Detection of cytosine methylation in Burkholderia cenocepacia by single-molecule real-time sequencing and whole-genome bisulfite sequencing.

Microbiology (Reading). 2021 Feb 10;:

Authors: Vandenbussche I, Sass A, Van Nieuwerburgh F, Pinto-Carbó M, Mannweiler O, Eberl L, Coenye T

Abstract
Research on prokaryotic epigenetics, the study of heritable changes in gene expression independent of sequence changes, led to the identification of DNA methylation as a versatile regulator of diverse cellular processes. Methylation of adenine bases is often linked to regulation of gene expression in bacteria, but cytosine methylation is also frequently observed. In this study, we present a complete overview of the cytosine methylome in Burkholderia cenocepacia, an opportunistic respiratory pathogen in cystic fibrosis patients. Single-molecule real-time (SMRT) sequencing was used to map all 4mC-modified cytosines, as analysis of the predicted MTases in the B. cenocepacia genome revealed the presence of a 4mC-specific phage MTase, M.BceJII, targeting GGCC sequences. Methylation motif GCGGCCGC was identified, and out of 6850 motifs detected across the genome, 2051 (29.9 %) were methylated at the fifth position. Whole-genome bisulfite sequencing (WGBS) was performed to map 5mC methylation and 1635 5mC-modified cytosines were identified in CpG motifs. A comparison of the genomic positions of the modified bases called by each method revealed no overlap, which confirmed the authenticity of the detected 4mC and 5mC methylation by SMRT sequencing and WGBS, respectively. Large inter-strain variation of the 4mC-methylated cytosines was observed when B. cenocepacia strains J2315 and K56-2 were compared, which suggests that GGCC methylation patterns in B. cenocepacia are strain-specific. It seems likely that 4mC methylation of GGCC is not involved in regulation of gene expression but rather is a remnant of bacteriophage invasion, in which methylation of the phage genome was crucial for protection against restriction-modification systems of B. cenocepacia.

PMID: 33565960 [PubMed - as supplied by publisher]

Differential diagnosis of perinatal Bartter, Bartter and Gitelman syndromes.

Clin Kidney J. 2021 Jan;14(1):36-48

Authors: Bamgbola OF, Ahmed Y

Abstract
The common finding of hypokalemic alkalosis in several unrelated disorders may confound the early diagnosis of salt-losing tubulopathy (SLT). Antenatal Bartter syndrome (BS) must be considered in idiopathic early-onset polyhydramnios. Fetal megabladder in BS may allow its distinction from third-trimester polyhydramnios that occurs in congenital chloride diarrhea (CCD). Fetal megacolon occurs in CCD while fecal chloride >90 mEq/L in infants is diagnostic. Failure-to-thrive, polydipsia and polyuria in early childhood are the hallmarks of classic BS. Unlike BS, there is low urinary chloride in hypokalemic alkalosis of intractable emesis and cystic fibrosis. Rarely, renal salt wasting may result from cystinosis, Dent disease, disorders of paracellular claudin-10b and Kir4.1 potassium-channel deficiency. Acquired BS may result from calcimimetic up-regulation of a calcium-sensing receptor or autoantibody inactivation of sodium chloride co-transporters in Sjögren syndrome. A relatively common event of heterozygous gene mutations for Gitelman syndrome increases the likelihood of its random occurrence in certain diseases of adult onset. Finally, diuretic abuse is the most common differential diagnosis of SLT. Unlike the persistent elevation in BS, urinary chloride concentration losses waxes and wanes on day-to-day assessment in patients with diuretic misuse.

PMID: 33564404 [PubMed]

Percutaneous endoscopic gastrostomy in children: A single center experience in Saudi Arabia.

Saudi Med J. 2021 Feb;42(2):205-208

Authors: Alhaffaf FA, Alqahtani AS, Alrobyan AA, Alqubaisi SN, Ahmad BA, Almutairi MR, Wali SA, Alhebbi HA

Abstract
OBJECTIVES: To evaluate the demographic data and complications in children who had undergone percutaneous endoscopic gastrostomy (PEG) over 9 years period.
METHODS: The demographic data, complications, length of hospital admission related to PEG insertion and follow-up findings of 39 patients who had undergone percutaneous endoscopic gastrostomy using the standard pull-through technique between 2011 and 2020 were examined. The study took place at the Gastroenterology Division, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia RESULTS: The most common indications of feeding with a gastrostomy tube include neurological diseases (n=30, 76.9%), followed by metabolic disorders (n=3, 7.69%), chronic diarrhea (n=2, 5.1%), chronic kidney diseases (n=2, 5.1%), cystic fibrosis (n=1, 2.56%), feeding aversion fibrosis (n=1, 2.56%). Out of the 39 patients, 20 (51%) did not have any complications. However, minor complication are expected. Most common complications included local infection (n=14, 35.89%) followed by granulation tissue (n=6, 15.38%), "buried bumper syndrome" developed in one.
CONCLUSION: Percutaneous endoscopic gastrostomy tube is the desirable method for patients who are unable to feed orally, feeding is not adequate for demands, has special feeding requirements, or swallowing dysfunction. The technique has become more widespread because of its simplicity, safety, and low cost. Major complications are rare. The procedure is safe and effective and could be carried out by pediatric gastroenterologists after training.

PMID: 33563740 [PubMed - in process]

Determinants of COVID-19 preventive behaviours among adults with chronic diseases in the USA: an analysis of the nationally representative COVID-19 impact survey.

BMJ Open. 2021 Feb 09;11(2):e044600

Authors: Islam JY, Vidot DC, Camacho-Rivera M

Abstract
BACKGROUND: Preventive behaviours have been recommended to control the spread of SARS-CoV-2. Adults with chronic diseases (CDs) are at higher risk of COVID-19-related mortality compared to the general population. Our objective was to evaluate adherence to COVID-19 preventive behaviours among adults without CDs compared with those with CDs and identify determinants of non-adherence to COVID-19 preventive behaviours.
STUDY DESIGN: Cross-sectional.
SETTING AND PARTICIPANTS: We used data from the nationally representative COVID-19 Impact Survey (n=10 760) conducted in the USA.
PRIMARY MEASURES: Adults with CDs were categorised based on a self-reported diagnosis of diabetes, high blood pressure, heart disease/heart attack/stroke, asthma, chronic obstructive pulmonary disease (COPD), bronchitis or emphysema, cystic fibrosis, liver disease, compromised immune system, or cancer (54%).
RESULTS: Compared with adults without CDs, adults with CDs were more likely to adhere to preventive behaviours including wearing a face mask (χ2-p<0.001), social distancing (χ2-p<0.001), washing or sanitising hands (χ2-p<0.001), and avoiding some or all restaurants (χ2-p=0.002) and public or crowded places (χ2-p=0.001). Adults with a high school degree or below [Adjusted prevalence ratio (aPR):1.82, 95% Confidence interval (CI)1.04 to 3.17], household income <US$50 000 (aPR:2.03, 95% CI 1.34 to 2.72), uninsured (aPR:1.65, 95% CI1.09 to 2.52), employed (aPR:1.48, 95% CI 1.02 to 2.17), residing in rural areas (aPR:1.70, 95% CI 1.01 to 2.85) and without any CD (aPR:1.78, 95% CI 1.24 to 2.55) were more likely to not adhere to COVID-19 preventive behaviours.
CONCLUSION: Adults with CDs are more likely to adhere to recommended COVID-19 preventive behaviours. Public health messaging targeting specific demographic groups and geographic areas, such as adults without CD or adults living in rural areas, should be prioritised.

PMID: 33563624 [PubMed - in process]

Erratum to 'From micro to macro; joining the dots of early CF lung disease' [Journal of Cystic Fibrosis (2020) 850-851/2102].

J Cyst Fibros. 2021 Feb 06;:

Authors: Linnane B

PMID: 33563566 [PubMed - as supplied by publisher]

Pulmonary Aspergillosis: Spectrum of Disease.

Am J Med Sci. 2020 Dec 13;:

Authors: Moldoveanu B, Gearhart AM, Jalil BA, Saad M, Guardiola JJ

Abstract
Aspergillus species are ubiquitous in the environment. Aspergillosis is acquired by inhalation of Aspergillus spores. In normal hosts, spore inhalation rarely causes lung disease. Pulmonary Aspergillosis covers a wide spectrum of clinical syndromes depending on the interaction between Aspergillus and the host (immune-status, prior bronchopulmonary disease). It runs the gamut from invasive Aspergillosis to Aspergillus bronchitis. Invasive Aspergillosis usually occurs in severely immunocompromised patients, typically in neutropenic but also in non-neutropenic patients. Chronic pulmonary Aspergillosis affects patients with chronic structural lung disease such as COPD or previous mycobacterial lung disease, but without other significant immunocompromise. Aspergillus bronchitis affects patients with bronchial disease such as bronchiectasis. Allergic bronchopulmonary Aspergillosis affects patients with bronchial asthma or cystic fibrosis, and is due to an allergic response to Aspergillus.

PMID: 33563417 [PubMed - as supplied by publisher]

Contribution of Drugs Interfering with Protein and Cell Wall Synthesis to the Persistence of Pseudomonas aeruginosa Biofilms: An In Vitro Model.

Int J Mol Sci. 2021 Feb 05;22(4):

Authors: Mangiaterra G, Carotti E, Vaiasicca S, Cedraro N, Citterio B, La Teana A, Biavasco F

Abstract
The occurrence of Pseudomonas aeruginosa (PA) persisters, including viable but non-culturable (VBNC) forms, subpopulations of tolerant cells that can survive high antibiotic doses, is the main reason for PA lung infections failed eradication and recurrence in Cystic Fibrosis (CF) patients, subjected to life-long, cyclic antibiotic treatments. In this paper, we investigated the role of subinhibitory concentrations of different anti-pseudomonas antibiotics in the maintenance of persistent (including VBNC) PA cells in in vitro biofilms. Persisters were firstly selected by exposure to high doses of antibiotics and their abundance over time evaluated, using a combination of cultural, qPCR and flow cytometry assays. Two engineered GFP-producing PA strains were used. The obtained results demonstrated a major involvement of tobramycin and bacterial cell wall-targeting antibiotics in the resilience to starvation of VBNC forms, while the presence of ciprofloxacin and ceftazidime/avibactam lead to their complete loss. Moreover, a positive correlation between tobramycin exposure, biofilm production and c-di-GMP levels was observed. The presented data could allow a deeper understanding of bacterial population dynamics during the treatment of recurrent PA infections and provide a reliable evaluation of the real efficacy of the antibiotic treatments against the bacterial population within the CF lung.

PMID: 33562782 [PubMed - in process]

Human Genetic Variation Influences Enteric Fever Progression.

Cells. 2021 Feb 06;10(2):

Authors: Ma PY, Tan JE, Hee EW, Yong DWX, Heng YS, Low WX, Wu XH, Cletus C, Kumar Chellappan D, Aung K, Yong CY, Liew YK

Abstract
In the 21st century, enteric fever is still causing a significant number of mortalities, especially in high-risk regions of the world. Genetic studies involving the genome and transcriptome have revealed a broad set of candidate genetic polymorphisms associated with susceptibility to and the severity of enteric fever. This review attempted to explain and discuss the past and the most recent findings on human genetic variants affecting the progression of Salmonella typhoidal species infection, particularly toll-like receptor (TLR) 4, TLR5, interleukin (IL-) 4, natural resistance-associated macrophage protein 1 (NRAMP1), VAC14, PARK2/PACRG, cystic fibrosis transmembrane conductance regulator (CFTR), major-histocompatibility-complex (MHC) class II and class III. These polymorphisms on disease susceptibility or progression in patients could be related to multiple mechanisms in eliminating both intracellular and extracellular Salmonella typhoidal species. Here, we also highlighted the limitations in the studies reported, which led to inconclusive results in association studies. Nevertheless, the knowledge obtained through this review may shed some light on the development of risk prediction tools, novel therapies as well as strategies towards developing a personalised typhoid vaccine.

PMID: 33562108 [PubMed - in process]

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

"Cystic Fibrosis"

These pubmed results were generated on 2021/02/10

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

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

"Cystic Fibrosis"

These pubmed results were generated on 2021/02/10

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

Telemedicine in Pediatrics: A Systematic Review of Randomized Controlled Trials.

JMIR Pediatr Parent. 2021 Feb 01;:

Authors: Shah AC, Badawy SM

Abstract
BACKGROUND: Telemedicine modalities, such as video conferencing, are used by healthcare providers to remotely deliver healthcare to patients. The use of telemedicine in pediatrics has increased in recent years to improve healthcare access, optimize disease management, monitor progress of health conditions, and minimize exposure to sick patients during pandemics, such as coronavirus disease-19 (COVID-19).
OBJECTIVE: To systematically evaluate the most recent evidence for the feasibility, accessibility, patient and provider satisfaction, and treatment outcomes related to the use of telemedicine across all health conditions in the pediatric populations.
METHODS: Studies were identified through PubMed database on May 10, 2020. We followed the guidelines for the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Included studies were randomized control trials from the last ten years that focused on telemedicine approaches as a study intervention in general or sub-specialty pediatric care. Title and abstracts were independently screened based on the eligibility criteria. Full texts were retrieved and independently screened based on the eligibility criteria. A standardized form including publication title, first author's name, publication year, participants' characteristics, study design, technology approach used, intervention characteristics, study goal, and study findings was used for data extraction.
RESULTS: Eleven articles met inclusion criteria and were included in this review. All studies were categorized as either randomized control trials (8/11) or cluster randomized trials (3/11). Number of participants in each study ranged from 22 to 400. Health conditions ranged from obesity (3/11), asthma (2/11), mental health (1/11), otitis media (1/11), skin conditions (1/11), type I diabetes (1/11), ADHD (1/11), and cystic fibrosis related pancreatic insufficiency (1/11). Telemedicine approaches used included traditional patient and doctor visits conducted via videoconferencing (5/11), smartphone-based interventions (3/11), telephone counseling (2/11), and telemedicine screening visits (1/11). Telemedicine interventions in all included studies showed comparable or improved outcomes related to symptom management, quality of life, satisfaction, medication adherence, visit completion rates, and disease progression, compared to control groups.
CONCLUSIONS: Although more research is needed, evidence from this review may suggest that telemedicine use in general and subspecialty pediatric care is comparable and occasionally more beneficial, compared to in person visits. Patients, healthcare professionals, patients and caregivers may benefit from utilizing telemedicine alongside traditional in person healthcare evaluations. Future research should emphasize improving access to care and cost effectiveness and eliminating barriers of telemedicine use to maximize its potential.
CLINICALTRIAL: Not applicable.

PMID: 33556030 [PubMed - as supplied by publisher]

Pulmonary Infection Secondary to Blastobotrys raffinosifermentans in a Cystic Fibrosis Patient: Review of the Literature.

Mycoses. 2021 Feb 08;:

Authors: Al-Obaidi M, Badali H, Cañete-Gibas C, Patterson HP, Wiederhold NP

Abstract
BACKGROUND: The genus Blastobotrys consists of at least 20 species. Disease in humans has been reported with B. adeninivorans, B. raffinosifermentans, B. proliferans, and B. serpentis, mostly in immunocompromised patients and those with cystic fibrosis.
OBJECTIVE: We report a lung infection secondary to B. raffinosifermentans in a cystic fibrosis patient successfully treated with isavuconazole and review the literature of invasive infections caused this genus. We also evaluated clinical isolates in our laboratory for species identification and antifungal susceptibility.
METHODS: Phylogenetic analysis was performed on a collection of 22 Blastobotrys isolates in our reference laboratory, and antifungal susceptibility patterns were determined for nine clinically available antifungals against 19 of these isolates.
RESULTS: By phylogenetic analysis 21 of the 22 isolates in our collection were identified as B. raffinosifermentans and only 1 as B. adeninivorans. Most were cultured from the respiratory tract, although others were recovered from other sources, including CSF and blood. Isavuconazole, caspofungin, and micafungin demonstrated the most potent in vitro activity, followed by amphotericin B. In contrast, fluconazole demonstrated poor activity. The patient in this case responded to isavuconazole treatment for breakthrough infection due to B. raffinosifermentans that was cultured from pleural fluid while on posaconazole prophylaxis post bi-lateral lung transplantation for cystic fibrosis.
CONCLUSIONS: Blastobotrys species are rare causes of infections in humans and primarily occur in immunocompromised hosts. In our collection the majority of isolates were identified as B. raffinosifermentans. To our knowledge this is the first report of successful treatment of such an infection with isavuconazole.

PMID: 33555073 [PubMed - as supplied by publisher]

Letter: Commentary: "Maximilian Sternberg" (1863-1934): The Man Behind Sternberg's Canal and His Contribution to the Modern-Day Skull Base Anatomy and Neuroscience Historical Vignette.

Neurosurgery. 2021 Feb 08;:

Authors: Koch CG, Grayson JW, Woodworth BA

PMID: 33555008 [PubMed - as supplied by publisher]

Antibiotic Efficacy Testing in an Ex vivo Model of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms in the Cystic Fibrosis Lung.

J Vis Exp. 2021 Jan 22;(167):

Authors: Harrington NE, Sweeney E, Alav I, Allen F, Moat J, Harrison F

Abstract
The effective prescription of antibiotics for the bacterial biofilms present within the lungs of individuals with cystic fibrosis (CF) is limited by a poor correlation between antibiotic susceptibility testing (AST) results using standard diagnostic methods (e.g., broth microdilution, disk diffusion, or Etest) and clinical outcomes after antibiotic treatment. Attempts to improve AST by the use of off-the-shelf biofilm growth platforms show little improvement in results. The limited ability of in vitro biofilm systems to mimic the physicochemical environment of the CF lung and, therefore bacterial physiology and biofilm architecture, also acts as a brake on the discovery of novel therapies for CF infection. Here, we present a protocol to perform AST of CF pathogens grown as mature, in vivo-like biofilms in an ex vivo CF lung model comprised of pig bronchiolar tissue and synthetic CF sputum (ex vivo pig lung, EVPL). Several in vitro assays exist for biofilm susceptibility testing, using either standard laboratory medium or various formulations of synthetic CF sputum in microtiter plates. Both growth medium and biofilm substrate (polystyrene plate vs. bronchiolar tissue) are likely to affect biofilm antibiotic tolerance. We show enhanced tolerance of clinical Pseudomonas aeruginosa and Staphylococcus aureus isolates in the ex vivo model; the effects of antibiotic treatment of biofilms is not correlated with the minimum inhibitory concentration (MIC) in standard microdilution assays or a sensitive/resistant classification in disk diffusion assays. The ex vivo platform could be used for bespoke biofilm AST of patient samples and as an enhanced testing platform for potential antibiofilm agents during pharmaceutical research and development. Improving the prescription or acceleration of antibiofilm drug discovery through the use of more in vivo-like testing platforms could drastically improve health outcomes for individuals with CF, as well as reduce the costs of clinical treatment and discovery research.

PMID: 33554970 [PubMed - in process]

Correction of the Gene Defect in Cystic Fibrosis: Is it too late for bone?

J Clin Endocrinol Metab. 2021 Feb 08;:

Authors: Tangpricha V

PMID: 33554249 [PubMed - as supplied by publisher]

Differential effects on the miRNome of the treatment of human airway epithelial Calu-3 cells with peptide-nucleic acids (PNAs) targeting microRNAs miR-101-3p and miR-145-5p: Next generation sequencing datasets.

Data Brief. 2021 Apr;35:106718

Authors: Gasparello J, Fabbri E, Gambari R, Finotti A

Abstract
Since the demonstration that microRNAs are deeply involved in the regulation of Cystic Fibrosis (CF) Transmembrane Conductance Regulator (CFTR) gene, a great attention has been dedicated to possible alteration of the CFTR gene expression by targeting miRNAs causing down-regulation of CFTR and CFTR-associated proteins. The data here presented are related to previously published studies on the effects of treatment of human bronchial cells of PNAs targeting miR-101-3p and miR-145-5p (microRNAs shown to regulate the CFTR mRNA). These data here presented are relative to two companion articles "Treatment of human airway epithelial Calu-3 cells with a Peptide-Nucleic Acid (PNA) targeting the microRNA miR-101-3p is associated with increased expression of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene" (published in European Journal of Medicinal Chemistry, 2020) and "Peptide Nucleic Acids for MicroRNA Targeting" (published in Methods in Molecular Biology, 2020). The data obtained indicate that, while the expression of most microRNAs is not affected by PNA treatment, some of them are strongly modulated. In particular, some microRNAs involved in CF and/or CFTR regulation are co-inhibited by miR-101-3p and miR-145-5p. Among them, miR-155-5p, miR-125b-5p, miR-132-3p and miR-6873-3p. This has been demonstrated by Next Generation Sequencing (NGS) followed by RT-qPCR and RT-ddPCR validation.

PMID: 33553515 [PubMed]

COVID-19 and Pediatric Lung Disease: A South African Tertiary Center Experience.

Front Pediatr. 2020;8:614076

Authors: Gray DM, Davies MA, Githinji L, Levin M, Mapani M, Nowalaza Z, Washaya N, Yassin A, Zampoli M, Zar HJ, Vanker A

Abstract
The COVID-19 pandemic led to rapid global spread with far-reaching impacts on health-care systems. Whilst pediatric data consistently shown a milder disease course, chronic lung disease has been identified as a risk factor for hospitalization and severe disease. In Africa, comprised predominantly of low middle-income countries (LMIC), the additional burden of HIV, tuberculosis, malnutrition and overcrowding is high and further impacts health risk. This paper reviewed the literature on COVID-19 and chronic lung disease in children and provides our experience from an African pediatric pulmonary center in Cape Town, South Africa. South African epidemiological data confirms a low burden of severe disease with children <18 years comprising 8% of all diagnosed cases and 3% of all COVID-19 admissions. A decrease in hospital admission for other viral lower respiratory tract infections was found. While the pulmonology service manages children with a wide range of chronic respiratory conditions including bronchiectasis, cystic fibrosis, asthma, interstitial lung disease and children with tracheostomies, no significant increase in COVID-19 admissions were noted and in those who developed COVID-19, the disease course was not severe. Current evidence suggests that pre-existing respiratory disease in children does not appear to be a significant risk factor for severe COVID-19. Longitudinal data are still needed to assess risk in children with immunosuppression and interstitial lung diseases. The indirect impacts of the pandemic response on child respiratory health are notable and still likely to be fully realized and quantified. Ensuring children have access to full preventive and care services during this time is priority.

PMID: 33553073 [PubMed]

Comparative Analysis of Clinical Parameters and Sputum Biomarkers in Establishing the Relevance of Filamentous Fungi in Cystic Fibrosis.

Front Cell Infect Microbiol. 2020;10:605241

Authors: Patel D, Dacanay KC, Pashley CH, Gaillard EA

Abstract
Background: The relationship between fungal culture (FC) positivity and airway inflammation in CF is largely unknown. Identifying the clinical significance of filamentous fungi in CF using both clinical parameters and biomarkers may change our antimicrobial therapeutic strategies.
Objectives: To investigate the clinical characteristics and airway biomarker profile in relation to the detection of filamentous fungi in respiratory samples obtained from CF patients.
Methods: A prospective cohort study over 24 months, including children and adults with CF. Participants provided sputum and/or bronchoalveolar lavage samples, which underwent processing for bacterial and fungal culture, leukocyte differential cell count and biomarker analysis for neutrophil elastase (NE), interleukin-8 (IL-8), galactomannan and tumor necrosis factor receptor type 2 (TNF-R2). We performed FC using neat sputum plugs, an approach shown to be more sensitive compared to routine laboratory testing.
Results: Sixty-one patients provided 76 respiratory samples (72 sputum and 4 BAL). Median age was 17 years (range 6 months-59 years). FC positivity was noted in 49% of the cohort. FC positivity was greater during pulmonary exacerbation compared to the stable state (67 versus 50%). Participants aged 5-30 years had a lower FEV1 within the FC positive group. A significant association between FC positivity and non-tuberculosis mycobacterial (NTM) culture was observed on non-parametric testing (p = 0.022) and regression analysis (p = 0.007). Exposure to indoor mold was a predictor for FC positivity (p = 0.047). There was a trend towards increased lung clearance index (LCI), bronchiectasis and intravenous antibiotic use in the FC positive group. There was no significant difference in biomarkers between FC positive and negative patients.
Conclusion: Aspergillus. fumigatus is the commonest filamentous fungi cultured from CF airways. We found no difference in the airway biomarker profile between FC positive and negative patients. The role of galactomannan and TNFR2 as fungal specific biomarkers in CF remains uncertain. FC positivity is associated with a lower FEV1 in younger patients, a lower LCI, NTM positivity, bronchiectasis, and intravenous antibiotic exposure. Larger trials are needed to determine the role of galactomannan and TNF-R2 as potential fungal biomarkers in CF.

PMID: 33553007 [PubMed - in process]

Prospective Evaluation of Aspergillus fumigatus-Specific IgG in Patients With Cystic Fibrosis.

Front Cell Infect Microbiol. 2020;10:602836

Authors: Eschenhagen P, Grehn C, Schwarz C

Abstract
Background: In Cystic Fibrosis (CF), the airways are often colonized by opportunistic fungi. The most frequently detected mold is Aspergillus fumigatus (Af). Af diseases are associated with significant morbidity and mortality. The most common clinical picture caused by Af is allergic bronchopulmonary aspergillosis (ABPA), triggered by an immunological reaction against Af. Af bronchitis and invasive aspergillosis rarely occur in CF as a result of spore colonization and germination. Since pulmonary mycoses and exacerbations by other pathogens overlap in clinical, radiological, and immunological characteristics, diagnosis still remains a challenge. The search for reliable, widely available biomarkers for Af diseases is therefore still an important task today.
Objectives: Af-specific IgG m3 is broadly available. Sensitivity and specificity data are contradictory and differ depending on the study population. In our prospective study on pulmonary Af diseases in CF, we determined specific IgG m3 in order to test its suitability as a biomarker for acute Af diseases and as a follow-up parameter.
Methods: In this prospective single center study, 109 patients with CF were screened from 2016 to 2019 for Af-associated diseases. According to diagnostic criteria, they were divided into four groups (control, bronchitis, ABPA, pneumonia). The groups were compared with respect to the level of Af-specific IgG (ImmunoCAP Gm3). We performed a receiver operating characteristic (ROC) curve analysis to determine cut-off, sensitivity and specificity. Twenty-one patients could be enrolled for a follow-up examination.
Results: Of the 109 patients, 36 were classified as acute Af-disease (Af bronchitis, ABPA, Af pneumonia). Of these, 21 patients completed follow up-screening. The median Af-specific Gm3 was higher in the acute Af-disease groups. There was a significant difference in Af-specific IgG m3 compared to the control group without acute Af-disease. Overall, there was a large interindividual distribution of Gm3. A cut-off value of 78.05 mg/L for Gm3 was calculated to discriminate controls and patients with ABPA/pneumonia with a specificity of 75% and a sensitivity of 74.6%. The follow up examination of 21 patients showed a decrease of Gm3 in most patients without statistical significance due to the small number of follow up patients.
Conclusion: Af specific IgG may be a useful biomarker for acute ABPA and Af pneumonia, but not for Af bronchitis in CF. However, due to the large interindividual variability of Gm3, it should only be interpreted alongside other biomarkers. Therefore, due to its broad availability, it could be suitable as a biomarker for ABPA and Af pneumonia in CF, if the results can be supported by a larger multicenter cohort.

PMID: 33553006 [PubMed - in process]

Production of CFTR-ΔF508 Rabbits.

Front Genet. 2020;11:627666

Authors: Yang D, Liang X, Pallas B, Hoenerhoff M, Ren Z, Han R, Zhang J, Chen YE, Jin JP, Sun F, Xu J

Abstract
Cystic Fibrosis (CF) is a lethal autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation is the deletion of phenylalanine residue at position 508 (ΔF508). Here we report the production of CFTR-ΔF508 rabbits by CRISPR/Cas9-mediated gene editing. After microinjection and embryo transfer, 77 kits were born, of which five carried the ΔF508 mutation. To confirm the germline transmission, one male ΔF508 founder was bred with two wild-type females and produced 16 F1 generation kits, of which six are heterozygous ΔF508/WT animals. Our work adds CFTR-ΔF508 rabbits to the toolbox of CF animal models for biomedical research.

PMID: 33552140 [PubMed]