-documented and accepted adjunct therapy for the maintenance and improvement of long-term health in cystic fibrosis (CF). Although the benefits of PA for CF populations are well-established, adherence to PA programmes within this population remains low. This study aimed to investigate the factors that influence engagement in physical activity, and to explore exercise preferences, among adults with cystic fibrosis (CF).MethodsSemi-structured telephone interviews were conducted. Participants were twenty-one adults (mean age 35 years, SD ± 8) with an established diagnosis of CF, living in Ireland. Interview scripts were digitally recorded and transcribed verbatim. Thematic analysis was used to analyse the data.ResultsFour main themes emerged: barriers, motives, value of exercise-related outcomes, and exercise preferences. The main barriers included: low energy levels, time, the weather, and exercise-related confidence. Enjoyment and perceived competence underpinned autonomous motivation. Participants who self-identified as being regularly active valued personally identified exercise-related outcomes such as, accomplishment and affect regulation. Participants indicated a preference for home-based physical activity programs compared to gym- or facility-based programs.ConclusionInterventions aimed at promoting physical activity among adults with CF should involve programs that foster autonomous motivation, enjoyable activities, personally identified outcomes, competence and that can be conducted from the home environment.Clinical implicationsTo increase physical activity participation among adults with CF, interventions that can be conducted from the home environment, that pay attention to the patients' personally-valued exercise outcomes may be required.
| S-EPMC8017094 | biostudies-literature
Project description:Cystic fibrosis (CF) intestinal disease is characterized by alterations in processes such as proliferation and apoptosis which are known to be regulated in part by microRNA’s. Herein, we completed microRNA expression profiling of the intestinal tissue from the cystic fibrosis mouse model of cystic fibrosis transmembrane conductance regulator (Cftr) deficient mice (BALBc/J Cftrtm1UNC), relative to that of wildtype littermates, to determine whether changes in microRNA expression level are part of this phenotype. We identified 24 microRNA's to be significantly differentially expressed in tissue from CF mice compared to wildtype, with the higher expression in tissue from CF mice. These data were confirmed with real time PCR measurements. A comparison of the list of genes previously reported to have decreased expression in the BALB x C57BL/6J F2 CF intestine to that of genes putatively targeted by the 24 microRNA’s, determined from target prediction software, revealed 20% of the gene expression profile to overlap with predicted targets. Pathway analysis identified these common genes to function in phosphatase and tensin homolog-, protein kinase A-, phosphoinositide-3 kinase/Akt- and peroxisome proliferator-activated receptor alpha/retinoid X receptor alpha signaling pathways, among others, and through real time PCR experiments genes of these pathways were demonstrated to have lower expression in the BALB CF intestine. We conclude that altered microRNA expression is a feature which putatively influences both metabolic abnormalities and the altered tissue homeostasis component of CF intestinal disease. Two condition experiment, Balbc/J Cftrtm1UNC -/- (Cystic Fibrosis (CF) Mice) and Balbc/J Cftrtm1UNC +/+ (Wild Type (WT) Mice). Biological Replicates: 7 WT, 8CF. Ileum Tissue.
2011-06-01 | E-GEOD-19621 | biostudies-arrayexpress
Project description:Variability in pulmonary disease severity is found in patients with cystic fibrosis (CF) who have identical mutations in the CF transmembrane conductance regulator (CFTR) gene. We hypothesized that one factor accounting for heterogeneity in pulmonary disease severity is variation in the family of genes affecting the biology of interleukin-1 (IL-1), which impacts acquisition and maintenance of Pseudomonas aeruginosa infection in animal models of chronic infection.We genotyped 58 single nucleotide polymorphisms (SNPs) in the IL-1 gene cluster in 808 CF subjects from the University of North Carolina and Case Western Reserve University (UNC/CWRU) joint cohort. All were homozygous for DeltaF508, and categories of "severe" (cases) or "mild" (control subjects) lung disease were defined by the lowest or highest quartile of forced expired volume (FEV(1)) for age in the CF population. After adjustment for age and gender, genotypic data were tested for association with lung disease severity. Odds ratios (ORs) comparing severe versus mild CF were also calculated for each genotype (with the homozygote major allele as the reference group) for all 58 SNPs. From these analyses, nine SNPs with a moderate effect size, OR < or =0.5 or >1.5, were selected for further testing. To replicate the case-control study results, we genotyped the same nine SNPs in a second population of CF parent-offspring trios (recruited from Children's Hospital Boston), in which the offspring had similar pulmonary phenotypes. For the trio analysis, both family-based and population-based associations were performed.SNPs rs1143634 and rs1143639 in the IL1B gene demonstrated a consistent association with lung disease severity categories (P < 0.10) and longitudinal analysis of lung disease severity (P < 0.10) in CF in both the case-control and family-based studies. In females, there was a consistent association (false discovery rate adjusted joint P-value <0.06 for both SNPs) in both the analysis of lung disease severity in the UNC/CWRU cohort and the family-based analysis of affection status.Our findings suggest that IL1beta is a clinically relevant modulator of CF lung disease.
| S-EPMC3716579 | biostudies-literature