[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]

Nutritional status of children with clinical conditions.

Clin Nutr. 2016 May 26;

Authors: Murphy AJ, Hill RJ, Buntain H, White M, Brookes D, Davies PS

Abstract
BACKGROUND & AIMS: Nutritional status is an important consideration in many pediatric clinical conditions. This paper aimed to examine and compare the nutritional status, represented by body cell mass (BCM), of children with cancer, Crohn's disease (CD), cystic fibrosis (CF) and anorexia nervosa (AN).
METHODS: Anthropometry was measured and BCM was calculated from whole body potassium-40 counting in 259 children being treated for clinical conditions (n = 66 cancer; n = 59 AN; n = 75 CF; n = 59 CD) and 108 healthy children. BCM was adjusted for height (BCMI) and expressed as a Z-score relative to laboratory reference data.
RESULTS: The CD (-0.80 ± 1.61; p = 0.0001) and AN (-1.13 ± 0.99; p = 0.0001) groups had significantly lower BMI Z-score than the healthy control (0.13 ± 0.75), cancer (0.50 ± 1.40) and CF groups (-0.09 ± 0.95). The cancer (-1.16 ± 1.60; p = 0.0001), CD (-1.13 ± 1.36; p = 0.0001) and AN (-0.97 ± 1.18; p = 0.0001) groups had significantly reduced BCM compared to the healthy control (0.07 ± 0.93) and CF group (0.31 ± 1.08). According to BCMI Z-score, 42.4% of patients with cancer, 41.7% of the patients with CD, 27.1% of patients with AN, and 4.0% of patients with CF were considered malnourished.
CONCLUSIONS: This study demonstrates that children undergoing treatment for clinical conditions may have alterations in BCM, independent of BMI. Children with cancer, CD and AN all had a high prevalence of malnutrition. Assessment of body composition, not just body size, is vital to understand nutritional status in children with clinical conditions.

PMID: 27289162 [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 2016/06/12

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 2016/06/11

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 2016/06/10

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.

21 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 2016/06/09

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.

Nontuberculous mycobacteria in cystic fibrosis patients on the Island of Gran Canaria. A population study.

J Infect Chemother. 2016 Jun 1;

Authors: Campos-Herrero MI, Chamizo FJ, Caminero JA, Gilarranz R, Cabrera G, Cuyás J

Abstract
OBJECTIVE: To determine the prevalence of nontuberculous mycobacteria (NTM) colonization and disease in cystic fibrosis (CF) patients.
PATIENTS AND METHODS: All the CF patients followed-up from 2002 to 2012 with three acid-fast bacilli (AFB) cultures were included. The American Thoracic Society (ATS) criteria for NTM lung disease were applied.
RESULTS: Forty-four of the 53 patients being followed-up were included. The mean time of follow-up was 7.0 years. A total of 18 patients (40.9%) were NTM positive. The NTN mean annual prevalence was 14.1%. The risk of Mycobacterium abscessus complex was higher in the group of 10-14 years-old (p < 0.001). Ten patients (22.7% of the entire cohort) met the ATS microbiological criteria. The mean annual prevalence of NTM disease was 10.4%. Seven patients (four with Mycobacterium simiae and three with M. abscessus complex) with multiple positive cultures, positive AFB smears and clinical worsening were treated. Three patients with M. simiae and none of those with M. abscessus were cured.
CONCLUSIONS: Overall NTM prevalence of colonization and disease were high in our CF patients. Patients <15 years old had a higher risk of M. abscessus complex colonization. Multiple positive cultures or positive AFB smears were associated with disease.

PMID: 27262751 [PubMed - as supplied by publisher]

Cystic fibrosis in Latin America-Improving the awareness.

J Cyst Fibros. 2016 Jun 1;

Authors: Silva Filho LV, Castaños C, Ruíz HH

Abstract
The burden of cystic fibrosis (CF) in Latin America is being increasingly recognized and is significant compared with other regions of the world. In this short communication, we assess the current situation in some Latin American countries and make suggestions for possible directions for future focus. We discuss the work that remains in deciphering how the various genetic, environmental and medical factors interact and influence outcomes in different ethnic groups. We also consider the need for consistency in both research and access to services across Latin America, including CF registries, neonatal screening programs, access to specialized CF healthcare practitioners, transition to adult clinics and treatment regimens. Progress in these areas is likely to build on the advances to date, and improve the lives of patients in Latin America who are affected by this debilitating and life-limiting disorder.

PMID: 27262748 [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 2016/06/05

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.

CAN ADJUVANT AGENTS REDUCE GASTRIC ACIDITY IN PATIENTS WITH CYSTIC FIBROSIS: EVIDENCE FROM A COCHRANE REVIEW.

Gastroenterol Nurs. 2016 May-Jun;39(3):246-248

Authors: Zhao S

PMID: 27258469 [PubMed - as supplied by publisher]

Sources of Variation in Sweat Chloride Measurements in Cystic Fibrosis.

Am J Respir Crit Care Med. 2016 Jun 3;

Authors: Collaco JM, Blackman SM, Raraigh KS, Corvol H, Rommens JM, Pace RG, Boelle PY, McGready J, Sosnay PR, Strug LJ, Knowles MR, Cutting GR

Abstract
RATIONALE: Expanding the use of CFTR potentiators and correctors for the treatment of cystic fibrosis (CF) requires precise and accurate biomarkers. Sweat chloride concentration provides an in vivo assessment of CFTR function, but it is unknown the degree to which CFTR mutations account for sweat chloride variation.
METHODS: 2639 sweat chloride measurements were obtained in 1761 twins/siblings from the CF Twin-Sibling Study, French CF Modifier Gene Study, and Canadian Consortium for Genetic Studies. Variance component estimation was performed by nested mixed modelling.
RESULTS: Across the tested CF population as a whole, CFTR gene mutations were found to be the primary determinant of sweat chloride variability (56.1% of variation) with contributions from variation over time (e.g., factors related to testing on different days; 13.8%), environmental factors (e.g., climate, family diet; 13.5%), other residual factors (e.g., test variability; 9.9%) and unique individual factors (e.g., modifier genes, unique exposures; 6.8%) (LR test p<0.001). Twin analysis suggested that modifier genes did not play a significant role as the heritability estimate was negligible (H2=0; 95%CI: 0.0, 0.35). For an individual with CF, variation in sweat chloride was primarily due to variation over time (58.1%) with the remainder attributable to residual/random factors (41.9%).
CONCLUSIONS: Variation in the CFTR gene is the predominant cause of sweat chloride variation; most of the non-CFTR variation is due to testing variability and unique environmental factors. If test precision and accuracy can be improved, sweat chloride measurement could be a valuable biomarker for assessing response to therapies directed at mutant CFTR.

PMID: 27258095 [PubMed - as supplied by publisher]

Adults with cystic fibrosis in Portugal: A first step towards improvement.

Rev Port Pneumol (2006). 2016 May-Jun;22(3):139-40

Authors: Raja TH, Flume PA

PMID: 27256624 [PubMed - in process]

Evaluation of a New Newborn Screening Model for Cystic Fibrosis.

J Pediatr. 2016 May 30;

Authors: Kharrazi M

PMID: 27255858 [PubMed - as supplied by publisher]

A Handling Study to Assess Use of the Respimat(®) Soft Mist™ Inhaler in Children Under 5 Years Old.

J Aerosol Med Pulm Drug Deliv. 2015 Oct;28(5):372-81

Authors: Kamin W, Frank M, Kattenbeck S, Moroni-Zentgraf P, Wachtel H, Zielen S

Abstract
BACKGROUND: Respimat(®) Soft Mist(™) Inhaler (SMI) is a hand-held device that generates an aerosol with a high, fine-particle fraction, enabling efficient lung deposition. The study objective was to assess inhalation success among children using Respimat SMI, and the requirement for assistance by the parent/caregiver and/or a valved holding chamber (VHC).
METHODS: This open-label study enrolled patients aged <5 years with respiratory disease and history of coughing and/or recurrent wheezing. Patients inhaled from the Respimat SMI (air only; no aerosol) using a stepwise configuration: "1" (dose released by child); "2" (dose released by parent/caregiver), and "3" (Respimat SMI with VHC, facemask, and parent/caregiver help). Co-primary endpoints included the ability to perform successful inhalation as assessed by the investigators using a standardized handling questionnaire and evaluation of the reasons for success. Inhalation profile in the successful handling configuration was verified with a pneumotachograph. Patient satisfaction and preferences were investigated in a questionnaire.
RESULTS: Of the children aged 4 to <5 years (n=27) and 3 to <4 years (n=30), 55.6% and 30.0%, respectively, achieved success without a VHC or help; with assistance, another 29.6% and 10.0%, respectively, achieved success, and the remaining children were successful with VHC. All children aged 2 to <3 years (n=20) achieved success with the Respimat SMI and VHC. Of those aged <2 years (n=22), 95.5% had successful handling of the Respimat SMI with VHC and parent/caregiver help. Inhalation flow profiles generally confirmed the outcome of the handling assessment by the investigators. Most parent/caregiver and/or child respondents were satisfied with operation, instructions for use, handling, and ease of holding the Respimat SMI with or without a VHC.
CONCLUSIONS: The Respimat SMI is suitable for children aged <5 years; however, children aged <5 years are advised to add a VHC to complement its use.

PMID: 25844687 [PubMed - indexed for MEDLINE]

CAR-engineered cytokine-induced killer cells overcome treatment resistance of pre-B-ALL and enhance survival.

Int J Cancer. 2016 Jun 2;

Authors: Oelsner S, Wagner J, Friede ME, Pfirrmann V, Genßler S, Rettinger E, Buchholz CJ, Pfeifer H, Schubert R, Ottmann OG, Ullrich E, Bader P, Wels WS

Abstract
Pre-emptive cancer immunotherapy by donor lymphocyte infusion (DLI) using cytokine-induced killer (CIK) cells may be beneficial to prevent relapse with a reduced risk of causing graft-versus-host-disease (GvHD). CIK cells are a heterogeneous effector cell population including T cells (CD3(+) CD56(-) ), natural killer (NK) cells (CD3(-) CD56(+) ) and natural killer T (T-NK) cells (CD3(+) CD56(+) ) that exhibit non-MHC-restricted cytotoxicity and are generated by ex vivo expansion of peripheral blood mononuclear cells (PBMC) in the presence of interferon (IFN)-γ, anti-CD3 antibody, interleukin-2 (IL-2) and interleukin-15 (IL-15). To facilitate selective target-cell recognition and enhance specific cytotoxicity against B-cell acute lymphoblastic leukemia (B-ALL), we transduced CIK cells with a lentiviral vector encoding a chimeric antigen receptor (CAR) that carries a composite CD28-CD3ζ domain for signaling and a CD19-specific scFv antibody fragment for cell binding (CAR 63.28.z). In vitro analysis revealed high and specific cell killing activity of CD19-targeted CIK/63.28.z cells against otherwise CIK-resistant cancer cell lines and primary B-ALL blasts, which was dependent on CD19 expression and CAR signaling. In a xenograft model in immunodeficient mice, treatment with CIK/63.28.z cells in contrast to therapy with unmodified CIK cells resulted in complete and durable molecular remissions of established primary pre-B-ALL. Our results demonstrate potent anti-leukemic activity of CAR-engineered CIK cells in vitro and in vivo, and suggest this strategy as a promising approach for adoptive immunotherapy of refractory pre-B-ALL. This article is protected by copyright. All rights reserved.

PMID: 27253354 [PubMed - as supplied by publisher]

Modeling and Re-Engineering of Azotobacter vinelandii Alginate Lyase to Enhance Its Catalytic Efficiency for Accelerating Biofilm Degradation.

PLoS One. 2016;11(6):e0156197

Authors: Jang CH, Piao YL, Huang X, Yoon EJ, Park SH, Lee K, Zhan CG, Cho H

Abstract
Alginate is known to prevent elimination of Pseudomonas aeruginosa biofilms. Alginate lyase (AlgL) might therefore facilitate treatment of Pseudomonas aeruginosa-infected cystic fibrosis patients. However, the catalytic activity of wild-type AlgL is not sufficiently high. Therefore, molecular modeling and site-directed mutagenesis of AlgL might assist in enzyme engineering for therapeutic development. AlgL, isolated from Azotobacter vinelandii, catalyzes depolymerization of alginate via a β-elimination reaction. AlgL was modeled based on the crystal structure template of Sphingomonas AlgL species A1-III. Based on this computational analysis, AlgL was subjected to site-directed mutagenesis to improve its catalytic activity. The kcat/Km of the K194E mutant showed a nearly 5-fold increase against the acetylated alginate substrate, as compared to the wild-type. Double and triple mutants (K194E/K245D, K245D/K319A, K194E/K245D/E312D, and K194E/K245D/K319A) were also prepared. The most potent mutant was observed to be K194E/K245D/K319A, which has a 10-fold improved kcat value (against acetylated alginate) compared to the wild-type enzyme. The antibiofilm effect of both AlgL forms was identified in combination with piperacillin/tazobactam (PT) and the disruption effect was significantly higher in mutant AlgL combined with PT than wild-type AlgL. However, for both the wild-type and K194E/K245D/K319A mutant, the use of the AlgL enzyme alone did not show significant antibiofilm effect.

PMID: 27253324 [PubMed - as supplied by publisher]

Lumacaftor/ivacaftor combination for cystic fibrosis patients homozygous for Phe508del-CFTR.

Drugs Today (Barc). 2016 Apr;52(4):229-37

Authors: Zhang W, Zhang X, Zhang YH, Strokes DC, Naren AP

Abstract
Cystic fibrosis (CF) is a life-shortening inherited disease caused by the loss or dysfunction of the CF transmembrane conductance regulator (CFTR) channel activity resulting from mutations in the CFTR gene. Phe508del is the most prevalent mutation, with approximately 90% of all CF patients carrying it on at least one allele. Over the past two or three decades, significant progress has been made in understanding the pathogenesis of CF, and in the development of effective CF therapies. The approval of Orkambi(R) (lumacaftor/ivacaftor) marks another milestone in CF therapeutics development, which, with the advent of personalized medicine, could potentially revolutionize CF care and management. This article reviews the rationale, progress and future direction in the development of lumacaftor/ivacaftor combination to treat CF patients.

PMID: 27252987 [PubMed - in process]

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 2016/06/02

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.