Desaturation during exercise is not a sufficient mechanism for prediction of osteoporosis in non-cystic fibrosis bronchiectasis.

BMC Pulm Med. 2020 Jan 28;20(1):23

Authors: Tomlinson OW, Vlachopoulos D

Abstract
BACKGROUND: Recent research has proposed an association between desaturation during a six minute walking test (6MWT) and osteoporosis in an elderly group of individuals with non-cystic fibrosis bronchiectasis. A causative pathway through activation of hypoxia-inducible factor 1-alpha (HIF-1α) has been proposed.
COMMENTARY: Queries regarding the statistical approaches used are identified and discussed within this correspondence. These predominate around the use of linear regression models to predict osteoporosis in a group that is already osteoporotic, presenting with extreme values for bone mineral density (BMD). Further queries are raised regarding the HIF-1α pathway, and physical activity (PA) is proposed as an upstream mechanism for both reduced exercise tolerance and low BMD.
CONCLUSIONS: It is suggested that osteoporosis cannot be predicted in a group that is already osteoporotic, and that PA is likely to be the causative mechanism between desaturation in the 6MWT and low BMD in non-cystic fibrosis bronchiectasis.

PMID: 31992237 [PubMed - in process]

Effects of low glycemic index/high-fat, high-calorie diet on glycemic control and lipid profiles of children and adolescence with cystic fibrosis: A randomized double-blind controlled clinical trial.

Diabetes Metab Syndr. 2020 Jan 08;14(2):87-92

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

Abstract
PURPOSE: Low glycemic index diets seem to be potentially effective to improve glycemic control and reduce lipid profiles. Hence, this study aimed to evaluate the effect of a low glycemic index/high fat, high-calorie diet on glycemic status and lipid profiles of patients with cystic fibrosis.
METHODS: In this randomized clinical trial, 44 children and adolescents with cystic fibrosis were randomized to receive for three months either a high fat, high-calorie diet (n = 22) or a low glycemic index/high fat, high-calorie diet (n = 22) with similar calorie and macronutrients composition. Patients in high fat, high-calorie diet arm were allowed to use all sources of carbohydrates with different glycaemic indices; whereas those in another arm consumed carbohydrates from low glycemic index sources. Serum levels of lipid profiles (triglyceride, total cholesterol, HDL cholesterol, LDL cholesterol), insulin, fasting blood glucose, and glycated hemoglobin were measured at baseline and after the intervention.
RESULTS: Between-group differences were significant only for fasting blood glucose (P < 0.001). However, fasting blood glucose (P = 0.003) and glycated hemoglobin (P = 0.002) significantly decreased after the intervention in the low glycemic index group, while in another group a significant increase in fasting blood glucose (P = 0.038) and triglyceride (P = 0.004) was found. No significant within-group differences were observed in other variables in both groups.
CONCLUSIONS: It seems that adherence to a low glycemic index/high fat, high-calorie diet can improve glycemic indices in children and adolescents with cystic fibrosis compared to the high fat, high-calorie diet.
TRIAL REGISTRATION: IRCT2017102325267N5.

PMID: 31991298 [PubMed - as supplied by publisher]

The RNFT2/IL3Rα axis regulates IL3 signaling and innate immunity.

JCI Insight. 2020 Jan 28;:

Authors: Tong Y, Lear TB, Evankovich J, Chen Y, Londino JD, Myerburg MM, Zhang Y, Popescu ID, McDyer JF, McVerry BJ, Lockwood KC, Jurczak MJ, Liu Y, Chen BB

Abstract
Interleukin-3 (IL3) receptor α (IL3Rα) is the alpha subunit of the ligand-specific IL3 receptor and initiates intracellular signaling in response to IL3. IL3 amplifies pro-inflammatory signaling and cytokine storm in murine sepsis models. Here we found that RNFT2 (RING finger transmembrane-domain containing protein 2, also TMEM118), a previously uncharacterized RING finger ubiquitin E3 ligase, negatively regulated IL3-dependent cellular responses through IL3Rα ubiquitination and degradation in the proteasome. In vitro, IL3 stimulation promoted IL3Rα proteasomal degradation dependent on RNFT2, and we identified IL3Rα Lysine 357 as a ubiquitin acceptor site. We determined that LPS-priming reduces RNFT2 abundance, extends IL3Rα half-life, and sensitizes cells to the effects of IL3, acting synergistically to increase pro-inflammatory signaling. In vivo, IL3 synergized with LPS to exacerbate lung inflammation in LPS and Pseudomonas aeruginosa-challenged mice; conversely, IL3 neutralization reduced LPS-induce lung injury. Further, RNFT2 over-expression reduced lung inflammation and injury, whereas Rnft2 knockdown exacerbated inflammatory responses in LPS-induced murine lung injury. Lastly, we examined RNFT2 and IL3Rα in human lung explants from patients with Cystic Fibrosis, and also showed that IL3 is elevated in mechanically-ventilated critically ill humans at risk for Acute Respiratory Distress Syndrome (ARDS). These results identify RNFT2 as a negative regulator of IL3Rα, and show a potential role for the RNFT2/IL3Rα/IL3 axis in regulating innate immune responses in the lung.

PMID: 31990690 [PubMed - as supplied by publisher]

Two years of newborn screening for cystic fibrosis in Turkey: Çukurova experience.

Turk J Pediatr. 2019;61(4):505-512

Authors: Şaşihüseyinoğlu AŞ, Altıntaş DU, Bişgin A, Doğruel D, Yılmaz M, Serbes M

Abstract
Şaşihüseyinoğlu AŞ, Altıntaş DU, Bişgin A, Doğruel D, Yılmaz M, Serbes M. Two years of newborn screening for cystic fibrosis in Turkey: Çukurova experience. Turk J Pediatr 2019; 61: 505-512. The severity of cystic fibrosis (CF) depends on the type of cystic fibrosis transmembrane conductance regulator (CFTR) mutation. The primary goal of newborn screening (NBS) is to decrease morbidity, mortality and associated disabilities. The National NBS for CF programme was initiated in Turkey since 01.01.2015. The aim of this study was to present two years of experience of our CF center which is located in the south of Turkey. The study population comprised of infants who were born in Adana between 1 January 2015 - 31 December 2016, referred to our CF center as part of NBS for CF and performed CFTR gene analysis. The infants were divided into three groups according to laboratory tests and symptoms as CF, CRMS (cystic fibrosis transmembrane conductance regulator-related metabolic syndrome) and false positive NBS. Between January 1, 2015 and December 31, 2016, NBS was performed in 77,437 newborns in Adana. Two hundred seven (0.26%) newborns screened were positive for CF. A total of 184 infants were included to the study. We reported 12 babies as CF with an incidence of 1:6,452. The babies diagnosed as CF constituted 6.5% of positive CF NBS. Rest of study group diagnosed with CRMS/CFSPID (54/184, 29.5%) and false positive (118/184, 64%). Positive predictive value (PPV) of NBS was 6.5%. The most common CFTR mutations were 508del, p.F1052L and p.L997 F. The implementation of CF-NBS program has been successful in Turkey. But it is too early to determine the specificity and sensitivity of the program.

PMID: 31990467 [PubMed - in process]

Effect of Amoxicillin in combination with Imipenem-Relebactam against Mycobacterium abscessus.

Sci Rep. 2020 Jan 27;10(1):928

Authors: Lopeman RC, Harrison J, Rathbone DL, Desai M, Lambert PA, Cox JAG

Abstract
Infections caused by Mycobacterium abscessus are increasing in prevalence in cystic fibrosis patients. This opportunistic pathogen's intrinsic resistance to most antibiotics has perpetuated an urgent demand for new, more effective therapeutic interventions. Here we report a prospective advance in the treatment of M. abscessus infection; increasing the susceptibility of the organism to amoxicillin, by repurposing the β-lactamase inhibitor, relebactam, in combination with the front line M. abscessus drug imipenem. We establish by multiple in vitro methods that this combination works synergistically to inhibit M. abscessus. We also show the direct competitive inhibition of the M. abscessus β-lactamase, BlaMab, using a novel assay, which is validated kinetically using the nitrocefin reporter assay and in silico binding studies. Furthermore, we reverse the susceptibility by overexpressing BlaMab in M. abscessus, demonstrating relebactam-BlaMab target engagement. Finally, we highlight the in vitro efficacy of this combination against a panel of M. abscessus clinical isolates, revealing the therapeutic potential of the amoxicillin-imipenem-relebactam combination.

PMID: 31988293 [PubMed - in process]

Unmasking catamenial hemoptysis in the era of CFTR modulator therapy.

J Cyst Fibros. 2020 Jan 24;:

Authors: Montemayor K, Claudio AT, Carson S, Lechtzin N, Christianson MS, West NE

Abstract
BACKGROUND: Thoracic endometriosis syndrome (TES) is a rare condition that occurs in women when endometriosis implants into the thoracic cavity. Catamenial hemoptysis, the occurrence of hemoptysis with menstruation, is a recognized clinical manifestation of TES commonly treated with hormonal therapy.
CASE SUMMARY: We present the first documented case describing the recrudescence of catamenial hemoptysis in the setting of Lumacaftor/Ivacaftor administration in a 25-year-old woman with cystic fibrosis (CF).
DISCUSSION: We review the literature on TES, pharmacologic management, and reported cystic fibrosis transmembrane conductance regulator (CFTR) modulator drug interactions. We propose that our patient's recrudescence of catamenial hemoptysis was secondary to a drug-drug interaction between Lumacaftor/Ivacaftor and oral contraceptive therapy.
CONCLUSION: Our case suggests that women with CF who have catamenial hemoptysis and a genetic mutation approved for Tezacaftor/Ivacaftor or Elexacaftor/Tezacaftor/Ivacaftor can be managed effectively with either CFTR modulator and hormonal contraceptive therapy.

PMID: 31987762 [PubMed - as supplied by publisher]

Nutritional rehabilitation for children with cystic fibrosis: Single center study.

Clin Nutr ESPEN. 2020 Feb;35:201-206

Authors: El-Koofy N, El-Mahdy M, Fathy M, El Falaki M, El Dine Hamed DH

Abstract
BACKGROUND: Cystic fibrosis (CF) is an inherited disorder that causes severe damage to multiple organs in the body. Nutritional management has a dramatic effect on growth and survival in CF patients. This study aimed to assess the nutritional status of Egyptian pediatric patients with CF before and after proper nutritional counseling and supplementation.
METHODS: This is an interventional observational study conducted on fifty children with CF recruited from CF clinic, Children's Hospital, Cairo University. The patients were subjected to history taking, clinical examination, full nutritional assessment, including signs of vitamins deficiencies, Subjective global assessment (SGA), anthropometric measurements, laboratory assessment (complete blood count, kidney, liver function tests and Prealbumin as a nutritional marker). After the initial assessment all the patients were subjected to a proper nutritional plan plus vitamin and mineral supplementations then reassessed them after 3 months.
RESULTS: SGA showed that 60% of the patients had severe malnutrition, 62%, 78%, and 48% of the patients were below -2 Z score for height, weight, and BMI respectively which decreased to 45%, 40%, and 32% after nutritional supplementation. 43% of the patients were anemic, 29% were hypoalbuminemic, and 80% had low serum Prealbumin levels. After 3 months of follow up, only 17% had anemia, 11% had hypoalbuminemia, and 41% had low serum Prealbumin. Compliance was detected in 76% of caregivers during the follow up.
CONCLUSION: CF patients had considerable impairment in their nutritional status. Proper caloric intake and vitamin supplementation had a valuable impact on their growth and prognosis.

PMID: 31987118 [PubMed - in process]

An atypical acute exacerbation of COPD due to Aspergillus fumigatus.

Monaldi Arch Chest Dis. 2020 Jan 27;90(1):

Authors: Tetikkurt C, Kubat B, Tetikkurt S, Karakas G

Abstract
A 64-year-old male with a history of stabile chronic obstructive pulmonary disease (COPD) presented with increasing dyspnea and sputum for the last two months. Complete blood count showed WBC 14x103/ml, Hgb: 14.2 g/dL and eosinophilia. Blood biochemistry was normal. Chest x-ray showed hyperlucency while thorax computed tomography (CT) revealed obstructive lung disease and bronchiectasis. Pulmonary function tests demonstrated severe obstructive lung disease and a negative bronchoreversibility with a moderately reduced diffusing capacity/alveolar volume (DLCO/VA). ABG gases revealed significant hypoxemia. Sputum culture was negative. Total IgE was 1140 ng/ml. Aspergillus RAST, precipitins and aspergillusgalactomannan antigen were positive. CF genetic screening tests gave negative results. Allergic bronchopulmonary aspergillosis  (ABPA) is a hypersensitivity reaction that occurs due to bronchial aspergillus colonization. It is most common in patients with asthma and cystic fibrosis. We present a COPD case with an acute exacerbation due to Aspergillus fumigatus that lead to an aberrant clinical profile unresponsive to conventional treatment. Clinicians should consider Aspergillus fumigatus as an etiologic agent in an atypical and severe COPD exacerbation.

PMID: 31986874 [PubMed - in process]

Brown Bowel Syndrome: A Multi-institutional Case Series.

Am J Surg Pathol. 2020 Jan 23;:

Authors: Arnold CA, Burke AP, Calomeni E, Mayer RC, Rishi A, Singhi AD, Stashek K, Voltaggio L, Tondon R

Abstract
Brown bowel syndrome (BBS) is a rare condition associated with vitamin E deficiency and defined by prominent lipofuscin deposition in the muscularis propria. Eight unique cases of BBS were identified: 5 men and 3 women (mean age=58.6 y). Pertinent comorbidities included bariatric surgery=2, malnourishment=2, Crohn=2, cystic fibrosis=1, alcohol and cocaine abuse=1, and prior small bowel resections=1. Presenting symptoms included abdominal pain=3, bleeding=1, nausea and vomiting=1, and nonresponsiveness=1. Imaging studies were often abnormal: thickened bowel wall=3 (1 with a mass), small bowel obstruction=2, and edematous and dilated bowel wall=2. Most specimens were surgical resections (n=7, autopsy=1): extended right colectomy=2, small bowel only=5 (terminal ileum=3, jejunum=2). Two specimens were grossly described as mahogany, and 1 case contained a perforation. Histologic sections of all cases showed finely granular, brown cytoplasmic pigment in smooth muscle cells on hematoxylin and eosin. This pigment was most conspicuous in the muscularis propria (small bowel>colon), and it was not identified in the mucosa. The pigment was reactive with Fontana-Masson, carbol lipofuscin, Periodic acid-Schiff, and Periodic acid-Schiff with diastase, and electron microscopy was compatible with lipofuscin. The mean clinical follow-up was 208 weeks: 1 patient died of complications of encephalitis, the others were alive and well. BBS is important to recognize because it is linked with malnutrition, specifically vitamin E deficiency, and it can (rarely) clinically simulate malignancy. The diagnosis is based on the identification of the lipofuscin pigment in the cytoplasm of smooth muscle cells, which is most easily seen in the muscularis propria of the small bowel.

PMID: 31985498 [PubMed - as supplied by publisher]

Intraclonal competitive fitness of longitudinal cystic fibrosis Pseudomonas aeruginosa airway isolates in liquid cultures.

Environ Microbiol. 2020 Jan 26;:

Authors: Cramer N, Fischer S, Hedtfeld S, Dorda M, Tümmler B

Abstract
The metabolically versatile Pseudomonas aeruginosa inhabits biotic and abiotic environments including the niche of cystic fibrosis (CF) airways. This study investigated how the adaptation to CF lungs affects the within-clone fitness of P. aeruginosa to grow and persist in liquid cultures in the presence of the clonal ancestors. Longitudinal clonal P. aeruginosa isolates that had been collected from 12 CF donors since the onset of colonization for up to 30 years were subjected to within-clone competition experiments. The relative quantities of individual strains were determined by marker-free amplicon sequencing of multiplex PCR products of strain-specific nucleotide sequence variants, a novel method that is generally applicable to studies in evolutionary genetics and microbial ecology with real-world strain collections. For ten of the twelve examined patient courses, P. aeruginosa isolates of the first years of colonization grew faster in the presence of their clonal progeny than alone. Single growth of individual strains showed no temporal trend with colonization time, but in co-culture the early isolates out-competed their clonal progeny. Irrespective of the genetic make-up of the clone and its genomic microevolution in CF lungs the early isolates expressed fitness traits to win the within-clone competition that were absent in their progeny. This article is protected by copyright. All rights reserved.

PMID: 31985137 [PubMed - as supplied by publisher]

CFTR deletion affects mouse osteoblasts in a gender-specific manner.

J Cell Physiol. 2020 Jan 27;:

Authors: Orlando V, Morin G, Laffont A, Lénart D, Solórzano Barrera C, Mustafy T, Sankhe S, Villemure I, Mailhot G

Abstract
Advancements in research and care have contributed to increase life expectancy of individuals with cystic fibrosis (CF). With increasing age comes a greater likelihood of developing CF bone disease, a comorbidity characterized by a low bone mass and impaired bone quality, which displays gender differences in severity. However, pathophysiological mechanisms underlying this gender difference have never been thoroughly investigated. We used bone marrow-derived osteoblasts and osteoclasts from Cftr+/+ and Cftr-/- mice to examine whether the impact of CF transmembrane conductance regulator (CFTR) deletion on cellular differentiation and functions differed between genders. To determine whether in vitro findings translated into in vivo observations, we used imaging techniques and three-point bending testing. In vitro studies revealed no osteoclast-autonomous defect but impairment of osteoblast differentiation and functions and aberrant responses to various stimuli in cells isolated from Cftr-/- females only. Compared with wild-type controls, knockout mice exhibited a trabecular osteopenic phenotype that was more pronounced in Cftr-/- males than Cftr-/- females. Bone strength was reduced to a similar extent in knockout mice of both genders. In conclusion, we find a trabecular bone phenotype in Cftr-/- mice that was slightly more pronounced in males than females, which is reminiscent of the situation found in patients. However, at the osteoblast level, the pathophysiological mechanisms underlying this phenotype differ between males and females, which may underlie gender differences in the way bone marrow-derived osteoblasts behave in absence of CFTR.

PMID: 31985038 [PubMed - as supplied by publisher]

Hospitalization rates among patients with cystic fibrosis using pancreatic enzyme replacement therapy.

Chron Respir Dis. 2020 Jan-Dec;17:1479973119900612

Authors: Trapnell BC, Chen S, Khurmi R, Bodhani A, Kapoor M, Haupt M

Abstract
We investigated the relationship between self-reported adherence to pancreatic enzyme replacement therapy (PERT), nutritional status, and all-cause hospitalization in cystic fibrosis (CF) patients with a record of PERT use. Association of self-reported annual PERT use rate (adherence) with annual hospital admission rate (HAR) and annual total hospital nights (THNs) were analyzed for 5301 children (2000-2012) and 13,989 adults (2000-2013) from the CF Foundation Patient Registry. Multivariate linear regression was used to determine the association of HAR and THN with mean annual PERT use rate, cumulative PERT use rate, mean body mass index (BMI) (adult) or BMI percentile (pediatric), age, and sex. The median annual PERT use rate was 87% in children and 80% in adults. Statistically, higher annual PERT use, longer cumulative PERT, and higher BMI percentile (children) or BMI (adults) were significantly (p < 0.0001) associated with lower annual HAR and fewer annual THN in children and adults. Female sex was associated with higher annual HAR and more annual THN in children and adults (p < 0.05). Results indicate self-reported adherence to PERT, increased BMI, and male sex were associated with fewer hospital admissions and annual hospital nights in CF patients.

PMID: 31984768 [PubMed - in process]

Efficacy and safety of ataluren in patients with nonsense-mutation cystic fibrosis not receiving chronic inhaled aminoglycosides: The international, randomized, double-blind, placebo-controlled Ataluren Confirmatory Trial in Cystic Fibrosis (ACT CF).

J Cyst Fibros. 2020 Jan 23;:

Authors: Konstan MW, VanDevanter DR, Rowe SM, Wilschanski M, Kerem E, Sermet-Gaudelus I, DiMango E, Melotti P, McIntosh J, De Boeck K, ACT CF Study Group

Abstract
BACKGROUND: Ataluren was developed for potential treatment of nonsense-mutation cystic fibrosis (CF). A previous phase 3 ataluren study failed to meet its primary efficacy endpoint, but post-hoc analyses suggested that aminoglycosides may have interfered with ataluren's action. Thus, this subsequent trial (NCT02139306) was designed to assess the efficacy and safety of ataluren in patients with nonsense-mutation CF not receiving aminoglycosides.
METHODS: Eligible subjects with nonsense-mutation CF (aged ≥6 years; percent predicted (pp) FEV1 ≥40 and ≤90) from 75 sites in 16 countries were randomly assigned in double-blinded fashion to receive oral ataluren or matching placebo thrice daily for 48 weeks. The primary endpoint was absolute change in average ppFEV1 from baseline to the average of Weeks 40 and 48.
FINDINGS: 279 subjects were enrolled; 138 subjects in the ataluren arm and 136 in the placebo arm were evaluable for efficacy. Absolute ppFEV1 change from baseline did not differ significantly between the ataluren and placebo groups at Week 40 (-0.8 vs -1.8) or Week 48 (-1.7 vs -2.4). Average ppFEV1 treatment difference from baseline to Weeks 40 and 48 was 0.6 (95% CI -1.3, 2.5; p = 0.54). Pulmonary exacerbation rate per 48 weeks was not significantly different (ataluren 0.95 vs placebo 1.13; rate ratio p = 0.40). Safety was similar between groups. No life-threatening adverse events or deaths were reported.
INTERPRETATION: Neither ppFEV1 change nor pulmonary exacerbation rate over 48 weeks were statistically different between ataluren and placebo groups. Development of a nonsense-mutation CF therapy remains elusive.

PMID: 31983658 [PubMed - as supplied by publisher]

Regulation effects of naringin on diesel particulate matter-induced abnormal airway surface liquid secretion.

Phytomedicine. 2019 Oct;63:153004

Authors: Shi R, Su WW, Zhu ZT, Guan MY, Cheng KL, Fan WY, Wei GY, Li PB, Yang ZY, Yao HL

Abstract
BACKGROUND: PM2.5 is closely related to the incidence and mortality of respiratory diseases. Diesel particulate matter (DPM) is the main component of particulate air pollution and an important source of PM2.5.
HYPOTHESIS/PURPOSE: This study mainly explored the effect of DPM on airway surface liquid (ASL) secretion and the regulation of naringin in this process, to evaluate therapeutic potentials of naringin for the treatment of abnormal secretion of the respiratory tract caused by PM2.5.
METHODS: The concentration of lysozyme was measured by Lysozyme Assay Kit. Total protein content was determined by the BCA Protein Assay Kit. The concentration of cAMP and MUC5AC, expressions of CFTR, AQP1, and AQP5 proteins were measured by ELISA. Expressions of CFTR, AQP1 and AQP5 mRNA were determined by qPCR. Amount of CFTR on the cell membrane was determined by immunofluorescence.
RESULTS: The in vitro and in vivo studies had indicated that DPM could inhibit ASL secretion and increased the viscosity of the liquid. Naringin had the functions to attenuate DPM-induced injury, reduce liquid viscosity by reducing MUC5AC and total protein secretion, increase DPM-induced CFTR, AQP1, and AQP5 mRNA and protein expression, positively regulate apical CFTR insertion and promote CFTR activation by increasing intracellular cAMP.
CONCLUSION: These results demonstrated that naringin had regulating effects on the DPM-induced abnormal secretion of the respiratory tract.

PMID: 31301536 [PubMed - indexed for MEDLINE]

Prenatal diagnosis of Pallister-Killian syndrome.

Ultrasound Obstet Gynecol. 2019 Jul;54(1):137-138

Authors: Santos W, Carneiro MS, do Amaral WN

PMID: 30125405 [PubMed - indexed for MEDLINE]

Identification of Mycobacterium porcinum in patients with cystic Fibrosis: Pathogen or contaminant?

J Cyst Fibros. 2020 Jan 22;:

Authors: Paul GR, Leber A, Nemastil CJ, Novak KJ, Brady M, Stack-Simone S, Greninger AL, Antonara S

Abstract
BACKGROUND: Mycobacterium porcinum is a non-tuberculous mycobacterium (NTM) identified in potable water. The identification and clinical impact of M. porcinum in patients with cystic fibrosis (CF) has not been described. In our institution, M. porcinum was isolated exclusively during hospitalization in a cluster of patients with CF.
METHODS: Patients with CF who were hospitalized between September 2016 and September 2018 and could expectorate sputum were included, and samples were processed per institutional guidelines. Post-hospitalization and one-year clinical outcomes on those who isolated M. porcinum in respiratory cultures were reviewed. Whole genome sequencing was performed on M. porcinum isolates obtained from patients and environmental sources to identify source of acquisition.
RESULTS: Review of 14 CF patients with 16 M. porcinum isolates revealed rapid time to culture positivity within 0.8 (0.04-8.0) days after admission. M. porcinum was isolated in teenagers and adults irrespective of baseline pulmonary function, body mass index, or CF genotype. Whole genome sequencing suggested all isolates belong to the same M. porcinum strain and confirmed the source of acquisition to the ice machine. Review of patients' clinical course, including three patients who underwent lung transplantation, suggested a pseudo-outbreak with minimal clinical impact.
CONCLUSIONS: NTM, including M. porcinum, are ubiquitous in potable water and institutional water reservoirs. Our findings suggest M. porcinum is a transient colonizer rather than a pathogen. Challenges exist in discerning the role of NTM as a contributor of pulmonary morbidity in patients with CF, and adherence to established guidelines regarding NTM related pulmonary disease remains important.

PMID: 31982335 [PubMed - as supplied by publisher]

Overweight, obesity and significant weight gain in adult patients with cystic fibrosis association with lung function and cardiometabolic risk factors.

Clin Nutr. 2020 Jan 10;:

Authors: Bonhoure A, Boudreau V, Litvin M, Colomba J, Bergeron C, Mailhot M, Tremblay F, Lavoie A, Rabasa-Lhoret R

Abstract
BACKGROUND: For patients with cystic fibrosis (CF), maintaining a normal BMI is associated with better pulmonary function (FEV1) and survival. Given therapy improvements, some patients are now overweight, obese or present rapid weight gain. However, the impact of being overweight on clinical outcomes (e.g. FEV1 & metabolic complications) remains unknown.
METHODS: Baseline data from 290 adult CF patients and observational follow-up (3.5 years; n = 158) were collected. BMI categories: underweight (UW < 18.5 kg/m2), normal (NW 18.5-26.9 kg/m2), and overweight/obese (OW ≥ 27 kg/m2). Follow-up data (weight change over time): weight loss (WL>10%), stable (WS), and weight gain (WG>10%). BMI categories and follow-up data were compared to FEV1 and cardiometabolic parameters: glucose tolerance, estimated insulin resistance (IR), blood pressure (BP), and lipid profile.
RESULTS: For BMI categories, 35 patients (12.1%) were UW, 235 (81.0%) NW, and 20 (6.9%) OW. Compared to UW and NW patients, OW patients are older (p < 0.001), had less pancreatic insufficiency (p = 0.009), a higher systolic BP (p = 0.004), higher LDL (p < 0.001), and higher IR (p < 0.001). Compared to UW patients, OW patients had a better FEV1 (p < 0.001). For weight change, WL was observed in 7 patients (4.4%), WS in 134 (84.8%) and WG in 17 patients (10.8%). Compared to WL and WS patients, WG patients had a 5% increase in FEV1 accompanied by higher IR (p = 0.017) and triglycerides (p < 0.001). No differences were observed for glucose tolerance for neither BMI nor weight change.
CONCLUSION: A higher weight or weight gain over time are associated with a better FEV1 but also some unfavorable cardiometabolic trends.

PMID: 31982192 [PubMed - as supplied by publisher]

Enteral nutrition in cystic fibrosis

Wiad Lek. 2019 Oct 31;72(10):1890-1893

Authors: Kędzior A, Łabuz-Roszak B, Jezierska S

Abstract
Introduction: Cystic fibrosis is a genetically determined disease. It is currently detected right after birth thanks to a screening program. This early detection allows for quick treatment inclusion. Cystic fibrosis therapy has a comprehensive character. The way of nutrition is also very important. The aim of this study was to evaluate the benefits and risks of enteral nutrition in patients with cystic fibrosis.
Material and methods: 53 people with cystic fibrosis participated in the study (15 men, 38 women). Qualification for the study required the fulfillment of three conditions: enteral nutrition used for at least one month, no increase in body weight when using a high energy diet, underweight. The research was carried with use of self-constructed questionnaire.
Results: The mean age of the respondents was 19.9 ± 4 years. The median weight gain after enteral nutrition was 7 kg. Most (n = 42, 79.2%) did not report any side effects. Few reported local infections (n = 9; 17%) or prolapse of the balloon (n = 2, 3.8%). On the other hand, everyone reported benefits - it was mainly weight gain and improved quality of life. In some cases (n = 22, 41.5%) with the use of enteral nutrition, a decrease in the frequency of respiratory infections was observed.
Conclusions: Enteral nutrition is a beneficial method in those patients with cystic fibrosis, in whom high-energy oral nutrition is inefficient.

PMID: 31982008 [PubMed - as supplied by publisher]

Nanograss sensor for selective detection of Pseudomonas aeruginosa by pyocyanin identification in airway samples.

Anal Biochem. 2020 Jan 22;:113586

Authors: AlZahra'a Alatraktchi F, Dimaki M, Støvring N, Johansen HK, Molin S, Svendsen WE

Abstract
Pyocyanin is a virulence factor solely produced by the pathogen Pseudomonas aeruginosa. Pyocyanin is also a redox active molecule that can be directly detected by electrochemical sensing. A nanograss (NG) based sensor for sensitive quantification of pyocyanin in sputum samples from cystic fibrosis (CF) patients is presented here. The NG sensors were custom made in a cleanroom environment by etching nanograss topography on the electrode surface followed by depositing 200 nm gold. The NG sensors were utilized for amperometric quantification of pyocyanin in spiked hypertonic saline samples, resulting in a linear calibration curve with a R2 value of 0.9901 and a limit of detection of 172 nM. The NG sensors were applied in a small pilot test on five airway samples from five CF patients. The NG sensor was capable of identifying P. aeruginosa in the airway samples in 60 s without any sample pretreatment.

PMID: 31981486 [PubMed - as supplied by publisher]

Outcome of fetal echogenic bowel: a systematic review and meta-analysis.

Prenat Diagn. 2020 Jan 25;:

Authors: D'Amico A, Buca D, Rizzo G, Khalil A, Silvi C, Makatsariya A, Nappi L, Liberati M, D'Antonio F

Abstract
The main aim of this systematic review was to explore the outcome of fetuses with isolated echogenic bowel (EB) on antenatal ultrasound. Inclusion criteria were singleton pregnancies with isolated EB no associated major structural anomalies at the time of diagnosis. The outcomes observed were: chromosomal anomalies, cystic fibrosis, associated structural anomalies detected only at follow-up scans and at birth, regression during pregnancy, congenital infections, intra-uterine (IUD), neonatal (NND) and perinatal (PND) death. Twenty-five studies (12971 fetuses) were included. Chromosomal anomalies occurred in 3.3% of the fetuses, mainly Trisomy 21 and aneuploidies involving the sex chromosomes. Cystic fibrosis occurred in 2.2%. Congenital infections affected 2.2%, mainly congenital CMV infection. The majority of fetuses with EB experienced regression or disappearance of the EB at follow-up scans. Associated anomalies were detected at a follow-up scan in 1.8%. Associated anomalies were detected at birth and missed at ultrasound in 2.1% of cases. IUD occurred in 3.2% of cases while the corresponding figures for NND and PND were 0.4% and 3.1%. Fetuses with EB are at increased risk of adverse perinatal outcome, highlighting the need for a thorough antenatal management and post-natal follow-up. Assessment during pregnancy and after birth should be performed in order to look for signs of fetal aneuploidy, congenital infections and associated structural anomalies. This article is protected by copyright. All rights reserved.

PMID: 31981377 [PubMed - as supplied by publisher]