Cystic fibrosis - Comparison between patients in paediatric and adult age.

Rev Port Pneumol (2006). 2016 Oct 13;:

Authors: Santos V, Cardoso AV, Lopes C, Azevedo P, Gamboa F, Amorim A

Abstract
Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians. Although most cases are diagnosed in childhood, diagnosis in adults is apparently increasing.
OBJECTIVE: Evaluate the adult population with CF, comparing patients who were diagnosed before and after 18 years of age.
METHODS: Retrospective analysis of patients followed in three main medical centres in Portugal in 2012. Comparison of two groups: G1 - patients diagnosed at <18 years and G2 - patients diagnosed at ≥18 years.
RESULTS: 89 adults were identified: 61.8% in G1, 38.2% in G2. Gender distribution was similar in both groups. Average age in G2 was higher (38.3±8.4 vs. 26.8±6.1 years, p<0.001). Respiratory symptoms most frequently led to CF diagnosis in all patients, mainly in adulthood. There was a greater percentage of patients homozygous for the mutation delF508 in G1 (43.6 vs. 8.8%, p=0.02). Respiratory and pancreatic function, and body mass index (BMI) showed a higher severity in G1 (G1 vs. G2: FEV1: 54.6±27.3 vs. 29.9±64.6%, p=0.177; pancreatic insufficiency 72.7 vs. 26.5%, p<0.001; BMI 20.2±3.4 vs. 22.2±4.8, p=0.018). Pseudomonas aeruginosa and methicillin-sensitive Staphylococcus aureus were the most frequently isolated microorganisms. Lung transplantation rate was higher in G2 (20.6 vs. 10.9%, p=0.231) while mortality rate was higher in G1 (0 vs. 3.6%, p=0.261). Hospital admission rate was higher in G1 as well as mortality rate.
CONCLUSION: The results suggest that patients with CF diagnosed in childhood have characteristics that distinguish them from those diagnosed in adulthood, and these differences may have implications for diagnosis, prognosis and life expectancy.

PMID: 27743767 [PubMed - as supplied by publisher]

12 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 2016/10/16

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.

Ventilatory limitation and dynamic hyperinflation during exercise testing in Cystic Fibrosis.

Pediatr Pulmonol. 2016 Oct 13;:

Authors: Karapanagiotis S, Gambazza S, Brivio A, D'Abrosca F, Colombo C

Abstract
OBJECTIVE: To investigate the presence of dynamic hyperinflation after the Modified Shuttle Test (MST) and its relationship with lung function, exercise tolerance, and clinical symptoms in Cystic Fibrosis (CF).
METHODS: Retrospective observational study. Subjects in clinically stable condition with a CF diagnosis based on a positive sweat test (chloride >60 mEq/L) and/or presence of two disease causing mutations, with available data on MST, spirometry, maximal voluntary ventilation, and inspiratory capacity manoeuvres were considered for the analysis. Breathing reserve was calculated and a threshold value of 0.7 was subsequently chosen as a value of pulmonary mechanical limit. Subjects were then categorized into two groups according to the change in the inspiratory capacity from rest to peak exercise. Unconditional logistic regression was used to estimate unadjusted odds ratios, 95% confidence intervals and P-values.
RESULTS: Twenty-two subjects demonstrated evidence of dynamic hyperinflation during the MST. Thirteen out of 22 subjects were ventilatory limited during exercise including 5 of those without evidence of dynamic hyperinflation (P = 0.24). No combination of variables resulted in a parsimonious regression model.
CONCLUSIONS: Dynamic hyperinflation is common in CF and it is not associated with traditionally defined ventilatory limitation parameters during the MST. Pediatr Pulmonol. © 2016 Wiley Periodicals, Inc.

PMID: 27736037 [PubMed - as supplied by publisher]

Inhalable Antimicrobials for Treatment of Bacterial Biofilm-Associated Sinusitis in Cystic Fibrosis Patients: Challenges and Drug Delivery Approaches.

Int J Mol Sci. 2016 Oct 09;17(10):

Authors: Kłodzińska SN, Priemel PA, Rades T, Mørck Nielsen H

Abstract
Bacterial biofilm-associated chronic sinusitis in cystic fibrosis (CF) patients caused by Pseudomonas aeruginosa infections and the lack of available treatments for such infections constitute a critical aspect of CF disease management. Currently, inhalation therapies to combat P. aeruginosa infections in CF patients are focused mainly on the delivery of antimicrobials to the lower respiratory tract, disregarding the sinuses. However, the sinuses constitute a reservoir for P. aeruginosa growth, leading to re-infection of the lungs, even after clearing an initial lung infection. Eradication of P. aeruginosa from the respiratory tract after a first infection has been shown to delay chronic pulmonary infection with the bacteria for up to two years. The challenges with providing a suitable treatment for bacterial sinusitis include: (i) identifying a suitable antimicrobial compound; (ii) selecting a suitable device to deliver the drug to the sinuses and nasal cavities; and (iii) applying a formulation design, which will mediate delivery of a high dose of the antimicrobial directly to the site of infection. This review highlights currently available inhalable antimicrobial formulations for treatment and management of biofilm infections caused by P. aeruginosa and discusses critical issues related to novel antimicrobial drug formulation design approaches.

PMID: 27735846 [PubMed - in process]

The cystic fibrosis transmembrane conductance regulator (CFTR) and its stability.

Cell Mol Life Sci. 2016 Oct 12;

Authors: Meng X, Clews J, Kargas V, Wang X, Ford RC

Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) is responsible for the disease cystic fibrosis (CF). It is a membrane protein belonging to the ABC transporter family functioning as a chloride/anion channel in epithelial cells around the body. There are over 1500 mutations that have been characterised as CF-causing; the most common of these, accounting for ~70 % of CF cases, is the deletion of a phenylalanine at position 508. This leads to instability of the nascent protein and the modified structure is recognised and then degraded by the ER quality control mechanism. However, even pharmacologically 'rescued' F508del CFTR displays instability at the cell's surface, losing its channel function rapidly and it is rapidly removed from the plasma membrane for lysosomal degradation. This review will, therefore, explore the link between stability and structure/function relationships of membrane proteins and CFTR in particular and how approaches to study CFTR structure depend on its stability. We will also review the application of a fluorescence labelling method for the assessment of the thermostability and the tertiary structure of CFTR.

PMID: 27734094 [PubMed - as supplied by publisher]

Identification of Burkholderia and Uncommon Glucose Non-fermenting Gram-Negative Bacilli Isolated from Patients with Cystic Fibrosis using Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS).

J Clin Microbiol. 2016 Oct 12;:

Authors: Plongla R, Panagea T, Pincus DH, Jones MC, Gilligan PH

Abstract
Environmental glucose non-fermenting Gram-negative bacilli other than Pseudomonas aeruginosa are frequently isolated from respiratory specimens of patients with cystic fibrosis (CF) (1).….

PMID: 27733629 [PubMed - as supplied by publisher]

Habitat-associated skew of clone abundance in the Pseudomonas aeruginosa population.

Environ Microbiol Rep. 2015 Dec;7(6):955-60

Authors: Wiehlmann L, Cramer N, Tümmler B

Abstract
The population structure of the cosmopolitan Pseudomonas aeruginosa was investigated by genotyping 2921 isolates from 1448 independent habitats with a custom-made 58 binary marker microarray. Of 323 identified clone types, 109 clones made up 82% of the population. The 20 most frequent clones had an absolute share of 44% indicating that the P. aeruginosa population is dominated by few epidemic clonal complexes. The frequency distribution of common clones was different between inanimate habitats and human niches. The three most abundant clones in the environment were rare among isolates from human infection. Conversely, disease-associated isolates either belonged to ubiquitous clones such as C and PA14 or to clones that were uncommon in the environment. The P. aeruginosa population consists of major clones that are just as versatile in their habitat and geographic origin as the whole species and of minor clones with preference for a peculiar niche.

PMID: 26419222 [PubMed - indexed for MEDLINE]

14 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 2016/10/13

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.

A Clinical and Molecular Survey of 62 Cystic Fibrosis Patients from Umbria (Central Italy) Disclosing a High Frequency (2.4%) of the 2184insA Allele: Implications for Screening.

Public Health Genomics. 2016 Oct 12;:

Authors: Prontera P, Isidori I, Mencarini V, Pennoni G, Mencarelli A, Stangoni G, Di Cara G, Verrotti A

Abstract
Genetic testing strategies and counseling in cystic fibrosis (CF) can be problematic due to its extreme allelic heterogeneity and the difficult clinical interpretation of rare variants. Since in a previous survey of Italian CF patients, Umbria (a small region with about 900,000 inhabitants) was excluded due to the low number of chromosomes tested (<50), we have performed a comprehensive retrospective clinical and molecular survey of 62 CF patients coming from this region. We have summarized all the genotypic and phenotypic data in a table, and we interviewed the older patients in order to obtain a comprehensive overview of their conditions. We found that the c.2052_2053insA (2184insA) variant, a class I mutation with high frequency in Eastern Europe but very rare in Italy, is the fourth most frequent allele in Umbria. The 2184insA variant was not included in the first-level regional screening, and we therefore suggest the implementation of this variant in the future.

PMID: 27728908 [PubMed - as supplied by publisher]

Homology Requirements for Efficient, Footprintless Gene Editing at the CFTR Locus in Human iPSCs with Helper-dependent Adenoviral Vectors.

Mol Ther Nucleic Acids. 2016 Oct 11;5(10):e372

Authors: Palmer DJ, Grove NC, Ing J, Crane AM, Venken K, Davis BR, Ng P

Abstract
Helper-dependent adenoviral vectors mediate high efficiency gene editing in induced pluripotent stem cells without needing a designer nuclease thereby avoiding off-target cleavage. Because of their large cloning capacity of 37 kb, helper-dependent adenoviral vectors with long homology arms are used for gene editing. However, this makes vector construction and recombinant analysis difficult. Conversely, insufficient homology may compromise targeting efficiency. Thus, we investigated the effect of homology length on helper-dependent adenoviral vector targeting efficiency at the cystic fibrosis transmembrane conductance regulator locus in induced pluripotent stem cells and found a positive correlation. With 23.8 and 21.4 kb of homology, the frequencies of targeted recombinants were 50-64.6% after positive selection for vector integration, and 97.4-100% after negative selection against random integrations. With 14.8 kb, the frequencies were 26.9-57.1% after positive selection and 87.5-100% after negative selection. With 9.6 kb, the frequencies were 21.4 and 75% after positive and negative selection, respectively. With only 5.6 kb, the frequencies were 5.6-16.7% after positive selection and 50% after negative selection, but these were more than high enough for efficient identification and isolation of targeted clones. Furthermore, we demonstrate helper-dependent adenoviral vector-mediated footprintless correction of cystic fibrosis transmembrane conductance regulator mutations through piggyBac excision of the selectable marker. However, low frequencies (≤ 1 × 10(-3)) necessitated negative selection for piggyBac-excision product isolation.

PMID: 27727248 [PubMed - in process]

A cross-sectional analysis of daytime versus nocturnal polysomnographic respiratory parameters in cystic fibrosis during early adolescence.

J Cyst Fibros. 2016 Oct 8;:

Authors: Waters KA, Lowe A, Cooper P, Vella S, Selvadurai H

Abstract
BACKGROUND: In Cystic Fibrosis (CF), early detection and treatment of respiratory disease is considered the standard for respiratory care. Overnight polysomnography (PSG) may help identify respiratory deterioration in young patients with CF.
METHODS: A prospective cohort study of 46 patients with CF, aged 8-12years, from a specialist clinic in a tertiary paediatric hospital. Daytime pulmonary function, shuttle test exercise testing and overnight PSG were studied.
RESULTS: Of 81 children aged 8-12years, 46 (57%) agreed to participate. FEV1 (% predicted, mean 74.6%) was normal in 23 (50%), mildly abnormal in 12 (26.1%), moderately abnormal in 10 (21.7%) and severely abnormal in 1 (2.2%). Amongst sleep study parameters, FEV1 (% predicted) showed significant correlation with the respiratory rate (RR) in slow wave sleep (SWS), CO2 change in REM, baseline SaO2, and the arousal index (h(-1)). Backward, stepwise linear regression modelling for FEV1 (% predicted) included the entire group with a wide spectrum of clinical severity. From sleep, variables remaining in the multivariate model for FEV1 (F=16.81, p<0.001) were the RR in SWS (min(-1)) and the CO2 change in REM (p=0.003, and 0.014, respectively). When daytime tests were included, the variables remaining were RR in SWS and SD score for BMI (BMIsds) (F=18.70, p<0.001).
CONCLUSIONS: Respiratory abnormalities on overnight sleep studies included elevated respiratory rates during SWS and mild CO2 retention in REM sleep, and these incorporated into a model correlating with FEV1 (% predicted). Thus, mild mechanical impairment of ventilation is evident on overnight sleep studies in children with cystic fibrosis although the significance of this finding will require further investigation.

PMID: 27727099 [PubMed - as supplied by publisher]

An Efficient Power Harvesting Mobile Phone-Based Electrochemical Biosensor for Point-of-Care Health Monitoring.

Sens Actuators B Chem. 2016 Nov 1;235:126-135

Authors: Sun AC, Yao C, Venkatesh AG, Hall DA

Abstract
Cellular phone penetration has grown continually over the past two decades with the number of connected devices rapidly approaching the total world population. Leveraging the worldwide ubiquity and connectivity of these devices, we developed a mobile phone-based electrochemical biosensor platform for point-of-care (POC) diagnostics and wellness tracking. The platform consists of an inexpensive electronic module (< $20) containing a low-power potentiostat that interfaces with and efficiently harvests power from a wide variety of phones through the audio jack. Active impedance matching improves the harvesting efficiency to 79%. Excluding loses from supply rectification and regulation, the module consumes 6.9 mW peak power and can measure < 1 nA bidirectional current. The prototype was shown to operate within the available power budget set by mobile devices and produce data that matches well with that of an expensive laboratory grade instrument. We demonstrate that the platform can be used to track the concentration of secretory leukocyte protease inhibitor (SLPI), a biomarker for monitoring lung infections in cystic fibrosis patients, in its physiological range via an electrochemical sandwich assay on disposable screen-printed electrodes with a 1 nM limit of detection.

PMID: 27725788 [PubMed - in process]

Respiratory Syncytial Virus-associated hospitalization in premature infants who did not receive palivizumab prophylaxis in Italy: a retrospective analysis from the Osservatorio Study.

Ital J Pediatr. 2016 Apr 26;42:40

Authors: Silvestri M, Marando F, Costanzo AM, di Luzio Paparatti U, Rossi GA

Abstract
BACKGROUND: Due to different social and epidemiological factors, the eligibility criteria to receive palivizumab prophylaxis may be different between countries, especially in "otherwise healthy" late preterm infants.
METHODS: We analyzed an Italian database of young children referred to emergency departments for acute lower respiratory tract infection (ALRI) during the RSV season over a four year period, when the use of palivizumab as prophylaxis for RSV disease was not widespread in premature infants. The demographic and environmental characteristics and the RSV positivity (RSV(+)) in hospitalized and not-hospitalized patients were compared. In the data analysis we divided children according to their chronologic age (age) and their week gestational age (wGA).
RESULTS: Out of the 100 children evaluated, 68 were infants (≤12 month-age): 7.5 and 20.6 % were in the <29 and 29- < 32 wGA groups respectively, and 72.0 % in the 32- < 35 wGA group. Positive hospitalized-to-not-hospitalized ratios were found in all three wGA groups, progressively decreasing (from 4.0 to 1.2), with increasing wGA (p = 0.35). The percentage of hospitalized infants that were also RSV(+) was also progressively decreasing (from 40.0 to 28.6 % and 18.4 %) with increasing wGA (p = 0.43). In the >12 month-age group (N = 32), there was positive hospitalized-to-not-hospitalized ratio only in the <29 wGA group with a low RSV(+) frequency (<29 %) in all wGA groups. In the ≤12 month-age group, 41 infants were evaluated with a ≤6 month-age and 27 with a >6-12 month-age. A positive hospitalized-to-not-hospitalized ratios was found in all wGA groups in ≤6 month-age infants, despite a low RSV(+) frequency in the 29- < 32 and 32- < 35 wGA group. In the >6-12 month-age group, all infants with a <29 and 29- < 32 wGA were hospitalized with a relatively high RSV(+) frequency whilst the 32- < 35 wGA group showed a negative hospitalized-to-not-hospitalized ratio with a lower RSV(+) frequency.
CONCLUSIONS: The hospitalized-to-not-hospitalized ratios and RSV(+) frequency in the first 12 months of age in infants born prematurely confirm the vulnerability of these children for clinically important RSV infection, most notably in the <32 wGA category.

PMID: 27112952 [PubMed - indexed for MEDLINE]

9 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 2016/10/11

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.

Molecular modelling and molecular dynamics of CFTR.

Cell Mol Life Sci. 2016 Oct 7;:

Authors: Callebaut I, Hoffmann B, Lehn P, Mornon JP

Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a member of the ATP-binding cassette (ABC) transporter superfamily that functions as an ATP-gated channel. Considerable progress has been made over the last years in the understanding of the molecular basis of the CFTR functions, as well as dysfunctions causing the common genetic disease cystic fibrosis (CF). This review provides a global overview of the theoretical studies that have been performed so far, especially molecular modelling and molecular dynamics (MD) simulations. A special emphasis is placed on the CFTR-specific evolution of an ABC transporter framework towards a channel function, as well as on the understanding of the effects of disease-causing mutations and their specific modulation. This in silico work should help structure-based drug discovery and design, with a view to develop CFTR-specific pharmacotherapeutic approaches for the treatment of CF in the context of precision medicine.

PMID: 27717958 [PubMed - as supplied by publisher]

Analysis of nasal potential in murine cystic fibrosis models.

Int J Biochem Cell Biol. 2016 Oct 4;:

Authors: Cunha MF, Simonin J, Sassi A, Freund R, Hatton A, Cottart CH, Elganfoud N, Zoubairi R, Dragu C, Jais JP, Hinzpeter A, Edelman A, Sermet-Gaudelus I

Abstract
The nasal epithelium of the mouse closely mimics the bioelectrical phenotype of the human airways. Ion transport across the nasal epithelium induces a nasal transepithelial potential difference. Its measurement by a relatively non-invasive method adapted from humans allows in vivo longitudinal measurements of CFTR-dependent ionic transport in the murine nasal mucosa. This test offers a useful tool to assess CFTR function in preclinical studies for novel therapeutics modulating CFTR activity. Here we extensively review work done to assess transepithelial transport in the murine respiratory epithelium in the basal state and after administration of CFTR modulators. Factors of variability and discriminative thresholds between the CF and the WT mice for different readouts are discussed.

PMID: 27717840 [PubMed - as supplied by publisher]

Inquilinus limosus in pulmonary disease: case report and review of the literature.

Diagn Microbiol Infect Dis. 2016 Sep 16;:

Authors: McHugh KE, Rhoads DD, Wilson DA, Highland KB, Richter SS, Procop GW

Abstract
Inquilinus limosus is a slow growing, gram-negative, oxidase-positive, non-fermentative bacillus that is rarely isolated from clinical samples. When clinically identified, I. limosus is almost exclusively isolated from the respiratory tracts of patients with cystic fibrosis (CF). We report the first case of I. limosus isolation from a pulmonary specimen in an individual without a diagnosis of CF. A review of the English-language literature has been made and shows 33 cases (excluding the present report) in which I. limosus was isolated from the respiratory tracts of patients. Our patient, at 60years of age, is more than two decades older than the any previously reported patient. Similar to previous reports, the I. limosus isolated from her lungs demonstrated intrinsic multidrug resistance. The pathogenicity, clinical relevance, and optimal therapeutic management of I. limosus remains largely unknown due to its infrequent recovery from clinical samples.

PMID: 27717651 [PubMed - as supplied by publisher]

10 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 2016/10/08

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 2016/10/07

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.

10 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 2016/10/06

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.