Expression of extracellular polysaccharides and proteins by clinical isolates of Pseudomonas aeruginosa in response to environmental conditions.

Int Microbiol. 2018 Sep;21(3):129-142

Authors: Lotfy WA, Atalla RG, Sabra WA, El-Helow ER

Abstract
The opportunistic pathogen Pseudomonas aeruginosa causes chronic respiratory infections in patients with cystic fibrosis (CF). Persistence of this bacterium is attributed to its ability to form biofilms which rely on an extracellular polymeric substance matrix. Extracellular polysaccharides (EPS) and secreted proteins are key matrix components of P. aeruginosa biofilms. Recently, nebulized magnesium sulfate has been reported as a significant bronchodilator for asthmatic patients including CF. However, the impact of magnesium sulfate on the virulence effect of P. aeruginosa is lacking. In this report, we investigated the influence of magnesium sulfate and other environmental factors on the synthesis of alginate and secretion of proteins by a mucoid and a non-mucoid strain of P. aeruginosa, respectively. By applying the Plackett-Burman and Box-Behnken experimental designs, we found that phosphates (6.0 g/l), ammonium sulfate (4.0 g/l), and trace elements (0.6 mg/l) markedly supported alginate production by the mucoid strain. However, ferrous sulfate (0.3 mg/l), magnesium sulfate (0.02 g/l), and phosphates (6.0 g/l) reinforced the secretion of proteins by the non-mucoid strain.

PMID: 30810953 [PubMed - in process]

RESPIRATORY IMPACT OF ELECTRONIC CIGARETTES AND "LOW-RISK" TOBACCO.

Rev Invest Clin. 2019;71(1):17-27

Authors: Thirión-Romero I, Pérez-Padilla R, Zabert G, Barrientos-Gutiérrez I

Abstract
Electronic cigarettes, handheld devices that generate an aerosol that may contain nicotine by heating a solution or e-liquid, have been increasingly used especially in the young population. The aerosol's composition is determined by temperature, and by the substances contained in the heated liquid: glycerin, propylene glycol, nicotine in variable concentrations, flavoring agents, and other non-nicotine compounds. >80 compounds (including known toxics, e.g., formaldehyde, acetaldehyde, metallic nanoparticles, and acrolein) have been found in e-liquid and aerosols. Airway irritation, mucus hypersecretion, and inflammatory response, including systemic changes, have been observed after the exposure to e-cigarettes, leading to an increase in respiratory symptoms and changes in respiratory function and the host defense mechanisms. E-cigarette has been linked with an increase of symptoms in individuals with asthma, cystic fibrosis, and chronic obstructive pulmonary disease. One of the major concerns in public health is the rise in e-cigarette experimentation among never-smokers, especially children and adolescents, which leads to nicotine addiction and increases the chances of becoming with time a conventional smoker. There is an urgent need to regulate e-cigarettes and electronic nicotine delivery systems, at least with the same restrictions to those applied to tobacco products, and not to consider them as harmless products.

PMID: 30810544 [PubMed - in process]

Non-visualization of fetal gallbladder (NVFGB) by ultrasound in second trimester of pregnancy: a systematic review of the literature on postnatal outcome.

Ultrasound Obstet Gynecol. 2019 Feb 27;:

Authors: di Pasquo E, Kuleva M, Rousseau A, Vitucci A, Sonigo P, Chardot C, Salomon LJ, Ville Y

Abstract
OBJECTIVES: To investigate the ultrasound characteristics and outcome in cases of non-visualization of fetal gallbladder (NVFGB) followed in our tertiary university hospital, and to provide a comprehensive review of literature on NVFGB.
METHODS: NVFGB was defined as non-visualization of the gallbladder at two targeted ultrasound (US) examinations within a 1-week period. Cases of NVFGB managed in our centre were revised and a systematic review of literature was performed. The incidence of chromosomal anomalies, later visualization of gallbladder, gallbladder agenesis, cystic fibrosis and biliary atresia in fetuses were assessed in isolated and non-isolated NVFGB.
RESULTS: 16 cases of NVFGB were followed in our centre, 10 (62.5%) of which were isolated. There was an incidence of 12.5% of biliary atresia and 12.5% of gallbladder agenesis, while no cystic fibrosis was reported. Gallbladder was visualized later in pregnancy or postnatally in 43.8% and 31.3% of cases, respectively. A total of 7 studies, including our cohort, concerning a total of 280 cases, met inclusion criteria for the systematic review. Overall, 20.6% of fetuses had associated ultrasound anomalies, the incidence of chromosomal anomalies in this group was 20.4%, while in cases with isolated NVFGB, incidence of chromosomal anomalies was 1.9%. In fetuses with normal karyotype and isolated NVFGB, gallbladder was later visualized in 70.4% of cases while the incidence of gallbladder agenesis, cystic fibrosis and biliary atresia was 25.2%, 3.1% and 4.8%, respectively. Negative predictive value (NPV) of amniotic fluid enzymes ranged between 94 and 100% for prediction of biliary atresia and cystic fibrosis in the included studies; after 22 weeks, NPV dropped to 88%.
CONCLUSION: In cases with persistent NVFGB, the risk of a severe postnatal condition should be considered. A detailed ultrasound scan should be offered and parents tested for cystic fibrosis. Invasive procedure for karyotyping, and liver enzymes concentrations before 22 weeks constitutes a reasonable work-up. This article is protected by copyright. All rights reserved.

PMID: 30809885 [PubMed - as supplied by publisher]

Correction: IFN-γ Stimulates Autophagy-Mediated Clearance of Burkholderia cenocepacia in Human Cystic Fibrosis Macrophages.

PLoS One. 2019;14(2):e0213092

Authors: Assani K, Tazi MF, Amer AO, Kopp BT

Abstract
[This corrects the article DOI: 10.1371/journal.pone.0096681.].

PMID: 30807600 [PubMed - in process]

Genetic association and transcriptome integration identify contributing genes and tissues at cystic fibrosis modifier loci.

PLoS Genet. 2019 Feb 26;15(2):e1008007

Authors: Gong J, Wang F, Xiao B, Panjwani N, Lin F, Keenan K, Avolio J, Esmaeili M, Zhang L, He G, Soave D, Mastromatteo S, Baskurt Z, Kim S, O'Neal WK, Polineni D, Blackman SM, Corvol H, Cutting GR, Drumm M, Knowles MR, Rommens JM, Sun L, Strug LJ

Abstract
Cystic Fibrosis (CF) exhibits morbidity in several organs, including progressive lung disease in all patients and intestinal obstruction at birth (meconium ileus) in ~15%. Individuals with the same causal CFTR mutations show variable disease presentation which is partly attributed to modifier genes. With >6,500 participants from the International CF Gene Modifier Consortium, genome-wide association investigation identified a new modifier locus for meconium ileus encompassing ATP12A on chromosome 13 (min p = 3.83x10-10); replicated loci encompassing SLC6A14 on chromosome X and SLC26A9 on chromosome 1, (min p<2.2x10-16, 2.81x10-11, respectively); and replicated a suggestive locus on chromosome 7 near PRSS1 (min p = 2.55x10-7). PRSS1 is exclusively expressed in the exocrine pancreas and was previously associated with non-CF pancreatitis with functional characterization demonstrating impact on PRSS1 gene expression. We thus asked whether the other meconium ileus modifier loci impact gene expression and in which organ. We developed and applied a colocalization framework called the Simple Sum (SS) that integrates regulatory and genetic association information, and also contrasts colocalization evidence across tissues or genes. The associated modifier loci colocalized with expression quantitative trait loci (eQTLs) for ATP12A (p = 3.35x10-8), SLC6A14 (p = 1.12x10-10) and SLC26A9 (p = 4.48x10-5) in the pancreas, even though meconium ileus manifests in the intestine. The meconium ileus susceptibility locus on chromosome X appeared shifted in location from a previously identified locus for CF lung disease severity. Using the SS we integrated the lung disease association locus with eQTLs from nasal epithelia of 63 CF participants and demonstrated evidence of colocalization with airway-specific regulation of SLC6A14 (p = 2.3x10-4). Cystic Fibrosis is realizing the promise of personalized medicine, and identification of the contributing organ and understanding of tissue specificity for a gene modifier is essential for the next phase of personalizing therapeutic strategies.

PMID: 30807572 [PubMed - as supplied by publisher]

AMP-activated protein kinase and adenosine are both metabolic modulators that regulate chloride secretion in the shark rectal gland ( Squalus acanthias).

Am J Physiol Cell Physiol. 2018 04 01;314(4):C473-C482

Authors: Neuman RI, van Kalmthout JAM, Pfau DJ, Menendez DM, Young LH, Forrest JN

Abstract
The production of endogenous adenosine during secretagogue stimulation of CFTR leads to feedback inhibition limiting further chloride secretion in the rectal gland of the dogfish shark (Squalus acanthias). In the present study, we examined the role of AMP-kinase (AMPK) as an energy sensor also modulating chloride secretion through CFTR. We found that glands perfused with forskolin and isobutylmethylxanthine (F + I), potent stimulators of chloride secretion in this ancient model, caused significant phosphorylation of the catalytic subunit Thr172 of AMPK. These findings indicate that AMPK is activated during energy-requiring stimulated chloride secretion. In molecular studies, we confirmed that the activating Thr172 site is indeed present in the α-catalytic subunit of AMPK in this ancient gland, which reveals striking homology to AMPKα subunits sequenced in other vertebrates. When perfused rectal glands stimulated with F + I were subjected to severe hypoxic stress or perfused with pharmacologic inhibitors of metabolism (FCCP or oligomycin), phosphorylation of AMPK Thr172 was further increased and chloride secretion was dramatically diminished. The pharmacologic activation of AMPK with AICAR-inhibited chloride secretion, as measured by short-circuit current, when applied to the apical side of shark rectal gland monolayers in primary culture. These results indicate that that activated AMPK, similar to adenosine, transmits an inhibitory signal from metabolism, that limits chloride secretion in the shark rectal gland.

PMID: 29351415 [PubMed - indexed for MEDLINE]

The bile acids, deoxycholic acid and ursodeoxycholic acid, regulate colonic epithelial wound healing.

Am J Physiol Gastrointest Liver Physiol. 2018 03 01;314(3):G378-G387

Authors: Mroz MS, Lajczak NK, Goggins BJ, Keely S, Keely SJ

Abstract
The intestinal epithelium constitutes an innate barrier which, upon injury, undergoes self-repair processes known as restitution. Although bile acids are known as important regulators of epithelial function in health and disease, their effects on wound healing processes are not yet clear. Here we set out to investigate the effects of the colonic bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA), on epithelial restitution. Wound healing in T84 cell monolayers grown on transparent, permeable supports was assessed over 48 h with or without bile acids. Cell migration was measured in Boyden chambers. mRNA and protein expression were measured by RT-PCR and Western blotting. DCA (50-150 µM) significantly inhibited wound closure in cultured epithelial monolayers and attenuated cell migration in Boyden chamber assays. DCA also induced nuclear accumulation of the farnesoid X receptor (FXR), whereas an FXR agonist, GW4064 (10 µM), inhibited wound closure. Both DCA and GW4064 attenuated the expression of CFTR Cl- channels, whereas inhibition of CFTR activity with either CFTR-inh-172 (10 µM) or GlyH-101 (25 µM) also prevented wound healing. Promoter/reporter assays revealed that FXR-induced downregulation of CFTR is mediated at the transcriptional level. In contrast, UDCA (50-150 µM) enhanced wound healing in vitro and prevented the effects of DCA. Finally, DCA inhibited and UDCA promoted mucosal healing in an in vivo mouse model. In conclusion, these studies suggest bile acids are important regulators of epithelial wound healing and are therefore good targets for development of new drugs to modulate intestinal barrier function in disease treatment. NEW & NOTEWORTHY The secondary bile acid, deoxycholic acid, inhibits colonic epithelial wound healing, an effect which appears to be mediated by activation of the nuclear bile acid receptor, FXR, with subsequent downregulation of CFTR expression and activity. In contrast, ursodeoxycholic acid promotes wound healing, suggesting it may provide an alternative approach to prevent the losses of barrier function that are associated with mucosal inflammation in IBD patients.

PMID: 29351391 [PubMed - indexed for MEDLINE]

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Bone involvement in young adults with cystic fibrosis awaiting lung transplantation for end-stage respiratory failure.

Osteoporos Int. 2019 Feb 23;:

Authors: Cairoli E, Eller-Vainicher C, Morlacchi LC, Tarsia P, Rossetti V, Pappalettera M, Arosio M, Chiodini I, Blasi F

Abstract
Patients with cystic fibrosis awaiting lung transplantation for end-stage respiratory failure have high prevalence of reduced bone mineral density and fragility fracture. Suboptimal 25-hydroxyvitamin D levels could significantly contribute to the development of cystic fibrosis-related bone disease.
INTRODUCTION: The assessment of the prevalence of cystic fibrosis-related bone disease (CFBD) and its associated risk factors in young adults with cystic fibrosis (CF) awaiting lung transplantation for end-stage respiratory failure.
METHODS: Clinical characteristics, bone mineral density (BMD), the parameters of calcium metabolism, including vitamin D (25OHVitD) levels, and the presence of fragility fractures were evaluated in 42 CF patients (24 females, age 34.0 ± 8.4 years) consecutively referred as lung transplant candidates.
RESULTS: Mean 25OHVitD levels (54.9 ± 26.2 nmol/L) were below the reference range and hypovitaminosis D (25OHVitD < 75 nmol/L) was found in 34 patients (81%) and daily calcium intakes (median 550 mg/day) were lower than recommended. A BMD below the expected range for age (Z-score of - 2.0 or lower) and at least one prevalent fragility fracture were found in 22 patients (52.4%) and 18 patients (45.2%), respectively. The coexistence of low BMD and the presence of fracture was observed in 13 patients (31.0%). In these patients, the prevalence of nephrolithiasis was higher than in the remaining ones (p = 0.046). The presence of kidney stones was associated with a worse bone status and with severe vitamin D deficiency. In the whole sample, femoral BMD Z-scores were directly correlated with albumin-adjusted calcium (p < 0.05) and 25OHVitD levels (p < 0.01).
CONCLUSIONS: Despite the improvement of CF care, CFBD is still highly prevalent in young adults awaiting lung transplantation for end-stage CF. Suboptimal 25OHVitD levels could significantly contribute to the development of CFBD. The presence of nephrolithiasis could be an additional warning about the need for a careful evaluation of bone health in CF patients.

PMID: 30798331 [PubMed - as supplied by publisher]

Origins of growth deficiencies in cystic fibrosis.

Thorax. 2019 Feb 23;:

Authors: Le TN, Schechter MS

PMID: 30798253 [PubMed - as supplied by publisher]

Cystic fibrosis: We see fungus among us, but should we care?

J Cyst Fibros. 2019 Feb 20;:

Authors: Hong G, Lechtzin N

PMID: 30797724 [PubMed - as supplied by publisher]

The role of SLC9A3 in Taiwanese patients with congenital bilateral absence of vas deferens (CBAVD).

J Formos Med Assoc. 2019 Feb 20;:

Authors: Chiang HS, Wang YY, Lin YH, Wu YN

Abstract
Congenital bilateral absence of vas deferens (CBAVD) is a special entity in obstructive azoospermia. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are involved in Taiwanese CBAVD but most heterozygous 5T variant. The solute carrier family 9 isoform 3 (SLC9A3) is the Na+/H+ exchanger, which interacts with CFTR and regulates the Ca2+ homeostasis. Loss of SLC9A3 decreases CFTR protein and causes obstructive azoospermia in mice. It also causes mal-reabsorption by the efferent tubules, which leads to the obstructive phenomenon and eventually results in testicular atrophy. In 6-month old SLC9A3 deficiency mice, the atrophy of their vas deferens and seminal vesicles become more prominent. Decreases of CFTR expression in the reproductive organ in the SLC9A3 deficient (-/-) mice prove the interaction between CFTR and SLC9A3 in the reproductive tract. Most of Taiwanese CBAVD have at least one variant of SLC9A3 deletion and CFTR IVS8-5T, which co-contribute to Taiwanese CBAVD. The report indicates SLC9A3 deficiency can reverse the pathological changes in the gastrointestinal tract of CF mice. Further research can explore the definite mechanism of SLC9A3 and its role interacting with CFTR in different organ systems, which can contribute to novel treatment for the patients with cystic fibrosis and CBAVD.

PMID: 30797621 [PubMed - as supplied by publisher]

Changes in microbiome diversity following beta-lactam antibiotic treatment are associated with therapeutic versus subtherapeutic antibiotic exposure in cystic fibrosis.

Sci Rep. 2019 Feb 22;9(1):2534

Authors: Hahn A, Fanous H, Jensen C, Chaney H, Sami I, Perez GF, Koumbourlis AC, Louie S, Bost JE, van den Anker JN, Freishtat RJ, Zemanick ET, Crandall KA

Abstract
In persons with cystic fibrosis (CF), decreased airway microbial diversity is associated with lower lung function. Conflicting data exist on the impact of short-term antibiotics for treatment of acute pulmonary exacerbations. However, whether differences in antibiotic exposure impacts airway microbiome changes has not been studied. We hypothesized that subtherapeutic beta-lactam antibiotic exposure, determined by the pharmacokinetics and pharmacodynamics (PK/PD) after intravenous (IV) antibiotic administration, would be associated with different patterns of changes in CF airway microbial diversity. Eligible children were enrolled when well; study assessments were performed around the time of pulmonary exacerbation. Plasma drug concentrations and bacterial minimum inhibitory concentrations (MICs) were used to determine therapeutic versus subtherapeutic beta-lactam antibiotic exposure. Respiratory samples were collected from children, and extracted bacterial DNA was amplified for the V4 region of the 16S rRNA gene. Twenty children experienced 31 APEs during the study; 45% (n = 14) of antibiotic courses were deemed therapeutic. Those in the therapeutic group had more significant decreases in alpha diversity at end of treatment and post-recovery compared to baseline than those in the subtherapeutic group. Therapeutic and subtherapeutic beta-lactam use is associated with different patterns of changes in CF airway microbial diversity following antibiotic administration.

PMID: 30796252 [PubMed - in process]

Interprofessional provider educational needs and preferences regarding the provision of sexual and reproductive health care in cystic fibrosis.

J Cyst Fibros. 2019 Feb 19;:

Authors: Kazmerski TM, Nelson EB, Newman LR, Haviland MJ, Luff D, Leichtner AM, Hayes MM, Miller E, Emans SJ, Sawicki GS

Abstract
BACKGROUND: Sexual and reproductive health (SRH) is an important disease-specific concern for adolescent and young adult (AYA) women that is not consistently addressed in cystic fibrosis (CF) centers. This study identifies educational needs and preferences of interprofessional CF providers regarding SRH in AYA women with CF.
METHODS: Interprofessional CF providers participated in an anonymous survey regarding general and CF-specific SRH knowledge and skills, factors for optimizing SRH care, and preferred approaches for SRH training. We calculated descriptive statistics for all respondents and stratified by provider type.
RESULTS: A total of 523 providers completed the survey (39% physicians/advanced practice providers, 19% nurses, 20% social workers, and 22% other disciplines). Half reported comfort responding to female AYA SRH concerns; however, only one-third were comfortable asking appropriate questions and confident taking a sexual history. Only 29% were comfortable with their current CF-specific SRH knowledge. Respondents' preferred SRH topics for further training included: pregnancy/parenthood planning, sexual functioning, urinary incontinence, intimate partner violence, and taking a sexual history. Nearly two-thirds felt having connection to women's health specialists familiar with CF would facilitate SRH care. Approximately one-third desired SRH educational materials for providers to view at point-of-care or through online case-based learning; <10% were interested in role playing SRH skills.
CONCLUSION: Many interprofessional CF providers lack comfort and skills in addressing SRH with AYA women with CF. Provider training needs and approaches identified in this study can be used to develop tailored educational interventions to improve comprehensive CF care.

PMID: 30795973 [PubMed - as supplied by publisher]

A first approach for an evidence-based in vitro digestion method to adjust pancreatic enzyme replacement therapy in cystic fibrosis.

PLoS One. 2019;14(2):e0212459

Authors: Calvo-Lerma J, Fornés-Ferrer V, Peinado I, Heredia A, Ribes-Koninckx C, Andrés A

Abstract
BACKGROUND: Patients with cystic fibrosis have to take enzymatic supplements to allow for food digestion. However, an evidence-based method to adjust Pancreatic Enzyme Replacement Therapy (PERT) is inexistent, and lipid content of meals is used as a rough criterion.
OBJECTIVE: In this study, an in vitro digestion model was set up to determine the theoretical optimal dose (TOD) of enzymatic supplement for a selection of foods, which is the dose that allows for maximum lipolysis extent.
METHODS: A static in vitro digestion model was applied to simulate digestion of eight foods covering a wide range of lipid contents. First, the dose of the enzymatic supplement was fixed at 2000 lipase units per gram of fat (LU/g fat) using intestinal pH and bile salt concentration as variables. Second, intestinal pH and bile salt concentrations were fixed and the variable was the dose of the enzymatic supplement. Lipolysis extent was determined by measuring the free fatty acids released from initial triglycerides content of foods after digestion. Results in terms of percentage of lipolysis extent were fitted into a linear-mixed segmented model and the deducted equations were used to predict the TOD to reach 90% of lipolysis in every food. In addition, the effect of intestinal pH and bile salt concentration were investigated.
RESULTS: The predictive equations obtained for the assessed foods showed that lipolysis was not only dependent on the dose of the enzyme supplement or the lipid content. Moreover, intestinal pH and bile salt concentration had significant effects on lipolysis. Therefore an evidence-based model can be developed taking into account these variables.
CONCLUSIONS: Depending on food characteristics, a specific TOD should be assigned to achieve an optimal digestion extent. This work represents a first step towards an evidence-based method for PERT dosing, which will be applied in an in vivo setting to validate its efficacy.

PMID: 30794618 [PubMed - in process]

Is there a place for dornase alfa therapy in lung transplantation?

Transpl Int. 2019 Feb 21;:

Authors: Harlander M, Vos R, Kneževič I

Abstract
Dornase alfa is a DNase, produced by recombinant gene technology, that digests extracellular deoxyribonucleic acid (DNA). Nebulized dornase alfa exerts a mucolytic effect. It is indicated for use in cystic fibrosis (CF) which is characterised by the presence of viscous purulent airways secretions rich in highly polymerized DNA. By cleaving DNA, it makes mucus less viscous and easier to expectorate. Compared to placebo, in CF patients dornase alfa improves lung function and reduces number of exacerbations (1). This article is protected by copyright. All rights reserved.

PMID: 30793383 [PubMed - as supplied by publisher]

Association Between Diverticular Disease Requiring Surgical Intervention and Mortality in The Post-Lung Transplant Population - a retrospective cohort study.

Transpl Int. 2019 Feb 21;:

Authors: Tague LK, Adams W, Young KA, Kwon OJ, Mahoney E, Lowery EM

Abstract
BACKGROUND: Lung Transplant recipients are at increased risk of complicated diverticular disease. We aim to assess the rate of diverticular surgery in a post-lung transplantation population and identify risk factors for surgery.
METHODS: We performed a retrospective cohort study of lung transplant recipients from 2007-2011. Demographic variables were evaluated with the Mann Whitney U and chi-squared tests. Cox regression was performed to evaluate 1- and 2-yr landmark survival, assess predictor variables of diverticular surgery and evaluate impact of surgery on CLAD development.
RESULTS: 17 of 158 patients (10.7%) underwent diverticular-related surgery. Surgical patients had significantly worse survival than nonsurgical patients at 1yr [aHR 2.93 (1.05-8.21), p = 0.041] and 2yr [aHR 4.17 (1.26-13.84), p=0.020] landmark analyses. Transplant indication of alpha-1 antitrypsin disease and cystic fibrosis were significantly associated with the need for diverticular surgery. Emergent surgery was associated with poorer survival [aHR 5.12(1.00-26.27), p=0.050].
CONCLUSIONS: Lung transplant patients requiring surgery for complicated diverticular disease have significantly poorer survival than those who do not require surgery. Surgery was more common in patients transplanted for A1AT and CF. Optimal assessment and risk stratification of diverticular disease is necessary to prevent excessive morbidity and mortality following transplantation. This article is protected by copyright. All rights reserved.

PMID: 30793380 [PubMed - as supplied by publisher]

Vitamin D for the Immune System in Cystic Fibrosis (DISC): a double-blind, multicenter, randomized, placebo-controlled clinical trial.

Am J Clin Nutr. 2019 Feb 22;:

Authors: Tangpricha V, Lukemire J, Chen Y, Binongo JNG, Judd SE, Michalski ES, Lee MJ, Walker S, Ziegler TR, Tirouvanziam R, Zughaier SM, Chesdachai S, Hermes WA, Chmiel JF, Grossmann RE, Gaggar A, Joseph PM, Alvarez JA

Abstract
BACKGROUND: Patients with cystic fibrosis (CF) have increased risk of vitamin D deficiency owing to fat malabsorption and other factors. Vitamin D deficiency has been associated with increased risk of pulmonary exacerbations of CF.
OBJECTIVES: The primary objective of this study was to examine the impact of a single high-dose bolus of vitamin D3 followed by maintenance treatment given to adults with CF during an acute pulmonary exacerbation on future recurrence of pulmonary exacerbations.
METHODS: This was a multicenter, double-blind, placebo-controlled, intent-to-treat clinical trial. Subjects with CF were randomly assigned to oral vitamin D3 given as a single dose of 250,000 International Units (IU) or to placebo within 72 h of hospital admission for an acute pulmonary exacerbation, followed by 50,000 IU of vitamin D3 or an identically matched placebo pill taken orally every other week starting at 3 mo after random assignment. The primary outcome was the composite endpoint of the time to next pulmonary exacerbation or death within 1 y. The secondary outcomes included circulating concentrations of the antimicrobial peptide cathelicidin and recovery of lung function as assessed by the percentage of predicted forced expiratory volume in 1 s (FEV1%).
RESULTS: A total of 91 subjects were enrolled in the study. There were no differences between the vitamin D3 and placebo groups in time to next pulmonary exacerbation or death at 1 y. In addition, there were no differences in serial recovery of lung function after pulmonary exacerbation by FEV1% or in serial concentrations of plasma cathelicidin.
CONCLUSIONS: Vitamin D3 initially given at the time of pulmonary exacerbation of CF did not alter the time to the next pulmonary exacerbation, 12-mo mortality, serial lung function, or serial plasma cathelicidin concentrations. This trial was registered at clinicaltrials.gov as NCT01426256.

PMID: 30793177 [PubMed - as supplied by publisher]

Successful Treatment of Scedosporium Sinusitis in Two Lung Transplant Recipients: Review of the Literature and Recommendations for Management.

Allergy Rhinol (Providence). 2019 Jan-Dec;10:2152656719827253

Authors: Ference EH, Kubak BM, Zhang P, Suh JD

Abstract
Background: Scedosporium fungal infection is an emerging disease which is difficult to diagnose and treat. Patients undergoing lung transplant may be colonized prior to transplantation and are at risk for lethal allograft infection after transplantation.
Objectives: To identify and evaluate treatment options.
Methods: This study is a retrospective review of patients treated at a tertiary academic medical center from 2007 to 2017 with positive sinonasal cultures. A review of the literature was also performed to identify additional cases.
Results: Two lung transplant patients had a positive culture for Scedosporium. The literature search resulted in 37 citations, which yielded only 2 prior cases of Scedosporium paranasal sinus colonization or infection in lung transplant recipients. Three of the 4 patients had cystic fibrosis. Two of the patients were colonized before initial transplant, while 1 patient was colonized before subsequent transplant. Three of the 4 patients survived, and all 3 had disease isolated to their sinuses and lungs treated with sinus surgery, while the fourth had disseminated disease and did not undergo sinus surgery. All patients were treated with multiple antifungals due to resistance patterns. One surviving patient cleared both sinus and lung cultures in less than 1 month, while the other 2 surviving patients achieved negative cultures after a minimum of 6 months.
Conclusions: Surgery may be especially important in patients with fungal sinus colonization or infection before or after lung transplantation. Chronic sinusitis is an important source for persistent fungal colonization and reinfection of the allograft which could be removed with surgical debridement before causing highly morbid pulmonary disease.

PMID: 30792939 [PubMed]

Repeated hot water and steam disinfection of pari LC Plus® nebulizers alters nebulizer output.

J Cyst Fibros. 2019 Feb 18;:

Authors: Collins MS, Murray TS

PMID: 30792172 [PubMed - as supplied by publisher]