Cystic Fibrosis

A Novel Inducible Prophage from Burkholderia Vietnamiensis G4 is Widely Distributed across the Species and Has Lytic Activity against Pathogenic Burkholderia.

Thu, 2020-06-04 06:57
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A Novel Inducible Prophage from Burkholderia Vietnamiensis G4 is Widely Distributed across the Species and Has Lytic Activity against Pathogenic Burkholderia.

Viruses. 2020 May 31;12(6):

Authors: Weiser R, Yap ZL, Otter A, Jones BV, Salvage J, Parkhill J, Mahenthiralingam E

Abstract
Burkholderia species have environmental, industrial and medical significance, and are important opportunistic pathogens in individuals with cystic fibrosis (CF). Using a combination of existing and newly determined genome sequences, this study investigated prophage carriage across the species B. vietnamiensis, and also isolated spontaneously inducible prophages from a reference strain, G4. Eighty-one B. vietnamiensis genomes were bioinformatically screened for prophages using PHASTER (Phage Search Tool Enhanced Release) and prophage regions were found to comprise up to 3.4% of total genetic material. Overall, 115 intact prophages were identified and there was evidence of polylysogeny in 32 strains. A novel, inducible Mu-like phage (vB_BvM-G4P1) was isolated from B. vietnamiensis G4 that had lytic activity against strains of five Burkholderia species prevalent in CF infections, including the Boston epidemic B. dolosa strain SLC6. The cognate prophage to vB_BvM-G4P1 was identified in the lysogen genome and was almost identical (>93.5% tblastx identity) to prophages found in 13 other B. vietnamiensis strains (17% of the strain collection). Phylogenomic analysis determined that the G4P1-like prophages were widely distributed across the population structure of B. vietnamiensis. This study highlights how genomic characterization of Burkholderia prophages can lead to the discovery of novel bacteriophages with potential therapeutic or biotechnological applications.

PMID: 32486377 [PubMed - in process]

Categories: Literature Watch

The Virulence Potential of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Cultured from the Airways of Cystic Fibrosis Patients.

Thu, 2020-06-04 06:57
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The Virulence Potential of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Cultured from the Airways of Cystic Fibrosis Patients.

Toxins (Basel). 2020 May 30;12(6):

Authors: Treffon J, Fotiadis SA, van Alen S, Becker K, Kahl BC

Abstract
Staphylococcus aureus is one of the most common pathogens that infects the airways of patients with cystic fibrosis (CF) and contributes to respiratory failure. Recently, livestock-associated methicillin-resistant S. aureus (LA-MRSA), usually cultured in farm animals, were detected in CF airways. Although some of these strains are able to establish severe infections in humans, there is limited knowledge about the role of LA-MRSA virulence in CF lung disease. To address this issue, we analyzed LA-MRSA, hospital-associated (HA-) MRSA and methicillin-susceptible S. aureus (MSSA) clinical isolates recovered early in the course of airway infection and several years after persistence in this hostile environment from pulmonary specimens of nine CF patients regarding important virulence traits such as their hemolytic activity, biofilm formation, invasion in airway epithelial cells, cytotoxicity, and antibiotic susceptibility. We detected that CF LA-MRSA isolates were resistant to tetracycline, more hemolytic and cytotoxic than HA-MRSA, and more invasive than MSSA. Despite the residence in the animal host, LA-MRSA still represent a serious threat to humans, as such clones possess a virulence potential similar or even higher than that of HA-MRSA. Furthermore, we confirmed that S. aureus individually adapts to the airways of CF patients, which eventually impedes the success of antistaphylococcal therapy of airway infections in CF.

PMID: 32486247 [PubMed - in process]

Categories: Literature Watch

Gene Therapy for Cystic Fibrosis: Progress and Challenges of Genome Editing.

Thu, 2020-06-04 06:57
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Gene Therapy for Cystic Fibrosis: Progress and Challenges of Genome Editing.

Int J Mol Sci. 2020 May 30;21(11):

Authors: Maule G, Arosio D, Cereseto A

Abstract
Since the early days of its conceptualization and application, human gene transfer held the promise of a permanent solution to genetic diseases including cystic fibrosis (CF). This field went through alternated periods of enthusiasm and distrust. The development of refined technologies allowing site specific modification with programmable nucleases highly revived the gene therapy field. CRISPR nucleases and derived technologies tremendously facilitate genome manipulation offering diversified strategies to reverse mutations. Here we discuss the advancement of gene therapy, from therapeutic nucleic acids to genome editing techniques, designed to reverse genetic defects in CF. We provide a roadmap through technologies and strategies tailored to correct different types of mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, and their applications for the development of experimental models valuable for the advancement of CF therapies.

PMID: 32486152 [PubMed - in process]

Categories: Literature Watch

Human Nasal Epithelial Organoids for Therapeutic Development in Cystic Fibrosis.

Thu, 2020-06-04 06:57
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Human Nasal Epithelial Organoids for Therapeutic Development in Cystic Fibrosis.

Genes (Basel). 2020 May 29;11(6):

Authors: Liu Z, Anderson JD, Deng L, Mackay S, Bailey J, Kersh L, Rowe SM, Guimbellot JS

Abstract
We describe a human nasal epithelial (HNE) organoid model derived directly from patient samples that is well-differentiated and recapitulates the airway epithelium, including the expression of cilia, mucins, tight junctions, the cystic fibrosis transmembrane conductance regulator (CFTR), and ionocytes. This model requires few cells compared to airway epithelial monolayer cultures, with multiple outcome measurements depending on the application. A novel feature of the model is the predictive capacity of lumen formation, a marker of baseline CFTR function that correlates with short-circuit current activation of CFTR in monolayers and discriminates the cystic fibrosis (CF) phenotype from non-CF. Our HNE organoid model is amenable to automated measurements of forskolin-induced swelling (FIS), which distinguishes levels of CFTR activity. While the apical side is not easily accessible, RNA- and DNA-based therapies intended for systemic administration could be evaluated in vitro, or it could be used as an ex vivo biomarker of successful repair of a mutant gene. In conclusion, this highly differentiated airway epithelial model could serve as a surrogate biomarker to assess correction of the mutant gene in CF or other diseases, recapitulating the phenotypic and genotypic diversity of the population.

PMID: 32485957 [PubMed - in process]

Categories: Literature Watch

Nontuberculous Mycobacterial Disease and Molybdenum in Colorado Watersheds.

Thu, 2020-06-04 06:57
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Nontuberculous Mycobacterial Disease and Molybdenum in Colorado Watersheds.

Int J Environ Res Public Health. 2020 May 29;17(11):

Authors: M Lipner E, French J, R Bern C, Walton-Day K, Knox D, Strong M, Prevots DR, L Crooks J

Abstract
Nontuberculous mycobacteria (NTM) are environmental bacteria that may cause chronic lung disease. Environmental factors that favor NTM growth likely increase the risk of NTM exposure within specific environments. We aimed to identify water-quality constituents (Al, As, Cd, Ca, Cu, Fe, Pb, Mg, Mn, Mo, Ni, K, Se, Na, Zn, and pH) associated with NTM disease across Colorado watersheds. We conducted a geospatial, ecological study, associating data from patients with NTM disease treated at National Jewish Health and water-quality data from the Water Quality Portal. Water-quality constituents associated with disease risk were identified using generalized linear models with Poisson-distributed discrete responses. We observed a highly robust association between molybdenum (Mo) in the source water and disease risk. For every 1- unit increase in the log concentration of molybdenum in the source water, disease risk increased by 17.0%. We also observed a statistically significant association between calcium (Ca) in the source water and disease risk. The risk of NTM varied by watershed and was associated with watershed-specific water-quality constituents. These findings may inform mitigation strategies to decrease the overall risk of exposure.

PMID: 32485845 [PubMed - in process]

Categories: Literature Watch

How to help the free market fight coronavirus.

Thu, 2020-06-04 06:57
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How to help the free market fight coronavirus.

Nature. 2020 04;580(7802):167

Authors: Burley SK

PMID: 32210376 [PubMed - indexed for MEDLINE]

Categories: Literature Watch

An integrative review on the positive expiratory pressure (PEP)-bottle therapy for patients with pulmonary diseases.

Thu, 2020-06-04 06:57
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An integrative review on the positive expiratory pressure (PEP)-bottle therapy for patients with pulmonary diseases.

Physiother Res Int. 2020 Jan;25(1):e1823

Authors: Liverani B, Nava S, Polastri M

Abstract
BACKGROUND AND PURPOSE: Positive expiratory pressure (PEP)-bottle device delivers a PEP within a range of 10-20 cmH2 O. PEP treatment is applied to different pathological conditions also in combination with other physiotherapeutic techniques. The primary aim of the present review was to investigate the effects of PEP-bottle therapy in patients with pulmonary diseases and, secondarily, to provide a physiological analysis of its use.
METHODS: The databases PubMed, Scopus, Web of Science, Cinahl, and Cochrane Library were searched for citations published from their inception until May 2019. Adult participants (>18 years) with pulmonary disease who underwent PEP-bottle treatment, with no restriction on gender, were included in the study. There were no restrictions about the therapeutic settings and the condition of the disease (either acute or chronic).
RESULTS: The literature review returned 97 citations. After duplicates removal, the remaining 77 articles have been screened: 66 have been assessed as not eligible at first because the abstract did not meet the inclusion criteria. Eleven articles were left after the first two steps of selection: four have been excluded after full-text reading.
CONCLUSION: PEP-bottle therapy has been proved to improve lung volume, to reduce hyperinflation, and to remove secretions. The device delivers a pressure equal to the water column only if the inner diameter of the tubing and the width of the air escape orifice are equal or greater than 8 mm, and the length of tubing ranges between 20 and 80 cm. The cost of a PEP-bottle device is significantly lower if compared with other commercially available devices having the same therapeutic purposes.

PMID: 31762162 [PubMed - indexed for MEDLINE]

Categories: Literature Watch

Carrier frequency of CFTR variants in the non-Caucasian populations by genome aggregation database (gnomAD)-based analysis.

Wed, 2020-06-03 06:32

Carrier frequency of CFTR variants in the non-Caucasian populations by genome aggregation database (gnomAD)-based analysis.

Ann Hum Genet. 2020 Jun 02;:

Authors: Nappo S, Mannucci L, Novelli G, Sangiuolo F, D'Apice MR, Botta A

Abstract
The complexity in the molecular diagnosis of Cystic Fibrosis (CF) also depends on the variable prevalence/incidence of the disease associated with the wide CFTR allelic heterogeneity among different populations. In fact, CF incidence in Asian and African countries is underestimated and the few patients reported so far have rare or unique CFTR pathogenic variants. To obtain insights into CF variants profile and frequency, we used the large population sequencing data in the Genome Aggregation Database (gnomAD). We selected 207 CF-causing/varying clinical consequence variants from CFTR2 database and additional 15 variants submitted to the ClinVar database. Only 14 of these variants were found in the East-Asian population, while for South-Asian and African populations we identified 43 and 52 variants, respectively, confirming the peculiarity of the CFTR allelic spectrum with only few population-specific variants. These data could be used to optimize CFTR carrier screening in non-Caucasian subjects, choosing between the full gene sequencing and cost and time-effective targeted panels.

PMID: 32484936 [PubMed - as supplied by publisher]

Categories: Literature Watch

National Newborn Screening for cystic fibrosis in the Republic of Ireland: genetic data from the first 6.5 years.

Wed, 2020-06-03 06:32
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National Newborn Screening for cystic fibrosis in the Republic of Ireland: genetic data from the first 6.5 years.

Eur J Hum Genet. 2020 Jun 01;:

Authors: Sasaki E, Kostocenko M, Lang N, Clark T, Rogers M, Muldowney R, Walsh O, O'Grady L, Edge G, Ward A, Linnane B, Borovickova I, Barton DE, Lynch SA

Abstract
Cystic fibrosis (CF) is the most common life-limiting autosomal recessive disease in the Republic of Ireland (ROI), with a previously quoted incidence of 1 in 1353 and carrier rate of 1 in 19. The National Newborn Screening (NBS) for CF was incorporated in July 2011 in the ROI. A cut-off point of the top 1% Immunoreactive Trypsinogen (IRT) was taken as an indication for 38 CFTR variant panel to maximise identification of affected CF cases and to minimise detection of carriers. All neonates from July 2011 to Dec 2017 with an elevated IRT on NBS were tested with 38 CFTR mutation panel and included. Clinical and laboratory database were analysed. In the first 6.5 years a total of 5,053 newborns (1.16% of total births) were screened with 38 CFTR panel. 170 CF affected cases, 320 unaffected carriers, 32 CF Screening Positive Inconclusive Diagnosis (CFSPID) were identified. There was one missed diagnosis. The most common disease-causing variant was c.1521_1523delCTT (p.(Phe508del)) followed by c.1652G>A (p.(Gly551Asp)). 95 out of 170 (55%) affected newborns were homozygous for c.1521_1523delCTT (p.(Phe08del)) and 25 (15%) carried at least one copy of c.1652G>A (p.(Gly551Asp)). Hence, 70% of affected newborns were eligible for CFTR modulator treatment. The NBS programme has identified almost triple the number of affected newborn with c.1652G>A (p.(Gly551Asp)) than previously quoted figures and identified less than 50% of carriers than predicted. The revised incidence and carrier frequency of CF in the ROI is 1 in 2570 and 1 in 25, respectively.

PMID: 32483343 [PubMed - as supplied by publisher]

Categories: Literature Watch

A longitudinal assessment of non-invasive biomarkers to diagnose and predict cystic fibrosis-associated liver disease.

Wed, 2020-06-03 06:32
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A longitudinal assessment of non-invasive biomarkers to diagnose and predict cystic fibrosis-associated liver disease.

J Cyst Fibros. 2020 May 30;:

Authors: Karnsakul W, Wasuwanich P, Ingviya T, Vasilescu A, Carson KA, Mogayzel PJ, Schwarz KB

Abstract
BACKGROUND & AIMS: A practical, inexpensive, and non-invasive biomarker of liver fibrosis is needed as a reliable screening test for cystic fibrosis-associated liver disease (CFLD). Studies have shown the utility of AST to Platelet Ratio Index (APRI), fibrosis index based on 4 factors (FIB-4), and gamma-glutamyl transferase (GGT) as good biomarkers for identifying CFLD. The goal of the study was to evaluate the effectiveness of APRI, FIB-4, AST/ALT ratio, platelet count, GGT, and GGT platelet ratio (GPR) in predicting CFLD development.
METHODS: Data was collected from CF Foundation Patient Registry for patients aged 3-21 years at Johns Hopkins from January 1, 2002 to December 31, 2014. Collected data included demographic characteristics, presence of splenomegaly, hepatomegaly, ascites, and variceal bleeding, AST, ALT, GGT, platelet count, and FEV1. The sensitivity and specificity of each biomarker were analyzed and reported by the area under receiver operating characteristic (AUROC) curve.
RESULTS: By the end of the study, 144 "healthy" CF, 12 CFLD, 19 CF-associated pulmonary disease (CFPD), and 4 CFLD with CFPD cases were identified. APRI scores were higher in CFLD, 0.85 versus 0.28 in "healthy" CF and 0.23 in CFPD groups (p<0.001). GPR had the highest AUROC curve at 0.91.
CONCLUSIONS: GPR, GGT, APRI score, and platelet count were potentially useful biomarkers while FIB-4 did not predict CFLD development. Cost-effectiveness studies are needed to analyze the utility of these biomarkers in clinical practice.

PMID: 32482593 [PubMed - as supplied by publisher]

Categories: Literature Watch

Disruption of the extracellular polymeric network of Pseudomonas aeruginosa biofilms by alginate lyase enhances pathogen eradication by antibiotics.

Wed, 2020-06-03 06:32
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Disruption of the extracellular polymeric network of Pseudomonas aeruginosa biofilms by alginate lyase enhances pathogen eradication by antibiotics.

J Cyst Fibros. 2020 May 30;:

Authors: Daboor SM, Rohde JR, Cheng Z

Abstract
BACKGROUND: Pseudomonas aeruginosa forms antibiotic-resistant biofilms that are responsible for the treatment failure or relapses of the bacterial infections in the lungs of patients with cystic fibrosis (CF). The alginate lyases that target extracellular polysaccharide alginate of P. aeruginosa biofilms are promising therapeutic candidates for treatment of P. aeruginosa biofilm infections.
METHODS: Immunofluorescent staining and thin layer chromatography were used to demonstrate the alginolytic activity of the alginate lyase enzyme (AlyP1400) purified from a marine Pseudoalteromonas bacterium. Anti-biofilm activities of AlyP1400 were tested alone or in combination with antibiotics on the biofilms of a mucoid Pseudomonas aeruginosa clinical isolate CF27 that were cultivated in 96-well plates and a flow cell.
RESULTS: We showed that AlyP1400 facilitated antibiotic activities to eliminate CF27 biofilms. The combination of AlyP1400 with antibiotics reduced the biofilm biomass and boosted bactericidal activity of antibiotics. Importantly, we demonstrated that the enzymatic activity of AlyP1400 was required for its biofilm disruption activity and its synergy with antibiotics to eradicate biofilm cells.
CONCLUSION: This work shed new light on the potential mechanisms of the therapeutic activity for the combinational use of alginate lyase and antibiotics to treat P. aeruginosa infections in CF lungs or other P. aeruginosa biofilm-related infections.

PMID: 32482592 [PubMed - as supplied by publisher]

Categories: Literature Watch

The Role of MicroRNA in the Airway Surface Liquid Homeostasis.

Wed, 2020-06-03 06:32
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The Role of MicroRNA in the Airway Surface Liquid Homeostasis.

Int J Mol Sci. 2020 May 28;21(11):

Authors: Mitash N, E Donovan J, Swiatecka-Urban A

Abstract
Mucociliary clearance, mediated by a coordinated function of cilia bathing in the airway surface liquid (ASL) on the surface of airway epithelium, protects the host from inhaled pathogens and is an essential component of the innate immunity. ASL is composed of the superficial mucus layer and the deeper periciliary liquid. Ion channels, transporters, and pumps coordinate the transcellular and paracellular movement of ions and water to maintain the ASL volume and mucus hydration. microRNA (miRNA) is a class of non-coding, short single-stranded RNA regulating gene expression by post-transcriptional mechanisms. miRNAs have been increasingly recognized as essential regulators of ion channels and transporters responsible for ASL homeostasis. miRNAs also influence the airway host defense. We summarize the most up-to-date information on the role of miRNAs in ASL homeostasis and host-pathogen interactions in the airway and discuss concepts for miRNA-directed therapy.

PMID: 32481719 [PubMed - in process]

Categories: Literature Watch

Haemoptysis management in cystic fibrosis: A case report and treatment pathway.

Tue, 2020-06-02 06:07

Haemoptysis management in cystic fibrosis: A case report and treatment pathway.

J Clin Pharm Ther. 2020 Jun 01;:

Authors: Gavioli E, Aung CC

Abstract
WHAT IS KNOWN AND OBJECTIVE: Haemoptysis is a major complication of cystic fibrosis (CF) and is associated with pulmonary exacerbations and admission to the hospital. The US CF Pulmonary Foundation guidelines fail to reach consensus on haemoptysis treatment regarding pharmacotherapy options.
CASE SUMMARY DESCRIPTION: We describe a case in which systemic tranexamic acid was utilized to treat haemoptysis in a CF adult patient who was experiencing progressively worsening haemoptysis despite numerous bronchial artery embolization procedures.
WHAT IS NEW AND CONCLUSION: The use of antifibrinolytic agents may be of potential benefit in refractory haemoptysis episodes in adult CF patients.

PMID: 32479647 [PubMed - as supplied by publisher]

Categories: Literature Watch

Metabolic Alkalosis and Cystic Fibrosis: A Case Report.

Tue, 2020-06-02 06:07

Metabolic Alkalosis and Cystic Fibrosis: A Case Report.

Ann Intern Med. 2020 Jun 02;:

Authors: Ghimire S, Yerneni H, Oyadomari TA, Sedlacek M

PMID: 32479172 [PubMed - as supplied by publisher]

Categories: Literature Watch

Survival of Mycobacterium abscessus and Staphylococcus aureus in saline waters of the Dead Sea: implications for health tourists.

Tue, 2020-06-02 06:07

Survival of Mycobacterium abscessus and Staphylococcus aureus in saline waters of the Dead Sea: implications for health tourists.

J Travel Med. 2020 Jun 01;:

Authors: Moore JE, Moore RE, Shteinberg M, Kis-Papo T, Millar BC

Abstract
M. abscessus persisted for over two weeks in Dead Sea brine and staphylococcal organisms were able to survive from three to 11 days. The uniqueness of the Dead Sea's chemical composition, particularly its extremely high salinity, eventually leads to the destruction of M. abscessus and S. aureus, including MRSA organisms.

PMID: 32478829 [PubMed - as supplied by publisher]

Categories: Literature Watch

Phage Therapy Application to Counteract Pseudomonas aeruginosa Infection in Cystic Fibrosis Zebrafish Embryos.

Tue, 2020-06-02 06:07

Phage Therapy Application to Counteract Pseudomonas aeruginosa Infection in Cystic Fibrosis Zebrafish Embryos.

J Vis Exp. 2020 May 12;(159):

Authors: Cafora M, Forti F, Briani F, Ghisotti D, Pistocchi A

Abstract
Antimicrobial resistance, a major consequence of diagnostic uncertainty and antimicrobial overprescription, is an increasingly recognized cause of severe infections, complications, and mortality worldwide with a huge impact on our society and on the health system. In particular, patients with compromised immune systems or pre-existing and chronic pathologies, such as cystic fibrosis (CF), are subjected to frequent antibiotic treatments to control the infections with the appearance and diffusion of multidrug resistant isolates. Therefore, there is an urgent need to address alternative therapies to counteract bacterial infections. Use of bacteriophages, the natural enemies of bacteria, can be a possible solution. The protocol detailed in this work describes the application of phage therapy against Pseudomonas aeruginosa infection in CF zebrafish embryos. Zebrafish embryos were infected with P. aeruginosa to demonstrate that phage therapy is effective against P. aeruginosa infections as it reduces lethality, bacterial burden and pro-inflammatory immune response in CF embryos.

PMID: 32478753 [PubMed - as supplied by publisher]

Categories: Literature Watch

Bacterial Community Interactions During Chronic Respiratory Disease.

Tue, 2020-06-02 06:07
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Bacterial Community Interactions During Chronic Respiratory Disease.

Front Cell Infect Microbiol. 2020;10:213

Authors: Welp AL, Bomberger JM

Abstract
Chronic respiratory diseases including chronic rhinosinusitis, otitis media, asthma, cystic fibrosis, non-CF bronchiectasis, and chronic obstructive pulmonary disease are a major public health burden. Patients suffering from chronic respiratory disease are prone to persistent, debilitating respiratory infections due to the decreased ability to clear pathogens from the respiratory tract. Such infections often develop into chronic, life-long complications that are difficult to treat with antibiotics due to the formation of recalcitrant biofilms. The microbial communities present in the upper and lower respiratory tracts change as these respiratory diseases progress, often becoming less diverse and dysbiotic, correlating with worsening patient morbidity. Those with chronic respiratory disease are commonly infected with a shared group of respiratory pathogens including Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and Moraxella catarrhalis, among others. In order to understand the microbial landscape of the respiratory tract during chronic disease, we review the known inter-species interactions among these organisms and other common respiratory flora. We consider both the balance between cooperative and competitive interactions in relation to microbial community structure. By reviewing the major causes of chronic respiratory disease, we identify common features across disease states and signals that might contribute to community shifts. As microbiome shifts have been associated with respiratory disease progression, worsening morbidity, and increased mortality, these underlying community interactions likely have an impact on respiratory disease state.

PMID: 32477966 [PubMed - in process]

Categories: Literature Watch

Circulating CRP and calprotectin to diagnose CF pulmonary exacerbations.

Tue, 2020-06-02 06:07
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Circulating CRP and calprotectin to diagnose CF pulmonary exacerbations.

J Cyst Fibros. 2020 May 28;:

Authors: Jung D, Dong K, Jang J, Lam GY, Wilcox PG, Quon BS

Abstract
Cystic fibrosis (CF) pulmonary exacerbations (PEx) remain underdiagnosed by CF clinicians. Serum C-reactive protein (CRP) and calprotectin are inflammatory biomarkers that have the potential to aid in the diagnosis of PEx. 19 subjects (56 stable, 46 PEx visits) from a longitudinal study were included and the diagnostic performance of absolute and fold-change CRP and calprotectin cut-offs to discriminate stable and PEx visits was assessed. Based on Youden's index, optimal absolute and fold-change thresholds to identify PEx were 9.5 mg/L (Sn 76%, Sp 73%; AUC 0.76) and 2.2-fold (Sn 50%, Sp 96%; AUC 0.78) for CRP and 8.1 mg/L (Sn 61%, Sp 79%; AUC 0.72) and 1.3-fold (Sn 57%, Sp 88%; AUC 0.74) for calprotectin. A step-wise algorithm was able to improve diagnostic performance (Sn 80%; Sp 88%). CRP and calprotectin could discriminate stable vs. PEx visits with good performance and appear promising as diagnostic biomarkers but further validation studies are required prior to implementing these diagnostic thresholds.

PMID: 32475777 [PubMed - as supplied by publisher]

Categories: Literature Watch

Motor dysfunction of the gut in cystic fibrosis.

Mon, 2020-06-01 08:42
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Motor dysfunction of the gut in cystic fibrosis.

Neurogastroenterol Motil. 2020 May 31;:e13883

Authors: Malagelada C, Bendezú RA, Seguí S, Vitrià J, Merino X, Nieto A, Sihuay D, Accarino A, Molero X, Azpiroz F

Abstract
BACKGROUND: Cystic fibrosis (CF) is a multisystem disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Cystic fibrosis transmembrane conductance regulator is extensively expressed in the intestine and has an important role in the regulation of the viscosity and pH of gut secretions. Several studies have reported a delay in small bowel and colonic transit times in patients with CF which have been attributed to the secretory dysfunction. Our aim was to determine whether intestinal contractility is affected in these patients.
METHODS: Consecutive patients with CF referred to our institution between 2014 and 2017 (n = 16) were prospectively investigated using automated non-invasive techniques for morpho-functional evaluation of the gut developed in our laboratory. On separate days, intraluminal images of the gut were obtained by capsule endoscopy and external images by abdominal MRI. Analysis of images (endoluminal and external) was performed with original, previously validated programs based on computer vision and machine learning techniques and compared with age- and sex-matched controls.
KEY RESULTS: Patients with CF exhibited important reduction in contractile activity and increased retention of static turbid luminal content in the small bowel by endoluminal image analysis. Morpho-volumetric analysis of MRI images found increased ileo-colonic volumes in CF. Significant correlations between abnormalities detected by intraluminal and external imaging techniques were found. The presence and severity of digestive symptoms were not related to abnormal gut function.
CONCLUSION AND INFERENCES: Impaired transit and pooling of gut contents in patients with CF is associated with impaired intestinal motility.

PMID: 32475007 [PubMed - as supplied by publisher]

Categories: Literature Watch

Susceptibility of the Mycobacterium abscessus complex to drying: Implications for nebulizer hygiene in patients with cystic fibrosis.

Mon, 2020-06-01 08:42
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Susceptibility of the Mycobacterium abscessus complex to drying: Implications for nebulizer hygiene in patients with cystic fibrosis.

Int J Mycobacteriol. 2020 Apr-Jun;9(2):173-175

Authors: Moore JE, Millar BC

Abstract
Background: Nebulizer hygiene and care is important in cystic fibrosis (CF) to minimize device contamination from bacteria, including nontuberculous mycobacteria (NTMs). Most nebulizer manufacturers recommend nebulizer drying, however there is little evidence to understand how nebulizer drying affects NTM survival.
Methods: Mycobacterium abscessus subsp. massiliense (n = 2), M. abscessus subsp. bolletii (n = 2), and M. abscessus subsp. abscessus (n = 2) were evaluated for their ability to survive simulated drying conditions associated with routine nebulizer care. Bacterial inocula (circa. 107 colony-forming units) were added to plastic and allowed to dry to completeness for 24 h, employing passive and active drying.
Results: NTM isolates of all subspecies could be recovered from all passive and active drying experiments, both in diluent and in sterile sputum, following drying (24 h). There was no combination of drying or physiology that supported NTM cell death, and there was no difference in observed survival with the three species of M. abscessus examined.
Conclusion: This study indicates that drying, either passively or actively, for 24 h at room temperature, is unable to eradicate all M. abscessus organisms from dry plastic surfaces, even in the presence of residual sputum contamination. Whilst drying may be advantageous for nebulizer performance, it should not be regarded as an absolute control for the elimination of NTM organisms. With nebulizer hygiene, NTM organisms would be able to survive on a nebulizer following drying for 24 h, which has not undergone any formal disinfection protocol. Therefore, for NTM eradication from washed nebulizers, CF patients should therefore seek an effective alternative control to drying for NTM eradication, i.e., heat disinfection in baby bottle disinfectors. CF patients and health-care professionals should not rely solely on nebulizer drying to achieve NTM eradication.

PMID: 32474539 [PubMed - as supplied by publisher]

Categories: Literature Watch

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