The role of rhinovirus infections in young children with cystic fibrosis.

J Clin Virol. 2020 Jun 01;129:104478

Authors: O Loughlin DW, Coughlan S, De Gascun CF, McNally P, Cox DW

Abstract
Rhinovirus (RV) is an important virus in children with chronic respiratory conditions such as asthma; however, little is known about its role in CF. Our aim was to examine the prevalence and clinical impact of different RV species in young children with CF. We collected clinical data and nasal swabs on patients at home and in the hospital setting. Parents filled out symptom diaries and collected nasal swabs when their children were symptomatic and asymptomatic. A novel RV typing PCR assay was used to determine the RV species present. We collected 55 nasal swab samples from ten preschool CF patients over a six month period. The quality of parent collected samples at home was sufficient for PCR analysis. RV was the most common virus detected in young children with CF. There was no difference in the frequency of RV species between symptomatic and asymptomatic subjects. However, parental home-sampling is an acceptable and feasible approach to monitoring young children with CF.

PMID: 32521465 [PubMed - as supplied by publisher]

Reply to: Clonally Related Viable Nontuberculous Mycobacteria in Gastric Juice and Sputum in People with Cystic Fibrosis.

Am J Respir Crit Care Med. 2020 Jun 10;:

Authors: Honda JR

PMID: 32521170 [PubMed - as supplied by publisher]

Clonally Related Viable Nontuberculous Mycobacteria in Gastric Juice and Sputum in People with Cystic Fibrosis.

Am J Respir Crit Care Med. 2020 Jun 10;:

Authors: Ward C, Al Momani H, Perry A, Perry JD, Krishnan A, Jones R, Griffin M, Pearson J, Bourke S

PMID: 32521166 [PubMed - as supplied by publisher]

Antibiotic treatment for nontuberculous mycobacteria lung infection in people with cystic fibrosis.

Cochrane Database Syst Rev. 2020 Jun 10;6:CD010004

Authors: Waters V, Ratjen F

Abstract
BACKGROUND: Nontuberculous mycobacteria are mycobacteria, other than those in the Mycobacterium tuberculosis complex, and are commonly found in the environment. Nontuberculous mycobacteria species (most commonly Mycobacterium avium complex and Mycobacterium abscessus) are isolated from the respiratory tract of approximately 5% to 40% of individuals with cystic fibrosis; they can cause lung disease in people with cystic fibrosis leading to more a rapid decline in lung function and even death in certain circumstances. Although there are guidelines for the antimicrobial treatment of nontuberculous mycobacteria lung disease, these recommendations are not specific for people with cystic fibrosis and it is not clear which antibiotic regimen may be the most effective in the treatment of these individuals. This is an update of a previous review.
OBJECTIVES: The objective of our review was to compare antibiotic treatment to no antibiotic treatment, or to compare different combinations of antibiotic treatment, for nontuberculous mycobacteria lung infections in people with cystic fibrosis. The primary objective was to assess the effect of treatment on lung function and pulmonary exacerbations and to quantify adverse events. The secondary objectives were to assess treatment effects on the amount of bacteria in the sputum, quality of life, mortality, nutritional parameters, hospitalizations and use of oral antibiotics.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search: 24 February 2020. We also searched a register of ongoing trials and the reference lists of relevant articles and reviews. Date of last search: 21 March 2019.
SELECTION CRITERIA: Any randomized controlled trials comparing nontuberculous mycobacteria antibiotics to no antibiotic treatment, as well as one nontuberculous mycobacteria antibiotic regimen compared to another nontuberculous mycobacteria antibiotic regimen, in individuals with cystic fibrosis.   DATA COLLECTION AND ANALYSIS: Data were not collected because in the one trial identified by the search, data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company.
MAIN RESULTS: One completed trial was identified by the searches, but data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company.
AUTHORS' CONCLUSIONS: This review did not find any evidence for the effectiveness of different antimicrobial treatment for nontuberculous mycobacteria lung disease in people with cystic fibrosis. Until such evidence becomes available, it is reasonable for clinicians to follow published clinical practice guidelines for the diagnosis and treatment of nodular or bronchiectatic pulmonary disease due to Mycobacterium avium complex or Mycobacterium abscessus in patients with cystic fibrosis.

PMID: 32521055 [PubMed - as supplied by publisher]

Standard versus biofilm antimicrobial susceptibility testing to guide antibiotic therapy in cystic fibrosis.

Cochrane Database Syst Rev. 2020 Jun 10;6:CD009528

Authors: Smith S, Waters V, Jahnke N, Ratjen F

Abstract
BACKGROUND: Clinicians typically select the antibiotics used to treat pulmonary infections in people with cystic fibrosis based on the results of antimicrobial susceptibility testing performed on bacteria traditionally grown in a planktonic mode (grown in a liquid). However, there is considerable evidence to suggest that Pseudomonas aeruginosa actually grows in a biofilm (or slime layer) in the airways of people with cystic fibrosis with chronic pulmonary infections. Therefore, choosing antibiotics based on biofilm rather than conventional antimicrobial susceptibility testing could potentially improve response to treatment of Pseudomonas aeruginosa in people with cystic fibrosis. This is an update of a previously published Cochrane Review.
OBJECTIVES: To compare biofilm antimicrobial susceptibility testing-driven therapy to conventional antimicrobial susceptibility testing-driven therapy in the treatment of Pseudomonas aeruginosa infection in people with cystic fibrosis.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Most recent search: 07 April 2020. We also searched two ongoing trials registries and the reference lists of relevant articles and reviews. Most recent searches: 07 April 2020 and 05 September 2017.
SELECTION CRITERIA: Randomized controlled trials (RCTs) of antibiotic therapy based on biofilm antimicrobial susceptibility testing compared to antibiotic therapy based on conventional antimicrobial susceptibility testing in the treatment of Pseudomonas aeruginosa pulmonary infection in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS: Two authors independently selected RCTs, assessed their risk of bias and extracted data from eligible trials. Additionally, the review authors contacted the trial investigators to obtain further information. The quality of the evidence was assessed using the GRADE criteria.
MAIN RESULTS: The searches identified two multicentre, double-blind RCTs eligible for inclusion in the review with a total of 78 participants (adults and children); one RCT was undertaken in people who were clinically stable, the second was in people experiencing pulmonary exacerbations. Both RCTs prospectively assessed whether the use of biofilm antimicrobial susceptibility testing improved microbiological and clinical outcomes in participants with cystic fibrosis who were infected with Pseudomonas aeruginosa. The primary outcome was the change in sputum Pseudomonas aeruginosa density from the beginning to the end of antibiotic therapy. Although the intervention was shown to be safe, the data from these two RCTs did not provide evidence that biofilm susceptibility testing was superior to conventional susceptibility testing either in terms of microbiological or lung function outcomes. One of the trials also measured risk and time to subsequent exacerbation as well as quality of life measures and did not demonstrate any difference between groups in these outcomes. Both RCTs had an overall low risk of bias and the quality of the evidence using GRADE criteria was deemed to be moderate to high for the outcomes selected.
AUTHORS' CONCLUSIONS: The current evidence is insufficient to recommend choosing antibiotics based on biofilm antimicrobial susceptibility testing rather than conventional antimicrobial susceptibility testing in the treatment of Pseudomonas aeruginosa pulmonary infections in people with cystic fibrosis. Biofilm antimicrobial susceptibility testing may be more appropriate in the development of newer, more effective formulations of drugs which can then be tested in clinical trials.

PMID: 32520436 [PubMed - as supplied by publisher]

Antisense oligonucleotide-mediated correction of CFTR splicing improves chloride secretion in cystic fibrosis patient-derived bronchial epithelial cells.

Nucleic Acids Res. 2020 Jun 10;:

Authors: Michaels WE, Bridges RJ, Hastings ML

Abstract
Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, encoding an anion channel that conducts chloride and bicarbonate across epithelial membranes. Mutations that disrupt pre-mRNA splicing occur in >15% of CF cases. One common CFTR splicing mutation is CFTR c.3718-2477C>T (3849+10 kb C>T), which creates a new 5' splice site, resulting in splicing to a cryptic exon with a premature termination codon. Splice-switching antisense oligonucleotides (ASOs) have emerged as an effective therapeutic strategy to block aberrant splicing. We test an ASO targeting the CFTR c.3718-2477C>T mutation and show that it effectively blocks aberrant splicing in primary bronchial epithelial (hBE) cells from CF patients with the mutation. ASO treatment results in long-term improvement in CFTR activity in hBE cells, as demonstrated by a recovery of chloride secretion and apical membrane conductance. We also show that the ASO is more effective at recovering chloride secretion in our assay than ivacaftor, the potentiator treatment currently available to these patients. Our findings demonstrate the utility of ASOs in correcting CFTR expression and channel activity in a manner expected to be therapeutic in patients.

PMID: 32520327 [PubMed - as supplied by publisher]

TREATMENT ADHERENCE AMONG CHILDREN AND ADOLESCENTS IN A CYSTIC FIBROSIS REFERENCE CENTER.

Rev Paul Pediatr. 2020;38:e2018338

Authors: Bonfim BS, Melo Filho VM, Fontenelle FM, Souza EL

Abstract
OBJECTIVE: To evaluate the level of self-referenced treatment adherence (TA) and its association with clinical and sociodemographic variables in patients with cystic fibrosis assisted at a reference center, as well as compare the level of self-referenced TA with that presumed by the multidisciplinary team.
METHODS: This is a cross-sectional study that included children and adolescents aged between 0-20 years with cystic fibrosis. Adolescents older than 14 years or their guardians, when younger than 14 years old, were interviewed using a standardized questionnaire. Professionals from the multidisciplinary clinic filled out another form with their impressions of the patients' TA. Clinical and laboratory data were obtained in the medical records. The TA was considered satisfactory if the total adherence index (TAI) was equal or higher than 80%.
RESULTS: 53 patients were included with a median age of 112 months. The mean TAI was 83.2%. The mean TAIs for dornase alfa, pancreatic enzymes, continued use of inhaled tobramycin, vitamins supplements, nutritional supplements and dietary orientation was respectively: 86.1; 96.6; 78.6; 88.1; 51.8 and 78%. Children younger than 14 years presented better TA (p=0.021). The correlation between the self-referenced TA and the one presumed by the multidisciplinary team ranged from 0,117 to 0.402, being higher for Psychology and Nutrition professionals.
CONCLUSIONS: The TAI was high particularly among children younger than 14 years. There was a positive correlation between the self-referenced TA and the one presumed by the Psychology (p=0.032) and the nutrition (p=0.012) professionals.

PMID: 32520296 [PubMed - as supplied by publisher]

Palliative care in cystic fibrosis.

BMJ Support Palliat Care. 2020 Jun 09;:

Authors: Blin T, Flament T, Mankikian J, Vibet S, Chaumier F

PMID: 32518129 [PubMed - as supplied by publisher]

Utility of Second-Look Endoscopy with Debridement After Pediatric Functional Endoscopic Sinus Surgery in Patients with Cystic Fibrosis.

Ann Otol Rhinol Laryngol. 2020 Jun 09;:3489420922865

Authors: Helmen ZM, Little RE, Robey T

Abstract
OBJECTIVES: To determine the utility of Second-look endoscopy with debridement (SLED) after functional endoscopic sinus surgery (ESS) in pediatric cystic fibrosis (CF) patients. To compare outcomes in pediatric CF patients undergoing sinus surgery for chronic sinusitis with or without SLED. To describe findings present at the time of SLED.
METHODS: Retrospective chart review of 61 ESS procedures performed at a tertiary care pediatric center from 2013 to 2016. Data collected included demographics, SLED findings, and 6-month pre-/postoperative disease specific outcomes including incidence of sinonasal and pulmonary exacerbations and revisions.
RESULTS: Sixty-one cases were reviewed. SLED was performed in 38 cases on average 22.4 days postoperatively. Average preoperative Lund-Mackay score was 14.9 and 14.8 among patients undergoing ESS with and without SLED, respectively. Pre-/postoperative intranasal steroid use and extent of surgery performed was similar among all patients. At the time of SLED, rates of synechiae, polyps and maxillary antrostomy obstruction were 26.3%, 23.7%, and 7.9%, respectively. The incidence and number of days to onset of postoperative sinonasal exacerbations requiring antibiotic therapy within 6 months of ESS were 1.0 (SD 1.0) and 85 days (SD 45.7); and 1.3 (SD 1.0) and 80.4 days (SD 40.5) for patients undergoing ESS with and without SLED, respectively (P value .33). The number of days to first pulmonary exacerbation was 113.9 (SD 45.5) and 47.4 (SD 34.1) among SLED and non-SLED patients, respectively (P value .01). No significant difference was observed in revision rates and time to revision ESS (30% and overall average 1.4 years, respectively).
CONCLUSION: The utility of SLED among pediatric CF patients remains unclear. While debridement did not have a significant impact on sinonasal exacerbations or revision rates, pulmonary exacerbations for patients undergoing SLED were delayed. Further studies are needed to clarify the impact of SLED.

PMID: 32517494 [PubMed - as supplied by publisher]

Review of Potential Pseudomonas Weaponry, Relevant to the Pseudomonas-Aspergillus Interplay, for the Mycology Community.

J Fungi (Basel). 2020 Jun 06;6(2):

Authors: Chatterjee P, Sass G, Swietnicki W, Stevens DA

Abstract
Pseudomonas aeruginosa is one of the most prominent opportunistic bacteria in airways of cystic fibrosis patients and in immunocompromised patients. These bacteria share the same polymicrobial niche with other microbes, such as the opportunistic fungus Aspergillus fumigatus. Their inter-kingdom interactions and diverse exchange of secreted metabolites are responsible for how they both fare in competition for ecological niches. The outcomes of their contests likely determine persistent damage and degeneration of lung function. With a myriad of virulence factors and metabolites of promising antifungal activity, P. aeruginosa products or their derivatives may prove useful in prophylaxis and therapy against A. fumigatus. Quorum sensing underlies the primary virulence strategy of P. aeruginosa, which serves as cell-cell communication and ultimately leads to the production of multiple virulence factors. Understanding the quorum-sensing-related pathogenic mechanisms of P. aeruginosa is a first step for understanding intermicrobial competition. In this review, we provide a basic overview of some of the central virulence factors of P. aeruginosa that are regulated by quorum-sensing response pathways and briefly discuss the hitherto known antifungal properties of these virulence factors. This review also addresses the role of the bacterial secretion machinery regarding virulence factor secretion and maintenance of cell-cell communication.

PMID: 32517271 [PubMed]

Human Sperm Capacitation Involves the Regulation of the Tyr-Phosphorylation Level of the Anion Exchanger 1 (AE1).

Int J Mol Sci. 2020 Jun 05;21(11):

Authors: Donà G, Tibaldi E, Andrisani A, Ambrosini G, Sabbadin C, Pagano MA, Brunati AM, Armanini D, Ragazzi E, Bordin L

Abstract
Bicarbonate uptake is one of the early steps of capacitation, but the identification of proteins regulating anion fluxes remains elusive. The aim of this study is to investigate the role of sperm solute carrier 4 (SLC4) A1 (spAE1) in the capacitation process. The expression, location, and tyrosine-phosphorylation (Tyr-P) level of spAE1 were assessed. Thereby, it was found that 4,4'-Diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS), an SLC4 family channel blocker, inhibited capacitation in a dose-dependent manner by decreasing acrosome reaction (ARC% 24.5 ± 3.3 vs 64.9 ± 4.3, p < 0.05) and increasing the percentage of not viable cells (NVC%), comparable to the inhibition by I-172, a cystic fibrosis transmembrane conductance regulator (CFTR) blocker (AR% 30.5 ± 4.4 and NVC% 18.6 ± 2.2). When used in combination, a synergistic inhibitory effect was observed with a remarkable increase of the percentage of NVC (45.3 ± 4.1, p < 0.001). spAE1 was identified in sperm membrane as a substrate for Tyr-protein kinases Lyn and Syk, which were identified as both soluble and membrane-bound pools. spAE1-Tyr-P level increased in the apical region of sperm under capacitating conditions and was negatively affected by I-172 or DIDS, and, to a far greater extent, by a combination of both. In conclusion, we demonstrated that spAE1 is expressed in sperm membranes and it is phosphorylated by Syk, but above all by Lyn on Tyr359, which are involved in sperm viability and capacitation.

PMID: 32517126 [PubMed - in process]

Vaccinations and Immune Response in Celiac Disease.

Vaccines (Basel). 2020 Jun 05;8(2):

Authors: Passanisi S, Dipasquale V, Romano C

Abstract
Immune response to vaccinations in celiac patients is of growing scientific interest. However, some aspects of the relationship between celiac disease (CD) and vaccines are still unclear. A comprehensive search of published literature using the PubMed database was carried out using the following key terms: "adaptive immunity", "celiac disease", "humoral immune response", "immunization", and "vaccination". To date, there is no evidence showing any causative association between vaccines and CD development. Therefore, vaccinations may be administered according to the modalities and timing of the National Immunization Schedule for each country. The rotavirus vaccine is currently recommended for the general population, and according to some data, it appears to reduce the risk for the development of CD autoimmunity in the early years of life. Regarding the hepatitis B virus, a booster dose of the vaccine is often required due to the low or the lost immune response rate in CD. Furthermore, determination of hepatitis B antibody titers could be useful in newly diagnosed CD subjects regardless of age at diagnosis. Finally, pneumococcal vaccines may be administered in patients with advancing age at diagnosis and concomitant risk factors. Future clinical practice guidelines for vaccination and monitoring programs in celiac patients could be recommended.

PMID: 32517026 [PubMed]

Assessing the Performance of Dried-Blood-Spot DNA Extraction Methods in Next Generation Sequencing.

Int J Neonatal Screen. 2020 Apr 30;6(2):1-15

Authors: Hendrix MM, Cuthbert CD, Cordovado SK

Abstract
An increasing number of newborn screening laboratories in the United States and abroad are moving towards incorporating next-generation sequencing technology, or NGS, into routine screening, particularly for cystic fibrosis. As more programs utilize this technology for both cystic fibrosis and beyond, it is critical to identify appropriate DNA extraction methods that can be used with dried blood spots that will result in consistent, high-quality sequencing results. To provide comprehensive quality assurance and technical assistance to newborn screening laboratories wishing to incorporate NGS assays, CDC's Newborn Screening and Molecular Biology Branch designed a study to evaluate the performance of nine commercial or laboratory-developed DNA extraction methods that range from a highly purified column extraction to a crude detergent-based no-wash boil prep. The DNA from these nine methods was used in two NGS library preparations that interrogate the CFTR gene. All DNA extraction methods including the cruder preps performed reasonably well with both library preps. One lower-concentration, older sample was excluded from one of the assay evaluations due to poor performance across all DNA extraction methods. When 84 samples, versus eight, were run on a flow cell, the DNA quality and quantity were more significant variables.

PMID: 32514487 [PubMed]

Airway microbial diversity is decreased in young children with cystic fibrosis compared to healthy controls but improved with CFTR modulation.

Heliyon. 2020 Jun;6(6):e04104

Authors: Hahn A, Burrell A, Ansusinha E, Peng D, Chaney H, Sami I, Perez GF, Koumbourlis AC, McCarter R, Freishtat RJ, Crandall KA, Zemanick ET

Abstract
Background: Culture-independent next generation sequencing has identified diverse microbial communities within the cystic fibrosis (CF) airway. The study objective was to test for differences in the upper airway microbiome of children with CF and healthy controls and age-related differences in children with CF.
Methods: Oropharyngeal swabs and clinical data were obtained from 25 children with CF and 50 healthy controls aged ≤6 years. Bacterial DNA was amplified and sequenced for the V4 region of 16S rRNA marker-gene. Alpha diversity was measured using operational taxonomic units (OTUs), Shannon diversity, and the inverse Simpson's index. Beta diversity was measured using Morisita-Horn and Bray-Curtis and Jaccard distances. General linear models were used for comparison of alpha diversity measures between groups to account for differences in demographics and exposures. Mixed effects general linear models were used for longitudinal comparisons 1) between children with CF of different ages and 2) between children with CF receiving CF transmembrane conductance regulator (CFTR) modulators, children with CF not receiving CFTR modulators, and healthy controls to adjust for repeated measures per subject.
Results: Children with CF were more likely to have received antibiotics in the prior year than healthy controls (92% vs 24%, p < 0.001). Controlling age, race, ethnicity, length of breastfeeding, and having siblings, children with CF had a lower richness than healthy controls: OTUs 62.1 vs 83, p = 0.022; and trended toward lower diversity: Shannon 2.09 vs 2.35, p = 0.057; inverse Simpson 5.7 vs 6.92, p = 0.118. Staphylococcus, three Rothia OTUs, and two Streptococcus OTUs were more abundant in CF children versus healthy controls (all p < 0.05). Bray-Curtis and Jaccard distances, which reflect overall microbial community composition, were also significantly different (both p = 0.001). In longitudinally collected samples from children with CF, Morisita-Horn trended toward more similarity in those aged 0-2 years compared to those aged 3-6 years (p = 0.070). In children >2 years of age, there was a significant trend in increasing alpha diversity measures between children with CF not receiving CFTR modulators, children with CF receiving CFTR modulators, and healthy controls: OTUs 63.7 vs 74.7 vs 97.6, p < 0.001; Shannon 2.11 vs 2.34 vs 2.56, p < 0.001; inverse Simpson 5.78 vs 7.23 vs 7.96, p < 0.001.
Conclusions: Children with CF have lower bacterial diversity and different composition of organisms compared with healthy controls. This appears to start in early childhood, is possibly related to the use of antibiotics, and may be partially corrected with the use of CFTR modulators.

PMID: 32514485 [PubMed]

Changes in LCI in F508del/F508del patients treated with lumacaftor/ivacaftor: Results from the prospect study.

J Cyst Fibros. 2020 Jun 06;:

Authors: Shaw M, Khan U, Clancy JP, Donaldson SH, Sagel SD, Rowe SM, Ratjen F, PROSPECT Investigators of the Cystic Fibrosis Foundation Therapeutics Development Network

Abstract
The PROSPECT study, a post-approval observational study in the U.S., showed no significant changes in lung function as measured by spirometry with clinical initiation of lumacaftor/ivacaftor. A sub-study within the PROSPECT study assessed the lung clearance index (LCI), as measured by multiple breath washout (MBW), a measure of lung function demonstrated to be sensitive among people with normal spirometry. Participants performed MBW prior to clinically initiating lumacaftor/ivacaftor therapy and for one year of follow-up. Similar to the whole PROSPECT study, this sub-study cohort (N = 49) had no significant absolute or relative changes in FEV1% predicted at any time point. LCI, however, decreased (improved) by 0.81 units or 5.3% (95% CI -9.7, -0.9%) at 1 month, 0.77 units or 5.9% at 3 months, 0.67 units or 5.9% at 6 months, and 0.55 units or 4.3% at 12 months. These results demonstrate the utility of the LCI in assessing treatment effects of relatively modest size in a heterogenous study population.

PMID: 32513528 [PubMed - as supplied by publisher]

The Effect of Sodium Bicarbonate, a Beneficial Adjuvant Molecule in Cystic Fibrosis, on Bronchial Epithelial Cells Expressing a Wild-Type or Mutant CFTR Channel.

Int J Mol Sci. 2020 Jun 04;21(11):

Authors: Gróf I, Bocsik A, Harazin A, Santa-Maria AR, Vizsnyiczai G, Barna L, Kiss L, Fűr G, Rakonczay Z, Ambrus R, Szabó-Révész P, Gosselet F, Jaikumpun P, Szabó H, Zsembery Á, Deli MA

Abstract
Clinical and experimental results with inhaled sodium bicarbonate as an adjuvant therapy in cystic fibrosis (CF) are promising due to its mucolytic and bacteriostatic properties, but its direct effect has not been studied on respiratory epithelial cells. Our aim was to establish and characterize co-culture models of human CF bronchial epithelial (CFBE) cell lines expressing a wild-type (WT) or mutant (deltaF508) CF transmembrane conductance regulator (CFTR) channel with human vascular endothelial cells and investigate the effects of bicarbonate. Vascular endothelial cells induced better barrier properties in CFBE cells as reflected by the higher resistance and lower permeability values. Activation of CFTR by cAMP decreased the electrical resistance in WT but not in mutant CFBE cell layers confirming the presence and absence of functional channels, respectively. Sodium bicarbonate (100 mM) was well-tolerated by CFBE cells: it slightly reduced the impedance of WT but not that of the mutant CFBE cells. Sodium bicarbonate significantly decreased the more-alkaline intracellular pH of the mutant CFBE cells, while the barrier properties of the models were only minimally changed. These observations indicate that sodium bicarbonate is beneficial to deltaF508-CFTR expressing CFBE cells. Thus, sodium bicarbonate may have a direct therapeutic effect on the bronchial epithelium.

PMID: 32512832 [PubMed - in process]

Molecular Diagnosis and Genetic Counseling of Cystic Fibrosis and Related Disorders: New Challenges.

Genes (Basel). 2020 Jun 04;11(6):

Authors: Bienvenu T, Lopez M, Girodon E

Abstract
Identification of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and its numerous variants opened the way to fantastic breakthroughs in diagnosis, research and treatment of cystic fibrosis (CF). The current and future challenges of molecular diagnosis of CF and CFTR-related disorders and of genetic counseling are here reviewed. Technological advances have enabled to make a diagnosis of CF with a sensitivity of 99% by using next generation sequencing in a single step. The detection of heretofore unidentified variants and ethnic-specific variants remains challenging, especially for newborn screening (NBS), CF carrier testing and genotype-guided therapy. Among the criteria for assessing the impact of variants, population genetics data are insufficiently taken into account and the penetrance of CF associated with CFTR variants remains poorly known. The huge diversity of diagnostic and genetic counseling indications for CFTR studies makes assessment of variant disease-liability critical. This is especially discussed in the perspective of wide genome analyses for NBS and CF carrier screening in the general population, as future challenges.

PMID: 32512765 [PubMed - in process]

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2020/06/09

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2020/06/09

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Immune competence and respiratory symptoms in patients with ataxia telangiectasia: A prospective follow-up study.

Clin Immunol. 2020 Jun 03;:108491

Authors: Wölke S, Donath H, Bakhtiar S, Trischler J, Schubert R, Zielen S

Abstract
Ataxia telangiectasia is a multi-system disorder characterized by progressive cerebellar ataxia, malignancies, chronic pulmonary disease and immunodeficiency. The aim of our study was to determine the immune competence and prevalence of respiratory infections and/or chronic cough in classical A-T patients compared to age-matched healthy controls.
STUDY DESIGN: We recruited 20 classical A-T not treated by immunoglobulins and 21 healthy age-matched control patients. The caregivers were advised to keep a daily diary with the following items (daytime and nighttime cough, runny nose, fever), number of cold episodes, number of antibiotic treatments.
RESULTS: Patients with A-T showed significant differences compared to healthy controls in symptom score, daytime and nighttime cough, days with symptoms and missed days in kindergarten/school. Severe infections with hospitalization occurred rarely. Respiratory symptoms did not correlate with immunoglobulin levels in A-T patients.
CONCLUSIONS: Mild symptoms like chronic cough were present in A-T patients, possibly indicating ongoing silent crippling disease.

PMID: 32504779 [PubMed - as supplied by publisher]