Interpretation of Cystic Fibrosis Centre rankings: Meaningful comparisons or biased statistics?

J Cyst Fibros. 2017 Aug 04;:

Authors: Stanojevic S

PMID: 28781231 [PubMed - as supplied by publisher]

The role of imaging in the diagnosis of bronchiectasis: the key is in the distribution.

Radiologia. 2017 Aug 03;:

Authors: Bueno J, Flors L

Abstract
Diseases that involve the medium caliber airways (segmental and subsegmental bronchi) are common and present clinically with nonspecific respiratory symptoms such as cough, recurrent respiratory infections and occasionally, hemoptysis. The abnormal and irreversible dilation of bronchi is known as "bronchiectasis". The diagnosis can be challenging and the analysis of the regional distribution of the bronchiectasis is the most useful diagnostic guide. The objective of this manuscript is to describe the main imaging findings of bronchiectasis and their classification, review the diseases that most commonly present with this abnormality, and provide an approach to the diagnosis based on their imaging appearance and anatomic distribution. Bronchiectasis is a frequent finding that may result from a broad range of disorders. Imaging plays a paramount role in diagnosis, both in the detection and classification, and in the diagnosis of the underlying pathology.

PMID: 28781148 [PubMed - as supplied by publisher]

The use of pulmonary clearance medications in the acutely ill patient.

Expert Rev Respir Med. 2017 Aug 07;:

Authors: Papacostas MF, Luckett P, Hupp S

Abstract
INTRODUCTION: Retention of airway secretions occurs in disease, leading to airway plugging, atelectasis, and worsened respiratory mechanics, making airway clearance an important therapeutic target. Areas Covered: Many medications designed to enhance clearance of airway secretions are available. We will review the medications available to enhance airway clearance, their mechanisms of action, and the evidence available for their use in acutely ill patients. Expert Commentary: In the cystic fibrosis (CF) population, beneficial effects have been shown in pulmonary function with the use of some of these agents. In the non-CF population, there is limited evidence regarding these medications. While some studies have found benefit, the quality of evidence is low, making it difficult to draw conclusions. While certain patients may derive benefit, the general use of these medications in acutely ill patients without CF cannot be recommended at this time.

PMID: 28780895 [PubMed - as supplied by publisher]

Association between F508 deletion in CFTR and chronic pancreatitis risk.

Dig Liver Dis. 2017 Jul 01;:

Authors: Zhao D, Xu Y, Li J, Fu S, Xiao F, Song X, Xie Z, Jiang M, He Y, Liu C, Wen Q, Yang X

Abstract
BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) has been reported to influence individual susceptibility to chronic pancreatitis (CP), but the results of previous studies are controversial.
AIMS: We performed a study to demonstrate the relationship between CFTR and CP.
METHODS: We searched PubMed, Scopus, and Embase for studies of patients with CP. Seven studies from 1995 to 2016 were identified, and included 64,832 patients. Pooled prevalence and 95% confidence intervals (CIs) were calculated.
RESULTS: F508 deletion in CFTR was significantly positively associated with CP risk in the overall analysis (odds ratio [OR]=3.20, 95% CI: 2.30-4.44, I(2)=31.7%). In subgroup analysis stratified by ethnicity, F508 deletion was significantly associated with CP risk in Indian populations, using a fixed effects model (ORs=5.45, 95% CI: 2.52-11.79, I(2)=0.0%), and in non-Indian populations, using a random effects model (ORs=3.59, 95% CI: 1.73-7.48, I(2)=60.9%). At the same time, we found that Indians with F508 deletion had much higher CP prevalence than non-Indians. Interestingly, F508 deletion was also associated with CP and idiopathic CP risk in subgroup analysis stratified by aeitiology, using the fixed effects model.
CONCLUSIONS: Based on current evidence, F508 deletion is a risk factor for CP, and Indians with F508 deletion have much higher CP morbidity.

PMID: 28780053 [PubMed - as supplied by publisher]

Respiratory viruses in healthy infants and infants with cystic fibrosis: a prospective cohort study.

Thorax. 2017 Aug 04;:

Authors: Korten I, Kieninger E, Klenja S, Mack I, Schläpfer N, Barbani MT, Regamey N, Kuehni CE, Hilty M, Frey U, Gorgievski M, Casaulta C, Latzin P, SCILD and BILD study groups

Abstract
RATIONALE: Acute viral respiratory tract infections in children with cystic fibrosis (CF) are known causes of disease exacerbation. The role of viral infections during infancy is, however, less known, although early infancy is thought to be a crucial period for CF disease development.We prospectively assessed symptomatic and asymptomatic viral detection in the first year of life in infants with CF and healthy controls.
METHODS: In a prospective cohort study, we included 31 infants with CF from the Swiss Cystic Fibrosis Infant Lung Development Cohort and 32 unselected, healthy infants from the Basel Bern Infant Lung Development Cohort and followed them throughout the first year of life. Respiratory symptoms were assessed by weekly telephone interviews. Biweekly nasal swabs were analysed for 10 different viruses and two atypical bacteria with real-time seven duplex PCR (CF=561, controls=712).
MEASUREMENTS AND RESULTS: Infants with CF and healthy controls showed similar numbers of swabs positive for virus (mean 42% vs 44%; OR 0.91, 95% CI 0.66 to 1.26, p=0.6). Virus-positive swabs were less often accompanied by respiratory symptoms in infants with CF (17% vs 23%; OR 0.64, 95% CI 0.43 to 0.95, p=0.026). This finding was pronounced for symptomatic human rhinovirus detection (7% vs 11%; OR 0.52, 95% CI 0.31 to 0.9, p=0.02).
CONCLUSIONS: Viral detection is not more frequent in infants with CF and respiratory symptoms during viral detection occur even less often than in healthy controls. It is likely an interplay of different factors such as local epithelial properties and immunological mechanisms that contribute to our findings.

PMID: 28778921 [PubMed - as supplied by publisher]

The top 10 research priorities in cystic fibrosis developed by a partnership between people with CF and healthcare providers.

Thorax. 2017 Aug 04;:

Authors: Rowbotham NJ, Smith S, Leighton PA, Rayner OC, Gathercole K, Elliott ZC, Nash EF, Daniels T, Duff AJA, Collins S, Chandran S, Peaple U, Hurley MN, Brownlee K, Smyth AR

Abstract
There remain many treatment uncertainties in cystic fibrosis (CF). With limited resources, research should focus on questions which are most important to the CF community. We conducted a James Lind Alliance Priority Setting Partnership in CF. Research questions were elicited and then prioritised in successive surveys. A workshop agreed the final top 10. Online methods avoided cross infection and widened participation. The elicitation survey had 482 respondents (1080 questions) and prioritisation survey 677 respondents. Participants were drawn equally from the patient and clinical communities globally. We have achieved a consensus on 10 research priorities which will be attractive to funders.

PMID: 28778919 [PubMed - as supplied by publisher]

Methodological and Ethical Issues in Pediatric Medication Safety Research.

Pediatrics. 2017 Aug 04;:

Authors: Carpenter D, Gonzalez D, Retsch-Bogart G, Sleath B, Wilfond B

Abstract
In May 2016, the Eshelman School of Pharmacy at The University of North Carolina at Chapel Hill convened the PharmSci conference to address the topic of "methodological and ethical issues in pediatric medication safety research." A multidisciplinary group of experts representing a diverse array of perspectives, including those of the US Food and Drug Administration, children's hospitals, and academia, identified important considerations for pediatric medication safety research and opportunities to advance the field. This executive summary describes current challenges that clinicians and researchers encounter related to pediatric medication safety research and identifies innovative and ethically sound methodologies to address these challenges to improve children's health. This article addresses 5 areas: (1) pediatric drug development and drug trials; (2) conducting comparative effectiveness research in pediatric populations; (3) child and parent engagement on study teams; (4) improving communication with children and parents; and (5) assessing child-reported outcomes and adverse drug events.

PMID: 28778857 [PubMed - as supplied by publisher]

Oscillating devices for airway clearance in people with cystic fibrosis.

Paediatr Respir Rev. 2017 Jul 14;:

Authors: Morrison L, Milroy S

PMID: 28778740 [PubMed - as supplied by publisher]

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

"Cystic Fibrosis"

These pubmed results were generated on 2017/08/05

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

Lung Cell-Specific Cre Deleter Mouse Strains: Going Back to Move Forward.

Am J Respir Cell Mol Biol. 2017 Aug;57(2):149-150

Authors: O'Neal WK

PMID: 28762768 [PubMed - in process]

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

"Cystic Fibrosis"

These pubmed results were generated on 2017/08/02

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

Interventions for treating intrahepatic cholestasis in people with sickle cell disease.

Cochrane Database Syst Rev. 2017 Jul 31;7:CD010985

Authors: Martí-Carvajal AJ, Martí-Amarista CE

Abstract
BACKGROUND: Sickle cell disease is the most common hemoglobinopathy occurring worldwide and sickle cell intrahepatic cholestasis is a complication long recognized in this population. Cholestatic liver diseases are characterized by impaired formation or excretion (or both) of bile from the liver. There is a need to assess the clinical benefits and harms of the interventions used to treat intrahepatic cholestasis in people with sickle cell disease. This is an update of a previously published Cochrane Review.
OBJECTIVES: To assess the benefits and harms of the interventions for treating intrahepatic cholestasis in people with sickle cell disease.
SEARCH METHODS: We searched the Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched the LILACS database (1982 to 23 May 2017), the WHO International Clinical Trials Registry Platform Search Portal (23 May 2017) and ClinicalTrials.gov.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 12 April 2017.
SELECTION CRITERIA: We searched for published or unpublished randomised controlled trials.
DATA COLLECTION AND ANALYSIS: Each author intended to independently extract data and assess the risk of bias of the trials by standard Cochrane methodologies; however, no trials were included in the review.
MAIN RESULTS: There were no randomised controlled trials identified.
AUTHORS' CONCLUSIONS: This updated Cochrane Review did not identify any randomised controlled trials assessing interventions for treating intrahepatic cholestasis in people with sickle cell disease. Randomised controlled trials are needed to establish the optimum treatment for this condition.

PMID: 28759700 [PubMed - as supplied by publisher]

Lumacaftor/ivacaftor combination therapy for cystic fibrosis: a nationwide survey among clinicians.

Clin Respir J. 2017 Jul 31;:

Authors: Casciaro R, Costa S, Dang P, Majo F, Ros M

PMID: 28759146 [PubMed - as supplied by publisher]

Fluid replacement therapy for acute episodes of pain in people with sickle cell disease.

Cochrane Database Syst Rev. 2017 Jul 31;7:CD005406

Authors: Okomo U, Meremikwu MM

Abstract
BACKGROUND: Treating vaso-occlusive painful crises in people with sickle cell disease is complex and requires multiple interventions. Extra fluids are routinely given as adjunct treatment, regardless of the individual's state of hydration with the aim of slowing or stopping the sickling process and thereby alleviating pain. This is an update of a previously published Cochrane Review.
OBJECTIVES: To determine the optimal route, quantity and type of fluid replacement for people with sickle cell disease with acute painful crises.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.We also conducted searches of Embase (November 2007), LILACS, www.ClinicalTrials.gov (05 January 2010), and the WHO ICTRP (30 June 2017).Date of most recent search of the Group's Haemoglobinopathies Trials Register: 16 February 2017.
SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared the administration of supplemental fluids adjunctive to analgesics by any route in people with any type of sickle cell disease during an acute painful episode, under medical supervision (inpatient, day care or community).
DATA COLLECTION AND ANALYSIS: No relevant trials have yet been identified.
MAIN RESULTS: Sixteen trials were identified by the searches, all of which were not eligible for inclusion in the review.
AUTHORS' CONCLUSIONS: Treating vaso-occlusive crises is complex and requires multiple interventions. Extra fluids, generally oral or intravenous, are routinely administered during acute painful episodes to people with sickle cell disease regardless of the individual's state of hydration. Reports of their use during these acute painful episodes do not state the efficacy of any single route, type or quantity of fluid compared to another. However, there are no randomised controlled trials that have assessed the safety and efficacy of different routes, types or quantities of fluid. This systematic review identifies the need for a multicentre randomised controlled trial assessing the efficacy and possible adverse effects of different routes, types and quantities of fluid administered to people with sickle cell disease during acute painful episodes.

PMID: 28759112 [PubMed - as supplied by publisher]

Establishment and long-term culture of human cystic fibrosis endothelial cells.

Lab Invest. 2017 Jul 31;:

Authors: Plebani R, Tripaldi R, Lanuti P, Recchiuti A, Patruno S, Di Silvestre S, Simeone P, Anile M, Venuta F, Prioletta M, Mucilli F, Del Porto P, Marchisio M, Pandolfi A, Romano M

Abstract
Endothelial cell (EC) dysfunction has been reported in cystic fibrosis (CF) patients. Thus, the availability of CF EC is paramount to uncover mechanisms of endothelial dysfunction in CF. Using collagenase digestion, we isolated cells from small fragments of pulmonary artery dissected from non-CF lobes or explanted CF lungs. These cells were a heterogeneous mixture, containing variable percentages of EC. To obtain virtually pure pulmonary artery endothelial cells (PAEC), we developed an easy, inexpensive, and reliable method, based on the differential adhesion time of pulmonary artery cells collected after collagenase digestion. With this method, we obtained up to 95% pure non-CF and CF-PAEC. Moreover, we also succeed at immortalizing both PAEC and CF-PAEC, which remained viable and with unchanged phenotype and proliferation rate over the 30th passage. These cells recapitulated cystic fibrosis transmembrane conductance regulator expression and functions of the parental cells. Thus, we isolated for the first time endothelial cells from CF patients, providing a valuable tool to define the emerging role of EC in CF lung and vascular disease.Laboratory Investigation advance online publication, 31 July 2017; doi:10.1038/labinvest.2017.74.

PMID: 28759010 [PubMed - as supplied by publisher]

A Different Microbiome Gene Repertoire in the Airways of Cystic Fibrosis Patients with Severe Lung Disease.

Int J Mol Sci. 2017 Jul 29;18(8):

Authors: Bacci G, Mengoni A, Fiscarelli E, Segata N, Taccetti G, Dolce D, Paganin P, Morelli P, Tuccio V, De Alessandri A, Lucidi V, Bevivino A

Abstract
In recent years, next-generation sequencing (NGS) was employed to decipher the structure and composition of the microbiota of the airways in cystic fibrosis (CF) patients. However, little is still known about the overall gene functions harbored by the resident microbial populations and which specific genes are associated with various stages of CF lung disease. In the present study, we aimed to identify the microbial gene repertoire of CF microbiota in twelve patients with severe and normal/mild lung disease by performing sputum shotgun metagenome sequencing. The abundance of metabolic pathways encoded by microbes inhabiting CF airways was reconstructed from the metagenome. We identified a set of metabolic pathways differently distributed in patients with different pulmonary function; namely, pathways related to bacterial chemotaxis and flagellar assembly, as well as genes encoding efflux-mediated antibiotic resistance mechanisms and virulence-related genes. The results indicated that the microbiome of CF patients with low pulmonary function is enriched in virulence-related genes and in genes encoding efflux-mediated antibiotic resistance mechanisms. Overall, the microbiome of severely affected adults with CF seems to encode different mechanisms for the facilitation of microbial colonization and persistence in the lung, consistent with the characteristics of multidrug-resistant microbial communities that are commonly observed in patients with severe lung disease.

PMID: 28758937 [PubMed - in process]

On the origin of worries about modern health hazards: Experimental evidence for a conjoint influence of media reports and personality traits.

Psychol Health. 2017 Jul 31;:1-20

Authors: Witthöft M, Freitag I, Nußbaum C, Bräscher AK, Jasper F, Bailer J, Rubin GJ

Abstract
OBJECTIVE: Worries about health threatening effects of potential health hazards of modern life (e.g. electric devices and pollution) represent a growing phenomenon in Western countries. Yet, little is known about the causes of this growing special case of affective risk perceptions termed Modern Health Worries (MHW). The purpose of this study is to examine a possible role of biased media reports in the formation of MHW.
DESIGN: In two experiments, we investigated whether typical television reports affect MHW. In Study 1, 130 participants were randomly assigned to a film on idiopathic environmental intolerance (IEI) or a control film about cystic fibrosis. In Study 2, 82 participants were randomly assigned to either a film on the dangers of electromagnetic fields or a control condition.
MAIN OUTCOME MEASURES: Increases in MHW after sensational media reports.
RESULTS: In Study 1, only participants high on the personality trait of absorption revealed increased MHW after watching the IEI film. In Study 2, specifically worries about radiation were found to be elevated after watching the film on the dangers of electromagnetic fields compared to the control film.
CONCLUSION: The results of both studies reveal a significant and specific influence of sensational short mass media reports on MHW. The influence of potential moderators such as absorption remains to be clarified.

PMID: 28758796 [PubMed - as supplied by publisher]

Thermo-physical properties of synthetic mucus for the study of airway clearance.

J Biomed Mater Res A. 2017 Jul 30;:

Authors: Lafforgue O, Bouguerra N, Poncet S, Seyssiecq I, Favier J, Elkoun S

Abstract
In this paper, dynamic viscosity, surface tension, density, heat capacity and thermal conductivity, of a bronchial mucus simulant proposed by Zahm et al. [1] were experiementally determined. This simulant is mainly composed of a galactomannan gum and a scleroglucan. It was shown that thermophysical properties of synthetic mucus are dependant of scleroglucan concentrations. More importantly and for some scleroglucan concentrations, the syntetic mucus, exhibits, somehow, comparable thermophysical propoerties to real bronchial mucus. An insight on the microstructure of this simulant is proposed and the different properties enounced previously have been measured for various scleroglucan concentrations and over a certain range of operating temperatures. This synthetic mucus is found to mimic well the rheological behavior and the surface tension of real mucus for different pathologies. Density and thermal properties have been measured for the first time. This article is protected by copyright. All rights reserved.

PMID: 28758330 [PubMed - as supplied by publisher]

Lung Transplantation Delays Gastric Motility in Patients without Prior Gastro-Intestinal Surgery - A Single Center Experience of 412 Consecutive patients.

Clin Transplant. 2017 Jul 31;:

Authors: Hirji SA, Gulack BC, Englum BR, Speicher PJ, Ganapathi AM, Osho AA, Shimpi RA, Perez A, Hartwig MG

Abstract
PURPOSE: To examine the impact of lung transplantation on gastric motility.
METHODS: Adult recipients at a large, single center, who were retrospectively evaluated with solid gastric emptying (SGE) study post lung transplantation, but had no history of gastrointestinal intervention (i.e. pyloroplasty or fundoplication), were selected between June 2005 and August 2013. Multivariable logistic regression was performed to determine risk factors associated with delayed gastric emptying (DGE) after transplantation.
RESULTS: DGE was noted in 236 patients (57%) after transplantation. On multivariable logistic regression, an underlining diagnosis of cystic fibrosis (CF)/bronchiectasis (Adjusted Odds Ratio (AOR) 3.26, p < 0.01) was a significant risk factor in predicting DGE after lung transplantation. There was no survival difference between patients with postoperative DGE versus those without (Log-rank test p=0.53) CONCLUSIONS: Delayed gastric emptying is very common following lung transplantation, occurring in over half of all lung transplant recipients with increased prevalence in CF patients. The association with cystic fibrosis could be secondary to extra-pulmonary manifestations of the underlying disease, or indicative of increased intra-operative vagal nerve injury. We speculate that DGE may play a substantial role in the increased reflux induced allograft injury seen after lung transplantation. Further prospective studies are needed to validate this hypothesis. This article is protected by copyright. All rights reserved.

PMID: 28758244 [PubMed - as supplied by publisher]

Tracheal diverticula in advanced cystic fibrosis: Prevalence, features, and outcomes after lung transplantation.

J Cyst Fibros. 2017 Jul 27;:

Authors: Kapnadak SG, Kicska GA, Ramos KJ, Marshall DA, Carroll TY, Pipavath SN, Mulligan MS, Goss CH, Aitken ML

Abstract
BACKGROUND: Tracheal diverticula (TD) are rare anomalies that may harbor infected secretions, posing potential risk to patients with lung disease. In an end-stage cystic fibrosis (CF) cohort, we describe the characteristics and associated post-lung transplant (LTx) outcomes of TD.
METHODS: Pre-transplant computed tomography (CT)'s were reviewed in CF patients undergoing LTx. TD were characterized radiographically and on autopsy when available. Pre-transplant clinical variables and post-transplant outcomes were compared by TD status.
RESULTS: Of 93 patients, 35 (37.6%) had TD. 58% of TD had fat-stranding, and post-mortem TD examinations revealed histology carrying intense submucosal inflammation, and purulent contents that cultured identical species to sputum. There was no difference in post-LTx survival [HR 1.77 (0.82-3.82), p=0.147], bacterial re-colonization, or rejection in patients with TD compared to those without. Patients with TD were more likely to die from infection, but the result was not statistically significant [HR 2.02 (0.62-6.63), p=0.245].
CONCLUSIONS: We found a high prevalence of TD in end-stage CF, where diverticula may represent a large-airway bacterial reservoir. TD were not associated with differences in post-LTx outcomes, but given the infectious concerns further investigation is necessary.

PMID: 28757079 [PubMed - as supplied by publisher]