Antimicrobial Susceptibility Testing for Glucose-Nonfermenting Gram-Negative Bacteria: the Tip of the Iceberg.

Antimicrob Agents Chemother. 2020 03 24;64(4):

Authors: Sfeir MM

PMID: 32209566 [PubMed - indexed for MEDLINE]

Management of Sinusitis in the Cystic Fibrosis Patient.

Immunol Allergy Clin North Am. 2020 May;40(2):371-383

Authors: Okafor S, Kelly KM, Halderman AA

Abstract
Chronic rhinosinusitis (CRS) is present in up to 100% of patients with cystic fibrosis (CF). CF-associated CRS is particularly recalcitrant, and sinus disease can have important implications in the health of the lower airways and overall quality of life in these patients. Both medical and surgical management play important roles in treating CF-associated CRS, but guidelines are lacking. This review summarizes the current literature on both medical and surgical management of this disease to provide an up-to-date analysis and recommendations on the treatment of CF-associated CRS.

PMID: 32278458 [PubMed - as supplied by publisher]

The Microbiome and Chronic Rhinosinusitis.

Immunol Allergy Clin North Am. 2020 May;40(2):251-263

Authors: Cho DY, Hunter RC, Ramakrishnan VR

Abstract
Chronic rhinosinusitis (CRS) is persistent inflammation and/or infection of the nasal cavity and paranasal sinuses. Recent advancements in culture-independent molecular techniques have enhanced understanding of interactions between sinus microbiota and upper airway microenvironment. The dysbiosis hypothesis-alteration of microbiota associated with perturbation of the local ecological landscape-is suggested as a mechanism involved in CRS pathogenesis. This review discusses the complex role of the microbiota in health and in CRS and considerations in sinus microbiome investigation, dysbiosis of sinus microbiota in CRS, microbial interactions in CRS, and development of preclinical models. The authors conclude with future directions for CRS-associated microbiome research.

PMID: 32278449 [PubMed - as supplied by publisher]

Challenges in paediatric inflammatory bowel diseases in the COVID-19 time.

Dig Liver Dis. 2020 Apr 07;:

Authors: Dipasquale V, Cucchiara S, Martinelli M, Miele E, Aloi M, Romano C

PMID: 32276846 [PubMed - as supplied by publisher]

Cystic Fibrosis from Childhood to Adulthood: What Is New in Imaging Assessment?

Radiol Clin North Am. 2020 May;58(3):475-486

Authors: Hota P, Madan R

Abstract
Advanced pulmonary disease continues to remain the leading cause of morbidity and mortality in patients with cystic fibrosis (CF), with pulmonary imaging playing a crucial role in early detection, longitudinal monitoring, as well as prelung and postlung transplant evaluation. This article reviews the specific imaging features of CF using conventional imaging modalities (chest radiographs and high-resolution computed tomography [HRCT]) as well as emerging imaging technologies (digital chest tomosynthesis and MR imaging). In addition, the authors review the CF-specific HRCT imaging findings that are essential in the evaluation of these patients in the pre-lung transplant and post-lung transplant settings.

PMID: 32276698 [PubMed - as supplied by publisher]

The Impact of the CFTR Gene Discovery on Cystic Fibrosis Diagnosis, Counseling, and Preventive Therapy.

Genes (Basel). 2020 Apr 08;11(4):

Authors: Farrell PM, Rock MJ, Baker MW

Abstract
Discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene was the long-awaited scientific advance that dramatically improved the diagnosis and treatment of cystic fibrosis (CF). The combination of a first-tier biomarker, immunoreactive trypsinogen (IRT), and, if high, DNA analysis for CF-causing variants, has enabled regions where CF is prevalent to screen neonates and achieve diagnoses within 1-2 weeks of birth when most patients are asymptomatic. In addition, IRT/DNA (CFTR) screening protocols simultaneously contribute important genetic data to determine genotype, prognosticate, and plan preventive therapies such as CFTR modulator selection. As the genomics era proceeds with affordable biotechnologies, the potential added value of whole genome sequencing will probably enhance personalized, precision care that can begin during infancy. Issues remain, however, about the optimal size of CFTR panels in genetically diverse regions and how best to deal with incidental findings. Because prospects for a primary DNA screening test are on the horizon, the debate about detecting heterozygote carriers will likely intensify, especially as we learn more about this relatively common genotype. Perhaps, at that time, concerns about CF heterozygote carrier detection will subside, and it will become recognized as beneficial. We share new perspectives on that issue in this article.

PMID: 32276344 [PubMed - as supplied by publisher]

Omega-3 fatty acid supplementation for cystic fibrosis.

Cochrane Database Syst Rev. 2020 Apr 10;4:CD002201

Authors: Watson H, Stackhouse C

Abstract
BACKGROUND: Studies suggest that a diet rich in omega-3 essential fatty acids may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis. This is an updated version of a previously published review.
OBJECTIVES: To determine whether there is evidence that omega-3 polyunsaturated fatty acid supplementation reduces morbidity and mortality and to identify any adverse events associated with supplementation.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of last search: 01 April 2020. We also searched online study registries and contacted authors. Date of last search: 12 February 2020.
SELECTION CRITERIA: Randomised controlled trials in people with cystic fibrosis comparing omega-3 fatty acid supplements with placebo.
DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion, extracted data and assessed the risk of bias of the studies. The quality of the evidence was assessed using GRADE.
MAIN RESULTS: The searches identified 23 studies; five studies with 106 participants (children and adults) were included; duration of studies and interventions differed. Two studies compared omega-3 fatty acids to olive oil for six weeks; one study compared omega-3 fatty acids and omega-6 fatty acids to control capsules (customised fatty acid blends) for three months; one study compared a liquid dietary supplement containing omega-3 fatty acids to one without for six months; and one study compared omega-3 fatty acids to a placebo for 12 months. Three studies had a low risk of bias for randomisation, but the risk was unclear in the remaining two studies; all studies had an unclear risk of bias for allocation concealment. Three of the studies adequately blinded participants; the risk of bias for selective reporting was high in one study and unclear for four studies. Two studies reported the number of respiratory exacerbations. At three months, one study (43 participants) reported no change in antibiotic usage. At 12 months the second study (15 participants) reported a reduction in the number of pulmonary exacerbations and cumulative antibiotic days in the supplement group compared to the previous year (no data for the control group); very low-quality evidence means we are unsure whether supplementation has any effect on this outcome. With regards to adverse events, one six-week study (12 participants) reported no difference in diarrhoea between omega-3 or placebo capsules; the very low-quality evidence means we are unsure if supplementation has any effect on this outcome. Additionally, one study reported an increase in steatorrhoea requiring participants to increase their daily dose of pancreatic enzymes, but three studies had already increased pancreatic enzyme dose at study begin so as to reduce the incidence of steatorrhoea. One study (43 participants) reported stomach pains at three months (treatment or control group not specified). One six-week study (19 participants) reported three asthma exacerbations leading to exclusion of participants since corticosteroid treatment could affect affect essential fatty acid metabolism. Four studies reported lung function. One six-week study (19 participants) reported an increase in forced expiratory volume in one second (FEV1) (L) and forced vital capacity (FVC) (L), but the very low-quality evidence means we are unsure if supplementation has any effect on lung function. The remaining studies did not report any difference in lung function at three months (unit of measurement not specified) or at six months and one year (FEV1 % predicted and FVC % predicted). No deaths were reported in any of the five studies. Four studies reported clinical variables. One study reported an increase in Schwachman score and weight alongside a reduction in sputum volume with supplementation compared to placebo at three months (data not analysable). However, three studies reported no differences in either weight at six weeks, in body mass index (BMI) standard deviation (SD) score at six months (very low-quality evidence) or BMI Z score at 12 months. Three studies reported biochemical markers of fatty acid status. One study showed an increase from baseline in both EPA and DHA content of serum phospholipids in the omega-3 group compared to placebo at three months and also a significant decrease in n-6/n-3 ratio in the supplement group compared to placebo; since the quality of the evidence is very low we are not certain that these changes are due to supplementation. One six-month cross-over study showed a higher EPA content of the neutrophil membrane in the supplement group compared to the placebo group, but, no difference in DHA membrane concentration. Furthermore, the leukotriene B4 to leukotriene B5 ratio was lower at six months in the omega-3 group compared to placebo. A one-year study reported a greater increase in the essential fatty acid profile and a decrease in AA levels in the treatment arm compared to placebo.
AUTHORS' CONCLUSIONS: This review found that regular omega-3 supplements may provide some limited benefits for people with cystic fibrosis with relatively few adverse effects: however, the quality of the evidence across all outcomes was very low. The current evidence is insufficient to draw firm conclusions or recommend routine use of these supplements in people with cystic fibrosis. A large, long-term, multicentre, randomised controlled study is needed to determine any significant therapeutic effect and to assess the influence of disease severity, dosage and duration of treatment. Future researchers should note the need for additional pancreatic enzymes when providing omega-3 supplementation or olive oil placebo capsules. More research is required to determine the exact dose of pancreatic enzyme required.

PMID: 32275788 [PubMed - as supplied by publisher]

Role of Stenotrophomonas maltophilia isolation in patients with non CF bronchiectasis.

QJM. 2020 Apr 10;:

Authors: Marra R, Sgalla G, Richeldi L, Conte EG, Hill AT

Abstract
BACKGROUND: Stenotrophomonas maltophilia is a bacteria whose role in patients with cystic fibrosis bronchiectasis has been previously studied; little is known about its role in non-CF bronchiectasis.
AIM: Investigate the risk factors for S. Maltophilia acquisition and its clinical impact on bronchiectasis patients.
DESIGN: A retrospective observational cohort study enrolling patients attending the Bronchiectasis Clinic at the Royal Infirmary of Edinburgh, Scotland, UK.
METHODS: 167 bronchiectasis patients undergoing intravenous antibiotic therapy were selected and divided according to single or chronic S. Maltophilia isolation in sputum. The risk factors and prognostic impact was studied.
RESULTS: Single isolation was independently associated with lower baseline % predicted FEV1 (OR 0.98; 95%CI 0.970-1,044; p = 0.025) and with less radiological involvement (OR 0.379; 95%CI 0.175-0.819; p = 0.01). Chronic isolation was associated with the number of intravenous antibiotic courses in the year before and after the first isolation (OR 1.2; 95%CI 1.053-1.398; p = 0.007) and with the absence of P. Aeruginosa colonisation (OR 0.207; 95%CI 0.056-0.764; p = 0.02). In the chronic isolation group, there were more exacerbations and more need of intravenous antibiotics in the year after the first isolation.
CONCLUSIONS: Poor lung function is the main independent risk factor for single isolation of S. maltophilia. For chronic colonisation, the main independent risk factor is the number of intravenous antibiotic courses and the absence of P. aeruginosa chronic colonisation. Only when chronically present, S. maltophilia had a clinical impact with more exacerbations.

PMID: 32275749 [PubMed - as supplied by publisher]

Age and environmental exposures influence the fecal bacteriome of young children with cystic fibrosis.

Pediatr Pulmonol. 2020 Apr 10;:

Authors: Loman BR, Shrestha CL, Thompson R, Groner JA, Mejias A, Ruoff KL, O'Toole GA, Bailey MT, Kopp BT

Abstract
BACKGROUND: Mechanisms that facilitate early infection and inflammation in cystic fibrosis (CF) are unclear. We previously showed that young CF children with secondhand smoke exposure (SHSe) have increased susceptibility to respiratory infections. We aimed to define the impact of SHSe and other external factors upon the fecal bacteriome in early CF.
METHODS: Twenty CF infants and children were enrolled, clinical data recorded, and hair nicotine measured as an objective surrogate of SHSe. Fecal samples were collected at clinic visits and bacteriome 16S rRNA gene sequencing performed.
RESULTS: SHSe was associated with increased alpha diversity and increased relative abundance of Acinetobacter and Akkermansia, along with decreased Bifidobacterium and Lactobacillus. Recent antibiotic exposure predicted bacterial population structure in children less than 2 years of age and was associated with decreased Bacteroides relative abundance. Age was the strongest predictor of overall fecal bacterial composition and positively associated with Blautia and Parabacteroides. Weight for length was negatively associated with Staphylococcus relative abundance.
CONCLUSIONS: SHSe and other external factors such as antibiotics appear to alter fecal bacterial composition in young CF children, but the strongest predictor of overall composition was age. These findings have implications for understanding the intestinal microbiome in young CF children.

PMID: 32275127 [PubMed - as supplied by publisher]

Pharmacological Inhibition and Activation of the Ca2+ Activated Cl- Channel TMEM16A.

Int J Mol Sci. 2020 Apr 07;21(7):

Authors: Centeio R, Cabrita I, Benedetto R, Talbi K, Ousingsawat J, Schreiber R, Sullivan JK, Kunzelmann K

Abstract
TMEM16A is a Ca2+ activated Cl- channel with important functions in airways, intestine, and other epithelial organs. Activation of TMEM16A is proposed as a therapy in cystic fibrosis (CF) to reinstall airway Cl- secretion and to enhance airway surface liquid (ASL). This CFTR-agnostic approach is thought to improve mucociliary clearance and lung function in CF. This could indeed improve ASL, however, mucus release and airway contraction may also be induced by activators of TMEM16A, particularly in inflamed airways of patients with asthma, COPD, or CF. Currently, both activators and inhibitors of TMEM16A are developed and examined in different types of tissues. Here we compare activation and inhibition of endogenous and overexpressed TMEM16A and analyze potential off-target effects. The three well-known blockers benzbromarone, niclosamide, and Ani9 inhibited both TMEM16A and ATP-induced Ca2+ increase by variable degrees, depending on the cell type. Niclosamide, while blocking Ca2+ activated TMEM16A, also induced a subtle but significant Ca2+ store release and inhibited store-operated Ca2+ influx. Niclosamide, benzbromarone and Ani9 also affected TMEM16F whole cell currents, indicating limited specificity for these inhibitors. The compounds Eact, cinnamaldehyde, and melittin, as well as the phosphatidylinositol diC8-PIP2 are the reported activators of TMEM16A. However, the compounds were unable to activate endogenous TMEM16A in HT29 colonic epithelial cells. In contrast, TMEM16A overexpressed in HEK293 cells was potently stimulated by these activators. We speculate that overexpressed TMEM16A might have a better accessibility to intracellular Ca2+, which causes spontaneous activity even at basal intracellular Ca2+ concentrations. Small molecules may therefore potentiate pre-stimulated TMEM16A currents, but may otherwise fail to activate silent endogenous TMEM16A.

PMID: 32272686 [PubMed - in process]

Monoacylglycerol Form of Omega-3s Improves Its Bioavailability in Humans Compared to Other Forms.

Nutrients. 2020 Apr 07;12(4):

Authors: Cuenoud B, Rochat I, Gosoniu ML, Dupuis L, Berk E, Jaudszus A, Mainz JG, Hafen G, Beaumont M, Cruz-Hernandez C

Abstract
Numerous benefits are attributed to omega-3 fatty acids (OM3) especially in cardiovascular health. However, bioavailability and clinical efficacy depend on numerous factors, including OM3 form, food matrix effects (especially the lipid content of the diet), and metabolic capacity. Here, we show in humans that a "pre-digested" OM3-sn-1(3)-monoacylglycerol lipid structure (OM3-MAG) has a significantly greater absorption at high therapeutic doses (2.9 g/day) than the most commonly OM3-ethyl ester (3.1 g/day) form (used for the treatment of hypertriglyceridemia), and a comparable profile to other pre-digested OM3 free fatty acids (OM3-FFA) structure (3.2 g/day). Nutritional supplement doses of MAG resulted in similar increases in OM3 blood level, compared to OM3 triacylglycerols (OM3-TAG) supplements in obese subjects (1.2 g/day) under low fat diet, and in children with cystic fibrosis (1.0 g/day). These results suggest that both forms of pre-digested OM3-MAG and OM3-FFA are effectively absorbed and re-incorporated effectively into triacylglycerols inside the enterocytes, before being exported into the chylomicrons lipid transport system. The pre-digested OM3-MAG might provide a more effective therapy in severe cardiovascular conditions where high doses of OM3 are required and a low-fat diet is indicated, which limited digestive lipase activity.

PMID: 32272659 [PubMed - in process]

CFTR gets together.

J Gen Physiol. 2019 06 03;151(6):705

Authors: Sedwick C

Abstract
JGP study shows that pro-secretory agonists prompt CFTR to assemble into large lipid platforms.

PMID: 31076449 [PubMed - indexed for MEDLINE]

Etiology, Clinical, Radiological, and Microbiological Profile of Patients with Non-cystic Fibrosis Bronchiectasis at a Tertiary Care Hospital of Pakistan.

Cureus. 2020 Mar 08;12(3):e7208

Authors: Sharif N, Baig MS, Sharif S, Irfan M

Abstract
Objectives To identify the etiology of non-cystic fibrosis bronchiectasis (NCFB), to assess the clinical presentation, radiological findings, and microbiological profile of patients presenting with a diagnosis of bronchiectasis in a tertiary care center of Pakistan. Methods This was a prospective observational cohort study where patients with a diagnosis of bronchiectasis proven by high-resolution computed tomography (HRCT) were evaluated for etiology, clinical characteristics, microbiology, radiology, spirometric profile, and in-hospital outcomes. Results During the study period, 196 patients were diagnosed with NCFB. The majority of the patients were men 76.5% (n = 150) and 83.6% (n = 163) of the total patients were younger than 60 years of age. The majority of these patients (58.7%, n = 111) had a duration of symptoms between 5-10 years. The etiology of bronchiectasis was identified in 92.9% of cases. Post-infectious bronchiectasis was the most common cause (67.8%, n = 133), followed by chronic obstructive pulmonary disease (COPD) (9.2%, n = 18), and allergic bronchopulmonary aspergillosis (ABPA) (7.1%, n = 14). Among the post infectious causes, a history of TB was present in 85% (n = 114/133) of patients. Obstructive impairment was the most common spirometric pattern, observed in 68.9% (n = 135) of patients. Pseudomonas aeruginosa was the most commonly isolated organism (36.2%, n = 71). Hemoptysis was the most frequent complication found in 20.9% of patients (n = 41). Out of these 196 patients, 94.4% (n = 185) received medical management and were discharged from the hospital. Respiratory failure was significantly associated with the Pseudomonas group as compared to non-pseudomonas group [(n = 21 (29%) vs n = 18 (14.4%) p = 0.01]. During hospitalization seven patients (3.6%) were died because of respiratory failure. Conclusions Post TB bronchiectasis was the leading cause of non-cystic fibrosis (CF) bronchiectasis in this cohort, with Pseudomonas was the commonest pathogen isolated from the respiratory specimen, which was significantly associated with respiratory failure. On spirometry, obstructive impairment was found in the majority of patients and hemoptysis was the most frequent complication.

PMID: 32269886 [PubMed]

Molecular and epidemiological analysis of a Burkholderia cepacia sepsis outbreak from a tertiary care hospital in Bangladesh.

PLoS Negl Trop Dis. 2020 Apr 09;14(4):e0008200

Authors: Farzana R, Jones LS, Rahman MA, Sands K, Portal E, Boostrom I, Kalam MA, Hasan B, Khan A, Walsh TR

Abstract
BACKGROUND: Burkholderia cepacia complex (Bcc) is a group of serious pathogens in cystic fibrosis patients and causes life threatening infections in immunocompromised patients. Species within the Bcc are widely distributed within the environment, can survive the presence of disinfectants and antiseptics, and are inherently multidrug resistant (MDR).
METHODS: Dhaka Medical College Hospital (DMCH) patients with a B. cepacia positive blood culture between 20 October 2016 to 23rd September 2017 were considered as outbreak cases. Blood stream infections (BSIs) were detected using BacT/ALERT 3D at DMCH. B. cepacia was isolated on chromogenic UTI media followed by MALDI-TOF. Minimum inhibitory concentration (MIC) of clinically relevant antibiotics was determined by agar dilution. Whole genome sequencing was performed on an Illumina MiSeq platform. Patients' demographic and clinical data were collected. Patients' clinical history and genomic data of the outbreak strains were merged to investigate possible outbreaks. Ninety-one B. cepacia genomes were downloaded from 'Burkholderia Genome Database' and the genomic background of the global strains were compared with our outbreak strains.
RESULTS: Among 236 BSIs, 6.35% (15/236) were B. cepacia. Outbreak cases were confined to the burn critical care unit and, to a lesser extent, the paediatrics department. There was a continuum of overlapping cases at DMCH between 23 October 2016 to 30 August 2017. Core genome SNPs showed that the outbreak strains were confined to a single clade, corresponded to a common clone (ST1578). The strains were shown to be MDR and associated with a mortality of 31% excluding discharge against medical advice. MIC profiles of the strains suggested that antibiotics deployed as empirical therapy were invariably inappropriate. The genetic background of the outbreak strains was very similar; however, a few variations were found regarding the presence of virulence genes. Compared to global genomic dataset from the Burkholderia Genome Database, the Bangladeshi strains were genetically distinct.
CONCLUSIONS: Environmental surveillance is required to investigate the aetiology and mode of transmission of the B. cepacia outbreak. Systematic management of nosocomial outbreaks, particularly in resource limited regions will mitigate transmission and improve patients' outcomes.

PMID: 32271750 [PubMed - as supplied by publisher]

Initiation of triple therapy maintenance treatment among patients with COPD.

Am J Manag Care. 2020 Apr 01;26(4):e106-e112

Authors: Li Y, Lim J, Stemkowski S, Kaila S, Renda A, Shaikh A

Abstract
OBJECTIVES: Triple therapy is indicated for patients with very severe chronic obstructive pulmonary disease (COPD). Use of this treatment in the appropriate patient population is important to ensure optimal outcomes. This study quantified the use of triple therapy and assessed concordance with 2013-2016 Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations within a national health plan.
STUDY DESIGN: Retrospective cohort study using data from a large national health plan.
METHODS: To estimate the prevalence of triple therapy using claims data, patients in the first of 2 cohorts were indexed on their first diagnosis of COPD between January 1, 2012, and December 31, 2014, and required to have 24 months postindex continuous enrollment. To assess concordance with GOLD recommendations, a second cohort was created and indexed on the date of triple therapy initiation between January 1, 2013, and November 30, 2016, and required to have 12 months preindex and 1 month postindex continuous enrollment. For both cohorts, patients were aged 40 years or older, with no International Classification of Diseases code for asthma, cystic fibrosis, or lung cancer during the study period.
RESULTS: In the first cohort of 92,248 patients with COPD receiving any COPD maintenance medication, 17% were prescribed triple therapy. In the second cohort (n = 19,645), the majority (60%) of patients on triple therapy were classified as GOLD group A or B (ie, no evidence of any exacerbation or only 1 exacerbation not resulting in hospitalization at baseline).
CONCLUSIONS: Results showed that triple therapy was often prescribed among patients classified as GOLD group A or B. Additional research is required, however, to further assess whether these patients may have had an exacerbation that was not evident in claims data. Treatment of COPD should be individualized to optimize outcomes and reduce adverse events.

PMID: 32270987 [PubMed - as supplied by publisher]

Functional Characterization of Clinical Isolates of the Opportunistic Fungal Pathogen Aspergillus nidulans.

mSphere. 2020 Apr 08;5(2):

Authors: Bastos RW, Valero C, Silva LP, Schoen T, Drott M, Brauer V, Silva-Rocha R, Lind A, Steenwyk JL, Rokas A, Rodrigues F, Resendiz-Sharpe A, Lagrou K, Marcet-Houben M, Gabaldón T, McDonnell E, Reid I, Tsang A, Oakley BR, Loures FV, Almeida F, Huttenlocher A, Keller NP, Ries LNA, Goldman GH

Abstract
Aspergillus nidulans is an opportunistic fungal pathogen in patients with immunodeficiency, and virulence of A. nidulans isolates has mainly been studied in the context of chronic granulomatous disease (CGD), with characterization of clinical isolates obtained from non-CGD patients remaining elusive. This study therefore carried out a detailed biological characterization of two A. nidulans clinical isolates (CIs), obtained from a patient with breast carcinoma and pneumonia and from a patient with cystic fibrosis that underwent lung transplantation, and compared them to the reference, nonclinical FGSC A4 strain. Both CIs presented increased growth in comparison to that of the reference strain in the presence of physiologically relevant carbon sources. Metabolomic analyses showed that the three strains are metabolically very different from each other in these carbon sources. Furthermore, the CIs were highly susceptible to cell wall-perturbing agents but not to other physiologically relevant stresses. Genome analyses identified several frameshift variants in genes encoding cell wall integrity (CWI) signaling components. Significant differences in CWI signaling were confirmed by Western blotting among the three strains. In vivo virulence studies using several different models revealed that strain MO80069 had significantly higher virulence in hosts with impaired neutrophil function than the other strains. In summary, this study presents detailed biological characterization of two A. nidulans sensu stricto clinical isolates. Just as in Aspergillus fumigatus, strain heterogeneity exists in A. nidulans clinical strains that can define virulence traits. Further studies are required to fully characterize A. nidulans strain-specific virulence traits and pathogenicity.IMPORTANCE Immunocompromised patients are susceptible to infections with opportunistic filamentous fungi from the genus Aspergillus Although A. fumigatus is the main etiological agent of Aspergillus species-related infections, other species, such as A. nidulans, are prevalent in a condition-specific manner. A. nidulans is a predominant infective agent in patients suffering from chronic granulomatous disease (CGD). A. nidulans isolates have mainly been studied in the context of CGD although infection with A. nidulans also occurs in non-CGD patients. This study carried out a detailed biological characterization of two non-CGD A. nidulans clinical isolates and compared the results to those with a reference strain. Phenotypic, metabolomic, and genomic analyses highlight fundamental differences in carbon source utilization, stress responses, and maintenance of cell wall integrity among the strains. One clinical strain had increased virulence in models with impaired neutrophil function. Just as in A. fumigatus, strain heterogeneity exists in A. nidulans clinical strains that can define virulence traits.

PMID: 32269156 [PubMed - in process]

Bronchodilator Responsiveness in Children with Cystic Fibrosis and Allergic Bronchopulmonary Aspergillosis.

Eur Respir J. 2020 Apr 08;:

Authors: Pollak M, Shaw M, Wilson D, Grasemann H, Ratjen F

PMID: 32269091 [PubMed - as supplied by publisher]

Caring for gender diverse youth with cystic fibrosis.

J Cyst Fibros. 2020 Apr 05;:

Authors: Kidd KM, Sequeira GM, Voss RV, Weiner DJ, Ramsey BW, Jain R, Kazmerski TM

Abstract
Gender diverse youth with cystic fibrosis have unique health needs. Providers should be aware of existing health disparities in this population as well as aspects of gender-affirming care including hormone therapy, chest binding, and use of affirming language. This communication provides an introduction to these concerns.

PMID: 32268993 [PubMed - as supplied by publisher]

La mucoviscidose.

Rev Infirm. 2020 01;69(257):15

Authors: Guillouët S

PMID: 32146955 [PubMed - indexed for MEDLINE]

From Genetics to Precision Therapy: Finding a Path through the Scientific Valley of Death.

Am J Respir Cell Mol Biol. 2019 12;61(6):671-672

Authors: Gupta R, Gaston B

PMID: 31233696 [PubMed - indexed for MEDLINE]