The latest medical research on Cystic Fibrosis
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about cystic fibrosis gathered by our medical AI research bot.
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Request AccessPre-transplant factors associated with mortality after lung transplantation in cystic fibrosis: A systematic review and meta-analysis.
J Cyst FibrosMortality risk stratification is essential in lung transplantation (LTx) to allow listing, prioritization and mitigating strategies. In cystic fibrosis (CF) patients, predictors of post-LTx mortality are not established.
For this systematic review and meta-analysis, seven databases were searched until January 3, 2018 to identify predictors of post-LTx mortality in CF. We excluded studies of multi-organ transplantation, re-transplantation and graft survival. For multiple studies assessing the same population during overlapping time-periods, the largest one was analyzed. Risk of bias was assessed with the Newcastle-Ottawa scale (NOS). Pooled hazard ratios were calculated using random-effects models.
Fifty-four studies were included in the systematic review and 11 studies in the meta-analyses (low-to-moderate bias risk, NOS score ≥ 5). Among 10 factors assessed in the meta-analysis, B. cepacia complex (BCC) (N = 1451, unadjusted HR = 2.35, 95%CI:1.80-3.06; I2 = 20.4% and adjusted HR = 2.49, 95%CI:1.74-3.57; I2 = 46.2%) and ascending chronological year of LTx (N = 4207, unadjusted HR = 0.98, 95%CI:0.97-0.98, I2 = 4.8%) were predictors of post-LTx mortality. Male gender (N = 2903, adjusted HR = 1.12, 95%CI:1.0-1.26, I2 = 0%) and age in adults (N = 3677, unadjusted HR = 0.99, 95%CI:0.97-1.00; I2 = 64.1% and N = 2605, adjusted HR = 0.98, 95%CI:0.97-0.99; I2 = 34.3%) had borderline significant associations with post-LTx mortality. P. aeruginosa colonization, forced expiratory volume in one second (FEV1), pulmonary hypertension, body mass index (BMI), pancreatic insufficiency and CF-related diabetes (CFRD) were not predictors of mortality.
BCC was associated with a higher post-LTx mortality whereas FEV1, pulmonary hypertension, BMI, CFRD and female gender were not associated with post-LTx mortality. These findings indicate that CF-specific risk estimates of post-LTx mortality should be considered.
The lung and gut microbiome: what has to be taken into consideration for cystic fibrosis?
J Cyst FibrosThe 15th European Cystic Fibrosis Society (ECFS) Basic Science pre-conference Symposium focused on the topic of the microbiome, asking the question...
Urinary metabolomics reveals unique metabolic signatures in infants with cystic fibrosis.
J Cyst FibrosUnited States ClinicalTrials.Gov registry NCT01424696 (clinicaltrials.gov).
Urine metabolomics was performed for 85 infants with predefined clinical phenotypes at approximately one year of age enrolled in BONUS via Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Samples were stratified by disease status (non-CF controls (n = 22); CF (n = 63, All-CF)) and CF clinical phenotype: respiratory hospitalization (CF Resp, n = 22), low length (CF LL, n = 23), and low weight (CF LW, n = 15).
Global urine metabolomics profiles in CF were heterogeneous, however there were distinct metabolic differences between the CF and non-CF groups. Top pathways altered in CF included tRNA charging and methionine degradation. ADCYAP1 and huntingtin were identified as predicted unique regulators of altered metabolic pathways in CF compared to non-CF. Infants with CF displayed alterations in metabolites associated with bile acid homeostasis, pentose sugars, and vitamins.
Predicted metabolic pathways and regulators were identified in CF infants compared to non-CF, but metabolic profiles were unable to discriminate between CF phenotypes. Targeted metabolomics provides an opportunity for further understanding of early CF disease.
Cystic fibrosis is associated with an increased risk of Barrett's esophagus.
J Cyst FibrosCystic fibrosis (CF) patients have increased risks of gastrointestinal cancers, including esophageal adenocarcinoma. Gastroesophageal reflux disease (GERD) is highly prevalent in CF and manifests at early ages. CF patients may be at increased risk for long-term sequelae of chronic GERD, including Barrett's esophagus (BE). We aimed to assess whether patients with CF have an increased risk of BE or related neoplasia.
A matched cohort study was performed of adults with and without CF who had undergone upper endoscopy. Non-CF patients were matched in a 4:1 ratio by age, sex, year of exam, and endoscopist. Odds ratios were calculated for the association between CF and BE or related neoplasia, and multivariable logistic regression modeling was performed to adjust for matching variables and additional potential confounders.
122 CF patients underwent endoscopy, and 488 matched controls were identified. Seven (5.7%) CF patients had BE or related neoplasia, including one GE junction adenocarcinoma. Mean age of affected CF patients was 36.0, and 85.7% had a prior solid organ transplant. The odds of BE was significantly increased in CF patients (OR 2.91, 95% CI 1.08-7.81). The risk remained significantly increased in a multivariable model including matching variables (OR 3.32, 95% CI 1.19-9.22) and in a parsimonious model (OR 2.99, 95% CI 1.06-8.42).
Adults with CF have a 3-fold increased risk of BE or related neoplasia and appears to develop at younger ages. Consideration should be given to screening for BE in select CF patients, especially those who have undergone solid organ transplantation.
Dental and periodontal manifestations in patients with cystic fibrosis - A systematic review.
J Cyst FibrosThe oral cavity is an important reservoir of microorganisms and can be a potential source of infection of the respiratory tract in CF patients. The literature on the oral health does not explicitly determine dental problems in these patients. The aim of the study was to systematically review the studies relating to oral status in CF patients.
A systematic review of papers published from 1997 to 2018 regarding oral status in CF children and adults, carried out in accordance with the Cochrane Collaboration guidelines.
The search resulted in 143 studies. Thirteen publications were included in the systematic review.
Antisense oligonucleotide eluforsen improves CFTR function in F508del cystic fibrosis.
J Cyst FibrosCystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. In this study we assessed the effect of antisense oligonucleotide eluforsen on CFTR biological activity measured by Nasal Potential Difference (NPD) in patients with the most common mutation, F508del-CFTR.
This multi-centre, exploratory, open-label study recruited adults with CF homozygous or compound heterozygous for the F508del-CFTR mutation. Subjects received intranasal eluforsen three times weekly for 4 weeks. The primary endpoint was the within-subject change from baseline in total chloride transport (Cl-free+iso), as assessed by NPD. Secondary endpoints included within-subject change from baseline in sodium transport.
In the homozygous cohort (n = 7; per-protocol population), mean change (90% confidence interval) in Cl-free+iso was -3.0 mV (-6.6; 0.6) at day 15, -4.1 mV (-7.8; -0.4, p = .04) at day 26 (end of treatment) and - 3.7 mV (-8.0; 0.6) at day 47. This was supported by improved sodium transport as assessed by an increase in average basal potential difference at day 26 of +9.4 mV (1.1; 17.7, p = .04). The compound heterozygous cohort (n = 7) did not show improved chloride or sodium transport NPD values. Eluforsen was well tolerated with a favourable safety profile.
In F508del-CFTR homozygous subjects, repeated intranasal administration of eluforsen improved CFTR activity as measured by NPD, an encouraging indicator of biological activity.
Pseudomonas aeruginosa colonization causes PD-L1 overexpression on monocytes, impairing the adaptive immune response in patients with cystic fibrosis.
J Cyst FibrosCystic fibrosis (CF) is an endotoxin tolerance (ET)-related disease. Given that increased PD-L1 has been reported in ET, its expression and physiological effects on cystic fibrosis monocytes should be studied.
We analyzed the phenotype and ex vivo response of immune system cells in 32 patients with CF, 19 of them colonized by Pseudomonas aeruginosa. An in vitro model was developed of Pseudomonas aeruginosa colonization using purified lipopolysaccharides (LPS) from one of the most prevalent strains in patients with CF (a CF-adapted Pseudomonas aeruginosa ST395 clone). Changes in the immune response, including cytokine production and T-lymphocyte proliferation, as well as expression of PD-L1, were evaluated.
PD-L1 was overexpressed in the monocytes of patients with CF compared with healthy volunteers, and levels of this immune checkpoint were associated with Pseudomonas aeruginosa colonization. In addition, patients with Pseudomonas aeruginosa colonization showed a patent ET status, including poor inflammatory response, reduced HLA-DR expression and T-lymphocyte proliferation impairment. PD-L1/PD-1 blocking assays reverted the impaired adaptive response. Ultimately, monocytes from healthy volunteers cultured in the presence of the clinically relevant strain of Pseudomonas aeruginosa or serum collected from patients with CF colonized by Pseudomonas aeruginosa reproduced the previous observed features.
Pseudomonas aeruginosa colonization in patients with CF was associated with PD-L1 overexpression and impaired T cell response, and LPS from this pathogen induced the observed phenotype. Our findings open new avenues for the use of anti-PD-1/PD-L1 immunotherapy in patients with CF who are colonized by Pseudomonas aeruginosa.
Comparison of lung clearance index determined by washout of N2 and SF6 in infants and preschool children with cystic fibrosis.
J Cyst FibrosMultiple-breath washout (MBW) has been shown to detect early impairment of lung function in children with cystic fibrosis (CF). Nitrogen (N2) or sulfur hexafluoride (SF6) can be used as tracer gas for MBW. Recent data indicated higher lung clearance index (LCI) values measured with N2-MBW than concurrent SF6-MBW in older children and adults, however, a comparison in infants and younger children, as well as to other outcome measures of CF lung disease is pending.
N2- and SF6-MBW were performed consecutively in 31 sedated infants and preschool children with CF (mean age, 2.3 ± 0.8 years) and 20 controls (mean age, 2.3 ± 1.1 years) using the Exhalyzer D system. Children with CF also underwent chest magnetic resonance imaging (MRI).
Mean difference (95% CI) in LCI between N2- and SF6-MBW was 1.1 ± 0.4 (0.9 to 1.3) in controls and 2.1 ± 1.9 (1.4 to 2.8) in CF. Agreement between N2- and SF6-LCI was poor in children with CF. N2-LCI and SF6-LCI correlated with MRI, however N2-LCI showed a higher concordance with MRI than SF6-LCI. The absolute difference between N2- and SF6-LCI values increased with the severity of CF lung disease as determined by MRI scores.
N2-LCI values were higher than SF6-LCI values in infants and preschool children with CF and controls. Better concordance of N2-LCI than SF6-LCI with chest MRI scores point towards of a higher sensitivity of N2-LCI to detect early lung disease in children with CF.
Glycosaminoglycans are differentially involved in bacterial binding to healthy and cystic fibrosis lung cells.
J Cyst FibrosGlycosaminoglycans (GAGs) are essential in many infections, including recurrent bacterial respiratory infections, the main cause of mortality in cystic fibrosis (CF) patients.
Using a cellular model of healthy and CF lung epithelium, a comparative transcriptomic study of GAG encoding genes was performed using qRT-PCR, and their differential involvement in the adhesion of bacterial pathogens analyzed by enzymatic degradation and binding competition experiments.
Various alterations in gene expression in CF cells were found which affect GAG structures and seem to influence bacterial adherence to lung epithelium cells. Heparan sulfate appears to be the most important GAG species involved in bacterial binding.
Adherence to lung epithelial cells of some of the main pathogens involved in CF is dependent on GAGs, and the expression of these polysaccharides is altered in CF cells, suggesting it could play an essential role in the development of infectious pathology.
Validation of the French 3-year prognostic score using the Canadian Cystic Fibrosis registry.
J Cyst FibrosStudies of large CF populations using registry data are important to identify people at high risk for death. Nkam et al. published a prognostic sco...
Higher Interleukin-7 serum concentrations in patients with cystic fibrosis correlate with impaired lung function.
J Cyst FibrosPatients with cystic fibrosis (CF) are highly susceptible to infection and colonization of pulmonary epithelia. Repeated and chronic infections may affect disease course and efficacy of host immune protection. Higher Interleukin (IL)-7 serum levels, indicating impaired T-cell response to IL-7, have been described for chronic viral and mycobacterial infections.
Time course measures of IL-7 serum concentrations in patients with CF (n = 164; n = 78 for the second time point) and healthy controls (n = 60) were done. CF patients were characterized for disease severity parameters as well as infection status and association with IL-7 serum levels was determined.
CF patients had significantly higher IL-7 serum concentrations as compared to healthy controls (9.79 pg/ml, IQR 6.76-13.6 versus 4.55 pg/ml, IQR 2.76-9.51, p < .001). IL-7 serum levels were negatively correlated with individual CF patient's BMI (r = -0.19, p = .021) and a tendency of increased IL-7 levels in Staphylococcus aureus infected CF patients was found. Linear regression of multiple parameters revealed significant negative correlation of FEV1%pred with IL-7 serum concentrations in patients with CF (ß-coefficient: -0.04, 95% confidence interval [-0.08; -0.003], p = .034). Time course analyses after 1 year +/- 6 months showed increased IL-7 serum levels (time point 1:9.26 pg/ml, IQR 6.94-13.12 time point 2:10.86 pg/ml, IQR 9.14-14.76, p = .016) that correlated negatively with decreased FEV1%pred during CF disease course.
High IL-7 serum levels were found in CF patients and correlated with impaired lung function during CF disease course. As a candidate biomarker of T-cell dysfunction, higher IL-7 serum level may also indicate worsened immune competence of patients with CF.
Functional characterization and phenotypic spectrum of three recurrent disease-causing deep intronic variants of the CFTR gene.
J Cyst FibrosThe CFTR genotype remains incomplete in 1% of Cystic Fibrosis (CF) cases, because only one or no disease-causing variants is detected after extended analysis. This fraction is probably higher in CFTR-Related Disorders (CFTR-RD). Deep-intronic CFTR variants are putative candidates to fill this gap. However, the recurrence, phenotypic spectrum and full molecular characterization of newly reported variants are unknown.
Minigenes and analysis of CFTR transcripts in nasal epithelial cells were used to determine the impact on CFTR splicing of intronic variants that we previously identified by next generation sequencing of the whole CFTR locus. Phenotypic data were collected in 19 patients with CF and CFTR-RD, in whom one of the deep intronic variants has been detected.
Three deep-intronic variants promoted the inclusion of pseudo-exons (PE) in the CFTR transcript, hindering the synthesis of a functional protein. The c.2989-313A > T variant, detected in four patients with CF or CFTR-RD from three different families, led to the inclusion of a 118 bp PE. The c.3469-1304C > G variant promoted the inclusion of a 214 bp-PE and was identified in five patients with CF from four families. Haplotype analysis confirmed that this variant was associated with one CF chromosome of African origin. The most represented variant in our cohort was the c.3874-4522A > G, detected in 10 patients with various phenotypes, from male infertility to CF with pancreatic insufficiency.
These three deep intronic CFTR variants are associated with a large phenotypic spectrum, including typical CF. They should be included in CF diagnostic testing and carrier screening strategies.
