Phenotypic characterization of trimeric autotransporter adhesin-defective bcaC mutant of Burkholderia cenocepacia: cross-talk towards the histidine kinase BCAM0218.

Microbes Infect. 2020 Jun 15;:

Authors: Pimenta AI, Mil-Homens D, Pinto SN, Fialho AM

Abstract
Burkholderia cenocepacia is a virulent species belonging to the Burkholderia cepacia complex (Bcc) and one of the most problematic agents of chronic lung infection in cystic fibrosis patients. B. cenocepacia possesses a large panel of virulence traits that include trimeric autotransporter adhesins (TAAs). Such proteins are obligate homotrimeric anchored in the outer membrane. They are players in the adhesion events that occur between bacteria and biotic/abiotic surfaces. In this study, we constructed two insertional-mutants for TAA bcaC and Histidine kinase (HK) BCAM0218 genes, which are clustered together within the B. cenocepacia K56-2 TAA cluster. The bcaC-mutant affects B. cenocepacia adhesion to extracellular matrix proteins and red blood cells hemagglutination. BcaC contributes to enhancing B. cenocepacia K56-2 adhesion to bronchial epithelial cells. The expression of bcaC seems to affect biofilm formation negatively. Due to a BCAM0218 disruption, the bcaC expression increases significantly, indicating that they are functionally linked. The overexpression of bcaC in the BCAM0218-mutant background rescues at least part of the BcaC functions. Altogether, these findings reveal the multifunctionality of BcaC as a novel B. cenocepacia K56-2 virulence factor and postulate the involvement of a sensor HK (BCAM0218) in the control of this TAA gene.

PMID: 32554104 [PubMed - as supplied by publisher]

Clinical service delivery of non-invasive prenatal diagnosis (NIPD) by relative haplotype dosage (RHDO) for single gene disorders.

J Mol Diagn. 2020 Jun 15;:

Authors: Young E, Bowns B, Gerrish A, Parks M, Court S, Clokie S, Mashayamombe-Wolfgarten C, Hewitt J, Williams D, Cole T, Allen S

Abstract
We have developed and implemented into routine clinical practice a relative haplotype dosage (RHDO) based method for non-invasive prenatal diagnosis (NIPD) of multiple single gene disorders: spinal muscular atrophy (SMA), Duchenne and Becker muscular dystrophies (DMD/BMD) and cystic fibrosis (CF). This review describes our experience of the first 152 pregnancies to have NIPD by RHDO as part of a routine clinical service. We have demonstrated that it is possible to provide a result within a clinically useful timeframe (mean 11 calendar days) with a very low failure rate (4%), none being due to a technical failure. Where follow up confirmatory testing was performed for audit purposes, 100% concordance was seen with the NIPD result and no discrepancies have been reported. The robust performance of our assay, together with high sensitivity and specificity, demonstrates that NIPD by RHDO is feasible for use in a clinical setting.

PMID: 32553884 [PubMed - as supplied by publisher]

Data driven decision making to characterize clinical personas of parents of children with cystic fibrosis: a mixed methods study.

BMC Pulm Med. 2020 Jun 18;20(1):174

Authors: Szczesniak RD, Pestian T, Duan LL, Li D, Stamper S, Ferrara B, Kramer E, Clancy JP, Grossoehme D

Abstract
BACKGROUND: Beginning at a young age, children with cystic fibrosis (CF) embark on demanding care regimens that pose challenges to parents. We examined the extent to which clinical, demographic and psychosocial features inform patterns of adherence to pulmonary therapies and how these patterns can be used to develop clinical personas, defined as aspects of adherence barriers that are presented by parents and/or perceived by clinicians, in order to enhance personalized CF care delivery.
METHODS: We undertook an explanatory sequential mixed-methods study consisting of i) multivariate clustering to create clusters corresponding to parental adherence patterns (quantitative phase); ii) parental participant interviews to create clinical personas interpreted from clustering (qualitative phase). Clinical, demographic and psychosocial features were used in supervised clustering against clinical endpoints, which included adherence to airway clearance and aerosolized medications and self-efficacy score, which was used as a feature for modeling adherence. Clinical implications were developed for each persona by combing quantitative and qualitative data (integration phase).
RESULTS: The quantitative phase showed that the 87 parent participants were segmented into three distinct patterns of adherence based on use of aerosolized medication and practice of airway clearance. Patterns were primarily influenced by self-efficacy, distance to CF care center and child BMI percentile. The two key patterns that emerged for the self-efficacy model were most heavily influenced by distance to CF care center and child BMI percentile. Eight clinical personas were developed in the qualitative phase from parent and clinician participant feedback of latent components from these models. Findings from the integration phase include recommendations to overcome specific challenges with maintaining treatment regimens and increasing support from social networks.
CONCLUSIONS: Adherence patterns from multivariate models and resulting parent personas with their corresponding clinical implications have utility as clinical decision support tools and capabilities for tailoring intervention study designs that promote adherence.

PMID: 32552880 [PubMed - in process]

Cell surface remodeling of Mycobacterium abscessus under cystic fibrosis airway growth conditions.

ACS Infect Dis. 2020 Jun 17;:

Authors: Wiersma C, Belardinelli JM, Avanzi C, Angala SK, Everall I, Angala B, Kendall E, Moura V, Verma D, Benoit J, Brown K, Jones V, Malcom K, Strong M, Nick J, Floto RA, Parkhill J, Ordway D, Davidson R, McNeil MR, Jackson MC

Abstract
Understanding the physiological processes underlying the ability of Mycobacterium abscessus to become a chronic pathogen of the cystic fibrosis (CF) lung is important to the development of prophylactic and therapeutic strategies to better control and treat pulmonary infections caused by these bacteria. Gene expression profiling of a diversity of M. abscessus complex isolates points to amino acids being significant sources of carbon and energy for M. abscessus in both CF sputum and synthetic CF medium, and to the bacterium undergoing an important metabolic reprogramming in order to adapt to this particular nutritional environment. Cell envelope analyses conducted on the same representative isolates further revealed unexpected structural alterations in major cell surface glycolipids known as the glycopeptidolipids (GPLs). Besides showing an increase in triglycosylated forms of these lipids, CF sputum- and synthetic CF medium-grown isolates presented as yet unknown forms of GPLs representing as much as 10 to 20% of the total GPL content of the cells, in which the classical amino alcohol located at the carboxy terminal of the peptide, alaninol, is replaced with the branched-chain amino alcohol, leucinol. Importantly, both these lipid changes were exacerbated by the presence of mucin in the culture medium. Collectively, our results reveal potential new drug targets against M. abscessus in the CF airway and point to mucin as an important host signal modulating the cell surface composition of this pathogen.

PMID: 32551551 [PubMed - as supplied by publisher]

A Case Report of Cystic Fibrosis Complicated by Burkholderia Cepacia and Cutaneous Vasculitis.

Cureus. 2020 May 16;12(5):e8158

Authors: Klimko A, Brandt A, Brustan MI, Balgradean M

Abstract
While the pulmonary and pancreatic involvement of cystic fibrosis (CF) is commonly described and therefore best studied, the cutaneous manifestations are frequently underdiagnosed, despite being important markers of disease severity. We report a case of antineutrophil cytoplasmic antibody-negative cutaneous vasculitis in a 15-year-old female CF patient in tandem with infection and subsequent colonization by Burkholderia cepacia complex (BCC). The flares of cutaneous vasculitis is associated closely with an infective exacerbation of CF and improved upon treatment of the infective exacerbation. We further discuss how the appearance of BCC colonization and cutaneous vasculitis affected both lung function and lung parenchyma by tracking spirometry and imaging changes over the subsequent four years.

PMID: 32550075 [PubMed]

Cystic Fibrosis mutation W19X in Tunisia: Second case identified.

Tunis Med. 2020 May;98(5):420-422

Authors: Lamouchi MT

Abstract
Cystic Fibrosis (CF) is a lethal autosomal recessive condition due to a defect at the level of the transmembrane conductance regulator gene which plays a role in cell homeostasis. Numerous mutations have been identified as the cause of this gene defect, with delF508 being one of the most common mutations in Tunisia. This is a case report describing, up to our knowledge, the second case of a patient with CF carrying a rare mutation: W19X. W19X is a nonsense mutation that has been previously identified in only one other Tunisian patient with CF. Since both incidence of this mutation have been described in Tunisia, it seems as if W19X is specific to Tunisian CF patient with significant morbidities. The information provided by this study contributes to defining the molecular spectrum of CF in Tunisia, in the aim of improving genetic testing and prenatal diagnosis.

PMID: 32548846 [PubMed - in process]

Bronchoalveolar Lavage-microRNAs Are Potential Novel Biomarkers of Outcome After Lung Transplantation.

Transplant Direct. 2020 May;6(5):e547

Authors: Palleschi A, Gaudioso G, Edefonti V, Musso V, Terrasi A, Ambrogi F, Franzi S, Rosso L, Tarsia P, Morlacchi LC, Ferrero S, Nosotti M, Vaira V

Abstract
Primary graft dysfunction, infections, and acute rejection (AR) worsen lung transplantation (LTx) outcome and patient survival. Despite significant efforts, reliable biomarkers of acute lung allograft dysfunction are lacking. To address this issue, we profiled the bronchoalveolar lavage (BAL) miRNome in LTx patients.
Methods: BAL-microRNAs (miRNAs) from 16 patients were collected 7 days (T0), 15 days (T1), and 3 months (T2) after bilateral LTx and profiled on low-density array. Unsupervised and supervised analyses were used to identify miRNAs associated with clinical features, pneumonia, or AR. Prognostic markers were identified using the Cox model. Targeted signaling pathways were predicted in silico. A second series of 11 patients were used to validate AR-associated miRNAs.
Results: Variation in BAL-miRNAs was associated with acute lung allograft dysfunction. Increased levels of miR-23b-3p at T2 were detected in patients with pneumonia, whereas let-7f-5p, miR-146b-3p, miR-22-5p, miR-29c-5p, miR-362-5p, and miR-452-5p were upregulated at T2 in patients with AR. miR-148b-5p and miR-744-3p distinguished LTx patients with AR in both cohorts. Low miR-148b-5p and high miR-744-3p expression levels were significantly associated with a shorter time to AR either within the first year after LTx or during follow-up. Combination of the 2 miRNAs identified LTx patients with higher AR risk independently of clinical variables.
Conclusions: Our data provide new insights into the roles of BAL-miRNAs in regulating the pulmonary environment after transplantation and suggest that these miRNAs could serve as biomarkers of early- or mid-stage events. If validated, these findings could pave the way to a personalized clinical approach in LTx patients.

PMID: 32548241 [PubMed]

Novel Administration of Clofazimine for the Treatment of Mycobacterium avium Infection.

Open Forum Infect Dis. 2020 Jun;7(6):ofaa183

Authors: Valinetz E, Stankiewicz Karita H, Pottinger PS, Jain R

Abstract
Clofazimine has demonstrated in vitro activity against many nontuberculous mycobacteria. We present the case of a woman with cystic fibrosis who developed disseminated macrolide-resistant Mycobacterium avium infection following lung transplantation treated in part with clofazimine. We describe the novel administration of clofazimine via gastrostomy tube.

PMID: 32548205 [PubMed]

Cystic fibrosis-related diabetes: The unmet need.

World J Diabetes. 2020 Jun 15;11(6):213-217

Authors: Pozo L, Bello F, Mendez Y, Surani S

Abstract
Cystic fibrosis (CF) is a common autosomal recessive disease. Life expectancy of patients with CF continues to improve mainly driven by the evolving therapies for CF-related organ dysfunction. The prevalence of CF-related diabetes (CFRD) increases exponentially as patients' age. Clinical care guidelines for CFRD from 2010, recommend insulin as the mainstay of treatment. Many patients with CFRD may not require exogenous insulin due to the heterogeneity of this clinical entity. Maintenance of euglycemia by enhancing endogenous insulin production, secretion and degradation with novel pharmacological therapies like glucagon-like peptide-1 agonist is an option that remains to be fully explored. As such, the scope of this article will focus on our perspective of glucagon-like peptide-1 receptor agonist in the context of CFRD. Other potential options such as sodium-glucose cotransporter-2 and dipeptidyl peptidase 4 inhibitors and their impact on this patient population is limited and further studies are required.

PMID: 32547695 [PubMed]

Tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for minimal function CFTR mutations.

J Cyst Fibros. 2020 Jun 13;:

Authors: Munck A, Kerem E, Ellemunter H, Campbell D, Wang LT, Ahluwalia N, Owen CA, Wainwright C

Abstract
BACKGROUND: Tezacaftor/ivacaftor is a CFTR modulator approved to treat people with cystic fibrosis (pwCF) who are homozygous (F/F) or heterozygous for the F508del-CFTR mutation and a residual function mutation (F/RF). This randomized, double-blind, placebo-controlled Phase 3 study evaluated the efficacy, safety, tolerability, and pharmacokinetics (PK) of tezacaftor/ivacaftor in participants ≥12 years of age heterozygous for the F508del-CFTR mutation and a minimal function mutation (F/MF), which produces no CFTR protein or a protein unresponsive to tezacaftor/ivacaftor in vitro.
METHODS: Participants were randomized 1:1 to receive tezacaftor/ivacaftor or placebo for 12 weeks. The primary endpoint was the absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) between the tezacaftor/ivacaftor and placebo groups through week 12. Key secondary endpoints included absolute change from baseline in CF Questionnaire-Revised respiratory domain scores and the number of pulmonary exacerbations through week 12 and the absolute change from baseline in body mass index at week 12. A prespecified interim analysis (IA) for futility was conducted when approximately 50% of a planned enrollment of 300 participants reached week 12 of the study.
RESULTS: At the time of the IA, 83 participants were randomized to tezacaftor/ivacaftor and 85 to placebo; 165 participants completed treatment. The study failed to demonstrate that tezacaftor/ivacaftor significantly improved ppFEV1 or any of the key secondary endpoints and was terminated for futility. The safety profile and PK parameters of tezacaftor/ivacaftor were similar to those reported in prior studies in participants ≥12 years of age with CF.
CONCLUSIONS: Tezacaftor/ivacaftor did not show a clinically meaningful benefit in participants with F/MF genotypes but was generally safe and well tolerated, consistent with the safety profile reported in other Phase 3 studies (NCT02516410).

PMID: 32546431 [PubMed - as supplied by publisher]

Newborn screening alone insufficient to improve pulmonary outcomes for cystic fibrosis.

J Cyst Fibros. 2020 Jun 13;:

Authors: Barreda CB, Farrell PM, Laxova A, Eickhoff JC, Braun AT, Coller RJ, Rock MJ

Abstract
BACKGROUND: The Wisconsin Cystic Fibrosis Neonatal Screening Project was a randomized clinical trial (RCT) revealing that children receiving an early diagnosis of CF via newborn screening (NBS) had improved nutritional outcomes but similar lung disease severity compared to those who presented clinically. Because the evaluations of these subjects by protocol ended in 2012, our objective was to assess long-term pulmonary and mortality outcomes.
METHODS: Retrospective analysis of the RCT cohort utilized longitudinal outcome measures obtained from the Cystic Fibrosis Foundation Patient Registry (CFFPR). Data included screening assignment, clinical characteristics, percent predicted forced expiratory volume in 1 s (ppFEV1) and mortality. A random intercept model was used to compare the ppFEV1 decline of subjects between the two groups up to age 26 years. Mortality was analyzed using the Kaplan-Meier method.
RESULTS: Of the 145 subjects who consented to the original study, 104 subjects met inclusion criteria and had adequate data in the CFFPR. Of 57 subjects in the screened group and 47 in the control group, the rates of ppFEV1 decline were 1.76%/year (95% CI 1.62 to 1.91%) and 1.43%/year (95% CI 1.26 to 1.60%), respectively (p<0.0002). Pseudomonas aeruginosa acquired before 2 years was partially responsible. There was no difference in mortality between the two groups.
CONCLUSIONS: NBS alone does not improve pulmonary outcomes in CF, particularly when other risk factors supervene. In an era prior to strict infection control and current therapies, NBS for CF may be associated with worse pulmonary outcomes.

PMID: 32546430 [PubMed - as supplied by publisher]

Changing clinical characteristics of non-cystic fibrosis bronchiectasis in children.

BMC Pulm Med. 2020 Jun 16;20(1):172

Authors: Eralp EE, Gokdemir Y, Atag E, Ikizoglu NB, Ergenekon P, Yegit CY, Kut A, Ersu R, Karakoc F, Karadag B

Abstract
BACKGROUND: The prevalence of non-cystic fibrosis (CF) bronchiectasis is increasing in both developed and developing countries in recent years. Although the main features remain similar, etiologies seem to change. Our aim was to evaluate the clinical and laboratory characteristics of our recent non-CF bronchiectasis patients and to compare these with our historical cohort in 2001.
METHODS: One hundred four children with non-CF bronchiectasis followed between 2002 and 2019 were enrolled. Age of diagnosis, underlying etiology and microorganisms in sputum culture were recorded. Clinical outcomes were evaluated in terms of lung function tests and annual pulmonary exacerbation rates at presentation and within the last 12 months.
RESULTS: Mean FEV1 and FVC %predicted at presentation improved compared to historical cohort (76.6 ± 17.1 vs. 63.3 ± 22.1 and 76.6 ± 15.1 vs. 67.3 ± 23.1, respectively; p <  0.001). There was a significant decrease in pulmonary exacerbation rate from 6.05 ± 2.88 at presentation to 3.23 ± 2.08 during follow-up (p <  0.0001). In 80.8% of patients, an underlying etiology was identified. There was an increase in primary ciliary dyskinesia (PCD) (32.7% vs. 6.3%; p = 0.001), decrease in idiopathic cases (19.2% vs. 37.8%; p = 0.03) with no change in postinfectious and immunodeficiencies as underlying etiology. Sputum cultures were positive in 77.9% of patients which was 46.9% in the historical cohort (p = 0.001).
CONCLUSION: Baseline pulmonary function tests were better and distribution of underlying etiology had changed with a remarkable increase in diagnosis of PCD in the recent cohort.

PMID: 32546272 [PubMed - in process]

IRE1 Endoribonuclease Activity Modulates Hypoxic HIF-1α Signaling in Human Endothelial Cells.

Biomolecules. 2020 Jun 11;10(6):

Authors: Moszyńska A, Collawn JF, Bartoszewski R

Abstract
While the role of hypoxia and the induction of the hypoxia inducible factors (HIFs) and the unfolded protein response (UPR) pathways in the cancer microenvironment are well characterized, their roles and relationship in normal human endothelium are less clear. Here, we examined the effects of IRE1 on HIF-1α protein levels during hypoxia in primary human umbilical vein endothelial cells (HUVECs). The results demonstrated that HIF-1α levels peaked at 6 h of hypoxia along with two of their target genes, GLUT1 and VEGFA, whereas at up to 12 h of hypoxia the mRNA levels of markers of the UPR, IRE1, XBP1s, BiP, and CHOP, did not increase, suggesting that the UPR was not activated. Interestingly, the siRNA knockdown of IRE1 or inhibition of IRE1 endonuclease activity with 4µ8C during hypoxia significantly reduced HIF-1α protein without affecting HIF1A mRNA expression. The inhibition of the endonuclease activity with 4µ8C in two other primary endothelial cells during hypoxia, human cardiac microvascular endothelial cells and human aortic endothelial cells showed the same reduction in the HIF-1α protein. Surprisingly, the siRNA knockdown of XBP1s during hypoxia did not decrease the HIF1α protein levels, indicating that the IRE1-mediated effect on stabilizing the HIF1α protein levels was XBP1s-independent. The studies presented here, therefore, provide evidence that IRE1 activity during hypoxia increases the protein levels of HIF1α in an XBP1s-independent manner.

PMID: 32545307 [PubMed - in process]

Pseudomonas aeruginosa strain sharing in early infection among children with cystic fibrosis.

Clin Infect Dis. 2020 Jun 16;:

Authors: Stapleton PJ, Izydorcyzk C, Clark S, Blanchard A, Wang PW, Yau Y, Waters V, Guttman DS

Abstract
BACKGROUND: We previously identified Pseudomonas aeruginosa isolates with characteristics typical of chronic infection in some early infections in children with Cystic Fibrosis (CF), suggesting these isolates may have been acquired from other patients. Our objective was to define the extent of P. aeruginosa strain sharing in early CF infections and its impact on antibiotic eradication treatment failure rates.
METHODS: We performed whole genome sequencing on isolates from early pediatric CF pulmonary infections and from comparator groups in the same hospital: chronic CF infection, sink drains, sterile site infections and asymptomatic carriage. Univariate logistic regression was used to assess factors associated with treatment failure.
RESULTS: In this retrospective observational study, 1,029 isolates were sequenced. The CF clones Strain B and Clone C were present. In 70 CF patients with early infections, 14 shared strains infected 29 (41%) patients over five years; 16% (n=14) of infections had mixed-strains. In the 70 children, approximately one third of shared strain infections were likely due to patient-to-patient transmission. Mixed-strain infections were associated with strain sharing (odds ratio 8.50; 95% confidence interval 2.2 - 33.4, P = 0.002). Strain sharing was not associated with antibiotic eradication treatment failure; however, nosocomial strain transmission was associated with establishment of chronic infection in a CF sibling pair.
CONCLUSIONS: Although early P. aeruginosa CF infection is thought to reflect acquisition of diverse strains from community reservoirs, we identified frequent early CF strain sharing which was associated with the presence of mixed-strains and instances of possible patient-to-patient transmission.

PMID: 32544950 [PubMed - as supplied by publisher]

Pseudomonas aeruginosa and children with cystic fibrosis.

Clin Infect Dis. 2020 Jun 16;:

Authors: Sala MA, Jain M

PMID: 32544945 [PubMed - as supplied by publisher]

The role of inflammation in cystic fibrosis pulmonary exacerbations.

Expert Rev Respir Med. 2020 Jun 16;:1-15

Authors: Houston CJ, Taggart CC, Downey DG

Abstract
INTRODUCTION: Cystic Fibrosis pulmonary exacerbations are critical events in the lives of people with CF that have deleterious effects on lung function, quality of life, and life expectancy. There are significant unmet needs in the management of exacerbations. We review here the associated inflammatory changes that underlie these events and are of interest for the development of biomarkers of exacerbation.
AREAS COVERED: Inflammatory responses in CF are abnormal and contribute to a sustained proinflammatory lung microenvironment, abundant in proinflammatory mediators and deficient in counter-regulatory mediators that terminate and resolve inflammation. There is increasing interest in these inflammatory pathways to discover novel biomarkers for pulmonary exacerbation management. In this review, we explore the inflammatory changes occurring during intravenous antibiotic therapy for exacerbation and how they may be applied as biomarkers to guide exacerbation therapy. A literature search was conducted using the PubMed database in February 2020.
EXPERT OPINION: Heterogeneity in inflammatory responses to treatment of a pulmonary exacerbation, a disease process with complex pathophysiology, limits the clinical utility of individual biomarkers. Biomarker panels may be a more successful strategy to capture informative changes within the CF population to improve pulmonary exacerbation management and outcomes.

PMID: 32544353 [PubMed - as supplied by publisher]

Impact at school age of early chronic methicillin-sensitive Staphylococcus aureus infection in children with cystic fibrosis.

Pediatr Pulmonol. 2020 Jun 16;:

Authors: Galodé F, Dournes G, Chateil JF, Fayon M, Collet C, Bui S

Abstract
BACKGROUND: Bacterial infection early in life may increase structural lung lesions in children with cystic fibrosis (CF).
METHODS: A 9-year monocentric (Bordeaux University Hospital, France) retrospective study in children with CF to evaluate the impact of the early onset (at one year of age, Y1) of chronic Meticillin-Sensitive Staphylococcus aureus (MSSA) infection on the severity of bronchiectasis and Bhalla score on CT-scan, clinical status, lung function tests, and serum IgG at the age of six years (Y6).
RESULTS: 37 children were included: 10 had contracted chronic MSSA infection at Y1 and 27 at a later date. Children with MSSA infection at Y1 showed increased Y6 CT-scan bronchiectasis severity scores vs late MSSA infection (mean + SD: 4.7+ 0.8 vs 2.5 + 0.5, p<0.05) and Bhalla scores (7.3+ 1.1 vs 4.7+ 0.8, p<0.05), but no significant decrease in lung function ((% reference values) FEV1: 83.7+ 6 vs 90.6+ 2.2, p=0.21; FEF25-75: 67.8+ 8.9 vs 76.3+ 3.9, p=0.18). In addition, Y6 serum IgG was greater in the early chronic Y1 MSSA group (11.3+ 0.7 vs 8.9+ 0.7 g/L, p<0.05). Clinical symptoms or nutritional status were similar in both infection groups.
CONCLUSION: Early chronic MSSA infection may enhance the progression of structural lung disease in CF at six years. This article is protected by copyright. All rights reserved.

PMID: 32543758 [PubMed - as supplied by publisher]

Effect of acupuncture on chronic bronchitis: A protocol for systematic review and meta-analysis.

Medicine (Baltimore). 2020 Jun 12;99(24):e20676

Authors: Mao D, Deng Y, Zhang L, Zhao Y, Li Y, Wang F

Abstract
INTRODUCTION: Chronic bronchitis (CB) is a clinically common and recurrent respiratory disease. However, many trials have shown that acupuncture can effectively treat CB. There is currently no systematic review of this therapy. The plan is to evaluate the effectiveness and safety of this treatment in patients with CB.
METHODS AND ANALYSIS: This systematic evaluation will entail an electronic and manual search of all acupuncture for CB from inception to December 31, 2020, regardless of the publication status or language. Databases include PubMed, Embase, Springer, Web of Science, the Cochrane Library, the World Health Organization International Clinical Trial Registration Platform, the Chinese Medicine Database, the China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the China Science Journal Database, and the Wanfang Database. Other sources of information, including bibliographies and meeting minutes for identified publications, will also be searched. A manual search for grey literature, including unpublished conference articles will be performed. Additionally, any clinical randomized controlled trials related to acupuncture for CB, regardless of the publication status and language limitations, will be included in the study. Study selection, data extraction, and research quality assessments will be conducted independently by 2 researchers. The main result was the Change in cystic fibrosis transmembrane conductance regulator function as measured by sweat chloride analysis or treatment effect. Secondary outcomes included Quality of life (eg, SF-36), change in Breathlessness, Cough, and Sputum Scale score, follow-up relapse rate, and adverse events. The system searches for randomized controlled trials of this therapy for CB. Implement the Cochrane RevMan V5.3 bias assessment tool to assess bias risk, data integration risk, meta-analysis risk, and subgroup analysis risk (if conditions are met). Mean difference, standard mean deviation, and binary data will be used to represent continuous results.
RESULTS: This study will provide a comprehensive review and evaluation of the available evidence for the treatment of CB using this therapy.
CONCLUSION: This study will provide new evidence to evaluate the effectiveness and side effects of acupuncture on CB. Because the data are not personalized, no formal ethical approval is required.
PROSPERO REGISTRATION NUMBER: CRD42020170287.

PMID: 32541514 [PubMed - in process]

Association of IVS6A GATT polymorphism of CFTR gene with cystic fibrosis: first study in CF and normal Tunisian population.

Ann Biol Clin (Paris). 2020 Jun 01;78(3):314-318

Authors: Chaima S, Sondess HF, Khedija B, Ahmed M, Taieb M

Abstract
BACKGROUND: Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians, caused by mutation in cystic fibrosis transmembrane conductance regulator (CFTR). The analysis of some extra and intragenic markers within or closely linked to CFTR gene is useful as a molecular method in clinical linkage analysis. Indeed, knowing that the molecular basis of CF is highly heterogeneous in our population is explained in the present study. In this work, we are interested for the first time to study the polymorphic marker IVS6a GATT in a CF Tunisian population.
METHODS: Our study involved 80 CF Tunisian patients with a positive sweat test. A cohort of 90 healthy controls was also enrolled. The analysis of the variant IVS6a GATT was conducted by analysis of the fragments on automatic sequencer (ABI Prism 310). A statistical analysis was performed on Statistical Package for the Social Sciences (SPSS) version 20 software.
RESULTS: The analysis of genotypic distribution of IVS6aGATT showed a significant difference between the control and CF groups suggesting the involvement of this marker in cystic fibrosis. Furthermore, we noted that the 6 GATT repetition in the homozygous state is more common in CF patients than in the control group (p <0.05). This while the 7GATT/7GATT genotype is more common among controls compared to CF patients (p = 0.002). Regarding the interest of this polymorphism on the clinical expression of cystic fibrosis, we have noted no significant association between 6/6 genotype with different clinical conditions in CF patients outside the CFTR mutation. While a significant association was found between respiratory involvement and mixed (respiratory and digestive) and the 6/6 genotype in patients with the mutation F508del homozygous (p <0.05). In addition, a significant association was also noted with gastrointestinal involvement for non F508del patients/F508del not (p = 0.014). Given that, phenotypic and genotypic heterogeneity of cystic fibrosis, several studies have sought to highlight the role of genetic markers linked to the CFTR gene in the expression and evolution of the disease.
CONCLUSION: Our study on the implication of polymorphic marker IVS6a GATT is one of the first works carried out in the Tunisian population and confirms the usefulness of this marker in the clinical expression of cystic fibrosis.

PMID: 32540817 [PubMed - in process]

Comparing effects of low glycemic index/high-fat, high-calorie diet and high-fat, high-calorie diet on cytokine levels of patients with cystic fibrosis: A randomized controlled clinical trial.

Eur Cytokine Netw. 2020 Mar 01;31(1):32-38

Authors: Gorji Z, Modaresi M, Yekanni-Nejad S, Rezaei N, Mahmoudi M

Abstract
The importance of the host inflammatory response, as a central pathological feature of cystic fibrosis, is well recognized. Additionally, hyperglycemia can induce an immune response and consecutively may exacerbate symptoms of this disease. Hence, adherence to a low glycemic index diet, through normalizing blood glucose levels, may reduce inflammation in patients with this disease. This study aimed to compare effects of a low glycemic index/high-fat, high-calorie diet and routine high-fat, high-calorie diet on inflammatory biomarkers in patients with cystic fibrosis. In this randomized clinical trial, 44 children and adolescents with cystic fibrosis were randomly assigned to receive for three months either a high-fat, high-calorie diet (n = 22) or a low glycemic index/high-fat, high-calorie diet (n = 22) with similar calorie and macronutrients composition to the control diet. Patients in first arm were allowed to use all sources of carbohydrates with different glycemic indices, whereas those in another arm consumed carbohydrates from low glycemic index sources. Serum levels of the pro-inflammatory cytokines IL-6, IL-17A, and IFNγ, and the anti-inflammatory cytokine IL-10 were measured at baseline and after the end of the trial. There were significant differences between groups for IL-6 (P = 0.02) and IL-17 (P = 0.01), in favor of the low glycemic diet, but no between-group differences were detected in IL-10 and IFN-γ. Although serum levels of IL-17 were reduced in both the groups as compared with the baseline values, this reduction was only significant in the group assigned to the low glycemic diet (P= 0.007), In addition, IL-6 serum levels decreased and those of IL-10 increased significantly as compared with the baseline values in the low glycemic diet (P= 0.01). It seems that adherence to a low glycemic index/high-fat, high-calorie diet for three months can improve some inflammatory biomarkers in children and adolescents with cystic fibrosis compared with the high-fat, high-calorie diet.

PMID: 32540806 [PubMed - in process]