An unusual case of disseminated adenovirus infection in a cystic fibrosis, liver transplant patient.

J Clin Virol. 2016 Jun 13;81:64-67

Authors: Mitchell SL, Kajon AE, Kaplan SL, Kim J, Cárdenas AM

PMID: 27331823 [PubMed - as supplied by publisher]

Inflammation induced by inhaled lipopolysaccharide depends on particle size in healthy volunteers.

Br J Clin Pharmacol. 2016 Jun 22;

Authors: Doyen VA, Pilcer G, Huy Duc Dinh P, Corazza F, Bernard A, Bergmann P, Lefevre N, Amighi K, Michel O

Abstract
AIM: In drug development, lung anti-inflammatory properties of new molecules are currently tested on the inhaled LPS model. The total and regional lung bioavailability of inhaled particles depends significantly on their size. The objective was to compare inflammatory responses in healthy volunteers after the inhalation of lipopolysaccharide (LPS) of varying droplet size.
METHODS: Three nebulizers were characterized by different droplet size distributions [mean mass median aerodynamic diameters: Microcirrus (2.0 µm), MB2 (3.2 µm), and Pari (7.9 µm)]. Participants inhaled three boluses of 20 µg (technetium 99 m-labeled) solution of LPS, randomly delivered by each nebulizer. We measured the lung deposition of the nebulized LPS by gamma-scintigraphy, while blood and sputum biomarkers were evaluated before and after challenges.
RESULTS: MB2 and Pari achieved greater lung deposition than Microcirrus [171.5 (±72.9) and 217.6 (±97.8) counts/pixel, respectively, versus 67.9 (±20.6) counts/pixel; p < 0.01]. MB2 and Pari caused greater blood C-reactive protein and more total cells and neutrophils in sputum compared to Microcirrus (p < 0.05). C-reactive protein level correlated positively with lung deposition (p < 0.01).
CONCLUSIONS: Inhalation of large droplets of LPS featured greater lung deposition and induced a more pronounced systemic and bronchial inflammatory response than small droplets. The systemic inflammatory response correlated with lung deposition. NCT01081392.

PMID: 27331367 [PubMed - as supplied by publisher]

Gastrointestinal Manifestations of Cystic Fibrosis.

Gastroenterol Hepatol (N Y). 2016 Jan;12(1):43-7

Authors: Sabharwal S

Abstract
Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis.

PMID: 27330503 [PubMed]

Diagnosis and Early Life Risk Factors for Bronchiectasis in Cystic Fibrosis: a Review.

Expert Rev Respir Med. 2016 Jun 22;

Authors: Sly PD, Wainwright CE

Abstract
INTRODUCTION: Lung disease in cystic fibrosis begins in early life with neutrophil-dominated inflammation and infection, is progressive and results in structural lung damage characterised by bronchial dilation and bronchiectasis. Preventative strategies must be employed in early life but require a better understanding of how bronchiectasis develops.
AREAS COVERED: In this review we have addressed the diagnosis and early life risk factors for bronchiectasis in young children with cystic fibrosis. A systematic review was not performed and the literature reviewed was known to the authors. Expert commentary: Bronchiectasis represents a process of progressive dilatation and damage of airway walls and is traditionally considered to be irreversible. Diagnosis is primarily by detecting a bronchial:arterial ratio of >1 on chest CT scan. Lung volume has a greater influence on airway diameter than on arterial making control of lung volume during scanning critical. Early life risk factors for the onset and progression bronchiectasis include: severe cystic fibrosis genotype; neutrophilic inflammation with free neutrophil elastase activity in the lung; and pulmonary infection. Bronchiectasis develops in the majority of children before they reach school age despite the best current therapy. To prevent bronchiectasis novel therapies are going to have to be given to infants.

PMID: 27329819 [PubMed - as supplied by publisher]

Paediatric nasal polyps in cystic fibrosis.

BMJ Case Rep. 2016;2016

Authors: Mohd Slim MA, Dick D, Trimble K, McKee G

Abstract
Patients with cystic fibrosis (CF) are at increased risk of nasal polyps. We present the case of a 17-month-old Caucasian patient with CF who presented with hypertelorism causing cycloplegic astigmatism, right-sided mucoid discharge, snoring and noisy breathing. Imaging suggested bilateral mucoceles in the ethmoid sinuses. Intraoperatively, bilateral soft tissue masses were noted, and both posterior choanae were patent. Polypectomy and bilateral mega-antrostomies were performed. Histological examination revealed inflammatory nasal polyposis typical of CF. The role of early functional endoscopic sinus surgery (FESS) in children with CF nasal polyposis remains questionable as the recurrence rate is higher, and no improvement in pulmonary function has been shown. Our case, however, clearly demonstrates the beneficial upper airway symptom relief and normalisation of facial appearance following FESS in a child with this condition.

PMID: 27329094 [PubMed - in process]

13 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 2016/06/22

PubMed comprises more than 24 million 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.

8 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 2016/06/21

PubMed comprises more than 24 million 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.

Identification and characterization of sulfated glycoproteins from small cell lung carcinoma cells assisted by management of molecular charges.

Glycoconj J. 2016 Jun 18;

Authors: Toyoda M, Kaji H, Sawaki H, Togayachi A, Angata T, Narimatsu H, Kameyama A

Abstract
Proteins carrying sulfated glycans (i.e., sulfated glycoproteins) are known to be associated with diseases, such as cancer, cystic fibrosis, and osteoarthritis. Sulfated glycoproteins, however, have not been isolated or characterized from complex biological samples due to lack of appropriate tools for their enrichment. Here, we describe a method to identify and characterize sulfated glycoproteins that are involved in chemical modifications to control the molecular charge of the peptides. In this method, acetohydrazidation of carboxyl groups was performed to accentuate the negative charge of the sulfate group, and Girard's T modification of aspartic acid was performed to assist in protein identification by MS tagging. Using this approach, we identified and characterized the sulfated glycoproteins: Golgi membrane protein 1, insulin-like growth factor binding protein-like 1, and amyloid beta precursor-like protein 1 from H2171 cells, a small cell lung carcinoma cell line. These sulfated glycoproteins carry a complex-type N-glycan with a core fucose and 4'-O-sulfated LacdiNAc as the major glycan.

PMID: 27318476 [PubMed - as supplied by publisher]

6 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 2016/06/19

PubMed comprises more than 24 million 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.

8 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 2016/06/18

PubMed comprises more than 24 million 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.

6 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 2016/06/17

PubMed comprises more than 24 million 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.

Partial restoration of pancreatic function in a child with cystic fibrosis.

Lancet Respir Med. 2016 May;4(5):e21-e22

Authors: Howlett C, Ronan NJ, NiChroinin M, Mullane D, Plant BJ

PMID: 27304562 [PubMed - as supplied by publisher]

The phospholipid flippase ATP8B1 mediates apical localization of the Cystic Fibrosis Transmembrane Regulator.

Biochim Biophys Acta. 2016 Jun 11;

Authors: van der Mark VA, de Jonge HR, Chang JC, Ho-Mok KS, Duijst S, Vidović D, Carlon MS, Elferink RP, Paulusma CC

Abstract
Progressive familial intrahepatic cholestasis type 1 (PFIC1) is caused by mutations in the gene encoding the phospholipid flippase ATP8B1. Apart from severe cholestatic liver disease, many PFIC1 patients develop extrahepatic symptoms characteristic of cystic fibrosis (CF), such as pulmonary infection, sweat gland dysfunction and failure to thrive. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel essential for epithelial fluid transport. Previously it was shown that CFTR transcript levels were strongly reduced in livers of PFIC1 patients. Here we have investigated the hypothesis that ATP8B1 is important for proper CFTR expression and function. We analyzed CFTR expression in ATP8B1-depleted intestinal and pulmonary epithelial cell lines and assessed CFTR function by measuring short-circuit currents across transwell-grown ATP8B1-depleted intestinal T84 cells and by a genetically-encoded fluorescent chloride sensor. In addition, we studied CFTR surface expression upon induction of CFTR transcription. We show that CFTR protein levels are strongly reduced in the apical membrane of human ATP8B1-depleted intestinal and pulmonary epithelial cell lines, a phenotype that coincided with reduced CFTR activity. Apical membrane insertion upon induction of ectopically-expressed CFTR was strongly impaired in ATP8B1-depleted cells. We conclude that ATP8B1 is essential for correct apical localization of CFTR in human intestinal and pulmonary epithelial cells, and that impaired CFTR localization underlies some of the extrahepatic phenotypes observed in ATP8B1 deficiency.

PMID: 27301931 [PubMed - as supplied by publisher]

The innate immune protein calprotectin promotes Pseudomonas aeruginosa and Staphylococcus aureus interaction.

Nat Commun. 2016;7:11951

Authors: Wakeman CA, Moore JL, Noto MJ, Zhang Y, Singleton MD, Prentice BM, Gilston BA, Doster RS, Gaddy JA, Chazin WJ, Caprioli RM, Skaar EP

Abstract
Microorganisms form biofilms containing differentiated cell populations. To determine factors driving differentiation, we herein visualize protein and metal distributions within Pseudomonas aeruginosa biofilms using imaging mass spectrometry. These in vitro experiments reveal correlations between differential protein distribution and metal abundance. Notably, zinc- and manganese-depleted portions of the biofilm repress the production of anti-staphylococcal molecules. Exposure to calprotectin (a host protein known to sequester metal ions at infectious foci) recapitulates responses occurring within metal-deplete portions of the biofilm and promotes interaction between P. aeruginosa and Staphylococcus aureus. Consistent with these results, the presence of calprotectin promotes co-colonization of the murine lung, and polymicrobial communities are found to co-exist in calprotectin-enriched airspaces of a cystic fibrosis lung explant. These findings, which demonstrate that metal fluctuations are a driving force of microbial community structure, have clinical implications because of the frequent occurrence of P. aeruginosa and S. aureus co-infections.

PMID: 27301800 [PubMed - in process]

19 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 2016/06/15

PubMed comprises more than 24 million 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.

Expiratory Flow Limitation for Monitoring Cystic Fibrosis. Ready for the Starting Gun?

Ann Am Thorac Soc. 2016 Jun;13(6):770-771

Authors: Bush A

PMID: 27295150 [PubMed - as supplied by publisher]

Cystic Fibrosis Revisited - a Review Study.

Med Chem. 2016 Jun 8;

Authors: Kuca K, Klimova B, Novotny M, Maresova P

Abstract
BACKGROUND: Cystic fibrosis (CF) is an incurable, chronic disease, which causes severe damages to respiratory and digestive tracts. It is the most common genetically inherited disease among caucasians. This disease is caused by defects in CF genes, the so-called mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene population. At present over 100,000 people suffer from this disease worldwide.
OBJECTIVE: The purpose of this review study is to describe the pathophysiology of CF and provide the latest information on its diagnosis and treatment therapies with respect to the improvement of patient's quality of life and emphasis on targeted specialized care.
METHOD: The methodological approaches include a method of literature review of available sources exploring the issue of cystic fibrosis both from a global and specific perspective point of view. A search was performed in the databases PubMed, MEDLINE, Web of Science, Scopus, Springer and ScienceDirect. Furthermore, other sources cited in the analyzed studies were also examined. On the basis of evaluation of these literature sources, the research issue was explored.
RESULTS: The main benefits (e.g., specialized centres for the treatment of CF exist or a new breakthrough in the gene therapy of CF has been made) and limitations (e.g., comorbidity of CF, lifelong and costly treatment, or adverse impact on patient's and caregiver's quality of life) in the treatment of narcolepsy are highlighted.
CONCLUSION: CF requires an integrated treatment approach in specialized CF centers, involving various factors contributing to a better patient's state of health in the form of relevant and well-balanced non-pharmacological and pharmacological therapies. In addition, further large scale clinical trials are needed in order to develop compounds that are aimed at the most common classes of CFTR.

PMID: 27292156 [PubMed - as supplied by publisher]

[Italian Cystic Fibrosis Register - Report 2010].

Epidemiol Prev. 2016 Mar-Apr;40(2 Suppl 2):1-47

Authors: Amato A, Ferrigno L, Salvatore M, Toccaceli V, Gruppo di lavoro RIFC/ICFR Working Group

Abstract
UNLABELLED: The Italian National CF Registry (INCFR) is based on the official agreement between the clinicians of the Italian National Referral Centers for Cystic Fibrosis and the researchers of the Istituto Superiore di Sanità (National Center for Rare Diseases; National Center for Epidemiology, Surveillance and Health Care Promotion). OBJECTIVES The main aim of INCFR is to contribute to the improvement in CF patients health care and clinical management through: i. the estimates of CF prevalence and incidence in Italy; ii. the analyses of medium and long term clinical and epidemiological trends of the disesase; iii. the identification of the main health care needs at regional and national level to contribute to the Health Care programmes and to the distribution of resources. MATERIALS AND METHODS Analyses and results described in the present Report are referred to patients in charge to the Italian National Referral Centers for Cystic Fibrosis in 2010. Data were sent by Centers by means of a specific software (Camilla, Ibis Informatica). The Italian National Referral Centers for Cystic Fibrosis sent a total of 5,271 individual records; 1,112 records were excluded from the analyses due to restricted inclusion criteria. The total number of patients included in INCFR for analyses is 4,159. RESULTS INCFR database includes all prevalent cases at 1th January 2010 as well as all new diagnoses done in 2010. The present Report has been organized into 9 sections. 1. Demography: estimated 2010 CF prevalence was 7/100,000 residents in Italy; 52% of the patients were male, CF distribution showed higher frequency in patients aged 7 to 35 years. In 2010, 48.9% of the patients were more than 18 years old. 2. Diagnoses: most of the CF patients were diagnosed before two years of age (66.7%); a significant percentage of patients (11.4%) was diagnosed in adult-age. 3. New diagnoses (2010): new diagnoses were 168. Sixty-five percent of them was diagnosed before the second year of age and 17%in adulthood. No differences were observed between male and female. Incidence at birth was estimated 1/4,854 living births. 4.
GENETICS: in 95.9% of patients, 2 (or more) CFTR mutations were identified. [delta]508F mutation was the most frequent (45.1%). 5. Respiratory function: analyses were performed on 2,966 out of 3,341 patients aged 7 years or older. FEV1 (Forced Expiratory Volume in the first second) scores progressively decreased before adult age, in accordance with the natural history of the disease. 6. Nutrition: most critical periods are during the first 6 months of life and during adolescence. Fourteen per cent of the patients within 2-18 years resulted malnourished. From 18 years onwards, optimal BodyMass Index (BMI) values were detected in 36.5%of males and in 28%of females. BMI also improved during age. 7. Transplantation: in 2010, 20 patients (10 males and 10 females) were bi-pulmunary transplanted; age was comprised between 11 and 46 years, median age at transplantation was 27.5 years. Eleven out of the 20 patients resulted still alive on the 31th December 2010. 8. Microbiology: analyses were performed on 3.272 patients (887 did not report these data) and were exclusively referred to tests performed in 2010. A percentage of 34 patients, younger than 18 years of age, was characterized by the presence of Pseudomonas aeruginosa compared to 61.8% of the older patients. Prevalence of Burkholderia Cepacia was 0.8% in patients aged up to 17 years; in patients aged more than 17 years, prevalence was 6.8%. Staphylococcus aureus meticillino sensitive prevalence was not correlated with patients' age. 9.
MORTALITY: 34 patients aged from 0 to 45 years died in 2010 (16 males and 18 females). Respiratory insufficiency was the main cause of death (73.5%). CONCLUSIONS The report aims at being an instrument for CF community, with particular attention to the needs of patients and their families. Information collected within INCFR are an important starting point for further studies from health care perspectives. Finally, INCFR represents an important tool to foster research and innovative treatment for CF, as the rareness of the disease is a constraint to clinical trials and other studies set-up. A significant subset of data are regularly sent to the European Registry of Cystic Fibrosis.

PMID: 27291389 [PubMed - in process]

Insulin secretion abnormalities in patients with cystic fibrosis.

J Cyst Fibros. 2016 Jun 8;

Authors: Schnyder MA, Benden C, Faulenbach M, Schmid C

PMID: 27289198 [PubMed - as supplied by publisher]

Bioelectrical impedance in young patients with cystic fibrosis: Validation of a specific equation and clinical relevance.

J Cyst Fibros. 2016 Jun 8;

Authors: Charatsi AM, Dusser P, Freund R, Maruani G, Rossin H, Boulier A, Le Bourgeois M, Chedevergne F, de Blic J, Letourneur A, Casimir G, Jais JP, Sermet-Gaudelus I

Abstract
BACKGROUND: Body composition (BC) analysis based on bioelectrical impedance analysis (BIA) provides conflicting results. The purpose of the study was to validate an equation specific for young patients with cystic fibrosis (CF), describe their BC and investigate its association with lung function.
METHODS: Fifty-four young CF patients were evaluated by BIA and dual X-ray absorptiometry (DXA). An empirically derived CF-specific equation for fat-free mass (FFM) estimation by BIA was elaborated after stepwise multivariate regression and the agreement between BIA and DXA was assessed by Bland-Altman plots. The association between BC and lung function was investigated by regression analysis.
RESULTS: The mean difference between the BIA and DXA assessment was close to zero. A total of 22.5% of patients (n=9) presented a FFM z-score≤-2. They had a worse pulmonary function and diaphragmatic impairment. Among these 9 patients, 7 had a normal BMI z-score>-1.
CONCLUSIONS: BIA, based on a CF-specific equation, is a reliable method for BC assessment and allows the identification of patients at risk of nutritional degradation and bad respiratory prognosis.

PMID: 27289197 [PubMed - as supplied by publisher]