Clinical relevance of Scedosporium spp. and Exophiala dermatitidis in patients with cystic fibrosis: A nationwide study.

Med Mycol. 2020 Feb 06;:

Authors: de Jong CCM, Slabbers L, Engel TGP, Yntema JB, van Westreenen M, Croughs PD, Roeleveld N, Brimicombe R, Verweij PE, Meis JF, Merkus PJ

Abstract
An increased prevalence of various filamentous fungi in sputum samples of patients with cystic fibrosis (CF) has been reported. The clinical significance, however, is mostly unclear. The aim of this study was to investigate the clinical relevance of Scedosporium spp. and Exophiala dermatitidis from sputum samples of patients with CF in the Netherlands. In this cross-sectional study, all CF patients of the Dutch national CF registry who were treated at five of the seven recognized CF centers during a 3-year period were included. We linked clinical data of the national CF registry with the national Dutch filamentous fungal database. We investigated the association between clinical characteristics and a positive sputum sample for Scedosporium spp. and E. dermatitidis, using logistic regression. Positive cultures for fungi were obtained from 3787 sputum samples from 699 of the 1312 patients with CF. Scedosporium spp. was associated with severe genotype, CF-related diabetes, several microorganisms, and inhaled antibiotics. E. dermatitidis was associated with older age, female sex, and Aspergillus spp. CF patients with and without Scedosporium spp. or E. dermatitidis seemed comparable in body mass index and lung function. This study suggests that Scedosporium spp. and E. dermatitidis are probably no major pathogens in CF patients in the Netherlands. Greater understanding of epidemiologic trends, risk factors, and pathogenicity of filamentous fungi in the respiratory tracts of patients with CF is needed.

PMID: 32030418 [PubMed - as supplied by publisher]

Cystic fibrosis patients at risk for disease progression marked by decline in FEV1% predicted: development of the cystic fibrosis risk of disease progression score.

J Thorac Dis. 2019 Dec;11(12):5557-5565

Authors: Marsteller NL, Nussbaum E, Morphew T, Randhawa IS

Abstract
Background: Cystic fibrosis (CF) is one of the most common recessively inherited disorders diagnosed in early childhood in the United States. Determining the phenotype of CF patients likely to experience a significant drop in FEV1% predicted will help target efforts for mitigating this deleterious disorder.
Methods: This retrospective cohort study evaluated potential risk variables that account for the decline in FEV1% predicted in 81 CF patients treated at Miller Children's and Women's Hospital, CA. Cystic fibrosis risk of disease progression (CF RD-Pro) score was evaluated as a tool to identify high-risk patients for accelerated disease progression (event = drop in FEV1% predicted ≥10 percentage points) based on risk variables identified as significant.
Results: ROC analysis determined classification of high versus low-moderate risk of FEV1% decline during year two based on RD-Pro score. Scores ≥2 applied as threshold for high-risk revealed relatively good validity estimates: sensitivity =82.8%, specificity =66.7%, PVP =77.4%, PVN =73.7%, and correct classification =76%. Patients with CF RD-Pro scores suggestive of high (≥2 points) vs. low-moderate (<2 points) risk were nearly 10 times more likely to experience significant disease progression (OR 9.6, 95% CI, 2.6-36.1, P=0.001).
Conclusions: Identification of patients at high risk for significant decline in lung function will enable address of potential therapeutic modalities, environmental exposures, and behavioral variants that may improve outcomes in these patients. The power of the CF RD-Pro Score lies in its simplicity. Our study provides a novel readily available score, which incorporates body mass index (BMI) and Staphylococcus aureus infection, both being alterable targets for slowing CF progression.

PMID: 32030275 [PubMed]

Nebuliser cleaning and disinfection practice in the home among patients with cystic fibrosis.

J Infect Prev. 2020 Jan;21(1):14-22

Authors: MacFarlane M, Carson L, Crossan A, Bell J, Moore JE, Millar BC

Abstract
Background: Nebulised delivery of different classes of drugs is of fundamental importance in therapeutic regimens relating to both the management of disease progression in cystic fibrosis disease and its associated complications. The aim of this study was to determine if current nebuliser hygiene practices in the home environment by paediatric and adult cystic fibrosis populations are appropriate to ensure appropriate infection control and prevention measures have been addressed.
Methods: An Audit Questionnaire Study was completed with adult cystic fibrosis patients (n=20) or with parents of cystic fibrosis children (n=24), through a healthcare professional interview on a one-to-one basis, during either a home visit or during patient/parent attendance at cystic fibrosis clinic.
Results: Hygienic practices relating to nebuliser care varied, with paediatric carers more likely to clean and disinfect their devices. This study suggests there is much variation and confusion with regard to how to clean and disinfect nebulisers, as well as who is responsible for delivering this advice.
Conclusion: The adult cystic fibrosis community in particular needs to be educated on practicalities associated with nebuliser hygiene and the reasons why this is important. Furthermore, to date there is a lack of a universally recommended guideline suitable for all types of cystic fibrosis nebulisers that all relevant pharmaceutical manufacturers advocate.

PMID: 32030099 [PubMed]

Incidence and prevalence of common respiratory pathogens before and after implementation of the Cystic Fibrosis Foundation Infection Prevention and Control Guideline.

J Infect Prev. 2020 Jan;21(1):7-13

Authors: Kim C, delaRiva-Velasco E, Budhram A, Farri F, Krich D, Nolan SS, Gjonaj S, Paul L, Dozor AJ, Welter JJ

Abstract
Background: The 2013 Cystic Fibrosis Foundation's Infection Prevention and Control Guideline (CFF IP&C) was developed to reduce the risk of acquisition and transmission of respiratory pathogens in patients with cystic fibrosis (CF).
Objective: We hypothesised that the incidence of common CF respiratory pathogens would decrease at our centre after implementation of the guideline.
Methods: All patients with CF seen at our centre from August 2012 through August 2017 who had respiratory cultures were included. Patients were excluded from incidence analysis if they did not have at least one culture per year. Quarterly data were collected for one year before and three years after implementation of the guidelines to determine the incidence and prevalence of seven organisms commonly found in respiratory cultures of patients with CF.
Results: Quarterly and annual incidence and prevalence rates of common organisms did not change during the study period.
Discussion: There were no significant differences in the incidence or prevalence of common respiratory organisms in the first three years after implementation of the CF IP&C guideline. Long-term follow-up is needed to determine if changes occur over time.

PMID: 32030098 [PubMed]

Neuropeptide regulation of secretion and inflammation in human airway gland serous cells.

Eur Respir J. 2020 Feb 06;:

Authors: McMahon DB, Carey RM, Kohanski MA, Tong CCL, Papagiannopoulos P, Adappa ND, Palmer JN, Lee RJ

Abstract
Airway submucosal gland serous cells are sites of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) and are important for fluid secretion in conducting airways. To elucidate how neuropeptides regulate serous cells, we tested if human nasal turbinate serous cells secrete bicarbonate (HCO3 -), important for mucus polymerisation and antimicrobial peptide function, during stimulation with cAMP-elevating vasoactive intestinal peptide (VIP) and if this requires CFTR. Serous cells stimulated with VIP exhibited a ∼15-20% cAMP-dependent decrease in cell volume and a ∼0.15 unit decrease in intracellular pH (pHi), reflecting activation of Cl- and HCO3 - secretion, respectively. HCO3 - secretion was directly dependent on CFTR and was absent in cells from CF patients. In contrast, neuropeptide Y (NPY) reduced VIP-evoked cAMP increases, CFTR activation, and Cl-/HCO3 - secretion. Culture of primary serous cells in a model that maintained a serous phenotype confirmed the activating and inhibiting effects of VIP and NPY, respectively, on fluid and HCO3 - secretion. Moreover, VIP enhanced antimicrobial peptide secretion and antimicrobial efficacy of secretions while NPY reduced antimicrobial efficacy. In contrast, NPY enhanced cytokine release while VIP reduced cytokine release through a mechanism requiring CFTR. As levels of VIP and NPY are up-regulated in diseases like allergy, asthma, and chronic rhinosinusitis, the balance of these two peptides in the airway may control mucus rheology and inflammatory responses in serous cells. Furthermore, the loss of CFTR conductance in serous cells may contribute to CF pathophysiology by increasing serous cells inflammatory responses in addition to directly impairing Cl- and HCO3 - secretion.

PMID: 32029445 [PubMed - as supplied by publisher]

Microbial contamination of home nebulizers in children with cystic fibrosis and clinical implication on the number of pulmonary exacerbations.

BMC Pulm Med. 2020 Feb 06;20(1):33

Authors: Tabatabaii SA, Khanbabaee G, Sadr S, Farahbakhsh N, Aghdam MK, Lotfollahzadeh S, Hosseini A, Dara N, Nanbakhsh M, Gorji FA

Abstract
BACKGROUND: Early detection of pulmonary contamination in children with cystic fibrosis (CF) is essential since these children are vulnerable to Pseudomonas aeruginosa (P. aeruginosa) colonization. In Iran, home nebulization of antibiotics is a widespread practice in treatment for patients with CF and, to the best our knowledge, no bacteriological surveys have been conducted till date in this regard.
METHOD: This observational, cross sectional study was conducted on 61 children with CF at Mofid Children's Hospital, Tehran, from September 2017 to march 2018. The swab sampling was performed from 61 home nebulizers used by children diagnosed with CF. Contemporaneous sputum sample or deep nasopharyngeal swab was taken from each patient for bacterial and fungal testing. Medical records of the patients were reviewed and the number of exacerbations were recorded over the last 12 months prior to the study enrollment.
RESULTS: The results of study showed that, 43 (70.5%) nebulizers were contaminated; 31 (50.8%) mouthpieces, 21 (34.4%) reservoirs, and 11 (18%) connecting tubes. The most common organism to be isolated was P. aeruginosa and was recovered from 19 (31%) nebulizers, 16 of them belonged to patients chronically colonized with P. aeruginosa. The remaining three had at least one positive sputum culture for P. aeruginosa in the past 1 year before the study. There was a significant increase in the number of CF exacerbations with an average number of exacerbation being 1.5 ± 1(SD) over last 12 months in children who had pathogenic organisms recovered from their home nebulizers compared with 0.4 ± 0.7(SD) exacerbations per year in whom non-pathogenic organisms were isolated from their nebulizers (P < 0.001).
CONCLUSION: The majority of domiciliary nebulizers used by children with CF were contaminated with microorganisms indicating that the nebulizers may serve as potential reservoirs of pathogens for the patients' lung. Perpetuating colonization is a possible concern in the ones recently colonized with P. aeruginosa and, therefore, decontamination of nebulizer requires more attention to prevent ongoing infection. The negative impact of contamination of nebulizer on CF exacerbation requires serious attention and further investigations.

PMID: 32028925 [PubMed - in process]

Why Is It Difficult to Diagnose My Child's Asthma? A Patient Physician Perspective of Asthma Management.

Pulm Ther. 2019 Dec;5(2):97-102

Authors: Jones K, Nagakumar P, Rao S

Abstract
This article is co-authored by the mother of a patient living with asthma, and two consultants in respiratory medicine from Birmingham Women's and Children's Hospital. The commentary article describes the mother's experience of the diagnosis and treatment process of her son's asthma. The consultants then discuss paediatric asthma diagnosis and management in the context of the patient's experiences.

PMID: 32026405 [PubMed]

Vasoactive Intestinal Peptide Derived From Liver Mesenchymal Cells Mediates Tight Junction Assembly in Mouse Intrahepatic Bile Ducts.

Hepatol Commun. 2020 Feb;4(2):235-254

Authors: Sato A, Kakinuma S, Miyoshi M, Kamiya A, Tsunoda T, Kaneko S, Tsuchiya J, Shimizu T, Takeichi E, Nitta S, Kawai-Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Koshikawa N, Seiki M, Nakauchi H, Asahina Y, Watanabe M

Abstract
Formation of intrahepatic bile ducts (IHBDs) proceeds in accordance with their microenvironment. Particularly, mesenchymal cells around portal veins regulate the differentiation and ductular morphogenesis of cholangiocytes in the developing liver; however, further studies are needed to fully understand the arrangement of IHBDs into a continuous hierarchical network. This study aims to clarify the interaction between biliary and liver mesenchymal cells during IHBD formation. To identify candidate factors contributing to this cell-cell interaction, mesenchymal cells were isolated from embryonic day 16.5 matrix metalloproteinase 14 (MMP14)-deficient (knockout [KO]) mice livers, in which IHBD formation is retarded, and compared with those of the wild type (WT). WT mesenchymal cells significantly facilitated the formation of luminal structures comprised of hepatoblast-derived cholangiocytes (cholangiocytic cysts), whereas MMP14-KO mesenchymal cells failed to promote cyst formation. Comprehensive analysis revealed that expression of vasoactive intestinal peptide (VIP) was significantly suppressed in MMP14-KO mesenchymal cells. VIP and VIP receptor 1 (VIPR1) were mainly expressed in periportal mesenchymal cells and cholangiocytic progenitors during IHBD development, respectively, in vivo. VIP/VIPR1 signaling significantly encouraged cholangiocytic cyst formation and up-regulated tight junction protein 1, cystic fibrosis transmembrane conductance regulator, and aquaporin 1, in vitro. VIP antagonist significantly suppressed the tight junction assembly and the up-regulation of ion/water transporters during IHBD development in vivo. In a cholestatic injury model of adult mice, exogenous VIP administration promoted the restoration of damaged tight junctions in bile ducts and improved hyperbilirubinemia. Conclusion: VIP is produced by periportal mesenchymal cells during the perinatal stage. It supports bile duct development by establishing tight junctions and up-regulating ion/water transporters in cholangiocytes. VIP contributes to prompt recovery from cholestatic damage through the establishment of tight junctions in the bile ducts.

PMID: 32025608 [PubMed]

Differing Pulmonary Structural Abnormalities Detected on Pulmonary MR Imaging in Cystic Fibrosis Patients with Varying Pancreatic Function.

Rofo. 2020 Feb 06;:

Authors: Kraus MS, Teufel M, Esser M, Kiefer LS, Fleischer S, Graepler-Mainka U, Hector A, Tsiflikas I, Schaefer JF

Abstract
PURPOSE:  In cystic fibrosis (CF) the phenotypic expression of complaints varies widely. Genotypes with sufficient pancreatic function (PS) exhibit milder lung disease compared to CF patients with insufficient pancreatic function (PI). The purpose of this study was to evaluate structural lung disease (SLD) in CF patients with differing pancreatic status but similar results on pulmonary function testing using a pulmonary magnetic resonance imaging score (MR-CF score).
MATERIALS AND METHODS:  In this retrospective study, 20 patients in our single-center CF database were included: 10 with PS (mean age 12.5 years; six male; BMI 17.4 kg/m2; FeV1 102 %) were matched by gender, age and lung function with 10 PI patients. Experienced observers semi-quantitatively assessed SLD for each lung lobe. The established MR-CF score measures the extent and the severity of bronchiectasis and bronchial wall thickening, mucus plugging, centrilobular opacity, consolidation, sacculation, and air trapping. The total score and sub-score values were compared to the pancreatic status.
RESULTS:  Patients with CF-PS had overall statistically significant lower MR-CF scores (p = 0.024), and therefore milder SLD, compared to CF-PI. The differences were most significant for bronchiectasis (p = 0.0042) and air trapping (p = 0.0304). SLD was more severe in the upper lobes in all patients. However, differences between CF-PS and CF-PI patients were present in both the upper and lower lung areas (p = 0.0247 and p = 0.0196, respectively).
CONCLUSION:  Our results demonstrated that CF patients with impaired pancreatic function show more severe lung pathology detected by MRI, especially bronchiectasis and air trapping.
KEY POINTS:   · Pulmonary MRI offers morphological and functional details without using ionizing radiation. · CF patients with pancreatic insufficiency show more severe pulmonary structural impairment. · Bronchiectasis and air trapping are the most common structural lung changes with predominance in the upper lung lobes..
CITATION FORMAT: · Kraus MS, Teufel M, Esser M et al. Differing Pulmonary Structural Abnormalities Detected on Pulmonary MR Imaging in Cystic Fibrosis Patients with Varying Pancreatic Function. Fortschr Röntgenstr 2020; DOI: 10.1055/a-1088-3537.

PMID: 32028538 [PubMed - as supplied by publisher]

Consensus Recommendations for the Use of Simulation in Therapeutic Patient Education.

Simul Healthc. 2020 Feb;15(1):30-38

Authors: Penneçot C, Gagnayre R, Ammirati C, Bertin É, Capelle D, Cheraitia E, Chiniara G, David V, De La Tribonnière X, Decelle B, Derambure P, Gignon M, Greffier C, Gross O, Lalande A, Lartiguet P, Letallec C, Mahé C, Mero Y, Mohammed R, Pétré B, Picchiottino P, Pougheon-Bertrand D, Secheresse T, Vaillant G, Van der Schueren-Etévé M, Verdier J, Benhaberou-Brun D, Bardou M, Marchand C

Abstract
INTRODUCTION: Simulation is rarely used to help individuals with chronic diseases develop skills. The aim of the study was to provide recommendations for the use of simulation in therapeutic patient education (S-TPE).
METHODS: Expert consensus was achieved with the participation of the following 3 groups of experts: (a) expert patients and caregivers; (b) health professionals specialized in therapeutic patient education (TPE); and (c) simulation experts. Each expert received a list of questions by e-mail in 3 iterations. The synthesis of the 2 first questionnaires resulted in 34 first recommendations voted during the consensus conference meeting. Each recommendation was subject to an extensive literature review. The quality of the evidence and the strength of the recommendations were assessed through the evaluation, development, and evaluation criteria categories (GRADE criteria). The third questionnaire selected and illustrated recommendations more specific to the use of S-TPE.
RESULTS: At the end of the process, the experts identified 26 recommendations specific to the use of S-TPE. They proposed examples of skills in different diseases and stressed the importance of adapting the conditions of use (location, equipment, time of the care) to the circumstances of the patient learner and skills to be developed. Experts should exercise great caution as this technique presents ethical considerations related to patient care.
CONCLUSIONS: These recommendations underline the fact that simulation could bring added value to TPE. They provide a framework and examples for the experimental use of simulation in TPE. Research into feasibility and acceptability is needed.

PMID: 32028445 [PubMed - in process]

Elicitation interview study to identify salient beliefs about exercise participation in adults with cystic fibrosis.

Physiotherapy. 2019 Oct 31;107:286-291

Authors: Dwyer TJ, Griffin BN, Bye PTP, Alison JA

Abstract
OBJECTIVES: Conduct an elicitation study, using the Theory of Planned Behaviour framework, to identify salient beliefs about exercise participation in adults with cystic fibrosis (CF). Specifically, identify attitudes on advantages and disadvantages of exercise (behavioural beliefs); individuals and groups who apply social pressure to exercise (normative beliefs); and perceived control over facilitators and barriers to exercise (control beliefs) for adults with CF.
DESIGN: Qualitative interviews using open-ended, structured questions.
SETTING: Adult CF clinic in a large Australian hospital.
PARTICIPANTS: Sixteen adults with CF, three relatives/friends of adults with CF and six CF clinic staff.
RESULTS: The most common positive attitudes about exercise were to keep fit and healthy (68%) and feel better and happier (60%), and negative attitude was to feel breathless (36%). Social pressure to exercise mainly came from parents/family (72%) and friends (52%), and 60% of participants reported that no-one discourages exercise. Having someone to exercise with (44%) and be encouraged (36%) were the most common facilitators of perceived control to exercise, whereas being unwell (96%) and not having sufficient time (56%) were the most common barriers.
CONCLUSIONS: Attitudes, social pressure and perceived control to exercise for adults with CF were similar to beliefs previously reported by the general population and some patient groups. A number of CF-specific exercise beliefs, mainly related to pulmonary function, were also reported. These findings can help develop questionnaires for larger groups of adults with CF, interpret relationships between exercise beliefs and participation, and inform clinicians to target interventions to increase exercise participation.

PMID: 32026831 [PubMed - as supplied by publisher]

Impact of hypertonic saline nebulisation combined with oscillatory positive expiratory pressure on sputum expectoration and related symptoms in cystic fibrosis: a randomised crossover trial.

Physiotherapy. 2019 Nov 11;107:243-251

Authors: San Miguel-Pagola M, Reychler G, Cebrià I Iranzo MA, Gómez-Romero M, Díaz-Gutiérrez F, Herrero-Cortina B

Abstract
OBJECTIVE: To evaluate the impact of combining nebulised hyaluronic acid plus hypertonic saline (HA+HS) with oscillatory positive expiratory pressure (oscillatory-PEP) on sputum expectoration and related symptoms in adults with cystic fibrosis (CF).
DESIGN: Randomised crossover trial.
SETTING: Seven centres.
PARTICIPANTS: Twenty-two outpatients with CF.
INTERVENTIONS: Usual care (HA+HS followed by autogenic drainage) and combined therapy (HA+HS with oscillatory-PEP followed by autogenic drainage]. Each treatment was performed for 5 days.
MAIN OUTCOME MEASURES: Sputum expectoration was measured during the nebulisation period (primary outcome), during autogenic drainage and for 24hours post intervention. The Cough and Sputum Assessment Questionnaire (CASA-Q) and its domains (cough symptoms, cough impact, sputum symptoms and sputum impact), the Leicester Cough Questionnaire (LCQ) and lung function tests were used. Tolerance and patient preference were registered.
RESULTS: Twenty-two participants [mean age 25 (standard deviation 8) years, percentage predicted forced expiratory volume in 1second 67 (22)] were recruited. Combined therapy promoted greater sputum expectoration than usual care during the nebulisation period {median difference 1.8ml [95% confidence interval (CI) 0.2-6.2]}. Both treatments led to similar expectoration during autogenic drainage and for 24hours post intervention. Combined therapy led to a greater improvement in the sputum symptoms domain [6.7 points (95% CI 3.3-13.3] and total CASA-Q score [2.4 points (95% CI 0.1-9.3)] compared with usual care. No differences in LCQ score or lung function were observed. Fewer adverse events were reported using combined therapy, which was selected as the preferred intervention.
CONCLUSIONS: Combined nebulisation increased immediate sputum expectoration, improved sputum symptoms and reduced adverse events compared with usual care in patients with CF.
CLINICAL TRIAL NUMBER: NCT02303808.

PMID: 32026826 [PubMed - as supplied by publisher]

Genotype patterns for mutations of the cystic fibrosis transmembrane conductance regulator gene: a retrospective descriptive study from Saudi Arabia.

Ann Saudi Med. 2020 Jan-Feb;40(1):15-24

Authors: Banjar HH, Tuleimat L, El Seoudi AAA, Mogarri I, Alhaider S, Nizami IY, AlMaghamsi T, Alkaf SA, Moghrabi N

Abstract
BACKGROUND: Cystic fibrosis (CF) occurs in populations in Saudi Arabia and the Gulf area. Approximately 2000 known variants have been identified for the CF transmembrane conductance regulator (CTFR) gene. Screening for ten of the most common variants can detect 80% of alleles.
OBJECTIVE: Determine the pattern of CFTR variants in the CF population of Saudi Arabia.
DESIGN: A retrospective, descriptive.
SETTING: Tertiary care center.
PATIENTS AND METHODS: We examined the medical records of 396 confirmed CF patients of all age groups that were positive for a CFTR variant from the period of 1 January 1998 to 1 December 2017.
MAIN OUTCOME MEASURES: Zygosity, morbidity and mortality patterns of different types of CFTR variants.
SAMPLE SIZE: 312 families that included 396 patients.
RESULTS: Of 48 variants identified, 6 were novel, having not been described in the medical literature. A homozygous state was found in 283 families (90.7%) and compound heterozygosity in 23 (7.4%). Six families were heterozygous (1.9%). Median age (interquartile range) was 10.2 months (4.4 months to 5.7 years) at diagnosis and 9.7 (5.4-16.5) years at follow up. Of 396 patients, 378 patients (95.5%) survived and 18 (4.5%) died. The ten most common variants identified in descending frequency were: p.Gly473GlufsX54 in 98 alleles (16%), p.Ile1234Val in 66 alleles (11%), F508del in 64 alleles (11%), 711+1G>T in 62 alleles (10%), 3120+1G>A in 62 alleles (11%), p.His139Leuin 38 alleles (6.4%), p.Gln637Hisfs in 30 alleles (5.2%), p.Ser549Arg in 27 alleles (4.5%), p.Asn1303Lys in 14 alleles (2.3%), delExon19-21in 10 alleles (1.6%). This analysis identified 79.2% of our CFTR variants.
CONCLUSION: CFTR mutational patterns in our CF population are characterized by a high allelic heterogeneity. The high prevalence of homozygous variants reflects the high level of consanguinity between parents.
LIMITATIONS: Our CFTR screening reflected only about 80% of CF patients in Saudi Arabia.
CONFLICT OF INTEREST: None.

PMID: 32026723 [PubMed - in process]

Genetics of the congenital absence of the vas deferens.

Hum Genet. 2020 Feb 05;:

Authors: Bieth E, Hamdi SM, Mieusset R

Abstract
Congenital absence of the vas deferens (CAVD) may have various clinical presentations depending on whether it is bilateral (CBAVD) or unilateral (CUAVD), complete or partial, and associated or not with other abnormalities of the male urogenital tract. CBAVD is usually discovered in adult men either during the systematic assessment of cystic fibrosis or other CFTR-related conditions, or during the exploration of isolated infertility with obstructive azoospermia. The prevalence of CAVDs in men is reported to be approximately 0.1%. However, this figure is probably underestimated, because unilateral forms of CAVD in asymptomatic fertile men are not usually diagnosed. The diagnosis of CAVDs is based on clinical, ultrasound, and sperm examinations. The majority of subjects with CAVD carry at least one cystic fibrosis-causing mutation that warrants CFTR testing and in case of a positive result, genetic counseling prior to conception. Approximately 2% of the cases of CAVD are hemizygous for a loss-of-function mutation in the ADGRG2 gene that may cause a familial form of X-linked infertility. However, despite this recent finding, 10-20% of CBAVDs and 60-70% of CUAVDs remain without a genetic diagnosis. An important proportion of these unexplained CAVDs coexist with a solitary kidney suggesting an early organogenesis disorder (Wolffian duct), unlike CAVDs related to CFTR or ADGRG2 mutations, which might be the result of progressive degeneration that begins later in fetal life and probably continues after birth. How the dysfunction of CFTR, ADGRG2, or other genes such as SLC29A3 leads to this involution is the subject of various pathophysiological hypotheses that are discussed in this review.

PMID: 32025909 [PubMed - as supplied by publisher]

Airway tapering: an objective image biomarker for bronchiectasis.

Eur Radiol. 2020 Feb 05;:

Authors: Kuo W, Perez-Rovira A, Tiddens H, de Bruijne M, Normal Chest CT study group

Abstract
PURPOSE: To estimate airway tapering in control subjects and to assess the usability of tapering as a bronchiectasis biomarker in paediatric populations.
METHODS: Airway tapering values were semi-automatically quantified in 156 children with control CTs collected in the Normal Chest CT Study Group. Airway tapering as a biomarker for bronchiectasis was assessed on spirometer-guided inspiratory CTs from 12 patients with bronchiectasis and 12 age- and sex-matched controls. Semi-automatic image analysis software was used to quantify intra-branch tapering (reduction in airway diameter along the branch), inter-branch tapering (reduction in airway diameter before and after bifurcation) and airway-artery ratios on chest CTs. Biomarkers were further stratified in small, medium and large airways based on three equal groups of the accompanying vessel size.
RESULTS: Control subjects showed intra-branch tapering of 1% and inter-branch tapering of 24-39%. Subjects with bronchiectasis showed significantly reduced intra-branch of 0.8% and inter-branch tapering of 19-32% and increased airway-artery ratios compared with controls (p < 0.01). Tapering measurements were significantly different between diseased and controls across all airway sizes. Difference in airway-artery ratio was only significant in small airways.
CONCLUSION: Paediatric normal values for airway tapering were established in control subjects. Tapering showed to be a promising biomarker for bronchiectasis as subjects with bronchiectasis show significantly less airway tapering across all airway sizes compared with controls. Detecting less tapering in larger airways could potentially lead to earlier diagnosis of bronchiectasis. Additionally, compared with the conventional airway-artery ratio, this novel biomarker has the advantage that it does not require pairing with pulmonary arteries.
KEY POINTS: • Tapering is a promising objective image biomarker for bronchiectasis that can be extracted semi-automatically and has good correlation with validated visual scoring methods. • Less airway tapering was observed in patients with bronchiectasis and can be observed sensitively throughout the bronchial tree, even in the more central airways. • Tapering values seemed to be less influenced by variety in scanning protocols and lung volume making it a more robust biomarker for bronchiectasis detection.

PMID: 32025831 [PubMed - as supplied by publisher]

mSphere of Influence: a Community To Study Communities.

mSphere. 2020 Feb 05;5(1):

Authors: Limoli D

Abstract
Dominique Limoli studies polymicrobial interactions during cystic fibrosis respiratory disease. In this mSphere of Influence article, she reflects on how two papers (D. A. Hogan, S. D. Willger, E. L. Dolben, T. H. Hampton, et al., PLoS One 11:e0149998, 2016, https://doi.org/10.1371/journal.pone.0149998, and P. Jorth, B. J. Staudinger, X. Wu, K. B. Hisert, et al., Cell Host & Microbe 18:307-319, 2015, https://doi.org/10.1016/j.chom.2015.07.006) have influenced her thinking and research direction, which aims to understand interspecies bacterial communication during airway infections. These studies highlighted for her a need for new perspectives on the pathology of chronic infections in order to improve interventions.

PMID: 32024707 [PubMed - in process]

Alginate-lyase Guided Silver Nanocomposites for Eradicating Pseudomonas Aeruginosa from lung.

ACS Appl Mater Interfaces. 2020 Feb 06;:

Authors: Wan B, Zhu Y, Tao J, Zhu F, Chen J, Li L, Zhao J, Wang L, Sun S, Yang Y, Zhang X, Zhang Y

Abstract
Pseudomonas aeruginosa (P. aeruginosa) infections lead to a high mortality rate for cystic fibrosis or immunocompromised patients. The alginate of the biofilm was believed to be the key factor disabling immune therapy and antibiotic treatments. A silver nanocomposite consisting of silver nanoparticles and a mesoporous organosilica layer was created to deliver two pharmaceutical compounds (alginate-lyase and ceftazidime) to degrade the alginate and eradicate P. aeruginosa from the lungs. The introduction of thioether-bridged mesoporous organosilica into the nanocomposites greatly benefited the conjunction of foreign functional molecules such as alginate-lyase and increased their hemocompatibility and drug-loading capacity. Silver nanocomposites with a uniform diameter (~ 39 nm) exhibited a high dispersity, good biocompatibility, and high ceftazidime loading capacity (380.96 mg/g). Notably, the silver nanocomposites displayed a low-pH dependent drug-release and degradation profiles (pH 6.4), guaranteeing the targeted release of the drugs in the acidic niches of the P. aeruginosa biofilm. Indeed, particles loaded with alginate-lyase and ceftazidime exhibited high inhibitory and degradation effects on the biofilm of P. aeruginosa PAO1 based on the specific catalytic activity of the enzyme to the alginate and antibacterial function of their loaded ceftazidime and silver ions. It should be noted that the enzyme-decorated nanocomposites succeeded in eradicating the P. aeruginosa PAO1 from the mouse lungs and decreasing the lung injuries. No deaths or serious side effects were observed during the experiments. We believe that the silver nanocomposites with high biocompatibility and organic group-incorporated framework have the potential to be used to deliver multiple functional molecules for antibacterial therapy in clinical application.

PMID: 32024363 [PubMed - as supplied by publisher]

Reshma Kewalramani.

Nat Rev Drug Discov. 2019 11;18(12):896-897

Authors: Mullard A

PMID: 31780855 [PubMed - indexed for MEDLINE]

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Whole Gene Sequencing of CFTR Reveals a High Prevalence of the Intronic Variant c.3874-4522A>G in Cystic Fibrosis.

Am J Respir Crit Care Med. 2020 Feb 04;:

Authors: Morris-Rosendahl DJ, Edwards M, McDonnell MJ, John S, Alton EW, Davies JC, Simmonds NJ

PMID: 32017858 [PubMed - as supplied by publisher]