WorldWideScience

Sample records for aeruginosa cystic fibrosis

  1. Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis

    DEFF Research Database (Denmark)

    Johansen, Helle Krogh; Gøtzsche, Peter C

    2013-01-01

    Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed.......Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed....

  2. Pseudomonas aeruginosa biofilms in cystic fibrosis

    DEFF Research Database (Denmark)

    Høiby, Niels; Ciofu, Oana; Bjarnsholt, Thomas

    2010-01-01

    The persistence of chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) patients is due to biofilm-growing mucoid (alginate-producing) strains. A biofilm is a structured consortium of bacteria, embedded in a self-produced polymer matrix consisting of polysaccharide, protein...... and DNA. In CF lungs, the polysaccharide alginate is the major part of the P. aeruginosa biofilm matrix. Bacterial biofilms cause chronic infections because they show increased tolerance to antibiotics and resist phagocytosis, as well as other components of the innate and the adaptive immune system....... As a consequence, a pronounced antibody response develops, leading to immune complex-mediated chronic inflammation, dominated by polymorphonuclear leukocytes. The chronic inflammation is the major cause of the lung tissue damage in CF. Biofilm growth in CF lungs is associated with an increased frequency...

  3. Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis

    DEFF Research Database (Denmark)

    Johansen, H.K.; Gøtzsche, Peter C.; Johansen, Helle Krogh

    2008-01-01

    BACKGROUND: Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. OBJECTIVES......: To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search May 2008) and PubMed using the terms vaccin* AND cystic...... fibrosis (last search May 2008). SELECTION CRITERIA: Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently selected trials...

  4. Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis

    DEFF Research Database (Denmark)

    Johansen, Helle Krogh; Gøtzsche, Peter C

    2015-01-01

    BACKGROUND: Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed....... This is an update of a previously published review. OBJECTIVES: To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30...... March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013). SELECTION CRITERIA: Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic...

  5. Typing of Pseudomonas aeruginosa strains in Norwegian cystic fibrosis patients

    DEFF Research Database (Denmark)

    Fluge, G; Ojeniyi, B; Høiby, N

    2001-01-01

    OBJECTIVES: Typing of Pseudomonas aeruginosa isolates from Norwegian cystic fibrosis (CF) patients with chronic Pseudomonas lung infection in order to see whether cross-infection might have occurred. METHODS: Isolates from 60 patients were collected during the years 1994-98, and typed by pulsed...

  6. Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis.

    Science.gov (United States)

    Johansen, Helle Krogh; Gøtzsche, Peter C

    2015-08-23

    Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. This is an update of a previously published review. To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30 March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013). Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis. The authors independently selected trials, assessed them and extracted data. Six trials were identified. Two trials were excluded since they were not randomised and one old, small trial because it was not possible to assess whether is was randomised. The three included trials comprised 483, 476 and 37 patients, respectively. No data have been published from one of the large trials, but the company stated in a press release that the trial failed to confirm the results from an earlier study and that further clinical development was suspended. In the other large trial, relative risk for chronic infection was 0.91 (95% confidence interval 0.55 to 1.49), and in the small trial, the risk was also close to one. In the large trial, one patient was reported to have died in the observation period. In that trial, 227 adverse events (4 severe) were registered in the vaccine group and 91 (1 severe) in the control group. In this large trial of a vaccine developed against flagella antigens, antibody titres against the epitopes contained in the vaccine were higher in the vaccine group compared to the placebo group (P Vaccines against

  7. Molecular detection of an atypical, highly resistant, clonal Pseudomonas aeruginosa isolate in cystic fibrosis patients.

    LENUS (Irish Health Repository)

    Keating, Deirdre

    2013-03-01

    The identification of Pseudomonas aeruginosa (P. aeruginosa) isolates in sputum from cystic fibrosis (CF) patients can be challenging due to the multitude of phenotypic changes isolates undergo during adaptation to the microenvironment of the CF lung.

  8. Pseudomonas aeruginosa host-adaptation in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Rau, Martin Holm

    Pseudomonas aeruginosa is an opportunistic pathogen capable of transition from an environmental lifestyle to a host-associated lifestyle, as exemplified in the life-long airway infection of cystic fibrosis (CF) patients. Long-term infection is associated with extensive genetic adaptation of P...... the framework upon which this thesis is based. Early P. aeruginosa colonization of the CF airways is the period in which the outcome of infection is determined, i.e. if the bacteria are eventually eradicated or persist. In three patient cases the evolutionary events from initiation of infection were explored...... to unravel the early adaptive processes possibly securing bacterial persistence. In this early stage, clinical isolates displayed few adaptive events however these included phenotypes often observed in late chronic infection isolates including the conversion to a mucoid phenotype and increased antibiotic...

  9. Evolution and Pathoadaptation of Pseudomonas aeruginosa in Cystic Fibrosis Patients

    DEFF Research Database (Denmark)

    Marvig, Rasmus Lykke

    , which is a transmissible clone isolated from chronically infected Danish CF patients over a period of 38 years. Whole-genome analysis of DK2 isolates enabled a finegrained reconstruction of the recent evolutionary history of the DK2 lineage and an identification of bacterial genes targeted by mutations...... to optimize pathogen fitness. The identification of such pathoadaptive genes gives new insight into how the pathogen evolves under the selective pressures of the host immune system and drug therapies. Furthermore, isolates with increased rates of mutation (hypermutator phenotype) emerged in the DK lineage...... is the dominating pathogen of chronic airway infections in patients with cystic fibrosis (CF), and the bacterial long-term persistence in CF hosts involves mutation and selection of genetic variants with increased fitness in the CF airways. We performed a retrospective study of the P. aeruginosa DK2 clone type...

  10. A case of failed eradication of cystic fibrosis-related sinus colonisation by Pseudomonas aeruginosa.

    LENUS (Irish Health Repository)

    Linnane, Barry

    2015-10-01

    Pseudomonas aeruginosa is a pathogen associated with cystic fibrosis that has potential to decrease lung function and cause respiratory failure. Paranasal sinuses are increasingly recognised as potential reservoirs for intermittent colonisation by P. aeruginosa. This case documents investigation and outcome of P. aeruginosa recurrence in a male paediatric patient over an eight year period.

  11. Polymorphonuclear leucocytes consume oxygen in sputum from chronic Pseudomonas aeruginosa pneumonia in cystic fibrosis

    DEFF Research Database (Denmark)

    Kolpen, Mette; Hansen, C. R.; Bjarnsholt, Thomas

    2010-01-01

    BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa is the most severe complication for patients with cystic fibrosis (CF). This infection is characterised by endobronchial mucoid biofilms surrounded by numerous polymorphonuclear leucocytes (PMNs). The mucoid phenotype offers protection...

  12. Within-host microevolution of Pseudomonas aeruginosa in Italian cystic fibrosis patients

    DEFF Research Database (Denmark)

    Marvig, Rasmus Lykke; Dolce, Daniela; Madsen Sommer, Lea Mette

    2015-01-01

    Chronic infection with Pseudomonas aeruginosa is a major cause of morbidity and mortality in cystic fibrosis (CF) patients, and a more complete understanding of P. aeruginosa within-host genomic evolution, transmission, and population genomics may provide a basis for improving intervention strate...

  13. Identification of outer membrane Porin D as a vitronectin-binding factor in cystic fibrosis clinical isolates of Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Paulsson, Magnus; Singh, Birendra; Al-Jubair, Tamim

    2015-01-01

    BACKGROUND: Pseudomonas aeruginosa is a pathogen that frequently colonizes patients with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). Several pathogens are known to bind vitronectin to increase their virulence. Vitronectin has been shown to enhance P. aeruginosa adhesion...

  14. Recent advances in the treatment of Pseudomonas aeruginosa infections in cystic fibrosis

    DEFF Research Database (Denmark)

    Høiby, Niels

    2011-01-01

    Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients is caused by biofilm-growing mucoid strains. Biofilms can be prevented by early aggressive antibiotic prophylaxis or therapy, and they can be treated by chronic suppressive therapy. New results from one small trial sug...... patients without P. aeruginosa infection did not improve lung function. Here I review the recent advances in the treatment of P. aeruginosa lung infections with a focus on inhalation treatments targeted at prophylaxis and chronic suppressive therapy....

  15. Draft Genome Sequences of Pseudomonas aeruginosa B3 Strains Isolated from a Cystic Fibrosis Patient Undergoing Antibiotic Chemotherapy

    DEFF Research Database (Denmark)

    Marvig, Rasmus Lykke; Jochumsen, Nicholas; Johansen, Helle Krogh

    2013-01-01

    Pseudomonas aeruginosa frequently establishes chronic infections in the airways of patients suffering from cystic fibrosis (CF). Here, we report the draft genome sequences of four P. aeruginosa B3 strains isolated from a chronically infected CF patient undergoing antibiotic chemotherapy.......Pseudomonas aeruginosa frequently establishes chronic infections in the airways of patients suffering from cystic fibrosis (CF). Here, we report the draft genome sequences of four P. aeruginosa B3 strains isolated from a chronically infected CF patient undergoing antibiotic chemotherapy....

  16. Diversity of metabolic profiles of cystic fibrosis Pseudomonas aeruginosa during the early stages of lung infection

    DEFF Research Database (Denmark)

    Jørgensen, Karin Meinike; Wassermann, Tina; Johansen, Helle Krogh

    2015-01-01

    Pseudomonas aeruginosa is the dominant pathogen infecting the airways of cystic fibrosis (CF) patients. During the intermittent colonization phase, P. aeruginosa resembles environmental strains but later evolves to the chronic adapted phenotype characterized by resistance to antibiotics and mutat......Pseudomonas aeruginosa is the dominant pathogen infecting the airways of cystic fibrosis (CF) patients. During the intermittent colonization phase, P. aeruginosa resembles environmental strains but later evolves to the chronic adapted phenotype characterized by resistance to antibiotics...

  17. T helper cell subsets specific for Pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Hannah K Bayes

    Full Text Available We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis.Peripheral blood human memory CD4(+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines.Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4(+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6(+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood.Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions.

  18. Molecular mechanisms of fluoroquinolone resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients

    DEFF Research Database (Denmark)

    Jalal, S; Ciofu, O; Høiby, Niels

    2000-01-01

    Twenty P. aeruginosa isolates were collected from six cystic fibrosis (CF) patients, aged 27 to 33, in 1994 (9 isolates) and 1997 (11 isolates) at the CF Center, Copenhagen, Denmark, and were typed by pulse-field gel electrophoresis (PFGE) or ribotyping. Five of the patients had isolates with the......Twenty P. aeruginosa isolates were collected from six cystic fibrosis (CF) patients, aged 27 to 33, in 1994 (9 isolates) and 1997 (11 isolates) at the CF Center, Copenhagen, Denmark, and were typed by pulse-field gel electrophoresis (PFGE) or ribotyping. Five of the patients had isolates...

  19. Epidemiology of Pseudomonas aeruginosa in cystic fibrosis and the possible role of contamination by dental equipment

    DEFF Research Database (Denmark)

    Jensen, E T; Giwercman, B; Ojeniyi, B

    1997-01-01

    Cystic fibrosis (CF) patients often suffer from Pseudomonas aeruginosa lung infection yet the source of this organism is not known. In order to determine whether CF patients might be contaminated with P. aeruginosa from dental equipment, a total of 103 water samples from 25 dental sessions...... samples (5.5%) from nine sessions (11%) were positive for P. aeruginosa. In one case, genotypically identical (RFLP, pulsed-field gel electrophoresis) P. aeruginosa strains were found both in water from the dental equipment and in the CF patients sputum. This indicates a small risk for acquiring P...

  20. SERS detection of the biomarker hydrogen cyanide from Pseudomonas aeruginosa cultures isolated from cystic fibrosis patients

    DEFF Research Database (Denmark)

    Lauridsen, Rikke Kragh; Madsen Sommer, Lea Mette; Johansen, Helle Krogh

    2017-01-01

    Pseudomonas aeruginosa is the primary cause of chronic airway infections in cystic fibrosis (CF) patients. Persistent infections are seen from the first P. aeruginosa culture in about 75% of young CF patients, and it is important to discover new ways to detect P. aeruginosa at an earlier stage...... long-term infection, a mutation in the patho-adaptive lasR gene can alter the expression of HCN, which is why it is sometimes not possible to detect HCN in the breath of chronically infected patients. Four P. aeruginosa reference strains and 12 clinical P. aeruginosa strains isolated from CF children...... were evaluated, and HCN was clearly detected from overnight cultures of all wild type-like isolates and half of the later isolates from the same patients. The clinical impact could be that P. aeruginosa infections could be detected at an earlier stage, because daily breath sampling with an immediate...

  1. Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients

    DEFF Research Database (Denmark)

    Kragh, Kasper Nørskov; Alhede, Morten; Jensen, Peter Østrup

    2014-01-01

    Cystic fibrosis (CF) patients have increased susceptibility to chronic lung infections by Pseudomonas aeruginosa, but the ecophysiology within the CF lung during infections is poorly understood. The aim of this study was to elucidate the in vivo growth physiology of P. aeruginosa within lungs...... of chronically infected CF patients. A novel, quantitative peptide nucleic acid (PNA) fluorescence in situ hybridization (PNA-FISH)-based method was used to estimate the in vivo growth rates of P. aeruginosa directly in lung tissue samples from CF patients and the growth rates of P. aeruginosa in infected lungs...... in a mouse model. The growth rate of P. aeruginosa within CF lungs did not correlate with the dimensions of bacterial aggregates but showed an inverse correlation to the concentration of polymorphonuclear leukocytes (PMNs) surrounding the bacteria. A growth-limiting effect on P. aeruginosa by PMNs was also...

  2. Genotypic and phenotypic analyses of a Pseudomonas aeruginosa chronic bronchiectasis isolate reveal differences from cystic fibrosis and laboratory strains

    NARCIS (Netherlands)

    Varga, J.J.; Barbier, Mariette; Mulet, Xavier; Bielecki, Piotr; Bartell, J.A.; Owings, J.P.; Martinez-Ramos, Inmaculada; Hittle, L.E.; Davis, M.R.; Damron, F.H.; Liechti, G.W.; Puchałka, Jacek; Martins dos Santos, Vitor; Ernst, R.K.; Papin, J.A.; Albertí, Sebastian; Oliver, Antonio; Goldberg, J.B.

    2015-01-01

    Background: Pseudomonas aeruginosa is an environmentally ubiquitous Gram-negative bacterium and important opportunistic human pathogen, causing severe chronic respiratory infections in patients with underlying conditions such as cystic fibrosis (CF) or bronchiectasis. In order to identify

  3. Occurrence of hypermutable Pseudomonas aeruginosa in cystic fibrosis patients is associated with the oxidative stress caused by chronic lung inflammation

    DEFF Research Database (Denmark)

    Ciofu, Oana; Riis, Bente; Pressler, Tacjana

    2005-01-01

    Oxidative stress caused by chronic lung inflammation in patients with cystic fibrosis (CF) and chronic lung infection with Pseudomonas aeruginosa is characterized by the reactive oxygen species (ROS) liberated by polymorphonuclear leukocytes (PMNs). We formulated the hypothesis that oxidation...

  4. Relative contribution of Prevotella intermedia and Pseudomonas aeruginosa to lung pathology in airways of patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Ulrich, Martina; Beer, Isabelle; Braitmaier, Peter

    2010-01-01

    Patients with cystic fibrosis (CF) with Pseudomonas aeruginosa lung infections produce endobronchial mucus plugs allowing growth of obligate anaerobes including Prevotella spp. Whether obligate anaerobes contribute to the pathophysiology of CF lung disease is unknown....

  5. Insights into the respiratory tract microbiota of patients with cystic fibrosis during early Pseudomonas aeruginosa colonization

    Energy Technology Data Exchange (ETDEWEB)

    Keravec, Marlene; Mounier, Jerome; Prestat , Emmanuel; Vallet, Sophie; Jansson, Janet K.; Bergaud , Gaetaqn; Rosec, Silvain; Gourious, Stephanie; Rault, Gilles; Coton, Emmanuel; Barbier, George; Hery-Arnaud, Geneveieve

    2015-08-09

    Abstract Pseudomonas aeruginosa plays a major role in cystic fibrosis (CF) progression. Therefore, it is important to understand the initial steps of P. aeruginosa infection. The structure and dynamics of CF respiratory tract microbial communities during the early stages of P. aeruginosa colonization were characterized by pyrosequencing and cloning-sequencing. The respiratory microbiota showed high diversity, related to the young age of the CF cohort (mean age 10 years). Wide inter- and intra-individual variations were revealed. A common core microbiota of 5 phyla and 13 predominant genera was found, the majority of which were obligate anaerobes. A few genera were significantly more prevalent in patients never infected by P. aeruginosa. Persistence of an anaerobic core microbiota regardless of P. aeruginosa status suggests a major role of certain anaerobes in the pathophysiology of lung infections in CF. Some genera may be potential biomarkers of pulmonary infection state.

  6. Relationship between cystic fibrosis respiratory tract bacterial communities and age, genotype, antibiotics and Pseudomonas aeruginosa.

    Science.gov (United States)

    Klepac-Ceraj, Vanja; Lemon, Katherine P; Martin, Thomas R; Allgaier, Martin; Kembel, Steven W; Knapp, Alixandra A; Lory, Stephen; Brodie, Eoin L; Lynch, Susan V; Bohannan, Brendan J M; Green, Jessica L; Maurer, Brian A; Kolter, Roberto

    2010-05-01

    Polymicrobial bronchopulmonary infections in cystic fibrosis (CF) cause progressive lung damage and death. Although the arrival of Pseudomonas aeruginosa often heralds a more rapid rate of pulmonary decline, there is significant inter-individual variation in the rate of decline, the causes of which remain poorly understood. By coupling culture-independent methods with ecological analyses, we discovered correlations between bacterial community profiles and clinical disease markers in respiratory tracts of 45 children with CF. Bacterial community complexity was inversely correlated with patient age, presence of P. aeruginosa and antibiotic exposure, and was related to CF genotype. Strikingly, bacterial communities lacking P. aeruginosa were much more similar to each other than were those containing P. aeruginosa, regardless of antibiotic exposure. This suggests that community composition might be a better predictor of disease progression than the presence of P. aeruginosa alone and deserves further study.

  7. 2-Aminoacetophenone as a potential breath biomarker for Pseudomonas aeruginosa in the cystic fibrosis lung

    Directory of Open Access Journals (Sweden)

    Laing Richard

    2010-11-01

    Full Text Available Abstract Background Pseudomonas aeruginosa infections are associated with progressive life threatening decline of lung function in cystic fibrosis sufferers. Growth of Ps. aeruginosa releases a "grape-like" odour that has been identified as the microbial volatile organic compound 2-aminoacetophenone (2-AA. Methods We investigated 2-AA for its specificity to Ps. aeruginosa and its suitability as a potential breath biomarker of colonisation or infection by Solid Phase Micro Extraction and Gas Chromatography-Mass Spectrometry (GC/MS. Results Cultures of 20 clinical strains of Ps. aeruginosa but not other respiratory pathogens had high concentrations of 2-AA in the head space of in vitro cultures when analysed by GC/MS. 2-AA was stable for 6 hours in deactivated glass sampling bulbs but was not stable in Tedlar® bags. Optimisation of GC/MS allowed detection levels of 2-AA to low pico mol/mol range in breath. The 2-AA was detected in a significantly higher proportion of subjects colonised with Ps. aeruginosa 15/16 (93.7% than both the healthy controls 5/17 (29% (p Ps. aeruginosa 4/13(30.7% (p Ps. aeruginosa in sputum and/or BALF was 93.8% (95% CI, 67-99 and 69.2% (95% CI, 38-89 respectively. The peak integration values for 2-AA analysis in the breath samples were significantly higher in Ps. aeruginosa colonised subjects (median 242, range 0-1243 than the healthy controls (median 0, range 0-161; p Ps. aeruginosa (median 0, range 0-287; p Conclusions Our results report 2-AA as a promising breath biomarker for the detection of Ps. aeruginosa infections in the cystic fibrosis lung.

  8. Convergent evolution and adaptation of Pseudomonas aeruginosa within patients with cystic fibrosis.

    Science.gov (United States)

    Marvig, Rasmus Lykke; Sommer, Lea Mette; Molin, Søren; Johansen, Helle Krogh

    2015-01-01

    Little is known about how within-host evolution compares between genotypically different strains of the same pathogenic species. We sequenced the whole genomes of 474 longitudinally collected clinical isolates of Pseudomonas aeruginosa sampled from 34 children and young individuals with cystic fibrosis. Our analysis of 36 P. aeruginosa lineages identified convergent molecular evolution in 52 genes. This list of genes suggests a role in host adaptation for remodeling of regulatory networks and central metabolism, acquisition of antibiotic resistance and loss of extracellular virulence factors. Furthermore, we find an ordered succession of mutations in key regulatory networks. Accordingly, mutations in downstream transcriptional regulators were contingent upon mutations in upstream regulators, suggesting that remodeling of regulatory networks might be important in adaptation. The characterization of genes involved in host adaptation may help in predicting bacterial evolution in patients with cystic fibrosis and in the design of future intervention strategies.

  9. Archetypal analysis of diverse Pseudomonas aeruginosa transcriptomes reveals adaptation in cystic fibrosis airways

    DEFF Research Database (Denmark)

    Thøgersen, Juliane Charlotte; Mørup, Morten; Pedersen, Søren Damkiær

    2013-01-01

    is to introduce a method for DNA microarray analysis that provides an intuitive interpretation of data through dimension reduction and pattern recognition. We present the first “Archetypal Analysis” of global gene expression. The analysis is based on microarray data from five integrated studies of Pseudomonas...... aeruginosa isolated from the airways of cystic fibrosis patients. RESULTS: Our analysis clustered samples into distinct groups with comprehensible characteristics since the archetypes representing the individual groups are closely related to samples present in the data set. Significant changes in gene....... This suggests positive selection in the cystic fibrosis lung environment, and changes in gene expression for these isolates are therefore most likely related to adaptation of the bacteria. CONCLUSIONS: Archetypal analysis succeeded in identifying adaptive changes of P. aeruginosa. The combination of clustering...

  10. PFGE and antibiotic susceptibility phenotype analysis of Pseudomonas aeruginosa strain chronically infecting Cystic Fibrosis patients

    Directory of Open Access Journals (Sweden)

    Giovanna Pulcrano

    2008-09-01

    Full Text Available Pseudomonas aeruginosa is the leading cause of chronic lung infection and following pulmonary worsening of cystic fibrosis patients. To verify whether bacterial modifications regarding motility, mucoidy, and serum susceptibility proceeded from an adaptation to chronic infection or a replacement with a new strain, sequential P. aeruginosa isolates of known phenotype collected from 5 cystic fibrosis patients were typed by pulsed-field gel electophoresis (PFGE. Antimicrobial susceptibility testing of all isolates was performed by the disc diffusion method. PFGE typing demonstrated that strains dissimilar in colony morphotype and of different antibiotic susceptibility patterns could be of the same genotype. Some patients were colonized with a rather constant P. aeruginosa flora, with strains of different phenotypes but of one genotype. Instead, some patients may be colonized by more than one genotype. Secretion of mucoid exopolysaccharide and acquisition of a new antibiotic susceptibility phenotype in these strain appear to evolve during chronic colonization in cystic fibrosis patients from specific adaptation to infection rather than from acquisition of new bacterial strains.

  11. Increased serum concentration of G-CSF in cystic fibrosis patients with chronic Pseudomonas aeruginosa pneumonia

    DEFF Research Database (Denmark)

    Jensen, Peter Østrup; Moser, C; Kharazmi, A

    2006-01-01

    BACKGROUND: Chronic Pseudomonas aeruginosa lung infection is the major reason for premature death in patients with cystic fibrosis (CF). Infected patients experience a progressive deterioration of the lung tissue caused by a persistent accumulation of PMNs. We investigated if the pulmonary...... was reduced. CONCLUSION: G-CSF in the sera may contribute to the pulmonary inflammation in CF patients with chronic P. aeruginosa lung infection by regulating the number of PMNs available for migration and may be considered as an indicator of clinical status....

  12. Molecular epidemiology and dynamics of Pseudomonas aeruginosa populations in lungs of cystic fibrosis patients

    DEFF Research Database (Denmark)

    Jelsbak, Lars; Johansen, Helle Krogh; Frost, Anne Louise Viborg

    2007-01-01

    The ability to establish lifelong persistent infections is a fundamental aspect of the interactions between many pathogenic microorganisms and their mammalian hosts. One example is chronic lung infections by the opportunistic pathogen Pseudomonas aeruginosa in cystic fibrosis (CF) patients....... This infection process is associated with extensive genetic adaptation and microevolution of the infecting bacteria. Through investigations of P. aeruginosa populations and infection dynamics in a group of CF patients followed at the Danish CF Clinic in Copenhagen, we have identified two distinct and dominant...

  13. Genome Sequence of Pseudomonas aeruginosa Strain DK1-NH57388A, a Stable Mucoid Cystic Fibrosis Isolate

    DEFF Research Database (Denmark)

    Norman, Anders; Ciofu, Oana; Amador Hierro, Cristina Isabel

    2016-01-01

    Pseudomonas aeruginosa is an important opportunistic pathogen associated with chronic pulmonary infections and mortality in cystic fibrosis (CF) patients. Here, we present the complete genome sequence of stable mucoid P. aeruginosa strain DK1-NH57388A, a CF isolate which has previously been used...

  14. SERS detection of the biomarker hydrogen cyanide from Pseudomonas aeruginosa cultures isolated from cystic fibrosis patients

    Science.gov (United States)

    Lauridsen, Rikke Kragh; Sommer, Lea M.; Johansen, Helle Krogh; Rindzevicius, Tomas; Molin, Søren; Jelsbak, Lars; Engelsen, Søren Balling; Boisen, Anja

    2017-03-01

    Pseudomonas aeruginosa is the primary cause of chronic airway infections in cystic fibrosis (CF) patients. Persistent infections are seen from the first P. aeruginosa culture in about 75% of young CF patients, and it is important to discover new ways to detect P. aeruginosa at an earlier stage. The P. aeruginosa biomarker hydrogen cyanide (HCN) contains a triple bond, which is utilized in this study because of the resulting characteristic C≡N peak at 2135 cm-1 in a Raman spectrum. The Raman signal was enhanced by surface-enhanced Raman spectroscopy (SERS) on a Au-coated SERS substrate. After long-term infection, a mutation in the patho-adaptive lasR gene can alter the expression of HCN, which is why it is sometimes not possible to detect HCN in the breath of chronically infected patients. Four P. aeruginosa reference strains and 12 clinical P. aeruginosa strains isolated from CF children were evaluated, and HCN was clearly detected from overnight cultures of all wild type-like isolates and half of the later isolates from the same patients. The clinical impact could be that P. aeruginosa infections could be detected at an earlier stage, because daily breath sampling with an immediate output could be possible with a point-of-care SERS device.

  15. Eradication of early P. aeruginosa infection in children age with cystic fibrosis: The early study.

    Science.gov (United States)

    Ratjen, Felix; Moeller, Alexander; McKinney, Martha L; Asherova, Irina; Alon, Nipa; Maykut, Robert; Angyalosi, Gerhild

    2018-04-20

    Antibiotic eradication treatment is the standard-of-care for cystic fibrosis (CF) patients with early Pseudomonas aeruginosa (Pa)-infection; however, evidence from placebo-controlled trials is limited. This double-blind, placebo-controlled trial randomised CF patients early Pa-infection to tobramycin inhalation solution (TOBI 300 mg) or placebo (twice daily) for 28 days with an optional cross-over on Day 35. Primary endpoint was proportion of patients having throat swabs/sputum free of Pa on Day 29. On Day 29, 84.6% patients in the TOBI versus 24.0% in the placebo group were Pa-free (p early Pa-infection with a favourable safety profile in young CF patients. NCT01082367. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  16. Cellular responses of A549 alveolar epithelial cells to serially collected Pseudomonas aeruginosa from cystic fibrosis patients at different stages of pulmonary infection

    DEFF Research Database (Denmark)

    Hawdon, Nicole A; Aval, Pouya Sadeghi; Barnes, Rebecca J

    2010-01-01

    Pseudomonas aeruginosa is the major cause of chronic pulmonary disease in cystic fibrosis (CF) patients. During chronic infection, P. aeruginosa lose certain virulence factors, transform into a mucoid phenotype, and develop antibiotic resistance. We hypothesized that these genetic and phenotypic ...

  17. Cystic fibrosis-niche adaptation of Pseudomonas aeruginosa reduces virulence in multiple infection hosts.

    Directory of Open Access Journals (Sweden)

    Nicola Ivan Lorè

    Full Text Available The opportunistic pathogen Pseudomonas aeruginosa is able to thrive in diverse ecological niches and to cause serious human infection. P. aeruginosa environmental strains are producing various virulence factors that are required for establishing acute infections in several host organisms; however, the P. aeruginosa phenotypic variants favour long-term persistence in the cystic fibrosis (CF airways. Whether P. aeruginosa strains, which have adapted to the CF-niche, have lost their competitive fitness in the other environment remains to be investigated. In this paper, three P. aeruginosa clonal lineages, including early strains isolated at the onset of infection, and late strains, isolated after several years of chronic lung infection from patients with CF, were analysed in multi-host model systems of acute infection. P. aeruginosa early isolates caused lethality in the three non-mammalian hosts, namely Caenorhabditis elegans, Galleria mellonella, and Drosophila melanogaster, while late adapted clonal isolates were attenuated in acute virulence. When two different mouse genetic background strains, namely C57Bl/6NCrl and Balb/cAnNCrl, were used as acute infection models, early P. aeruginosa CF isolates were lethal, while late isolates exhibited reduced or abolished acute virulence. Severe histopathological lesions, including high leukocytes recruitment and bacterial load, were detected in the lungs of mice infected with P. aeruginosa CF early isolates, while late isolates were progressively cleared. In addition, systemic bacterial spread and invasion of epithelial cells, which were detected for P. aeruginosa CF early strains, were not observed with late strains. Our findings indicate that niche-specific selection in P. aeruginosa reduced its ability to cause acute infections across a broad range of hosts while maintaining the capacity for chronic infection in the CF host.

  18. Pseudomonas aeruginosa Alters Staphylococcus aureus Sensitivity to Vancomycin in a Biofilm Model of Cystic Fibrosis Infection

    Directory of Open Access Journals (Sweden)

    Giulia Orazi

    2017-07-01

    Full Text Available The airways of cystic fibrosis (CF patients have thick mucus, which fosters chronic, polymicrobial infections. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent respiratory pathogens in CF patients. In this study, we tested whether P. aeruginosa influences the susceptibility of S. aureus to frontline antibiotics used to treat CF lung infections. Using our in vitro coculture model, we observed that addition of P. aeruginosa supernatants to S. aureus biofilms grown either on epithelial cells or on plastic significantly decreased the susceptibility of S. aureus to vancomycin. Mutant analyses showed that 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO, a component of the P. aeruginosa Pseudomonas quinolone signal (PQS system, protects S. aureus from the antimicrobial activity of vancomycin. Similarly, the siderophores pyoverdine and pyochelin also contribute to the ability of P. aeruginosa to protect S. aureus from vancomycin, as did growth under anoxia. Under our experimental conditions, HQNO, P. aeruginosa supernatant, and growth under anoxia decreased S. aureus growth, likely explaining why this cell wall-targeting antibiotic is less effective. P. aeruginosa supernatant did not confer additional protection to slow-growing S. aureus small colony variants. Importantly, P. aeruginosa supernatant protects S. aureus from other inhibitors of cell wall synthesis as well as protein synthesis-targeting antibiotics in an HQNO- and siderophore-dependent manner. We propose a model whereby P. aeruginosa causes S. aureus to shift to fermentative growth when these organisms are grown in coculture, leading to reduction in S. aureus growth and decreased susceptibility to antibiotics targeting cell wall and protein synthesis.

  19. Challenges with current inhaled treatments for chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis.

    LENUS (Irish Health Repository)

    Greally, Peter

    2012-06-01

    Pseudomonas aeruginosa (Pa) is the predominant pathogen infecting the airways of patients with cystic fibrosis (CF). Initial colonization is usually transient and associated with non-mucoid strains, which can be eradicated if identified early. This strategy can prevent, or at least delay, chronic Pa infection, which eventually develops in the majority of patients by their late teens or early adulthood. This article discusses the management and latest treatment developments of Pa lung infection in patients with CF, with a focus on nebulized antibiotic therapy.

  20. Evolution of the Pseudomonas aeruginosa Aminoglycoside Mutational Resistome In Vitro and in the Cystic Fibrosis Setting.

    Science.gov (United States)

    López-Causapé, Carla; Rubio, Rosa; Cabot, Gabriel; Oliver, Antonio

    2018-04-01

    Inhaled administration of high doses of aminoglycosides is a key maintenance treatment of Pseudomonas aeruginosa chronic respiratory infections in cystic fibrosis (CF). We analyzed the dynamics and mechanisms of stepwise high-level tobramycin resistance development in vitro and compared the results with those of isogenic pairs of susceptible and resistant clinical isolates. Resistance development correlated with fusA1 mutations in vitro and in vivo. pmrB mutations, conferring polymyxin resistance, were also frequently selected in vitro In contrast, mutational overexpression of MexXY, a hallmark of aminoglycoside resistance in CF, was not observed in in vitro evolution experiments. Copyright © 2018 American Society for Microbiology.

  1. Controlled trial of inhaled budesonide in patients with cystic fibrosis and chronic bronchopulmonary Psuedomonas aeruginosa infection

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, S S; Nielsen, K G

    1997-01-01

    The efficacy and safety of anti-inflammatory treatment with inhaled glucocorticosteroids in patients with cystic fibrosis (CF) and complicating chronic Pseudomonas aeruginosa (P.a.) lung infection was studied in a placebo-controlled, parallel, double-blind single center trial. Active treatment...... consisted of budesonide dry powder, 800 microg twice daily, delivered from a Turbuhaler. The study period covered two successive 3-mo intervals between elective courses of intravenous anti-Pseudomonas antibiotics. Fifty-five patients entered the study, with a mean age of 20 yr and a mean FEV1 of 63...

  2. Evolution and adaptation of Pseudomonas aeruginosa in cystic fibrosis airways

    DEFF Research Database (Denmark)

    Madsen Sommer, Lea Mette

    of natural environments, the primary obstacle is re-sampling of the samepopulation over time, especially if the population is small.Nevertheless, it has been accomplished: Chronic airway infections of cystic fibrosis (CF) patients have offered a unique view into the adaptationand evolution of Pseudomonas...... to the CF airways. From this analysis we found common clonal lineages among the patients, evidence of patient-to-patient transmission, historic contingencies, and convergent evolution of 52 candidate pathoadaptive genes. By further genome sequencing 26 P. aeruginosa isolates from four Italian CF patients...

  3. Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: an evolutionary perspective

    DEFF Research Database (Denmark)

    Folkesson, Anders; Jelsbak, Lars; Yang, Lei

    2012-01-01

    evolves from a state of early, recurrent intermittent colonization of the airways of patients with CF to a chronic infection state, and how this process offers opportunities to study bacterial evolution in natural environments. We believe that such studies are valuable not only for our understanding......The airways of patients with cystic fibrosis (CF) are nearly always infected with many different microorganisms. This environment offers warm, humid and nutrient-rich conditions, but is also stressful owing to frequent antibiotic therapy and the host immune response. Pseudomonas aeruginosa...... is commonly isolated from the airways of patients with CF, where it most often establishes chronic infections that usually persist for the rest of the lives of the patients. This bacterium is a major cause of mortality and morbidity and has therefore been studied intensely. Here, we discuss how P. aeruginosa...

  4. Archetypal analysis of diverse Pseudomonas aeruginosa transcriptomes reveals adaptation in cystic fibrosis airways

    Science.gov (United States)

    2013-01-01

    Background Analysis of global gene expression by DNA microarrays is widely used in experimental molecular biology. However, the complexity of such high-dimensional data sets makes it difficult to fully understand the underlying biological features present in the data. The aim of this study is to introduce a method for DNA microarray analysis that provides an intuitive interpretation of data through dimension reduction and pattern recognition. We present the first “Archetypal Analysis” of global gene expression. The analysis is based on microarray data from five integrated studies of Pseudomonas aeruginosa isolated from the airways of cystic fibrosis patients. Results Our analysis clustered samples into distinct groups with comprehensible characteristics since the archetypes representing the individual groups are closely related to samples present in the data set. Significant changes in gene expression between different groups identified adaptive changes of the bacteria residing in the cystic fibrosis lung. The analysis suggests a similar gene expression pattern between isolates with a high mutation rate (hypermutators) despite accumulation of different mutations for these isolates. This suggests positive selection in the cystic fibrosis lung environment, and changes in gene expression for these isolates are therefore most likely related to adaptation of the bacteria. Conclusions Archetypal analysis succeeded in identifying adaptive changes of P. aeruginosa. The combination of clustering and matrix factorization made it possible to reveal minor similarities among different groups of data, which other analytical methods failed to identify. We suggest that this analysis could be used to supplement current methods used to analyze DNA microarray data. PMID:24059747

  5. Pulmonary bacteriophage therapy on Pseudomonas aeruginosa cystic fibrosis strains: first steps towards treatment and prevention.

    Directory of Open Access Journals (Sweden)

    Eric Morello

    Full Text Available Multidrug-resistant bacteria are the cause of an increasing number of deadly pulmonary infections. Because there is currently a paucity of novel antibiotics, phage therapy--the use of specific viruses that infect bacteria--is now more frequently being considered as a potential treatment for bacterial infections. Using a mouse lung-infection model caused by a multidrug resistant Pseudomonas aeruginosa mucoid strain isolated from a cystic fibrosis patient, we evaluated bacteriophage treatments. New bacteriophages were isolated from environmental samples and characterized. Bacteria and bacteriophages were applied intranasally to the immunocompetent mice. Survival was monitored and bronchoalveolar fluids were analysed. Quantification of bacteria, bacteriophages, pro-inflammatory and cytotoxicity markers, as well as histology and immunohistochemistry analyses were performed. A curative treatment (one single dose administrated 2 h after the onset of the infection allowed over 95% survival. A four-day preventive treatment (one single dose resulted in a 100% survival. All of the parameters measured correlated with the efficacy of both curative and preventive bacteriophage treatments. We also showed that in vitro optimization of a bacteriophage towards a clinical strain improved both its efficacy on in vivo treatments and its host range on a panel of 20 P. aeruginosa cystic fibrosis strains. This work provides an incentive to develop clinical studies on pulmonary bacteriophage therapy to combat multidrug-resistant lung infections.

  6. Garlic as an inhibitor of Pseudomonas aeruginosa quorum sensing in cystic fibrosis--a pilot randomized controlled trial

    DEFF Research Database (Denmark)

    Smyth, Alan R; Cifelli, Paramita M; Ortori, Catharine A

    2010-01-01

    Pseudomonas aeruginosa forms biofilms in the cystic fibrosis lung. Quorum sensing (QS) controls biofilm maturation, immune evasion, antibiotic tolerance and virulence factor production. Garlic shows QS inhibitory activity in vitro and in animal models. We report the first clinical trial in man of...

  7. Production of N-acyl-L-homoserine lactones by P. aeruginosa isolates from chronic lung infections associated with cystic fibrosis

    DEFF Research Database (Denmark)

    Geisenberger, O; Givskov, M; Riedel, K

    2000-01-01

    The N-acyl-L-homoserine lactones (AHLs) produced by sequential Pseudomonas aeruginosa isolates from chronically infected patients with cystic fibrosis were analyzed by thin-layer chromatography. It is demonstrated that both the amounts and the types of molecules synthesized by isolates from...

  8. IgG avidity to Pseudomonas aeruginosa over the course of chronic lung biofilm infection in cystic fibrosis

    DEFF Research Database (Denmark)

    Mauch, Renan Marrichi; Nørregaard, Lena Lingren; Ciofu, Oana

    2018-01-01

    Background and objectives: The mechanisms leading to low effectiveness of the humoral immune response against P. aeruginosa in cystic fibrosis (CF) are poorly understood. The aim of the present study was to assess the avidity maturation of specific antipseudomonal IgG before and during the develo...

  9. Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection.

    Directory of Open Access Journals (Sweden)

    Mette Kolpen

    Full Text Available Chronic lung infection by Pseudomonas aeruginosa is the major severe complication in cystic fibrosis (CF patients, where P. aeruginosa persists and grows in biofilms in the endobronchial mucus under hypoxic conditions. Numerous polymorphonuclear leukocytes (PMNs surround the biofilms and create local anoxia by consuming the majority of O2 for production of reactive oxygen species (ROS. We hypothesized that P. aeruginosa acquires energy for growth in anaerobic endobronchial mucus by denitrification, which can be demonstrated by production of nitrous oxide (N2O, an intermediate in the denitrification pathway. We measured N2O and O2 with electrochemical microsensors in 8 freshly expectorated sputum samples from 7 CF patients with chronic P. aeruginosa infection. The concentrations of NO3(- and NO2(- in sputum were estimated by the Griess reagent. We found a maximum median concentration of 41.8 µM N2O (range 1.4-157.9 µM N2O. The concentration of N2O in the sputum was higher below the oxygenated layers. In 4 samples the N2O concentration increased during the initial 6 h of measurements before decreasing for approximately 6 h. Concomitantly, the concentration of NO3(- decreased in sputum during 24 hours of incubation. We demonstrate for the first time production of N2O in clinical material from infected human airways indicating pathogenic metabolism based on denitrification. Therefore, P. aeruginosa may acquire energy for growth by denitrification in anoxic endobronchial mucus in CF patients. Such ability for anaerobic growth may be a hitherto ignored key aspect of chronic P. aeruginosa infections that can inform new strategies for treatment and prevention.

  10. Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection.

    Science.gov (United States)

    Kolpen, Mette; Kühl, Michael; Bjarnsholt, Thomas; Moser, Claus; Hansen, Christine Rønne; Liengaard, Lars; Kharazmi, Arsalan; Pressler, Tanja; Høiby, Niels; Jensen, Peter Østrup

    2014-01-01

    Chronic lung infection by Pseudomonas aeruginosa is the major severe complication in cystic fibrosis (CF) patients, where P. aeruginosa persists and grows in biofilms in the endobronchial mucus under hypoxic conditions. Numerous polymorphonuclear leukocytes (PMNs) surround the biofilms and create local anoxia by consuming the majority of O2 for production of reactive oxygen species (ROS). We hypothesized that P. aeruginosa acquires energy for growth in anaerobic endobronchial mucus by denitrification, which can be demonstrated by production of nitrous oxide (N2O), an intermediate in the denitrification pathway. We measured N2O and O2 with electrochemical microsensors in 8 freshly expectorated sputum samples from 7 CF patients with chronic P. aeruginosa infection. The concentrations of NO3(-) and NO2(-) in sputum were estimated by the Griess reagent. We found a maximum median concentration of 41.8 µM N2O (range 1.4-157.9 µM N2O). The concentration of N2O in the sputum was higher below the oxygenated layers. In 4 samples the N2O concentration increased during the initial 6 h of measurements before decreasing for approximately 6 h. Concomitantly, the concentration of NO3(-) decreased in sputum during 24 hours of incubation. We demonstrate for the first time production of N2O in clinical material from infected human airways indicating pathogenic metabolism based on denitrification. Therefore, P. aeruginosa may acquire energy for growth by denitrification in anoxic endobronchial mucus in CF patients. Such ability for anaerobic growth may be a hitherto ignored key aspect of chronic P. aeruginosa infections that can inform new strategies for treatment and prevention.

  11. Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone.

    Science.gov (United States)

    López-Causapé, Carla; Sommer, Lea Mette; Cabot, Gabriel; Rubio, Rosa; Ocampo-Sosa, Alain A; Johansen, Helle Krogh; Figuerola, Joan; Cantón, Rafael; Kidd, Timothy J; Molin, Soeren; Oliver, Antonio

    2017-07-17

    Emergence of epidemic clones and antibiotic resistance development compromises the management of Pseudomonas aeruginosa cystic fibrosis (CF) chronic respiratory infections. Whole genome sequencing (WGS) was used to decipher the phylogeny, interpatient dissemination, WGS mutator genotypes (mutome) and resistome of a widespread clone (CC274), in isolates from two highly-distant countries, Australia and Spain, covering an 18-year period. The coexistence of two divergent CC274 clonal lineages was revealed, but without evident geographical barrier; phylogenetic reconstructions and mutational resistome demonstrated the interpatient transmission of mutators. The extraordinary capacity of P. aeruginosa to develop resistance was evidenced by the emergence of mutations in >100 genes related to antibiotic resistance during the evolution of CC274, catalyzed by mutator phenotypes. While the presence of classical mutational resistance mechanisms was confirmed and correlated with resistance phenotypes, results also showed a major role of unexpected mutations. Among them, PBP3 mutations, shaping up β-lactam resistance, were noteworthy. A high selective pressure for mexZ mutations was evidenced, but we showed for the first time that high-level aminoglycoside resistance in CF is likely driven by mutations in fusA1/fusA2, coding for elongation factor G. Altogether, our results provide valuable information for understanding the evolution of the mutational resistome of CF P. aeruginosa.

  12. Mechanisms of humoral immune response against Pseudomonas aeruginosa biofilm infection in cystic fibrosis

    DEFF Research Database (Denmark)

    Mauch, Renan Marrichi; Jensen, Peter Østrup; Moser, Claus

    2018-01-01

    P. aeruginosa chronic lung infection is the major cause of morbidity and mortality in patients with cystic fibrosis (CF), and is characterized by a biofilm mode of growth, increased levels of specific IgG antibodies and immune complex formation. However, despite being designed to combat...... this infection, such elevated humoral response is not associated with clinical improvement, pointing to a lack of anti-pseudomonas effectiveness. The mode of action of specific antibodies, as well as their structural features, and even the background involving B-cell production, stimulation and differentiation...... into antibody-producing cells in the CF airways are poorly understood. Thus, the aim of this review is to discuss studies that have addressed the intrinsic features of the humoral immune response and provide new insights regarding its insufficiency in the CF context....

  13. The emergence of multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis patients on inhaled antibiotics

    Directory of Open Access Journals (Sweden)

    Atqah AbdulWahab

    2017-01-01

    Full Text Available Introduction: Multidrug-resistant Pseudomonas aeruginosa (MDR-PA is an important and growing issue in the care of patients with cystic fibrosis (CF, and a major cause of morbidity and mortality. Objective: The objective of the study was to describe the frequency of MDR-PA recovered from the lower respiratory samples of pediatric and adult CF patients, and its antibiotic resistance pattern to commonly used antimicrobial agents including β-lactams, aminoglycosides, and fluoroquinolones. Materials and Methods: The lower respiratory isolates of P. aeruginosa were obtained from inpatients and outpatients CF clinics from a tertiary care teaching hospital for the period from October 2014 to September 2015. The identification and antimicrobial susceptibility for all the isolates were performed by using the BD Phoenix™ and E-test in compliance with Clinical and Laboratory Standards Institute (CLSI guidelines. Results: A total of 61 P. aeruginosa samples were isolated from thirty CF patients from twenty families. Twelve sputum samples were positive for MDR-PA (seven nonmucoid and five mucoid isolates from five CF patients (five families with moderate-to-very severe lung disease given MDR-PA frequency of 19.7%. The median age of the study group was 20 (range 10–30 years. Three CF patients were on chronic inhaled tobramycin and two on nebulized colistin. The antimicrobial patterns of isolates MDR-PA showed the highest rate of resistance toward each gentamycin, amikacin, and cefepime (100%, followed by 91.7% to ciprofloxacin, 75% to tobramycin, 58.3% to meropenem, and 50% to piperacillin-tazobactam. None of the isolates were resistant to colistin during the study period. Conclusion: The study results emphasize that the emergence of a significant problem in the clinical isolates of P. aeruginosa in CF patients that dictate appropriate attention to the antibiotic management after proper surveillance.

  14. THE PERFORMANCE OF A LONG-TERM ANTIBACTERIAL THERAPY IN CHILDREN WITH CYSTIC FIBROSIS DURING PRIMARY PLATING OF PSEUDOMONAS AERUGINOSA

    Directory of Open Access Journals (Sweden)

    О. I. Simonova

    2014-01-01

    Full Text Available Background: A long-term plating of Pseudomonas aeruginosa in patients with cystic fibrosis is a sign of damage of the lung tissues with rapid progression of the disease and decrease in a respiratory function. The early pathogen detection is necessary for the timely prescription of an antibiotic for the purpose of a complete eradication of P. aeruginosa. Objective: Our aim was to determine the efficiency and safety of an inhalation form of the colistimethate sodium antibiotic in children with cystic fibrosis during the initial detection of P. aeruginosa. Methods: In a retrospective continuous study it was analyzed the results of inhalation use of the colistimethate sodium in a dose of 2 million IU/day in children with moderate cystic fibrosis with newly diagnosed P. aeruginosa. Results: The analysis included data of 25 children at the age of 2–10 years, 17 of them were treated with colistimethate sodium for 6 months, 8 — for 12 months. P. aeruginosa eradication was detected in 22 (88% children. Children, who received antibiotic therapy for 6 months, at the end of the treatment showed an increase in forced expiratory volume for the 1st second (FEV-1 from 67.1 ± 2.2 to 80.4 ± 1.9% (р = 0.012, but in 3 months without inhalations there was a decrease in indicator values (to 75.9 ± 5.7%; p = 0.069. With the duration of inhalations of 12 months, the value FEV-1 indicator also increased: from 65.9 ± 3.8 to 81.5 ± 3.1% (р = 0.011. However, in the following 3 months without therapy these children did not have any significant decrease in FEV-1 (80.6 ± 3.4%; р = 0.073. There were no allergic reactions during the treatment; bronchospasm was observed in one child. For the entire period of management any P. aeruginosa strain, resistant to the colistimethate sodium, was not revealed. Conclusion: During the initial detection of P. aeruginosa in children with cystic fibrosis, a long-term therapy, including inhalations with colistimethate sodium

  15. Chromosomal mechanisms of aminoglycoside resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients

    DEFF Research Database (Denmark)

    Islam, S; Oh, H; Jalal, S

    2009-01-01

    pump protein MexY was determined by real-time PCR and correlated with susceptibilities to amikacin and tobramycin. The chromosomal genes mexZ, rplY, galU, PA5471 and nuoG, which were found to have a role in the gradual increase in MICs of aminoglycoside antibiotics in laboratory mutants of P....... aeruginosa, were analysed. MexY mRNA overproduction was found in 17/20 isolates collected in 1994 and 1997, and was correlated with decreased susceptibility to aminoglycosides. Alteration of the MexXY-OprM efflux system has been the main mechanism of resistance to aminoglycoside antibiotics in CF P......In total, 40 Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients were included in this study. Twenty of these were collected in 1994 and 1997, from six CF patients, and the rest were collected from different CF patients in 2000 and 2001. The relative expression of mRNA for the efflux...

  16. Ciprofloxacin-loaded PLGA nanoparticles against cystic fibrosis P. aeruginosa lung infections.

    Science.gov (United States)

    Günday Türeli, Nazende; Torge, Afra; Juntke, Jenny; Schwarz, Bianca C; Schneider-Daum, Nicole; Türeli, Akif Emre; Lehr, Claus-Michael; Schneider, Marc

    2017-08-01

    Current pulmonary treatments against Pseudomonas aeruginosa infections in cystic fibrosis (CF) lung suffer from deactivation of the drug and immobilization in thick and viscous biofilm/mucus blend, along with the general antibiotic resistance. Administration of nanoparticles (NPs) with high antibiotic load capable of penetrating the tight mesh of biofilm/mucus can be an advent to overcome the treatment bottlenecks. Biodegradable and biocompatible polymer nanoparticles efficiently loaded with ciprofloxacin complex offer a solution for emerging treatment strategies. NPs were prepared under controlled conditions by utilizing MicroJet Reactor (MJR) to yield a particle size of 190.4±28.6nm with 0.089 PDI. Encapsulation efficiency of the drug was 79% resulting in a loading of 14%. Release was determined to be controlled and medium-independent in PBS, PBS+0.2% Tween 80 and simulated lung fluid. Cytotoxicity assays with Calu-3 cells and CF bronchial epithelial cells (CFBE41o - ) indicated that complex-loaded PLGA NPs were non-toxic at concentrations ≫ MIC cipro against lab strains of the bacteria. Antibacterial activity tests revealed enhanced activity when applied as nanoparticles. NPs' colloidal stability in mucus was proven. Notably, a decrease in mucus turbidity was observed upon incubation with NPs. Herewith, ciprofloxacin complex-loaded PLGA NPs are introduced as promising pulmonary nano drug delivery systems against P.aeruginosa infections in CF lung. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Estrogen aggravates inflammation in Pseudomonas aeruginosa pneumonia in cystic fibrosis mice

    Directory of Open Access Journals (Sweden)

    Gagnon Stéphane

    2010-11-01

    Full Text Available Abstract Background Among patients with cystic fibrosis (CF, females have worse pulmonary function and survival than males, primarily due to chronic lung inflammation and infection with Pseudomonas aeruginosa (P. aeruginosa. A role for gender hormones in the causation of the CF "gender gap" has been proposed. The female gender hormone 17β-estradiol (E2 plays a complex immunomodulatory role in humans and in animal models of disease, suppressing inflammation in some situations while enhancing it in others. Helper T-cells were long thought to belong exclusively to either T helper type 1 (Th1 or type 2 (Th2 lineages. However, a distinct lineage named Th17 is now recognized that is induced by interleukin (IL-23 to produce IL-17 and other pro-inflammatory Th17 effector molecules. Recent evidence suggests a central role for the IL-23/IL-17 pathway in the pathogenesis of CF lung inflammation. We used a mouse model to test the hypothesis that E2 aggravates the CF lung inflammation that occurs in response to airway infection with P. aeruginosa by a Th17-mediated mechanism. Results Exogenous E2 caused adult male CF mice with pneumonia due to a mucoid CF clinical isolate, the P. aeruginosa strain PA508 (PA508, to develop more severe manifestations of inflammation in both lung tissue and in bronchial alveolar lavage (BAL fluid, with increased total white blood cell counts and differential and absolute cell counts of polymorphonuclear leukocytes (neutrophils. Inflammatory infiltrates and mucin production were increased on histology. Increased lung tissue mRNA levels for IL-23 and IL-17 were accompanied by elevated protein levels of Th17-associated pro-inflammatory mediators in BAL fluid. The burden of PA508 bacteria was increased in lung tissue homogenate and in BAL fluid, and there was a virtual elimination in lung tissue of mRNA for lactoferrin, an antimicrobial peptide active against P. aeruginosa in vitro. Conclusions Our data show that E2 increases the

  18. Novel experimental Pseudomonas aeruginosa lung infection model mimicking long-term host-pathogen interactions in cystic fibrosis

    DEFF Research Database (Denmark)

    Moser, Claus; van Gennip, Maria; Bjarnsholt, Thomas

    2009-01-01

    Moser C, van Gennip M, Bjarnsholt T, Jensen PO, Lee B, Hougen HP, Calum H, Ciofu O, Givskov M, Molin S, Hoiby N. Novel experimental Pseudomonas aeruginosa lung infection model mimicking long-term host-pathogen interactions in cystic fibrosis. APMIS 2009; 117: 95-107. The dominant cause of premature...... death in patients suffering from cystic fibrosis (CF) is chronic lung infection with Pseudomonas aeruginosa. The chronic lung infection often lasts for decades with just one clone. However, as a result of inflammation, antibiotic treatment and different niches in the lungs, the clone undergoes...... and 2003) of the chronic lung infection of one CF patient using the seaweed alginate embedment model. The results showed that the non-mucoid clones reduced their virulence over time, resulting in faster clearing of the bacteria from the lungs, improved pathology and reduced pulmonary production...

  19. Differences in prevalence and treatment of Pseudomonas aeruginosa in cystic fibrosis centres in Denmark, Norway and Sweden

    DEFF Research Database (Denmark)

    Knudsen, Per Kristian; Olesen, Hanne V; Hoiby, Niels

    2009-01-01

    BACKGROUND: Chronic Pseudomonas aeruginosa (PA) infection causes increased morbidity and mortality in cystic fibrosis (CF). This study aimed to answer the following questions: Does the prevalence of chronic infection with PA differ between the CF centres in Scandinavia? Which differences exist......) (p=0.037). The pulmonary function was similar. CONCLUSIONS: It is possible to maintain a very low prevalence of chronic PA infection in CF patients

  20. Role of IL-1β in experimental cystic fibrosis upon P. aeruginosa infection.

    Directory of Open Access Journals (Sweden)

    Jennifer Palomo

    Full Text Available Cystic fibrosis is associated with increased inflammatory responses to pathogen challenge. Here we revisited the role of IL-1β in lung pathology using the experimental F508del-CFTR murine model on C57BL/6 genetic background (Cftr(tm1eur or d/d, on double deficient for d/d and type 1 interleukin-1 receptor (d/d X IL-1R1-/-, and antibody neutralization. At steady state, young adult d/d mice did not show any signs of spontaneous lung inflammation. However, IL-1R1 deficiency conferred partial protection to repeated P. aeruginosa endotoxins/LPS lung instillation in d/d mice, as 50% of d/d mice succumbed to inflammation, whereas all d/d x IL-1R1-/- double mutants survived with lower initial weight loss and less pulmonary collagen and mucus production, suggesting that the absence of IL-1R1 signaling is protective in d/d mice in LPS-induced lung damage. Using P. aeruginosa acute lung infection we found heightened neutrophil recruitment in d/d mice with higher epithelial damage, increased bacterial load in BALF, and augmented IL-1β and TNF-α in parenchyma as compared to WT mice. Thus, F508del-CFTR mice show enhanced IL-1β signaling in response to P. aeruginosa. IL-1β antibody neutralization had no effect on lung homeostasis in either d/d or WT mice, however P. aeruginosa induced lung inflammation and bacterial load were diminished by IL-1β antibody neutralization. In conclusion, enhanced susceptibility to P. aeruginosa in d/d mice correlates with an excessive inflammation and with increased IL-1β production and reduced bacterial clearance. Further, we show that neutralization of IL-1β in d/d mice through the double mutation d/d x IL-1R1-/- and in WT via antibody neutralization attenuates inflammation. This supports the notion that intervention in the IL-1R1/IL-1β pathway may be detrimental in CF patients.

  1. The immune response to chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is predominantly of the Th2 type

    DEFF Research Database (Denmark)

    Moser, C; Kjaergaard, S; Pressler, T

    2000-01-01

    Most cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa lung infection have a persistent acute type lung inflammation dominated by polymorphonuclear neutrophils (PMN) and a pronounced antibody response against P. aeruginosa. We speculated whether this immune response in CF...... is of the Th2 type and whether a change to a Th1 type immune response could improve the prognosis. Therefore, we studied 14 CF patients with (CF +P) and 14 CF patients without (CF -P) chronic P. aeruginosa lung infection. The specific production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4......: Rho=0.524; ptype immune response is most frequent in CF patients with chronic P. aeruginosa lung infection, and the patients with a Th1-dominated immune response had the best lung function. The clinical implication is that a change to a Th1 type immune response might...

  2. Genotypic Diversity within a Single Pseudomonas aeruginosa Strain Commonly Shared by Australian Patients with Cystic Fibrosis.

    Directory of Open Access Journals (Sweden)

    Anna Sze Tai

    Full Text Available In cystic fibrosis (CF, Pseudomonas aeruginosa undergoes intra-strain genotypic and phenotypic diversification while establishing and maintaining chronic lung infections. As the clinical significance of these changes is uncertain, we investigated intra-strain diversity in commonly shared strains from CF patients to determine if specific gene mutations were associated with increased antibiotic resistance and worse clinical outcomes. Two-hundred-and-one P. aeruginosa isolates (163 represented a dominant Australian shared strain, AUST-02 from two Queensland CF centres over two distinct time-periods (2001-2002 and 2007-2009 underwent mexZ and lasR sequencing. Broth microdilution antibiotic susceptibility testing in a subset of isolates was also performed. We identified a novel AUST-02 subtype (M3L7 in adults attending a single Queensland CF centre. This M3L7 subtype was multi-drug resistant and had significantly higher antibiotic minimum inhibitory concentrations than other AUST-02 subtypes. Prospective molecular surveillance using polymerase chain reaction assays determined the prevalence of the 'M3L7' subtype at this centre during 2007-2009 (170 patients and 2011 (173 patients. Three-year clinical outcomes of patients harbouring different strains and subtypes were compared. MexZ and LasR sequences from AUST-02 isolates were more likely in 2007-2009 than 2001-2002 to exhibit mutations (mexZ: odds ratio (OR = 3.8; 95% confidence interval (CI: 1.1-13.5 and LasR: OR = 2.5; 95%CI: 1.3-5.0. Surveillance at the adult centre in 2007-2009 identified M3L7 in 28/509 (5.5% P. aeruginosa isolates from 13/170 (7.6% patients. A repeat survey in 2011 identified M3L7 in 21/519 (4.0% P. aeruginosa isolates from 11/173 (6.4% patients. The M3L7 subtype was associated with greater intravenous antibiotic and hospitalisation requirements, and a higher 3-year risk of death/lung transplantation, than other AUST-02 subtypes (adjusted hazard ratio [HR] = 9.4; 95%CI: 2

  3. Advances toward the elucidation of hypertonic saline effects on Pseudomonas aeruginosa from cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Anne-Laure Michon

    Full Text Available OBJECTIVES: Nebulized hypertonic saline (HTS has beneficial effects including reducing pulmonary exacerbations in Cystic Fibrosis (CF patients. Several mechanisms may explain these effects but antimicrobial activity of NaCl remains largely unexplored. We aimed to measure the antimicrobial effect of NaCl on Pseudomonas aeruginosa isolated from the respiratory tract in CF patients. METHODS: NaCl minimal inhibitory concentration (MIC and minimal bactericidal concentration (MBC were determined for strains characterized for mucoidy, antimicrobial resistance, and ability to form biofilm using 0,9% to 15% NaCl solutions. NaCl effects on biofilm formation, preformed biofilm, and mobility were evaluated. Kinetics of antimicrobial effects was studied. RESULTS: The growth of all isolates (n = 85 from 34 patients was inhibited by 6% NaCl solution. A 10% concentration had a bactericidal activity on 90% of the isolates. Mucoid and multidrug resistant (MDR isolates displayed lower MICs compared to non-mucoid and to non-MDR isolates, respectively. Time-kill kinetics showed that NaCl exhibited a rapid, dose and growth phase dependent bactericidal effect. Three percent or more of NaCl inhibited biofilm formation for 69% of strongly adherent isolates. A dose-dependent decrease of preformed biofilm viability and an inhibitory activity on bacterial motility were observed. CONCLUSIONS: NaCl inhibited the growth of all isolates and killed 38% of tested isolates within concentration range currently used in therapeutics. Our results suggest that anti-pseudomonal activity is another mechanism of action of HTS to add to those already established. Clinical trials are needed to compare diverse HTS conditions of use (rhythm, dose and mode of delivery to obtain efficient and optimized anti-P. aeruginosa effects. More generally, NaCl effect on other opportunistic pathogens as well as on global microbiotae recovered during polymicrobial diseases warrants further investigations.

  4. A gacS deletion in Pseudomonas aeruginosa cystic fibrosis isolate CHA shapes its virulence.

    Directory of Open Access Journals (Sweden)

    Khady Mayebine Sall

    Full Text Available Pseudomonas aeruginosa, a human opportunistic pathogen, is capable of provoking acute and chronic infections that are associated with defined sets of virulence factors. During chronic infections, the bacterium accumulates mutations that silence some and activate other genes. Here we show that the cystic fibrosis isolate CHA exhibits a unique virulence phenotype featuring a mucoid morphology, an active Type III Secretion System (T3SS, hallmark of acute infections, and no Type VI Secretion System (H1-T6SS. This virulence profile is due to a 426 bp deletion in the 3' end of the gacS gene encoding an essential regulatory protein. The absence of GacS disturbs the Gac/Rsm pathway leading to depletion of the small regulatory RNAs RsmY/RsmZ and, in consequence, to expression of T3SS, while switching off the expression of H1-T6SS and Pel polysaccharides. The CHA isolate also exhibits full ability to swim and twitch, due to active flagellum and Type IVa pili. Thus, unlike the classical scheme of balance between virulence factors, clinical strains may adapt to a local niche by expressing both alginate exopolysaccharide, a hallmark of membrane stress that protects from antibiotic action, host defences and phagocytosis, and efficient T3S machinery that is considered as an aggressive virulence factor.

  5. Genome Sequence of Pseudomonas aeruginosa Strain DK1-NH57388A, a Stable Mucoid Cystic Fibrosis Isolate

    DEFF Research Database (Denmark)

    Norman, Anders; Ciofu, Oana; Amador Hierro, Cristina Isabel

    2016-01-01

    Pseudomonas aeruginosa is an important opportunistic pathogen associated with chronic pulmonary infections and mortality in cystic fibrosis (CF) patients. Here, we present the complete genome sequence of stable mucoid P. aeruginosa strain DK1-NH57388A, a CF isolate which has previously been used ...

  6. An antisense peptide nucleic acid against Pseudomonas aeruginosa inhibiting bacterial-induced inflammatory responses in the cystic fibrosis IB3-1 cellular model system

    DEFF Research Database (Denmark)

    Montagner, Giulia; Bezzerri, Valentino; Cabrini, Giulio

    2017-01-01

    of the essential acpP gene of P. aeruginosa, and previously shown to inhibit bacterial growth, concomitantly also strongly inhibits induced up-regulation of the pro-inflammatory markers IL-8, IL-6, G-CSF, IFN-γ, IP-10, MCP-1 and TNF-α in IB3-1 cystic fibrosis cells infected by P. aeruginosa PAO1. Remarkably...... are significant considering the key role of this protein in the cystic fibrosis inflammatory process exacerbated by P. aeruginosa infection....

  7. Glucocorticoids can affect Pseudomonas aeruginosa (ATCC 27853) internalization and intracellular calcium concentration in cystic fibrosis bronchial epithelial cells.

    Science.gov (United States)

    Hussain, Rashida; Shahror, Rami; Karpati, Ferenc; Roomans, Godfried M

    2015-01-01

    Glucocorticoids (GCs) are anti-inflammatory agents, but their use in cystic fibrosis (CF) is controversial. In CF, the early colonization with Pseudomonas aeruginosa is mainly due to nonmucoid strains that can internalize, and induce apoptosis in the epithelial cells. Uptake of P. aeruginosa by the epithelial cells and subsequent apoptosis may prevent colonization of P. aeruginosa in CF airways. In the airway epithelia, several other biological effects, including an anti-secretory role by decreasing intracellular Ca(2+) concentration have been described for this anti-inflammatory drug. However, the effects of GCs on the nonmucoid P. aeruginosa internalization and intracellular Ca(2+) in CF bronchial epithelial cells have not been evaluated. We used cultured human CF bronchial airway epithelial cell (CFBE) monolayers to determine P. aeruginosa internalization, apoptosis, and intracellular Ca(2+)concentration in CF bronchial epithelial cells. Cells were treated with IL-6, IL-8, dexamethasone, betamethasone, or budesonide. GCs in co-treatments with IL-6 reversed the effect of IL-6 by decreasing the internalization of P. aeruginosa in the CFBE cells. GCs decreased the extent of apoptosis in CFBE cells infected with internalized P. aeruginosa, and increased the intracellular Ca(2+) concentration. These findings suggest that if internalization of P. aeruginosa reduces infection, GC therapy would increase the risk of pulmonary infection by decreasing the internalization of P. aeruginosa in CF cells, but GCs may improve airway hydration by increasing the intracellular Ca(2+) concentration. Whether the benefits of GC treatment outweigh the negative effects is questionable, and further clinical studies need to be carried out.

  8. Face Masks and Cough Etiquette Reduce the Cough Aerosol Concentration of Pseudomonas aeruginosa in People with Cystic Fibrosis.

    Science.gov (United States)

    Wood, Michelle E; Stockwell, Rebecca E; Johnson, Graham R; Ramsay, Kay A; Sherrard, Laura J; Jabbour, Nassib; Ballard, Emma; O'Rourke, Peter; Kidd, Timothy J; Wainwright, Claire E; Knibbs, Luke D; Sly, Peter D; Morawska, Lidia; Bell, Scott C

    2018-02-01

    People with cystic fibrosis (CF) generate Pseudomonas aeruginosa in droplet nuclei during coughing. The use of surgical masks has been recommended in healthcare settings to minimize pathogen transmission between patients with CF. To determine if face masks and cough etiquette reduce viable P. aeruginosa aerosolized during coughing. Twenty-five adults with CF and chronic P. aeruginosa infection were recruited. Participants performed six talking and coughing maneuvers, with or without face masks (surgical and N95) and hand covering the mouth when coughing (cough etiquette) in an aerosol-sampling device. An Andersen Cascade Impactor was used to sample the aerosol at 2 meters from each participant. Quantitative sputum and aerosol bacterial cultures were performed, and participants rated the mask comfort levels during the cough maneuvers. During uncovered coughing (reference maneuver), 19 of 25 (76%) participants produced aerosols containing P. aeruginosa, with a positive correlation found between sputum P. aeruginosa concentration (measured as cfu/ml) and aerosol P. aeruginosa colony-forming units. There was a reduction in aerosol P. aeruginosa load during coughing with a surgical mask, coughing with an N95 mask, and cough etiquette compared with uncovered coughing (P masks during coughing; yet, participants rated the surgical masks as more comfortable (P = 0.013). Cough etiquette provided approximately half the reduction of viable aerosols of the mask interventions during voluntary coughing. Talking was a low viable aerosol-producing activity. Face masks reduce cough-generated P. aeruginosa aerosols, with the surgical mask providing enhanced comfort. Cough etiquette was less effective at reducing viable aerosols.

  9. Sputum Active Polymyxin Lipopeptides: Activity against Cystic Fibrosis Pseudomonas aeruginosa Isolates and Their Interactions with Sputum Biomolecules.

    Science.gov (United States)

    Schneider-Futschik, Elena K; Paulin, Olivia K A; Hoyer, Daniel; Roberts, Kade D; Ziogas, James; Baker, Mark A; Karas, John; Li, Jian; Velkov, Tony

    2018-05-11

    The mucoid biofilm mode of growth of Pseudomonas aeruginosa ( P. aeruginosa) in the lungs of cystic fibrosis patients makes eradication of infections with antibiotic therapy very difficult. The lipopeptide antibiotics polymyxin B and colistin are currently the last-resort therapies for infections caused by multidrug-resistant P. aeruginosa. In the present study, we investigated the antibacterial activity of a series of polymyxin lipopeptides (polymyxin B, colistin, FADDI-003, octapeptin A 3 , and polymyxin A 2 ) against a panel of polymyxin-susceptible and polymyxin-resistant P. aeruginosa cystic fibrosis isolates grown under planktonic or biofilm conditions in artificial sputum and their interactions with sputum component biomolecules. In sputum media under planktonic conditions, the lipopeptides FADDI-003 and octapeptin A 3 displayed very promising activity against the polymyxin-resistant isolate FADDI-PA066 (polymyxin B minimum inhibitory concentration (MIC) = 32 mg/L), while retaining their activity against the polymyxin-sensitive strains FADDI-PA021 (polymyxin B MIC = 1 mg/L) and FADDI-PA020 (polymyxin B MIC = 2 mg/L). Polymyxin A 2 was only effective against the polymyxin-sensitive isolates. However, under biofilm growth conditions, the hydrophobic lipopeptide FADDI-003 was inactive compared to the more hydrophilic lipopeptides, octapeptin A 3 , polymyxin A 2 , polymyxin B, and colistin. Transmission electron micrographs revealed octapeptin A 3 caused reduction in the cell numbers in biofilm as well as biofilm disruption/"antibiofilm" activity. We therefore assessed the interactions of the lipopeptides with the component sputum biomolecules, mucin, deoxyribonucleic acid (DNA), surfactant, F-actin, lipopolysaccharide, and phospholipids. We observed the general trend that sputum biomolecules reduce lipopeptide antibacterial activity. Collectively, our data suggests that, in the airways, lipopeptide binding to component sputum biomolecules may reduce

  10. Convergent evolution and adaptation of Pseudomonas aeruginosa within patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Marvig, Rasmus Lykke; Madsen Sommer, Lea Mette; Molin, Søren

    2015-01-01

    fibrosis. Our analysis of 36 P. aeruginosa lineages identified convergent molecular evolution in 52 genes. This list of genes suggests a role in host adaptation for remodeling of regulatory networks and central metabolism, acquisition of antibiotic resistance and loss of extracellular virulence factors....... Furthermore, we find an ordered succession of mutations in key regulatory networks. Accordingly, mutations in downstream transcriptional regulators were contingent upon mutations in upstream regulators, suggesting that remodeling of regulatory networks might be important in adaptation. The characterization...

  11. Ciprofloxacin-loaded PLGA nanoparticles against Cystic Fibrosis P. aeruginosa Lung Infections.

    OpenAIRE

    Günday Türeli, Nazende; Torge, Afra; Juntke, Jenny; Schwarz, Bianca C; Schneider-Daum, Nicole; Türeli, Akif Emre; Lehr, Claus-Michael; Schneider, Marc

    2017-01-01

    Current pulmonary treatments against Pseudomonasaeruginosa infections in cystic fibrosis (CF) lung suffer from deactivation of the drug and immobilization in thick and viscous biofilm/mucus blend, along with the general antibiotic resistance. Administration of nanoparticles (NPs) with high antibiotic load capable of penetrating the tight mesh of biofilm/mucus can be an advent to overcome the treatment bottlenecks. Biodegradable and biocompatible polymer nanoparticles efficiently loaded with c...

  12. Platelet 3H-serotonin releasing immune complexes induced by pseudomonas aeruginosa in cystic fibrosis

    International Nuclear Information System (INIS)

    Permin, H.; Stahl Skov, P.; Norn, S.; Hoeiby, N.; Schioetz, P.O.

    1982-01-01

    In vitro formation of immune complexes was studied by 3 H-serotonin release from human platelets by P. aeruginosa antigens in the presence of serum from 22 cyctic fibrosis patients, chronically infected with mucoid P. aeruginosa (CF+P) and with a pronounced antibody response against these bacteria, and in 24 patients without P. aeruginosa (CF-P). All CF+P patients responded with 3 H-serotonin release (16-34%), whereas CF-P patients released less than 15%. In the group of CF+P patients the number of P. aeruginosa precipitins was correlated to the serotonin titer. Time courses indicated that 3 H-serotonin release was maximal between 2 and 5 min, and that no further release was observed up to 20 min. There was a gradual increase in 3 H-serotonin release with higher platelet concentrations. The response was not changed by complement inactivation, and fractionation of serum demonstrated that the serotonin release was dependent on the presence of the immunoglobulin fraction. These experiments support the suggestion of a type III reaction being involved in the lung damage in CF+P patients and also suggest a possible involvement of serotonin in the inflammatory reaction during chronic P. aeruginosa lung infection. (author)

  13. Cystic Fibrosis (CF): Chloride Sweat Test

    Science.gov (United States)

    ... on this topic for: Parents Kids Teens Cystic Fibrosis Cystic Fibrosis and Nutrition Cystic Fibrosis (CF) Respiratory Screen: Sputum Cystic Fibrosis: Diet and Nutrition Cystic Fibrosis Cystic Fibrosis: Diet and Nutrition View more Partner Message ...

  14. Cystic fibrosis: case report

    International Nuclear Information System (INIS)

    Park, Si Hyun; Lee, Hyun Ju; Kim, Ji Hye; Park, Chol Heui

    2002-01-01

    Cystic fibrosis is an autosomal recessive genetic disease. Among Caucasians, it is the most common cause of pulmonary insufficiency during the first three decades of life. The prevalence of cystic fibrosis varies according to ethnic origin: it is common among Caucasians but rare among Asians. We report a case in which cystic fibrosis with bronchiectasis and hyperaeration was revealed by high-resolution CT, and mutation of the cystic fibrosis conductance transmembrane regulator gene (CFTR) by DNA analysis

  15. Cystic fibrosis: case report

    International Nuclear Information System (INIS)

    Park, Si Hyun; Lee, Hyun Ju; Kim, Ji Hye; Park, Chol Heui

    2002-01-01

    Cystic fibrosis is a autosomal recessive genetic disease. Among caucasians, it is the most common cause of pulmonary insufficiency during the first three decades of life. The prevalence of cystic fibrosis varies according to ethnic origin: it is common among caucasians but rare among Asians. We report a case in which cystic fibrosis with bronchiectasis and hyperaeration was revealed by high-resolution CT, and mutation of the cystic fibrosis conductance transmembrane regulator gene (CFTR) by DNA analysis

  16. Differentiation of pulmonary bacterial pathogens in cystic fibrosis by volatile metabolites emitted by their in vitro cultures: Pseudomonas aeruginosa, Staphylococcus aureus, Stenotrophomonas maltophilia and the Burkholderia cepacia complex

    Czech Academy of Sciences Publication Activity Database

    Dryahina, Kseniya; Sovová, Kristýna; Nemec, A.; Španěl, Patrik

    2016-01-01

    Roč. 10, AUG 2016 (2016), s. 037102 ISSN 1752-7155 R&D Projects: GA ČR(CZ) GA14-14534S Institutional support: RVO:61388955 Keywords : Burkholderia cepacia complex * Pseudomonas aeruginosa * cystic fibrosis Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.318, year: 2016

  17. Relative contribution of Prevotella intermedia and Pseudomonas aeruginosa to lung pathology in airways of patients with cystic fibrosis.

    Science.gov (United States)

    Ulrich, Martina; Beer, Isabelle; Braitmaier, Peter; Dierkes, Michaela; Kummer, Florian; Krismer, Bernhard; Schumacher, Ulrike; Gräpler-Mainka, Ute; Riethmüller, Joachim; Jensen, Peter Ø; Bjarnsholt, Thomas; Høiby, Niels; Bellon, Gabriel; Döring, Gerd

    2010-11-01

    Patients with cystic fibrosis (CF) with Pseudomonas aeruginosa lung infections produce endobronchial mucus plugs allowing growth of obligate anaerobes including Prevotella spp. Whether obligate anaerobes contribute to the pathophysiology of CF lung disease is unknown. The virulence of Prevotella intermedia and Ps aeruginosa was investigated in vitro and in mice, antibodies against P intermedia in CF sera were assessed and a culture-independent detection method for P intermedia/P nigrescens in CF sputum was tested. P intermedia reached cell numbers of >10(5)->10(7) colony-forming units (CFU)/ml sputum. The majority of patients with CF (16/17; 94.1%) produced antibodies against two immunoreactive antigens of P intermedia. Culture supernatant fluids, collected from 10(9) P intermedia cells, were more cytotoxic to respiratory epithelial cells in vitro and inflammatory in mouse lungs than respective fluids from anaerobically grown Ps aeruginosa, while fluids from aerobically grown Ps aeruginosa had the highest cytotoxicity and inflammation. Both pathological effects were largely reduced when culture supernatant fluids from 10(7) cells of either species were used. P intermedia cells (∼10(6)CFU/lung) did not induce mortality in the agar beads lung infection mouse model, while Ps aeruginosa cells caused death in 30% of mice due to rapid multiplication. A P intermedia/P nigrescens-specific PNA probe was significantly more sensitive than culture-dependent diagnostic assays to detect these strict anaerobes. Ps aeruginosa and P intermedia become significantly virulent in vitro and in vivo when cell numbers exceed 10(8) CFU/lung.

  18. Assessment of serology and spirometry and the combination of both to complement microbiological isolation for earlier detection of Pseudomonas aeruginosa infection in children with cystic fibrosis.

    Science.gov (United States)

    Kotnik Pirš, Ana; Krivec, Uroš; Simčič, Saša; Seme, Katja

    2016-11-25

    The aim of this study was to assess whether serology and spirometry and the combination of both can complement culture-based detection for earlier recognition of Pseudomonas aeruginosa infection in children with cystic fibrosis. A 4 year longitudinal prospective study that included 67 Slovenian children with cystic fibrosis with a mean age of 10.5 years was conducted. Serology, spirometry and a scoring system combining serology and spirometry were assessed and compared. Infection was confirmed with isolation of Pseudomonas aeruginosa from respiratory samples. There was a significantly positive correlation between serology and the combination of serology and spirometry and Pseudomonas aeruginosa isolation (P spirometry and Pseudomonas aeruginosa isolation (P spirometry the highest sensitivity (0.90). Both had a high negative predictive value (0.93 and 0.79 respectively). Using serology and the combination of serology and lung function measurement can be beneficial for earlier detection of infection with Pseudomonas aeruginosa in children with cystic fibrosis when done simultaneously with standard culture-based detection from respiratory samples.

  19. Phenotypic and Genotypic Comparison of Epidemic and Non-Epidemic Strains of Pseudomonas aeruginosa from Individuals with Cystic Fibrosis.

    Directory of Open Access Journals (Sweden)

    Jessica Duong

    Full Text Available Epidemic strains of Pseudomonas aeruginosa have been found worldwide among the cystic fibrosis (CF patient population. Using pulse-field gel electrophoresis, the Prairie Epidemic Strain (PES has recently been found in one-third of patients attending the Calgary Adult CF Clinic in Canada. Using multi-locus sequence typing, PES isolates from unrelated patients were found to consistently have ST192. Though most patients acquired PES prior to enrolling in the clinic, some patients were observed to experience strain replacement upon transitioning to the clinic whereby local non-epidemic P. aeruginosa isolates were displaced by PES. Here we genotypically and phenotypically compared PES to other P. aeruginosa epidemic strains (OES found around the world as well as local non-epidemic CF P. aeruginosa isolates in order to characterize PES. Since some epidemic strains are associated with worse clinical outcomes, we assessed the pathogenic potential of PES to determine if these isolates are virulent, shared properties with OES, and if its phenotypic properties may offer a competitive advantage in displacing local non-epidemic isolates during strain replacement. As such, we conducted a comparative analysis using fourteen phenotypic traits, including virulence factor production, biofilm formation, planktonic growth, mucoidy, and antibiotic susceptibility to characterize PES, OES, and local non-epidemic isolates. We observed that PES and OES could be differentiated from local non-epidemic isolates based on biofilm growth with PES isolates being more mucoid. Pairwise comparisons indicated that PES produced significantly higher levels of proteases and formed better biofilms than OES but were more susceptible to antibiotic treatment. Amongst five patients experiencing strain replacement, we found that super-infecting PES produced lower levels of proteases and elastases but were more resistant to antibiotics compared to the displaced non-epidemic isolates. This

  20. Pseudomonas aeruginosa adaptation to lungs of cystic fibrosis patients leads to lowered resistance to phage and protist enemies.

    Directory of Open Access Journals (Sweden)

    Ville-Petri Friman

    Full Text Available Pathogenic life styles can lead to highly specialized interactions with host species, potentially resulting in fitness trade-offs in other ecological contexts. Here we studied how adaptation of the environmentally transmitted bacterial pathogen, Pseudomonas aeruginosa, to cystic fibrosis (CF patients affects its survival in the presence of natural phage (14/1, ΦKZ, PNM and PT7 and protist (Tetrahymena thermophila and Acanthamoebae polyphaga enemies. We found that most of the bacteria isolated from relatively recently intermittently colonised patients (1-25 months, were innately phage-resistant and highly toxic for protists. In contrast, bacteria isolated from long time chronically infected patients (2-23 years, were less efficient in both resisting phages and killing protists. Moreover, chronic isolates showed reduced killing of wax moth larvae (Galleria mellonella probably due to weaker in vitro growth and protease expression. These results suggest that P. aeruginosa long-term adaptation to CF-lungs could trade off with its survival in aquatic environmental reservoirs in the presence of microbial enemies, while lowered virulence could reduce pathogen opportunities to infect insect vectors; factors that are both likely to result in poorer environmental transmission. From an applied perspective, phage therapy could be useful against chronic P. aeruginosa lung infections that are often characterized by multidrug resistance: chronic isolates were least resistant to phages and their poor growth will likely slow down the emergence of beneficial resistance mutations.

  1. Bacteriophage-derived enzyme that depolymerizes the alginic acid capsule associated with cystic fibrosis isolates of Pseudomonas aeruginosa.

    Science.gov (United States)

    Glonti, T; Chanishvili, N; Taylor, P W

    2010-02-01

    To identify enzymes associated with bacteriophages infecting cystic fibrosis (CF) strains of Pseudomonas aeruginosa that are able to degrade extracellular alginic acids elaborated by the host bacterium. Plaques produced by 21 Ps. aeruginosa-specific phages were screened for the presence of haloes, an indicator of capsule hydrolytic activity. Four phages produced haloed plaques, and one (PT-6) was investigated further. PT-6 was shown by electron microscopy to belong to Podoviridae family C1, to reduce the viscosity of four alginate preparations using a rolling ball viscometer and to release uronic acid-containing fragments from the polymers, as judged by spectrophotometry and thin layer chromatography. The alginase was partially purified by gel filtration chromatography and shown to be a 37 kDa polypeptide. Infection of CF strains of Ps. aeruginosa by phage PT-6 involves hydrolysis of the exopolysaccharide secreted by the host. The alginase produced by PT-6 has the potential to increase the well-being of CF suffers by improving the surface properties of sputum, accelerating phagocytic uptake of bacteria and perturbing bacterial growth in biofilms.

  2. Macrolides decrease the minimal inhibitory concentration of anti-pseudomonal agents against Pseudomonas aeruginosa from cystic fibrosis patients in biofilm

    Directory of Open Access Journals (Sweden)

    Lutz Larissa

    2012-09-01

    Full Text Available Abstract Background Biofilm production is an important mechanism for bacterial survival and its association with antimicrobial resistance represents a challenge for the patient treatment. In this study we evaluated the in vitro action of macrolides in combination with anti-pseudomonal agents on biofilm-grown Pseudomonas aeruginosa recovered from cystic fibrosis (CF patients. Results A total of 64 isolates were analysed. The biofilm inhibitory concentration (BIC results were consistently higher than those obtained by the conventional method, minimal inhibitory concentration, (MIC for most anti-pseudomonal agents tested (ceftazidime: P = 0.001, tobramycin: P = 0.001, imipenem: P P = 0.005. When macrolides were associated with the anti-pseudomonal agents, the BIC values were reduced significantly for ceftazidime (P  0.001 and tobramycin (P  0.001, regardless the concentration of macrolides. Strong inhibitory quotient was observed when azithromycin at 8 mg/L was associated with all anti-pseudomonal agents tested in biofilm conditions. Conclusions P. aeruginosa from CF patients within biofilms are highly resistant to antibiotics but macrolides proved to augment the in vitro activity of anti-pseudomonal agents.

  3. Cystic Fibrosis Transmembrane Conductance Regulator Attaches Tumor Suppressor PTEN to the Membrane and Promotes Anti Pseudomonas aeruginosa Immunity.

    Science.gov (United States)

    Riquelme, Sebastián A; Hopkins, Benjamin D; Wolfe, Andrew L; DiMango, Emily; Kitur, Kipyegon; Parsons, Ramon; Prince, Alice

    2017-12-19

    The tumor suppressor PTEN controls cell proliferation by regulating phosphatidylinositol-3-kinase (PI3K) activity, but the participation of PTEN in host defense against bacterial infection is less well understood. Anti-inflammatory PI3K-Akt signaling is suppressed in patients with cystic fibrosis (CF), a disease characterized by hyper-inflammatory responses to airway infection. We found that Ptenl -/- mice, which lack the NH 2 -amino terminal splice variant of PTEN, were unable to eradicate Pseudomonas aeruginosa from the airways and could not generate sufficient anti-inflammatory PI3K activity, similar to what is observed in CF. PTEN and the CF transmembrane conductance regulator (CFTR) interacted directly and this interaction was necessary to position PTEN at the membrane. CF patients under corrector-potentiator therapy, which enhances CFTR transport to the membrane, have increased PTEN amounts. These findings suggest that improved CFTR trafficking could enhance P. aeruginosa clearance from the CF airway by activating PTEN-mediated anti-bacterial responses and might represent a therapeutic strategy. Published by Elsevier Inc.

  4. Neonatal cystic fibrosis screening test

    Science.gov (United States)

    Cystic fibrosis screening - neonatal; Immunoreactive trypsinogen; IRT test; CF - screening ... Cystic fibrosis is a disease passed down through families. CF causes thick, sticky mucus to build up in ...

  5. Early adaptive developments of Pseudomonas aeruginosa after the transition from life in the environment to persistent colonization in the airways of human cystic fibrosis hosts

    DEFF Research Database (Denmark)

    Rau, Martin Holm; Hansen, Susse Kirkelund; Johansen, H. K.

    2010-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen ubiquitous to the natural environment but with the capability of moving to the host environment. Long-term infection of the airways of cystic fibrosis patients is associated with extensive genetic adaptation of P. aeruginosa, and we have studied...... cases of the initial stages of infection in order to characterize the early adaptive processes in the colonizing bacteria. A combination of global gene expression analysis and phenotypic characterization of longitudinal isolates from cystic fibrosis patients revealed well-known characteristics...... such as conversion to a mucoid phenotype by mucA mutation and increased antibiotic resistance by nfxB mutation. Additionally, upregulation of the atu operon leading to enhanced growth on leucine provides a possible example of metabolic optimization. A detailed investigation of the mucoid phenotype uncovered profound...

  6. Metabolite Profiling to Characterize Disease-related Bacteria GLUCONATE EXCRETION BY PSEUDOMONAS AERUGINOSA MUTANTS AND CLINICAL ISOLATES FROM CYSTIC FIBROSIS PATIENTS

    OpenAIRE

    Behrends, V; Bell, TJ; Liebeke, M; Cordes-Blauert, A; Ashraf, SN; Nair, C; Zlosnik, JEA; Williams, HD; Bundy, JG

    2013-01-01

    Metabolic footprinting of supernatants has been proposed as a tool for assigning gene function. We used NMR spectroscopy to measure the exometabolome of 86 single-gene transposon insertion mutant strains (mutants from central carbon metabolism and regulatory mutants) of the opportunistic pathogen Pseudomonas aeruginosa, grown on a medium designed to represent the nutritional content of cystic fibrosis sputum. Functionally related genes had similar metabolic profiles. E.g. for two-component sy...

  7. Initial Pseudomonas aeruginosa infection in patients with cystic fibrosis: characteristics of eradicated and persistent isolates

    DEFF Research Database (Denmark)

    Tramper-Stranders, G. A.; van der Ent, C. K.; Molin, Søren

    2012-01-01

    Clin Microbiol Infect 2012; 18: 567574 Abstract Despite intensive eradication therapy, some CF patients with early Pseudomonas aeruginosa infection rapidly develop a chronic infection. To elucidate factors associated with this persistence, bacterial characteristics of early P. aeruginosa isolates...

  8. Diagnosis of cystic fibrosis

    NARCIS (Netherlands)

    H.J. Veeze

    1995-01-01

    textabstractApplying the sweat-test as the first choice of test when a diagnosis of cystic fibrosis is suspected is still common practice and advisable. Since the cloning of the CFTR gene more than 400 different cystic fibrosis (CF) mutations have already been identified. The use of CF mutation

  9. Clonal dissemination, emergence of mutator lineages and antibiotic resistance evolution in Pseudomonas aeruginosa cystic fibrosis chronic lung infection.

    Directory of Open Access Journals (Sweden)

    Carla López-Causapé

    Full Text Available Chronic respiratory infection by Pseudomonas aeruginosa is a major cause of mortality in cystic fibrosis (CF. We investigated the interplay between three key microbiological aspects of these infections: the occurrence of transmissible and persistent strains, the emergence of variants with enhanced mutation rates (mutators and the evolution of antibiotic resistance. For this purpose, 10 sequential isolates, covering up to an 8-year period, from each of 10 CF patients were studied. As anticipated, resistance significantly accumulated overtime, and occurred more frequently among mutator variants detected in 6 of the patients. Nevertheless, highest resistance was documented for the nonmutator CF epidemic strain LES-1 (ST-146 detected for the first time in Spain. A correlation between resistance profiles and resistance mechanisms evaluated [efflux pump (mexB, mexD, mexF, and mexY and ampC overexpression and OprD production] was not always obvious and hypersusceptibility to certain antibiotics (such as aztreonam or meropenem was frequently observed. The analysis of whole genome macrorestriction fragments through Pulsed-Field Gel Electrophoresis (PFGE revealed that a single genotype (clone FQSE-A produced persistent infections in 4 of the patients. Multilocus Sequence typing (MLST identified clone FQSE-A as the CF epidemic clone ST-274, but striking discrepancies between PFGE and MLST profiles were evidenced. While PFGE macrorestriction patterns remained stable, a new sequence type (ST-1089 was detected in two of the patients, differing from ST-274 by only two point mutations in two of the genes, each leading to a nonpreviously described allele. Moreover, detailed genetic analyses revealed that the new ST-1089 is a mutS deficient mutator lineage that evolved from the epidemic strain ST-274, acquired specific resistance mechanisms, and underwent further interpatient spread. Thus, presented results provide the first evidence of interpatient dissemination

  10. Biofilm Filtrates of Pseudomonas aeruginosa Strains Isolated from Cystic Fibrosis Patients Inhibit Preformed Aspergillus fumigatus Biofilms via Apoptosis.

    Science.gov (United States)

    Shirazi, Fazal; Ferreira, Jose A G; Stevens, David A; Clemons, Karl V; Kontoyiannis, Dimitrios P

    2016-01-01

    Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) colonize cystic fibrosis (CF) patient airways. Pa culture filtrates inhibit Af biofilms, and Pa non-CF, mucoid (Muc-CF) and nonmucoid CF (NMuc-CF) isolates form an ascending inhibitory hierarchy. We hypothesized this activity is mediated through apoptosis induction. One Af and three Pa (non-CF, Muc-CF, NMuc-CF) reference isolates were studied. Af biofilm was formed in 96 well plates for 16 h ± Pa biofilm filtrates. After 24 h, apoptosis was characterized by viability dye DiBAc, reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, DNA fragmentation and metacaspase activity. Muc-CF and NMuc-CF filtrates inhibited and damaged Af biofilm (pbiofilms (3.7- fold) compared to treatment with filtrates from Muc-CF- (2.5- fold) or non-CF Pa (1.7- fold). Depolarization of mitochondrial potential was greater upon exposure to NMuc-CF (2.4-fold) compared to Muc-CF (1.8-fold) or non-CF (1.25-fold) (pbiofilm, compared to control, mediated by metacaspase activation. In conclusion, filtrates from CF-Pa isolates were more inhibitory against Af biofilms than from non-CF. The apoptotic effect involves mitochondrial membrane damage associated with metacaspase activation.

  11. Diversity, Prevalence, and Longitudinal Occurrence of Type II Toxin-Antitoxin Systems of Pseudomonas aeruginosa Infecting Cystic Fibrosis Lungs

    Directory of Open Access Journals (Sweden)

    Sandra B. Andersen

    2017-06-01

    Full Text Available Type II toxin-antitoxin (TA systems are most commonly composed of two genes encoding a stable toxin, which harms the cell, and an unstable antitoxin that can inactivate it. TA systems were initially characterized as selfish elements, but have recently gained attention for regulating general stress responses responsible for pathogen virulence, formation of drug-tolerant persister cells and biofilms—all implicated in causing recalcitrant chronic infections. We use a bioinformatics approach to explore the distribution and evolution of type II TA loci of the opportunistic pathogen, Pseudomonas aeruginosa, across longitudinally sampled isolates from cystic fibrosis lungs. We identify their location in the genome, mutations, and gain/loss during infection to elucidate their function(s in stabilizing selfish elements and pathogenesis. We found (1 26 distinct TA systems, where all isolates harbor four in their core genome and a variable number of the remaining 22 on genomic islands; (2 limited mutations in core genome TA loci, suggesting they are not under negative selection; (3 no evidence for horizontal transmission of elements with TA systems between clone types within patients, despite their ability to mobilize; (4 no gain and limited loss of TA-bearing genomic islands, and of those elements partially lost, the remnant regions carry the TA systems supporting their role in genomic stabilization; (5 no significant correlation between frequency of TA systems and strain ability to establish as chronic infection, but those with a particular TA, are more successful in establishing a chronic infection.

  12. Investigation of the algT operon sequence in mucoid and non-mucoid Pseudomonas aeruginosa isolates from 115 Scandinavian patients with cystic fibrosis and in 88 in vitro non-mucoid revertants

    DEFF Research Database (Denmark)

    Ciofu, Oana; Lee, Baoleri; Johannesson, Marie

    2008-01-01

    Pseudomonas aeruginosa is the dominant pathogen causing chronic lung infections in patients with cystic fibrosis (CF). After an initial phase characterized by intermittent colonizations, a chronic infection is established upon conversion of P. aeruginosa from the non-mucoid to the mucoid, alginate...

  13. Cooperative pathogenicity in cystic fibrosis: Stenotrophomonas maltophilia modulates Pseudomonas aeruginosa virulence in mixed biofilm

    Directory of Open Access Journals (Sweden)

    Arianna ePompilio

    2015-09-01

    Full Text Available The present study was undertaken in order to understand more about the interaction occurring between S. maltophilia and P. aeruginosa, which are frequently co-isolated from CF airways. For this purpose, S. maltophilia RR7 and P. aeruginosa RR8 strains, co-isolated from the lung of a chronically infected CF patient during a pulmonary exacerbation episode, were evaluated for reciprocal effect during planktonic growth, adhesion and biofilm formation onto both polystyrene and CF bronchial cell monolayer, motility, as well as for gene expression in mixed biofilms. P. aeruginosa significantly affected S. maltophilia growth in both planktonic and biofilm cultures, due to an inhibitory activity probably requiring direct contact. Conversely, no effect was observed on P. aeruginosa by S. maltophilia. Compared with monocultures, the adhesiveness of P. aeruginosa on CFBE41o- cells was significantly reduced by S. maltophilia, which probably acts by reducing P. aeruginosa's swimming motility. An opposite trend was observed for biofilm formation, confirming the findings obtained using polystyrene. When grown in mixed biofilm with S. maltophilia, P. aeruginosa significantly over-expressed aprA, and algD - codifying for protease and alginate, respectively - while the quorum sensing related rhlR and lasI genes were down-regulated. The induced alginate expression by P. aeruginosa might be responsible for the protection of S. maltophilia against tobramycin activity we observed in mixed biofilms. Taken together, our results suggest that the existence of reciprocal interference of S. maltophilia and P. aeruginosa in CF lung is plausible. In particular, S. maltophilia might confer some selective fitness advantage to P. aeruginosa under the specific conditions of chronic infection or, alternatively, increase the virulence of P. aeruginosa thus leading to pulmonary exacerbation.

  14. Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, Peter Østrup; Fiandaca, Mark J

    2009-01-01

    therapy, explanted lungs from 3 intensively treated chronically P. aeruginosa infected CF patients and routine sputum from 77 chronically P. aeruginosa infected CF patients. All samples were investigated microscopically using hematoxylin-eosin (HE), Gram and alcian-blue stain, PNA FISH...

  15. Evolutionary insight from whole-genome sequencing of Pseudomonas aeruginosa from cystic fibrosis patients

    DEFF Research Database (Denmark)

    Marvig, Rasmus Lykke; Madsen Sommer, Lea Mette; Jelsbak, Lars

    2015-01-01

    is suggested to be due to the large genetic repertoire of P. aeruginosa and its ability to genetically adapt to the host environment. Here, we review the recent work that has applied whole-genome sequencing to understand P. aeruginosa population genomics, within-host microevolution and diversity, mutational...

  16. Evaluation of the efficacy of real-time polymerase chain reaction for the routine early detection of Pseudomonas aeruginosa in cystic fibrosis sputum and throat swab specimens.

    LENUS (Irish Health Repository)

    Logan, Catriona

    2012-02-01

    A longitudinal study of 2099 sputa and throat swabs received from 183 pediatric cystic fibrosis patients over a 29-month period was used to evaluate the efficacy of real-time polymerase chain reaction (PCR) for the early detection of Pseudomonas aeruginosa as compared to microbiologic culture. Real-time PCR resulted in an increased number of specimens identified as P. aeruginosa positive. The sensitivity of culture was 82% (373\\/453) and of PCR was 93% (420\\/453) when considering both positive culture and PCR results as true positives. Of the 80 specimens identified as PCR positive\\/culture negative for P. aeruginosa, the subsequent patient sample in 32.5% (26\\/80) of specimens concerned was identified as P. aeruginosa culture positive, suggesting that PCR has the potential to detect P. aeruginosa earlier than the microbiologic culture. Real-time PCR analysis found no evidence of the Liverpool and Manchester epidemic P. aeruginosa strains in the cohort examined. The findings of this study highlight the importance of specimen collection protocols to ensure that adequate samples are received at the laboratory for testing, thereby minimizing the potential for reporting of false-negative P. aeruginosa culture results.

  17. Caracterización, por RAPD-PCR, de aislados de Pseudomonas aeruginosa obtenidos de pacientes con fibrosis quística RAPD-PCR characterization of Pseudomonas aeruginosa strains obtained from cystic fibrosis patients

    Directory of Open Access Journals (Sweden)

    Maribel Ortiz-Herrera

    2004-04-01

    fibrosis quística permite llevar a cabo estudios más precisos de la epidemiología de esta importante relación huésped-parásito.OBJECTIVE: To characterize P aeruginosa strains isolated from bronchoalveolar lavage fluid of cystic fibrosis (CF patients over a 3 year period. MATERIAL AND METHODS: A prospective follow-up study was carried out in a population of cystic fibrosis patients. The random amplified polymorphic DNA (RAPD technique was used to amplify DNA of P aeruginosa strains isolated from bronchoalveolar lavage fluid samples of five CF patients from the Servicio de Neumología y Cirugía del Tórax del Instituto Nacional de Pediatría (Mexico City Chest Clinic of the National Pediatrics Institute in Mexico City, between June 1996 and June 2002. Amplification patterns were established for each isolate to accurately identify all strains and to carry out an epidemiological analysis of P aeruginosa among the selected CF patients. RESULTS: Eighteen different DNA amplification patterns were defined and used to identify each P aeruginosa strain isolated from the different bronchoalveolar lavage samples. No correlation was observed between the different P aeruginosa strain genotypes and mucoid or non-mucoid phenotypes, as strains with different phenotypes showed similar amplification patterns. Several strains with different amplification patterns were identified in samples obtained from the same patient, suggesting coinfection with more than one P aeruginosa strain. Two siblings with CF shared similar genotypes, suggesting the occurrence of cross-contamination. Similar genotypes of P aeruginosa strains were isolated throughout the study period. CONCLUSION: Genotypic characterization of P aeruginosa strains in CF patients allows more accurate epidemiological analyses of this important host-agent relationship.

  18. Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection

    DEFF Research Database (Denmark)

    Kolpen, Mette; Kühl, Michael; Bjarnsholt, Thomas

    2014-01-01

    local anoxia by consuming the majority of O2 for production of reactive oxygen species (ROS). We hypothesized that P. aeruginosa acquires energy for growth in anaerobic endobronchial mucus by denitrification, which can be demonstrated by production of nitrous oxide (N2O), an intermediate...

  19. Phenotypic shift in Pseudomonas aeruginosa populations from cystic fibrosis lungs after 2-week antipseudomonal treatment

    DEFF Research Database (Denmark)

    Fernandez-Barat, Laia; Ciofu, Oana; Kragh, Kasper N.

    2017-01-01

    ) colony-forming units (CFU/mL), b) frequency of mucoids and non-mucoids, c) resistance pattern to anti-pseudomonal drugs, d) hypermutability, e) transcriptomic profiles, and f) presence of biofilms. Results We collected 23 sputum samples (12 before antibiotic treatment and 11 after) and 77 P. aeruginosa...

  20. Role of quorum sensing by Pseudomonas aeruginosa in microbial keratitis and cystic fibrosis

    DEFF Research Database (Denmark)

    Willcox, M.D.P.; Zhu, H.; Conibear, T.C.R.

    2008-01-01

    to control the expression of many virulence factors is the N-acylated homoserine lactone (AHL) regulatory system. Hence, there is considerable interest in targeting this regulatory pathway to develop novel therapeutics for infection control. P. aeruginosa is the principal cause of microbial keratitis...

  1. SERS detection of the biomarker hydrogen cyanide from Pseudomonas aeruginosa cultures isolated from cystic fibrosis patients

    DEFF Research Database (Denmark)

    Lauridsen, Rikke Kragh; Madsen Sommer, Lea Mette; Johansen, Helle Krogh

    2017-01-01

    . The P. aeruginosa biomarker hydrogen cyanide (HCN) contains a triple bond, which is utilized in this study because of the resulting characteristic C≡N peak at 2135 cm-1 in a Raman spectrum. The Raman signal was enhanced by surface-enhanced Raman spectroscopy (SERS) on a Au-coated SERS substrate. After...

  2. Tipificación molecular de aislamientos de Pseudomonas aeruginosa obtenidos de pacientes con fibrosis quística Molecular typification of Pseudomonas aeruginosa strains isolated from patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    N. G. Iglesias

    2008-03-01

    Full Text Available La fibrosis quística es la enfermedad genética letal de mayor frecuencia en la población caucásica. La infección pulmonar crónica es la principal causa de morbilidad de la enfermedad, siendo la infección por Pseudomonas aeruginosa la más importante, ya que resulta de difícil erradicación. El Centro de Referencia Provincial de Fibrosis Quística que funciona en el Hospital de Niños "Sor María Ludovica" de La Plata asiste a alrededor de 220 pacientes con fibrosis quística cuyas edades oscilan entre los dos meses y los 45 años. La edad de sobrevida depende de una serie de factores entre los que se encuentran el diagnóstico temprano de la enfermedad y la adquisición de la infección pulmonar crónica por P. aeruginosa. La misma puede adquirirse en forma directa, por transmisión persona a persona o de forma indirecta a través del uso de elementos hospitalarios contaminados. El objetivo de este trabajo fue la tipificación molecular de aislamientos de P. aeruginosa obtenidos de pacientes con fibrosis quística, con el fin de evaluar la relación genómica entre los mismos. El estudio se llevó a cabo mediante RAPD-PCR. El análisis demostró que existe gran heterogeneidad genética entre los aislamientos. La separación en cohortes de pacientes de acuerdo con su bacteriología, que implica la asistencia en días diferentes y las hospitalizaciones en habitaciones aisladas ha demostrado, junto a otras estrategias, disminuir las infecciones cruzadas.Cystic fibrosis is the most frequent lethal genetic disease that affects the caucasian population. The main cause of morbidity is the chronic lung infection, being the infection caused by Pseudomonas aeruginosa the most difficult to eradicate. This bacteria can be acquired in direct form, by person-to-person transfer, or indirectly, by hospital acquired infection. The Centro Provincial de Referencia de Fibrosis Quística functioning in the Hospital de Niños "Sor María Ludovica", in La

  3. A laminar flow model of aerosol survival of epidemic and non-epidemic strains of Pseudomonas aeruginosa isolated from people with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Denton Miles

    2008-06-01

    Full Text Available Abstract Background Cystic fibrosis (CF is an inherited multi-system disorder characterised by chronic airway infection with pathogens such as Pseudomonas aeruginosa. Acquisition of P. aeruginosa by patients with CF is usually from the environment, but recent studies have demonstrated patient to patient transmission of certain epidemic strains, possibly via an airborne route. This study was designed to examine the survival of P. aeruginosa within artificially generated aerosols. Results Survival was effected by the solution used for aerosol generation. Within the aerosols it was adversely affected by an increase in air temperature. Both epidemic and non-epidemic strains of P. aeruginosa were able to survive within the aerosols, but strains expressing a mucoid phenotype had a survival advantage. Conclusion This would suggest that segregating individuals free of P. aeruginosa from those with chronic P. aeruginosa infection who are more likely to be infected with mucoid strains may help reduce the risk of cross-infection. Environmental factors also appear to influence bacterial survival. Warming and drying the air within clinical areas and avoidance of humidification devices may also be beneficial in reducing the risk of cross-infection.

  4. Novel mouse model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis

    DEFF Research Database (Denmark)

    Hoffmann, Nadine; Rasmussen, Thomas Bovbjerg; Jensen, Peter Østrup

    2005-01-01

    (NH57388C) from the mucoid isolate (NH57388A) and a nonmucoid isolate (NH57388B) deficient in AHL were almost cleared from the lungs of the mice. This model, in which P. aeruginosa is protected against the defense system of the lung by alginate, is similar to the clinical situation. Therefore...... pulmonary mouse model without artificial embedding. The model is based on a stable mucoid CF sputum isolate (NH57388A) with hyperproduction of alginate due to a deletion in mucA and functional N-acylhomoserine lactone (AHL)-based quorum-sensing systems. Chronic lung infection could be established in both CF...

  5. Heterogeneity of biofilms formed by nonmucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Lee, Baoleri; Haagensen, Janus Anders Juul; Ciofu, O.

    2005-01-01

    lactone quorum-sensing molecules). Compared with wild-type strain PAO 1, most P. aeruginosa isolates demonstrated different degrees of reduction of adherence on polystyrene surfaces. The in vitro biofilm formation of isolates was investigated in a hydrodynamic flow system. Confocal laser scanning...... to phenotypic changes and in vitro biofilm formation. The physiological alterations were associated with a loss of motility (35% were nonmotile) and with decreased production of virulence factors (pyocyanin, proteases) and quorum-sensing molecules (45% of the isolates were unable to produce 3-O-C(12)-homoserine...

  6. Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone

    DEFF Research Database (Denmark)

    López-Causapé, Carla; Madsen Sommer, Lea Mette; Cabot, Gabriel

    2017-01-01

    ) and resistome of a widespread clone (CC274), in isolates from two highly-distant countries, Australia and Spain, covering an 18-year period. The coexistence of two divergent CC274 clonal lineages was revealed, but without evident geographical barrier; phylogenetic reconstructions and mutational resistome...... for the first time that high-level aminoglycoside resistance in CF is likely driven by mutations in fusA1/fusA2, coding for elongation factor G. Altogether, our results provide valuable information for understanding the evolution of the mutational resistome of CF P. aeruginosa....

  7. Cysteamine re-establishes the clearance of Pseudomonas aeruginosa by macrophages bearing the cystic fibrosis-relevant F508del-CFTR mutation.

    Science.gov (United States)

    Ferrari, Eleonora; Monzani, Romina; Villella, Valeria R; Esposito, Speranza; Saluzzo, Francesca; Rossin, Federica; D'Eletto, Manuela; Tosco, Antonella; De Gregorio, Fabiola; Izzo, Valentina; Maiuri, Maria C; Kroemer, Guido; Raia, Valeria; Maiuri, Luigi

    2017-01-12

    Cystic fibrosis (CF), the most common lethal monogenic disease in Caucasians, is characterized by recurrent bacterial infections and colonization, mainly by Pseudomonas aeruginosa, resulting in unresolved airway inflammation. CF is caused by mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which functions as a chloride channel in epithelial cells, macrophages, and other cell types. Impaired bacterial handling by macrophages is a feature of CF airways, although it is still debated how defective CFTR impairs bacterial killing. Recent evidence indicates that a defective autophagy in CF macrophages leads to alterations of bacterial clearance upon infection. Here we use bone marrow-derived macrophages from transgenic mice to provide the genetic proof that defective CFTR compromises both uptake and clearance of internalized Pseudomonas aeruginosa. We demonstrate that the proteostasis regulator cysteamine, which rescues the function of the most common F508del-CFTR mutant and hence reduces lung inflammation in CF patients, can also repair the defects of CF macrophages, thus restoring both bacterial internalization and clearance through a process that involves upregulation of the pro-autophagic protein Beclin 1 and re-establishment of the autophagic pathway. Altogether these results indicate that cysteamine restores the function of several distinct cell types, including that of macrophages, which might contribute to its beneficial effects on CF.

  8. Respiratory bacterial infections in cystic fibrosis

    DEFF Research Database (Denmark)

    Ciofu, Oana; Hansen, Christine R; Høiby, Niels

    2013-01-01

    PURPOSE OF REVIEW: Bacterial respiratory infections are the main cause of morbidity and mortality in patients with cystic fibrosis (CF). Pseudomonas aeruginosa remains the main pathogen in adults, but other Gram-negative bacteria such as Achromobacter xylosoxidans and Stenotrophomonas maltophilia...... respiratory tract (nasal sampling) should be investigated and both infection sites should be treated....

  9. Chemotaxis and Binding of Pseudomonas aeruginosa to Scratch-Wounded Human Cystic Fibrosis Airway Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Christian Schwarzer

    Full Text Available Confocal imaging was used to characterize interactions of Pseudomonas aeruginosa (PA, expressing GFP or labeled with Syto 11 with CF airway epithelial cells (CFBE41o-, grown as confluent monolayers with unknown polarity on coverglasses in control conditions and following scratch wounding. Epithelia and PAO1-GFP or PAK-GFP (2 MOI were incubated with Ringer containing typical extracellular salts, pH and glucose and propidium iodide (PI, to identify dead cells. PAO1 and PAK swam randomly over and did not bind to nonwounded CFBE41o- cells. PA migrated rapidly (began within 20 sec, maximum by 5 mins and massively (10-80 fold increase, termed "swarming", but transiently (random swimming after 15 mins, to wounds, particularly near cells that took up PI. Some PA remained immobilized on cells near the wound. PA swam randomly over intact CFBE41o- monolayers and wounded monolayers that had been incubated with medium for 1 hr. Expression of CFTR and altered pH of the media did not affect PA interactions with CFBE41o- wounds. In contrast, PAO1 swarming and immobilization along wounds was abolished in PAO1 (PAO1ΔcheYZABW, no expression of chemotaxis regulatory components cheY, cheZ, cheA, cheB and cheW and greatly reduced in PAO1 that did not express amino acid receptors pctA, B and C (PAO1ΔpctABC and in PAO1 incubated in Ringer containing a high concentration of mixed amino acids. Non-piliated PAKΔpilA swarmed normally towards wounded areas but bound infrequently to CFBE41o- cells. In contrast, both swarming and binding of PA to CFBE41o- cells near wounds were prevented in non-flagellated PAKΔfliC. Data are consistent with the idea that (i PA use amino acid sensor-driven chemotaxis and flagella-driven swimming to swarm to CF airway epithelial cells near wounds and (ii PA use pili to bind to epithelial cells near wounds.

  10. Coexistence and Within-Host Evolution of Diversified Lineages of Hypermutable Pseudomonas aeruginosa in Long-term Cystic Fibrosis Infections

    DEFF Research Database (Denmark)

    Feliziani, Sofia; Marvig, Rasmus Lykke; Lujan, Adela M.

    2014-01-01

    The advent of high-throughput sequencing techniques has made it possible to follow the genomic evolution of pathogenic bacteria by comparing longitudinally collected bacteria sampled from human hosts. Such studies in the context of chronic airway infections by Pseudomonas aeruginosa in cystic...... to investigate within-host population diversity or long-term evolution of mutators in CF airways. We sequenced the genomes of 13 and 14 isolates of P. aeruginosa mutator populations from an Argentinian and a Danish CF patient, respectively. Our collection of isolates spanned 6 and 20 years of patient infection...... history, respectively. We sequenced 11 isolates from a single sample from each patient to allow in-depth analysis of population diversity. Each patient was infected by clonal populations of bacteria that were dominated by mutators. The in vivo mutation rate of the populations was similar to 100 SNPs...

  11. The effect of short-term, high-dose oral N-acetylcysteine treatment on oxidative stress markers in cystic fibrosis patients with chronic P-aeruginosa infection - A pilot study

    DEFF Research Database (Denmark)

    Skov, Marianne; Pressler, Tacjana; Lykkesfeldt, Jens

    2015-01-01

    Background: Patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa lung infection have increased oxidative stress as a result of an imbalance between the production of reactive oxygen species caused by inflammation and their inactivation by the impaired antioxidant systems. Supplem...

  12. Combination of hypothiocyanite and lactoferrin (ALX-109) enhances the ability of tobramycin and aztreonam to eliminate Pseudomonas aeruginosa biofilms growing on cystic fibrosis airway epithelial cells.

    Science.gov (United States)

    Moreau-Marquis, Sophie; Coutermarsh, Bonita; Stanton, Bruce A

    2015-01-01

    Chelating iron may be a promising new therapy to eliminate Pseudomonas aeruginosa biofilms in the lungs of cystic fibrosis (CF) patients. Here, we investigate whether ALX-109 [a defined combination of an investigational drug containing lactoferrin (an iron-binding glycoprotein) and hypothiocyanite (a bactericidal agent)], alone and in combination with tobramycin or aztreonam, reduces P. aeruginosa biofilms grown on human CF airway epithelial cells. P. aeruginosa (PAO1 and six clinical isolates of Pseudomonas) biofilms grown at the apical surface of confluent monolayers of CF airway epithelial cells were treated with ALX-109, either alone or in combination with tobramycin or aztreonam. Bacterial cfu remaining after treatment were determined by plate counting. ALX-109 alone reduced PAO1 biofilm formation, but had no effect on established biofilms. ALX-109 enhanced the ability of tobramycin and aztreonam to inhibit PAO1 biofilm formation and to reduce established PAO1 biofilms. ALX-109 and tobramycin were additive in disrupting established biofilms formed by six clinical isolates of P. aeruginosa obtained from the sputum of CF patients. Mucoid P. aeruginosa isolates were most susceptible to the combination of ALX-109 and tobramycin. In addition, ALX-109 also enhanced the ability of aztreonam to reduce established PAO1 biofilms. Inhalation therapy combining hypothiocyanite and lactoferrin with TOBI(®) (tobramycin) or Cayston(®) (aztreonam) may be beneficial to CF patients by decreasing the airway bacterial burden of P. aeruginosa. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. γδ T lymphocytes from cystic fibrosis patients and healthy donors are high TNF-α and IFN-γ-producers in response to Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Martínez Natalia

    2003-09-01

    Full Text Available Abstract Background γδ T cells have an important immunoregulatory and effector function through cytokine release. They are involved in the responses to Gram-negative bacterium and in protection of lung epithelium integrity. On the other hand, they have been implicated in airway inflammation. Methods The aim of the present work was to study intracytoplasmic IL-2, IL-4, IFN-γ and TNF-α production by γδ and αβ T lymphocytes from cystic fibrosis patients and healthy donors in response to Pseudomonas aeruginosa (PA. Flow cytometric detection was performed after peripheral blood mononuclear cells (PBMC culture with a cytosolic extract from PA and restimulation with phorbol ester plus ionomycine. Proliferative responses, activation markers and receptor usage of γδ T cells were also evaluated. Results The highest production of cytokine was of TNF-α and IFN-γ, γδ being better producers than αβ. No differences were found between patients and controls. The Vγ9δ2 subset of γδ T cells was preferentially expanded. CD25 and CD45RO expression by the αβ T subset and PBMC proliferative response to PA were defective in cystic fibrosis lymphocytes. Conclusion Our results support the hypothesis that γδ T lymphocytes play an important role in the immune response to PA and in the chronic inflammatory lung reaction in cystic fibrosis patients. They do not confirm the involvement of a supressed Th1 cytokine response in the pathogenesis of this disease.

  14. Sinonasal inhalation of tobramycin vibrating aerosol in cystic fibrosis patients with upper airway Pseudomonas aeruginosa colonization: results of a randomized, double-blind, placebo-controlled pilot study

    Science.gov (United States)

    Mainz, Jochen G; Schädlich, Katja; Schien, Claudia; Michl, Ruth; Schelhorn-Neise, Petra; Koitschev, Assen; Koitschev, Christiane; Keller, Peter M; Riethmüller, Joachim; Wiedemann, Baerbel; Beck, James F

    2014-01-01

    Rationale In cystic fibrosis (CF), the paranasal sinuses are sites of first and persistent colonization by pathogens such as Pseudomonas aeruginosa. Pathogens subsequently descend to the lower airways, with P. aeruginosa remaining the primary cause of premature death in patients with the inherited disease. Unlike conventional aerosols, vibrating aerosols applied with the PARI Sinus™ nebulizer deposit drugs into the paranasal sinuses. This trial assessed the effects of vibrating sinonasal inhalation of the antibiotic tobramycin in CF patients positive for P. aeruginosa in nasal lavage. Objectives To evaluate the effects of sinonasal inhalation of tobramycin on P. aeruginosa quantification in nasal lavage; and on patient quality of life, measured with the Sino-Nasal Outcome Test (SNOT-20), and otologic and renal safety and tolerability. Methods Patients were randomized to inhalation of tobramycin (80 mg/2 mL) or placebo (2 mL isotonic saline) once daily (4 minutes/nostril) with the PARI Sinus™ nebulizer over 28 days, with all patients eligible for a subsequent course of open-label inhalation of tobramycin for 28 days. Nasal lavage was obtained before starting and 2 days after the end of each treatment period by rinsing each nostril with 10 mL of isotonic saline. Results Nine patients participated, six initially receiving tobramycin and three placebo. Sinonasal inhalation was well tolerated, with serum tobramycin <0.5 mg/L and stable creatinine. P. aeruginosa quantity decreased in four of six (67%) patients given tobramycin, compared with zero of three given placebo (non-significant). SNOT-20 scores were significantly lower in the tobramycin than in the placebo group (P=0.033). Conclusion Sinonasal inhalation of vibrating antibiotic aerosols appears promising for reducing pathogen colonization of paranasal sinuses and for control of symptoms in patients with CF. PMID:24596456

  15. Microbial pathogenesis in cystic fibrosis: co-ordinate regulation of heat-shock response and conversion to mucoidy in Pseudomonas aeruginosa.

    Science.gov (United States)

    Schurr, M J; Deretic, V

    1997-04-01

    Conversion of Pseudomonas aeruginosa to the mucoid phenotype plays a major role in the pathogenesis of respiratory infections in cystic fibrosis (CF). One mechanism responsible for mucoidy is based on mutations that inactivate the anti-sigma factor, MucA, which normally inhibits the alternative sigma factor, AIgU. The loss of MucA allows AIgU to freely direct transcription of the genes responsible for the production of the exopolysaccharide alginate resulting in mucoid colony morphology. In Escherichia coli, a close homologue of AIgU, sigma(E), directs transcription of several genes under conditions of extreme heat shock. Here we examined whether AIgU, besides its role in controlling alginate production, affects the heat-shock response in P. aeruginosa. The P. aeruginosa rpoH gene encoding a homologue of the major heat-shock sigma factor, sigma32, was found to be transcribed by AIgU containing RNA polymerase from one of its promoters (P3) identified in this study. Transcription of rpoH from P3 was elevated upon exposure to extreme heat shock in an aIgU-dependent manner. Importantly, the AIgU-dependent promoter of rpoH was found to be activated in mucoid mucA mutants. In keeping with this observation, introduction of a wild-type mucA gene abrogated AIgU-dependent rpoH transcription in mucoid P. aeruginosa laboratory isolates and CF isolates. These results suggest that conversion to mucoidy and the heat-shock response are co-ordinately regulated in P. aeruginosa. The simultaneous activation of both systems in mucA mutants, selected in the lungs of CF patients, may have significance for the inflammatory processes characteristic of the establishment of chronic infection and ensuing clinical deterioration in CF.

  16. Anaerobic Pseudomonas aeruginosa and other obligately anaerobic bacterial biofilms growing in the thick airway mucus of chronically infected cystic fibrosis patients: an emerging paradigm or "Old Hat"?

    Science.gov (United States)

    Su, Shengchang; Hassett, Daniel J

    2012-09-01

    The cystic fibrosis (CF) airway mucus is an ideal niche in which many bacteria can develop antibiotic- and phagocyte-resistance in unique structures known as "mode II biofilms" where bacteria are embedded within the mucus, yet unattached to airway epithelial cells. Pseudomonas aeruginosa is the dominant CF pathogen, yet herein the authors provide burgeoning evidence that obligate anaerobic bacteria (e.g., Prevotella) actually thrive within the CF mucus, a paradigmatic shift that chronic CF is an "aerobic" disease. Interestingly, CF organisms repress virulence factor production (e.g., P. aeruginosa) while others (e.g., S. aureus) increase them under anaerobic conditions. The authors shed additional light on (i) the anoxic nature of the CF airway mucus, (ii) the relative commonality of anaerobic bacteria isolated from CF sputum, (iii) virulence factor production and cross-talk between obligate anaerobes and P. aeruginosa relative to disease progression/remission, (iv) the role of mucoidy in CF, and (v) the role of nitrosative stress in activation of bacteriophage and pyocins within biofilms. The authors conclude with insight as to how we might treat some CF bacteria during mode II biofilm infections that utilizes a metabolite of bacterial anaerobic respiration and an aerobic oxidation product of airway-generated NO, acidified NO(2)(-).

  17. Cystic fibrosis in adults

    Directory of Open Access Journals (Sweden)

    C. Damas

    2007-05-01

    Full Text Available The authors reviewed adult cystic fibrosis patients followed in the Pulmonology Unit from 1994-2004 (n = 8, five female and three male, aged 20-34 years old (median = 27 years. Patients were diagnosed at 18 months - 31 years old by sweat testing (positive in six patients and genotyping (four patients homozygous for ΔF508 mutation.Respiratory involvement was characterised by sinusitis and bronchiectasis. Pulmonary involvement was accompanied by functional abnormalities and gas exchange impairment in the majority of the patients. Bronchial tree was colonised permanently in five patients: Pseudomonas aeruginosa in four and Staphilococcus aureus in four (three patients affected by both agents simultaneously.The main causes of exacerbation were respiratory infections and haemoptysis.Non-respiratory involvement was variable. Four patients had digestive involvement (one with hepatic cirrhosis, one had renal failure and only one had a sperm count to document infertility. Four patients had osteopaenia.Treatment included chest physiotherapy, bronchodilators, dornase alfa, mucolytics, digestive enzymes, vitamins, antibiotics and oxygen therapy.At review, one had left follow-up, one had died, one was awaiting lung transplant and the others evidenced no difference in clinical characteristics.In this group of patients the severity of the pulmonary disease was not related to a late diagnosis. It can be explained by the diversity of cystic fibrosis presentation in adults Resumo: Os autores efectuaram uma revisão de doentes adultos com fibrose quística (FQ, seguidos na consulta de Pneumologia no período de 1994-2004 (n = 8: cinco mulheres e três homens, com idades compreendidas entre 20 e 34 anos (mediana  =  27 anos, cuja idade de diagnóstico variou entre os 18 meses e os 31 anos.O diagnóstico foi obtido por prova de suor (positiva em seis doentes e estudo genético (homozigotia para a mutação ΔF508 em

  18. Use of artificial sputum medium to test antibiotic efficacy against Pseudomonas aeruginosa in conditions more relevant to the cystic fibrosis lung.

    Science.gov (United States)

    Kirchner, Sebastian; Fothergill, Joanne L; Wright, Elli A; James, Chloe E; Mowat, Eilidh; Winstanley, Craig

    2012-06-05

    There is growing concern about the relevance of in vitro antimicrobial susceptibility tests when applied to isolates of P. aeruginosa from cystic fibrosis (CF) patients. Existing methods rely on single or a few isolates grown aerobically and planktonically. Predetermined cut-offs are used to define whether the bacteria are sensitive or resistant to any given antibiotic. However, during chronic lung infections in CF, P. aeruginosa populations exist in biofilms and there is evidence that the environment is largely microaerophilic. The stark difference in conditions between bacteria in the lung and those during diagnostic testing has called into question the reliability and even relevance of these tests. Artificial sputum medium (ASM) is a culture medium containing the components of CF patient sputum, including amino acids, mucin and free DNA. P. aeruginosa growth in ASM mimics growth during CF infections, with the formation of self-aggregating biofilm structures and population divergence. The aim of this study was to develop a microtitre-plate assay to study antimicrobial susceptibility of P. aeruginosa based on growth in ASM, which is applicable to both microaerophilic and aerobic conditions. An ASM assay was developed in a microtitre plate format. P. aeruginosa biofilms were allowed to develop for 3 days prior to incubation with antimicrobial agents at different concentrations for 24 hours. After biofilm disruption, cell viability was measured by staining with resazurin. This assay was used to ascertain the sessile cell minimum inhibitory concentration (SMIC) of tobramycin for 15 different P. aeruginosa isolates under aerobic and microaerophilic conditions and SMIC values were compared to those obtained with standard broth growth. Whilst there was some evidence for increased MIC values for isolates grown in ASM when compared to their planktonic counterparts, the biggest differences were found with bacteria tested in microaerophilic conditions, which showed a much

  19. Non-Tuberculous Mycobacteria multispecies biofilms in cystic fibrosis: development of an in vitro Mycobacterium abscessus and Pseudomonas aeruginosa dual species biofilm model.

    Science.gov (United States)

    Rodríguez-Sevilla, Graciela; García-Coca, Marta; Romera-García, David; Aguilera-Correa, John Jairo; Mahíllo-Fernández, Ignacio; Esteban, Jaime; Pérez-Jorge, Concepción

    2018-04-01

    Lung disease in cystic fibrosis (CF) is characterized by the progressive colonization of the respiratory tract by different bacteria, which develop polymicrobial biofilms. In the past decades, there has been an increase in the number of CF patients infected with Non-Tuberculous Mycobacteria (NTM). Although Mycobacterium abscessus is the main NTM isolated globally, little is known about M. abscessus multispecies biofilm formation. In the present study we developed an in vitro model to study the phenotypic characteristics of biofilms formed by M. abscessus and Pseudomonas aeruginosa, a major pathogen in CF. For that purpose, dual species biofilms were grown on polycarbonate membranes with a fixed concentration of P. aeruginosa and different inoculums of M. abscessus. The biofilms were sampled at 24, 48, and 72 h and bacteria were quantified in specific media. The results revealed that the increasing initial concentration of M. abscessus in dual species biofilms had an effect on its population only at 24 and 48 h, whereas P. aeruginosa was not affected by the different concentrations used of M. abscessus. Time elapsed increased biofilm formation of both species, specially between 24 and 48 h. According to the results, the conditions to produce a mature dual species biofilm in which the relative species distribution remained stable were 72 h growth of the mixed microbial culture at a 1:1 ratio. A significant decrease in mycobacterial population in dual compared to single species biofilms was found, suggesting that P. aeruginosa has a negative influence on M. abscessus. Finally, in a proof of concept experiment, young and mature dual species biofilms were exposed to clarithromycin. Copyright © 2018 Elsevier GmbH. All rights reserved.

  20. l-Methionine anti-biofilm activity against Pseudomonas aeruginosa is enhanced by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor.

    Science.gov (United States)

    Cho, Do-Yeon; Lim, Dong-Jin; Mackey, Calvin; Weeks, Christopher G; Peña Garcia, Jaime A; Skinner, Daniel; Grayson, Jessica W; Hill, Harrison S; Alexander, David K; Zhang, Shaoyan; Woodworth, Bradford A

    2018-05-01

    Biofilms may contribute to refractory chronic rhinosinusitis (CRS), as they lead to antibiotic resistance and failure of effective clinical treatment. l-Methionine is an amino acid with reported biofilm-inhibiting properties. Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator with mild antimicrobial activity via inhibition of bacterial DNA gyrase and topoisomerase IV. The objective of this study was to evaluate whether co-treatment with ivacaftor and l-methionine can reduce the formation of Pseudomonas aeruginosa biofilms. P aeruginosa (PAO-1 strain) biofilms were studied in the presence of l-methionine and/or ivacaftor. For static biofilm assays, PAO-1 was cultured in a 48-well plate for 72 hours with stepwise combinations of these agents. Relative biofilm inhibitions were measured according to optical density of crystal violet stain at 590 nm. Live/dead assays (BacTiter-Glo™ assay, Promega) were imaged with laser scanning confocal microscopy. An agar diffusion test was used to confirm antibacterial effects of the drugs. l-Methionine (0.5 μM) significantly reduced PAO-1 biofilm mass (32.4 ± 18.0%; n = 4; p l-methionine (two-way analysis of variane, p = 0.0415) compared with corresponding concentrations of l-methionine alone. Ivacaftor enhanced the anti-biofilm activity of l-methionine against the PAO-1 strain of P aeruginosa. Further studies evaluating the efficacy of ivacaftor/l-methionine combinations for P aeruginosa sinusitis are planned. © 2018 ARS-AAOA, LLC.

  1. Imaging from cystic fibrosis

    International Nuclear Information System (INIS)

    Schmidt, H.; Posselt, H.G.

    2008-01-01

    Cystic fibrosis (CF) is the most frequent metabolic disorder with autosomal recessive inheritance in the Caucasian population. The gene defect is located on the long arm of chromosome 7. In Germany today, the actual median survival is 37 years. The genetic defect caused by chloride anion disturbances affects multiple body systems but the morbidity and mortality is due to lung disease. The secretion of highly viscous mucus promotes viral and bacterial pulmonary infections leading to airway obstruction and consecutive destruction of the lung parenchyma. This article will review and discuss both the clinical aspects of the disease and the diagnostic methods, referring in particular to new imaging strategies. (orig.)

  2. Co-colonisation with Aspergillus fumigatus and Pseudomonas aeruginosa is associated with poorer health in cystic fibrosis patients: an Irish registry analysis.

    Science.gov (United States)

    Reece, Emma; Segurado, Ricardo; Jackson, Abaigeal; McClean, Siobhán; Renwick, Julie; Greally, Peter

    2017-04-21

    Pulmonary infection is the main cause of death in cystic fibrosis (CF). Aspergillus fumigatus (AF) and Pseudomonas aeruginosa (PA) are the most prevalent fungal and bacterial pathogens isolated from the CF airway, respectively. Our aim was to determine the effect of different colonisation profiles of AF and PA on the clinical status of patients with CF. A retrospective analysis of data from the Cystic Fibrosis Registry of Ireland from 2013 was performed to determine the effect of intermittent and persistent colonisation with AF or PA or co-colonisation with both microorganisms on clinical outcome measures in patients with CF. Key outcomes measured included forced expiratory volume in one second (FEV 1 ), number of hospitalisations, respiratory exacerbations and antimicrobials prescribed, and complications of CF, including CF related diabetes (CFRD) and allergic bronchopulmonary aspergillosis (ABPA). The prevalence of AF and PA colonisation were 11% (5% persistent, 6% intermittent) and 31% (19% persistent, 12% intermittent) in the Irish CF population, respectively. Co-colonisation with both pathogens was associated with a 13.8% reduction in FEV 1 (p = 0.016), higher levels of exacerbations (p = 0.042), hospitalisations (p = 0.023) and antimicrobial usage (p = 0.014) compared to non-colonised patients and these clinical outcomes were comparable to those persistently colonised with PA. Intermittent and persistent AF colonisation were not associated with poorer clinical outcomes or ABPA. Patients with persistent PA had a higher prevalence of CFRD diagnosis (p = 0.012). CF patients co-colonised with AF and PA had poor clinical outcomes comparable to patients persistently colonised with PA, emphasising the clinical significance of co-colonisation with these microorganisms.

  3. Phenotypes selected during chronic lung infection in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Ciofu, Oana; Mandsberg, Lotte F; Wang, Hengzhuang

    2012-01-01

    During chronic lung infection of patients with cystic fibrosis, Pseudomonas aeruginosa can survive for long periods of time under the challenging selective pressure imposed by the immune system and antibiotic treatment as a result of its biofilm mode of growth and adaptive evolution mediated by g...... the importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis....

  4. Gastrointestinal Manifestations of Cystic Fibrosis

    Science.gov (United States)

    2016-01-01

    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

  5. Inhaled antibiotics for the treatment of chronic Pseudomonas aeruginosa infection in cystic fibrosis patients: challenges to treatment adherence and strategies to improve outcomes

    Directory of Open Access Journals (Sweden)

    Bodnár R

    2016-02-01

    Full Text Available Réka Bodnár,1,2 Ágnes Mészáros,2 Máté Oláh,2 Tamás Ágh3 1Department of Pediatric Pulmonology, Heim Pál Children’s Hospital, Budapest, Hungary; 2University Pharmacy Department of Pharmacy Administration, Semmelweis University, Budapest, Hungary; 3Syreon Research Institute, Budapest, Hungary Background: Inhaled antibiotics (ABs are recommended for use in the therapy of chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF. The aim of this systematic literature review was to identify level of adherence to inhaled ABs and to determine predictors and consequences of nonadherence in CF. Methods: A systematic literature search of English-language articles was conducted in April 2015 using Medline and Embase. No publication date limit was applied. The literature screening was conducted by two independent reviewers. All of the included studies were assessed for quality. Results: The search yielded 193 publications, of which ten met the inclusion criteria and underwent data extraction. Seven studies focused on inhaled tobramycin, one on inhaled colistimethate, one on inhaled levofloxacin, and one on inhaled aztreonam lysine. Medication adherence to inhaled ABs was analyzed by pharmacy refill history, daily phone diary, parent and child self-reports, vials counting, or electronic monitoring. In randomized controlled trials (n=3, proportion of adherent patients (>75%–80% of required doses taken ranged from 86% to 97%; in prospective cohort studies (n=3, adherence rates ranged between 36% and 92%, and in retrospective studies (n=4 it ranged between 60% and 70%. The adherence to inhaled ABs in CF was found to be associated with the complexity of treatment, time of drug administration, age of patients, treatment burden (adverse events, taste, and patient satisfaction. Conclusion: The high diversity of adherence data was because of the different study designs (randomized controlled trials vs real-world studies and the lack

  6. Profile of cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Mona M. El-Falaki

    2014-09-01

    Full Text Available It was generally believed that Cystic fibrosis (CF is rare among Arabs; however, the few studies available from Egypt and other Arabic countries suggested the presence of many undiagnosed patients. The aim of the present study was to determine the frequency of CF patients out of the referred cases in a single referral hospital in Egypt. A total of 100 patients clinically suspected of having CF were recruited from the CF clinic of the Allergy and Pulmonology Unit, Children’s Hospital, Cairo University, Egypt, throughout a 2 year period. Sweat chloride testing was done for all patients using the Wescor macroduct system for collection of sweat. Quantitative analysis for chloride was then done by the thiocyanate colorimetric method. Patients positive for sweat chloride (⩾60 mmol/L were tested for the ΔF508 mutation using primer specific PCR for cystic fibrosis transmembrane conductance regulator (CFTR gene. Thirty-six patients (36% had a positive sweat chloride test. The main clinical presentations in patients were chronic cough in 32 (88.9%, failure to thrive in 27 (75%, steatorrhea in 24 (66.7%, and hepatobiliary involvement in 5 (13.9%. Positive consanguinity was reported in 50% of CF patients. Thirty-two patients were screened for ΔF508 mutation. Positive ΔF508 mutation was detected in 22 (68.8% patients, 8 (25% were homozygous, 14 (43.8% were heterozygous, and 10 (31.3% tested were negative. CF was diagnosed in more than third of patients suspected of having the disease on clinical grounds. This high frequency of CF among referred patients indicates that a high index of suspicion and an increasing availability of diagnostic tests lead to the identification of a higher number of affected individuals.

  7. Breakdown in Breathing: The Complexities of Cystic Fibrosis

    Science.gov (United States)

    ... Healthier Lungs in Kids Wise Choices Living with Cystic Fibrosis In between checkups, practice good self-care and ... Links What Is Cystic Fibrosis? Learning About Cystic Fibrosis NIH Cystic Fibrosis Fact Sheet Genetic and Rare Diseases Information ...

  8. Cystic fibrosis with normal sweat chloride concentration: case report

    Directory of Open Access Journals (Sweden)

    Silva Filho Luiz Vicente Ferreira da

    2003-01-01

    Full Text Available Cystic fibrosis is a genetic disease usually diagnosed by abnormal sweat testing. We report a case of an 18-year-old female with bronchiectasis, chronic P. aeruginosa infection, and normal sweat chloride concentrations who experienced rapid decrease of lung function and clinical deterioration despite treatment. Given the high suspicion ofcystic fibrosis, broad genotyping testing was performed, showing a compound heterozygous with deltaF508 and 3849+10kb C->T mutations, therefore confirming cystic fibrosis diagnosis. Although the sweat chloride test remains the gold standard for the diagnosis of cystic fibrosis, alternative diagnostic tests such as genotyping and electrophysiologic measurements must be performed if there is suspicion of cystic fibrosis, despite normal or borderline sweat chloride levels.

  9. Evidence for the efficacy of aztreonam for inhalation solution in the management of Pseudomonas aeruginosa in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Hansen, Christine; Skov, Marianne

    2015-01-01

    and the clinical outcome of this infection; this article focuses on the use of inhaled antibiotics in chronic P. aeruginosa infection in CF, and specifically on studies including the use of inhaled aztreonam lysine in P. aeruginosa infection. Studies were identified using PubMed and ClinicalTrials.gov, searching...

  10. Early aggressive eradication therapy for intermittent Pseudomonas aeruginosa airway colonization in cystic fibrosis patients: 15 years experience

    DEFF Research Database (Denmark)

    Hansen, C.R.; Pressler, T.; Høiby, Niels

    2008-01-01

    BACKGROUND: Since 1989, CF-patients intermittently colonized with Pseudomonas aeruginosa have been treated with inhaled colistin and oral ciprofloxacin in the Copenhagen CF-centre. The study evaluates 15 years results of this treatment. METHODS: All isolates of P. aeruginosa from CF-patients inte......BACKGROUND: Since 1989, CF-patients intermittently colonized with Pseudomonas aeruginosa have been treated with inhaled colistin and oral ciprofloxacin in the Copenhagen CF-centre. The study evaluates 15 years results of this treatment. METHODS: All isolates of P. aeruginosa from CF......-patients intermittently colonized with P. aeruginosa from 1989 to 2003 were identified All anti-P. aeruginosa treatments were evaluated for antibiotics used, treatment duration, pseudomonas-free interval and development of chronic infection. All P. aeruginosa isolates were assessed for resistance and for non......-mucoid or mucoid phenotype. RESULTS: 146 CF-patients were included in the study (1106 patient-years). 99 patients had first ever isolate during the study period. Median observation time 7 years (0.1-14.9). 12 patients developed chronic infection. A Kaplan Meyer plot showed protection from chronic infection in up...

  11. In Vitro Activity of Fusidic Acid (CEM-102, Sodium Fusidate) against Staphylococcus aureus Isolates from Cystic Fibrosis Patients and Its Effect on the Activities of Tobramycin and Amikacin against Pseudomonas aeruginosa and Burkholderia cepacia▿

    Science.gov (United States)

    McGhee, Pamela; Clark, Catherine; Credito, Kim; Beachel, Linda; Pankuch, Glenn A.; Appelbaum, Peter C.; Kosowska-Shick, Klaudia

    2011-01-01

    We tested the MICs of fusidic acid (CEM-102) plus other agents against 40 methicillin-resistant Staphylococcus aureus (MRSA) isolates from cystic fibrosis patients and the activities of fusidic acid with or without tobramycin or amikacin against Pseudomonas aeruginosa, MRSA, and Burkholderia cepacia isolates from cystic fibrosis patients in a 24-h time-kill study. Fusidic acid was potent (MICs, 0.125 to 0.5 μg/ml; a single 500-mg dose of fusidic acid at 8 h averaged 8 to 12. 5 μg/ml with 91 to 97% protein binding) against all MRSA strains. No antagonism was observed; synergy occurred for one MRSA strain treated with fusidic acid plus tobramycin. PMID:21343445

  12. In vitro activity of fusidic acid (CEM-102, sodium fusidate) against Staphylococcus aureus isolates from cystic fibrosis patients and its effect on the activities of tobramycin and amikacin against Pseudomonas aeruginosa and Burkholderia cepacia.

    Science.gov (United States)

    McGhee, Pamela; Clark, Catherine; Credito, Kim; Beachel, Linda; Pankuch, Glenn A; Appelbaum, Peter C; Kosowska-Shick, Klaudia

    2011-05-01

    We tested the MICs of fusidic acid (CEM-102) plus other agents against 40 methicillin-resistant Staphylococcus aureus (MRSA) isolates from cystic fibrosis patients and the activities of fusidic acid with or without tobramycin or amikacin against Pseudomonas aeruginosa, MRSA, and Burkholderia cepacia isolates from cystic fibrosis patients in a 24-h time-kill study. Fusidic acid was potent (MICs, 0.125 to 0.5 μg/ml; a single 500-mg dose of fusidic acid at 8 h averaged 8 to 12. 5 μg/ml with 91 to 97% protein binding) against all MRSA strains. No antagonism was observed; synergy occurred for one MRSA strain treated with fusidic acid plus tobramycin.

  13. Computed tomography of cystic pancreatic fibrosis

    International Nuclear Information System (INIS)

    Brachlow, M.; Zaunbauer, W.; Haertel, M.

    1984-01-01

    The computer tomographic appearances of atrophic and lipomatous degeneration of the pancreas in cystic pancreatic fibrosis are described. CT exploration of the pancreas in recommended, particularly in differential diagnostic aspects of cystic fibrosis. (orig.) [de

  14. PmrB Mutations Promote Polymyxin Resistance of Pseudomonas aeruginosa Isolated from Colistin-Treated Cystic Fibrosis Patients

    DEFF Research Database (Denmark)

    Moskowitz, Samuel M; Brannon, Mark K; Dasgupta, Nandini

    2012-01-01

    Pseudomonas aeruginosa can develop resistance to polymyxin and other cationic antimicrobial peptides. Previous work has shown that mutations in the PmrAB and PhoPQ regulatory systems can confer low to moderate levels of colistin (polymyxin E) resistance in laboratory strains and clinical isolates...

  15. Mucoid conversion of Pseudomonas aeruginosa by hydrogen peroxide: a mechanism for virulence activation in the cystic fibrosis lung

    DEFF Research Database (Denmark)

    Mathee, Kalai; Ciofu, Oana; Sternberg, Claus

    1999-01-01

    leukocytes (PMNs), which release free oxygen radicals such as H(2)O(2) The mucoid phenotype among the strains infecting CF patients indicates overproduction of a linear polysaccharide called alginate. To mimic the inflammatory environment of the CF lung, P. aeruginosa PAO1, a typical non-mucoid strain....... These findings indicate that gene activation in bacteria by toxic oxygen radicals, similar to that found in plants and mammalian cells, may serve as a defence mechanism for the bacteria. This suggests that mucoid conversion is a response to oxygen radical exposure and that this response is a mechanism of defence...... by the bacteria. This is the first report to show that PMNs and their oxygen radicals can cause this phenotypic and genotypic change which is so typical of the intractable form of P. aeruginosa in the CF lung. These findings may provide a basis for the development of anti-oxidant and anti-inflammatory therapy...

  16. Lung function in South African children with cystic fibrosis | Zar ...

    African Journals Online (AJOL)

    Objective: To determine the pattern of lung function in stable cystic fibrosis (CF) patients and to investigate the relationship of abnormal lung function to demographic variables, CF genotype and pulmonary colonisation with Pseudomonas aeruginosa (PA). Design: A descriptive study done at the CF clinic at Red Cross War ...

  17. Diagnosis of biofilm infections in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Høiby, Niels; Bjarnsholt, Thomas; Moser, Claus

    2017-01-01

    Chronic Pseudomonas aeruginosa biofilm lung infection in cystic fibrosis patients is the best described biofilm infection in medicine. The initial focus can be the paranasal sinuses and then follows repeated colonization and infection of the lungs by aspiration. The matrix of the biofilms is domi...... by other pathogens e.g., Stenotrophomonas, Burkholderia multivorans, Achromobacter xylosoxidans and Mycobacterium abscessus complex....

  18. [Genetic counseling in cystic fibrosis].

    Science.gov (United States)

    Julia, S; Bieth, E

    2000-08-01

    Genetic counseling is an important part of health care in patients with cystic fibrosis or respiratory diseases associated with the CFTR (cystic fibrosis transmembrane conductance regulator) gene, including certain types of allergic bronchopulmonary aspergilloses or bronchial diseases (diffuse bronchiectasia). The basic goal is to provide patients with information on the transmission of cystic fibrosis and to asses the risk of recurrence. This risk is determined from molecular biology analyses examining the CFTR gene. Genotyping is the only means of screening for the heterozygous state, frequent in the French population (about 1/30). Because of the large number of mutated alleles not covered entirely by the genetic tests, there remains a question of probability expressed as a residual risk of a heterozygous state. A prenatal genotype diagnosis should be proposed to heterozygous couples who have a 25% risk of having a diseased child. Technically, this is almost always possible and the results are highly reliable. Nevertheless, there remains the risks related to sample taking and the ethical issue about which the patients must be informed. Management of these at risk couples who desire a child must be based on a multidisciplinary approach, particularly important when one of the parents has overt cystic fibrosis.

  19. Rnaseq As A Method To Study Microbial Interactions Arising In The Cystic Fibrosis Airways

    DEFF Research Database (Denmark)

    Amador Hierro, Cristina Isabel; Jelsbak, Lars

    2015-01-01

    Introduction: In previous studies from our laboratory, a Pseudomonas aeruginosa lineage, named DK2, has been identified and characterized as highly successful, transmissible and persistent over four decades in cystic fibrosis (CF) patients. This lineage underwent substantial phenotypic and geneti...

  20. Denitrification by cystic fibrosis pathogens - Stenotrophomonas maltophilia is dormant in sputum

    DEFF Research Database (Denmark)

    Kolpen, Mette; Kragh, Kasper Nørskov; Bjarnsholt, Thomas

    2015-01-01

    OBJECTIVE: Chronic Pseudomonas aeruginosa lung infection is the most severe complication for cystic fibrosis (CF) patients. Infected endobronchial mucus of CF patients contains anaerobic zones mainly due to the respiratory burst of polymorphonuclear leukocytes. We have recently demonstrated ongoi...

  1. Inflammation in Achromobacter xylosoxidans infected cystic fibrosis patients

    DEFF Research Database (Denmark)

    Hansen, C. R.; Pressler, T.; Nielsen, K. G.

    2010-01-01

    BACKGROUND: Achromobacter xylosoxidans infection may cause conspicuous chronic pulmonary inflammation in cystic fibrosis (CF) patients similar to Pseudomonas aeruginosa and the Burkholderia cepacia complex (Bcc). Evolution in lung function was compared in chronically infected patients. Cytokine...

  2. Diversity, Prevalence, and Longitudinal Occurrence of Type II Toxin-Antitoxin Systems of Pseudomonas aeruginosa Infecting Cystic Fibrosis Lungs

    DEFF Research Database (Denmark)

    Breum Andersen, Sandra; Ghoul, Melanie; Griffin, Ashleigh S.

    2017-01-01

    Type II toxin-antitoxin (TA) systems are most commonly composed of two genes encoding a stable toxin, which harms the cell, and an unstable antitoxin that can inactivate it. TA systems were initially characterized as selfish elements, but have recently gained attention for regulating general stress...... responses responsible for pathogen virulence, formation of drug-tolerant persister cells and biofilms—all implicated in causing recalcitrant chronic infections. We use a bioinformatics approach to explore the distribution and evolution of type II TA loci of the opportunistic pathogen, Pseudomonas aeruginosa...... in their core genome and a variable number of the remaining 22 on genomic islands; (2) limited mutations in core genome TA loci, suggesting they are not under negative selection; (3) no evidence for horizontal transmission of elements with TA systems between clone types within patients, despite their ability...

  3. Quantitative analysis of the IgG and IgG subclass immune responses to chromosomal Pseudomonas aeruginosa beta-lactamase in serum from patients with cystic fibrosis by western blotting and laser scanning densitometry

    DEFF Research Database (Denmark)

    Petersen, T D; Ciofu, O; Pressler, T

    1996-01-01

    BACKGROUND: Antibodies against chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) are markers of the development of resistance of P aeruginosa to beta-lactam antibiotics in patients with cystic fibrosis and chronic lung infection. The role of these antibodies in patients with chronic...... of the chronic infection the a beta ab titres were higher in patients with good lung function than in those with poor lung function. CONCLUSIONS: The association of a weak IgG3 and a strong IgG4 a beta ab response suggests that the contribution of a beta ab antibodies to lung diseases mediated by immune...... complexes might be less important than other antipseudomonal antibodies. A beneficial neutralising effect of the a beta ab antibodies on the antibiotic destroying enzymes may be an additional factor....

  4. Microbial ecology and adaptation in cystic fibrosis airways

    DEFF Research Database (Denmark)

    Yang, Lei; Jelsbak, Lars; Molin, Søren

    2011-01-01

    Chronic infections in the respiratory tracts of cystic fibrosis (CF) patients are important to investigate, both from medical and from fundamental ecological points of view. Cystic fibrosis respiratory tracts can be described as natural environments harbouring persisting microbial communities...... constitute the selective forces that drive the evolution of the microbes after they migrate from the outer environment to human airways. Pseudomonas aeruginosa adapts to the new environment through genetic changes and exhibits a special lifestyle in chronic CF airways. Understanding the persistent...... colonization of microbial pathogens in CF patients in the context of ecology and evolution will expand our knowledge of the pathogenesis of chronic infections and improve therapeutic strategies....

  5. Early detection of Pseudomonas aeruginosa – comparison of conventional versus molecular (PCR detection directly from adult patients with cystic fibrosis (CF

    Directory of Open Access Journals (Sweden)

    Moore John E

    2004-10-01

    Full Text Available Abstract Background Pseudomonas aeruginosa (PA is the most important bacterial pathogen in patients with cystic fibrosis (CF patients. Currently, routine bacteriological culture on selective/non- selective culture media is the cornerstone of microbiological detection. The aim of this study was to compare isolation rates of PA by conventional culture and molecular (PCR detection directly from sputum. Methods Adult patients (n = 57 attending the regional adult CF centre in Northern Ireland, provided fresh sputum following airways clearance exercise. Following processing of the specimen with sputasol (1:1 vol, the specimen was examined for the presence of PA by plating onto a combination of culture media (Pseudomonas isolation agar, Blood agar & McConkey agar. In addition, from the same specimen, genomic bacterial DNA was extracted (1 ml and was amplified employing two sequence-specific targets, namely (i the outer membrane protein (oprL gene locus and (ii the exotoxin A (ETA gene locus. Results By sputum culture, there were 30 patients positive for PA, whereas by molecular techniques, there were 35 positive patients. In 39 patients (22 PA +ve & 17 PA -ve, there was complete agreement between molecular and conventional detection and with both PCR gene loci. The oprL locus was more sensitive than the ETA locus, as the former was positive in 10 more patients and there were no patients where the ETA was positive and the oprL target negative. Where a PCR +ve/culture -ve result was recorded (10 patients, we followed these patients and recorded that 5 of these patients converted to being culture-positive at times ranging from 4–17 months later, with a mean lag time of 4.5 months. Conclusions This study indicates that molecular detection of PA in sputum employing the oprL gene target, is a useful technique in the early detection of PA, gaining on average 4.5 months over conventional culture. It now remains to be established whether aggressive antibiotic

  6. Dendrimer-based selective autophagy-induction rescues ΔF508-CFTR and inhibits Pseudomonas aeruginosa infection in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Scott Mackenzie Brockman

    Full Text Available Cystic Fibrosis (CF is a genetic disorder caused by mutation(s in the CF-transmembrane conductance regulator (Cftr gene. The most common mutation, ΔF508, leads to accumulation of defective-CFTR protein in aggresome-bodies. Additionally, Pseudomonas aeruginosa (Pa, a common CF pathogen, exacerbates obstructive CF lung pathology. In the present study, we aimed to develop and test a novel strategy to improve the bioavailability and potentially achieve targeted drug delivery of cysteamine, a potent autophagy-inducing drug with anti-bacterial properties, by developing a dendrimer (PAMAM-DEN-based cysteamine analogue.We first evaluated the effect of dendrimer-based cysteamine analogue (PAMAM-DENCYS on the intrinsic autophagy response in IB3-1 cells and observed a significant reduction in Ub-RFP and LC3-GFP co-localization (aggresome-bodies by PAMAM-DENCYS treatment as compared to plain dendrimer (PAMAM-DEN control. Next, we observed that PAMAM-DENCYS treatment shows a modest rescue of ΔF508-CFTR as the C-form. Moreover, immunofluorescence microscopy of HEK-293 cells transfected with ΔF508-CFTR-GFP showed that PAMAM-DENCYS is able to rescue the misfolded-ΔF508-CFTR from aggresome-bodies by inducing its trafficking to the plasma membrane. We further verified these results by flow cytometry and observed significant (p<0.05; PAMAM-DEN vs. PAMAM-DENCYS rescue of membrane-ΔF508-CFTR with PAMAM-DENCYS treatment using non-permeabilized IB3-1 cells immunostained for CFTR. Finally, we assessed the autophagy-mediated bacterial clearance potential of PAMAM-DENCYS by treating IB3-1 cells infected with PA01-GFP, and observed a significant (p<0.01; PAMAM-DEN vs. PAMAM-DENCYS decrease in intracellular bacterial counts by immunofluorescence microscopy and flow cytometry. Also, PAMAM-DENCYS treatment significantly inhibits the growth of PA01-GFP bacteria and demonstrates potent mucolytic properties.We demonstrate here the efficacy of dendrimer-based autophagy

  7. Recommendations for quality improvement in genetic testing for cystic fibrosis European Concerted Action on Cystic Fibrosis

    NARCIS (Netherlands)

    Dequeker, E; Cuppens, H; Dodge, J; Estivill, [No Value; Goossens, M; Pignatti, PF; Scheffer, H; Schwartz, M; Schwarz, M; Tummler, B; Cassiman, JJ

    These recommendations for quality improvement of cystic fibrosis genetic diagnostic testing provide general guidelines for the molecular genetic testing of cystic fibrosis in patients/individuals. General strategies for testing as well as guidelines for laboratory procedures, internal and external

  8. MRI in mucoviscidosis (cystic fibrosis)

    International Nuclear Information System (INIS)

    Eichinger, M.; Puderbach, M.; Kauczor, H.-U.; Heussel, C.-P.

    2006-01-01

    Cystic fibrosis (CF) is a multi-systemic disease with major impact on the lungs. Pulmonary manifestation is crucial for the prognosis and life expectancy of patients. Imaging modalities and lung function tests reflect the pulmonary status in these patients. The standard imaging modality for diagnosis and follow-up of pulmonary changes is chest x-ray. The gold standard for the detection of parenchymal lung changes remains high resolution computed tomography (HRCT), but this is not used routinely for CF-patients due to radiation exposure. Magnetic resonance imaging (MRI) used to be of no importance in monitoring cystic fibrosis lung disease, as shown in studies from the 1980s and early 1990s. The continuing improvement of MRI techniques, however, has allowed for an adequate application of this non-radiation method in diagnosing the major pulmonary findings in CF, in addition to the assessment of lung function. (orig.) [de

  9. [Historical compilation of cystic fibrosis].

    Science.gov (United States)

    Navarro, Salvador

    2016-01-01

    Cystic fibrosis is the most common life-shortening recessively inherited disorder in the Caucasian population. The genetic mutation that most frequently provokes cystic fibrosis (ΔF508) appeared at least 53,000years ago. For many centuries, the disease was thought to be related to witchcraft and the "evil eye" and it was only in 1938 that Dorothy H. Andersen characterized this disorder and suspected its genetic origin. The present article reviews the pathological discoveries and diagnostic and therapeutic advances made in the last 75 years. The review ends with some considerations for the future. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  10. Lactate in cystic fibrosis sputum

    DEFF Research Database (Denmark)

    Bensel, Tobias; Stotz, Martin; Borneff-Lipp, Marianne

    2011-01-01

    Antibiotic therapy is thought to improve lung function in patients with cystic fibrosis (CF) by decreasing neutrophil-derived inflammation. We investigated the origin and clinical significance of lactate in the chronically inflamed CF lung. Methods Lactate was measured in sputa of 18 exacerbated...... and 25 stable CF patients via spectrophotometry and gaschromatography. Lung function was assessed via spirometry. Seven patients with chronic obstructive pulmonary disease (COPD) and three patients with acute lung inflammation served as control groups. Neutrophil and bacterial lactate production...

  11. Anorexia nervosa in cystic fibrosis.

    Science.gov (United States)

    Linkson, Lynette; Macedo, Patricia; Perrin, Felicity M R; Elston, Caroline M

    2018-03-01

    This article explores the challenges associated with diagnosing and managing eating disorders such as anorexia nervosa amongst adolescents and adults with cystic fibrosis. It reviews the known risk factors, generic verses disease specific eating disorder risk screening tools and considers the ethical dilemmas associated with critically low body mass indices. A case review is included to illustrate the complexities of managing both conditions in the context of declining respiratory function. Copyright © 2017. Published by Elsevier Ltd.

  12. Cystic Fibrosis-Related Diabetes

    Directory of Open Access Journals (Sweden)

    Kayani Kayani

    2018-02-01

    Full Text Available Cystic fibrosis (CF is the most common autosomal recessive disorder in Caucasian populations. Individuals with CF have seen significant increases in life expectancy in the last 60 years. As a result, previously rare complications are now coming to light. The most common of these is cystic fibrosis-related diabetes (CFRD, which affects 40–50% of CF adults. CFRD significantly impacts the pulmonary function and longevity of CF patients, yet a lack of consensus on the best methods to diagnose and treat CFRD remains. We begin by reviewing our understanding of the pathogenesis of CFRD, as emerging evidence shows the cystic fibrosis transmembrane conductance regulator (CFTR also has important roles in the release of insulin and glucagon and in the protection of β cells from oxidative stress. We then discuss how current recommended methods of CFRD diagnosis are not appropriate, as continuous glucose monitoring becomes more effective, practical, and cost-effective. Finally, we evaluate emerging treatments which have narrowed the mortality gap within the CF patient group. In the future, pharmacological potentiators and correctors directly targeting CFTR show huge promise for both CFRD and the wider CF patient groups.

  13. Microbiological surveillance in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Paola Gualdi

    2010-06-01

    Full Text Available Pulmonary infections in patients with cystic fibrosis (CF, are a major cause of morbidity and mortality. Prevention, diagnosis and therapy in cystic fibrosis, lead to the necessary collaboration between clinical and laboratory to identify effective strategies and appropriate solutions to address the problems inherent isolation micro-organisms, antibiotic strategies, overcoming of bacterial resistance and other problems management of these patients. The task of the microbiology laboratory and research in quickly and accurately, the agents responsible for these infectious processes, in order to isolate them from material, identify and determine their sensitivity antibiotics. A microbiological surveillance on 34 patients (13 males and 21 females with CF and related to the “Support Services Provincial Trento for the treatment of cystic fibrosis “in the period July 2005 - August 2008, was carried out. 180 Gram positive and 278 of Gram negative bacteria as well as 235 fungi wre collected. Staphylococcus aureus was the most frequently organism found in patients with CF with an incidence of 23% on 156 strains isolated, Pseudomonas aeruginosa was collected 19% of all microorganisms isolated corresponding to 131 strains, Candida albicans is the yeast often isolated with a frequency 22% equal to 149 isolates, Aspergillus fumigatus was isolated at a rate of 8%. From the data we collected and processed has been noted that the local epidemiology of CF patients reflects as reported in the scientific literature and national international consulting, both as a type microorganisms that frequency also isolated compared to age groups. Considering the score of Bartlett as discriminating respiratory fitness of the material, it has been observed that only 32 samples over 327 total (10% would materials insignificant. It follows therefore that the time of sample collection, followed by personnel (physiotherapists dedicated to CF patients, represents a crucial step

  14. Otorhinolaryngologic manifestations of cystic fibrosis: literature review

    Directory of Open Access Journals (Sweden)

    Carvalho, Carolina Pimenta

    2008-12-01

    Full Text Available Introduction: Cystic Fibrosis is the most common recessive autosomic genetic disease among Caucasians. It's caused by mutations in the gene that decodes regulatory protein for transmembrane conductance, resulting in defective transport of chlorine. Objective: Review the literature about Cystic Fibrosis, with emphasis on otorhinolaryngologic manifestations. Method: The online Pub Med databases were researched and we applied the following search terms Fibrosis Cystic and Sinusitis, and Mucoviscidosis and Sinusitis. Conclusions: Although it is not the main cause of death, the otorhinolaryngologic manifestations of the Cystic Fibrosis bring important morbidity to these patients.

  15. The Sociology and Entrenchment. A Cystic Fibrosis Test for Everyone?

    DEFF Research Database (Denmark)

    Koch, Lene; Stemerding, Dirk

    1994-01-01

    Socialmedicine, genetic screening, cystic fibrosis, ethics, political regulation, sociology of technology......Socialmedicine, genetic screening, cystic fibrosis, ethics, political regulation, sociology of technology...

  16. Outcome in cystic fibrosis liver disease.

    LENUS (Irish Health Repository)

    Rowland, Marion

    2011-01-01

    Evidence suggests that cystic fibrosis liver disease (CFLD) does not affect mortality or morbidity in patients with cystic fibrosis (CF). The importance of gender and age in outcome in CF makes selection of an appropriate comparison group central to the interpretation of any differences in mortality and morbidity in patients with CFLD.

  17. Laparoscopic cholecystectomy in adult cystic fibrosis.

    LENUS (Irish Health Repository)

    McGrath, D S

    2012-02-03

    Two female patients with Cystic Fibrosis, attending the Adult Regional Cystic Fibrosis centre at the Cork University Hospital, were investigated for upper abdominal pain and found to have gallstones at ultrasonography. Laparoscopic cholecystectomy was performed successfully and, without complication, in both patients.

  18. Self-management education for cystic fibrosis.

    LENUS (Irish Health Repository)

    Savage, Eileen

    2011-01-01

    Self-management education may help patients with cystic fibrosis and their families to choose, monitor and adjust treatment requirements for their illness, and also to manage the effects of illness on their lives. Although self-management education interventions have been developed for cystic fibrosis, no previous systematic review of the evidence of effectiveness of these interventions has been conducted.

  19. Pulmonary complications of cystic fibrosis

    International Nuclear Information System (INIS)

    Ng, M.Y.; Flight, W.; Smith, E.

    2014-01-01

    The life expectancy of patients with cystic fibrosis (CF) has steadily increased over recent decades with a corresponding increase in the frequency of complications of the disease. Radiologists are increasingly involved with managing and identifying the pulmonary complications of CF. This article reviews the common manifestations of CF lung disease as well as updating radiologists with a number of less well-known complications of the condition. Early and accurate detection of the pulmonary effects of CF are increasingly important to prevent irreversible lung damage and give patients the greatest possibility of benefiting from the new therapies becoming available, which correct the underlying defect causing CF

  20. Liver manifestations of cystic fibrosis

    International Nuclear Information System (INIS)

    Akata, Deniz; Akhan, Okan

    2007-01-01

    Chronic liver disease is one of the major complications of cystic fibrosis (CF). Significant liver disease is seen in 13-25% of children with CF. Improved life expectancy and prolonged follow-up have favored better characterization of the hepatic manifestations of CF and allowed direct observation of an increasing number of liver-related events. Liver disease typically develops in the first decade of life, with the incidence dropping rapidly after the age of 10 years. The wide spectrum of liver disease ranging from asymptomatic gallbladder abnormalities to biliary cirrhosis will be reviewed in this article

  1. Endocrine Disorders in Cystic Fibrosis.

    Science.gov (United States)

    Blackman, Scott M; Tangpricha, Vin

    2016-08-01

    Cystic fibrosis is frequently complicated by endocrine disorders. Diabetes can be expected to affect most with CF and pancreatic insufficiency and varies widely in age of onset, but early identification and treatment improve morbidity and mortality. Short stature can be exacerbated by relative delay of puberty and by use of inhaled corticosteroids. Bone disease in CF causes fragility fractures and should be assessed by monitoring bone mineral density and optimizing vitamin D status. Detecting and managing endocrine complications in CF can reduce morbidity and mortality in CF. These complications can be expected to become more common as the CF population ages. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Vitamin D deficiency as a risk factor for cystic fibrosis-related diabetes in the Scandinavian Cystic Fibrosis Nutritional Study

    DEFF Research Database (Denmark)

    Pincikova, T; Nilsson, Kristine Kahr; Moen, I E

    2011-01-01

    Many cystic fibrosis patients are vitamin D-insufficient. Cystic fibrosis-related diabetes is a major complication of cystic fibrosis. The literature suggests that vitamin D might possess certain glucose-lowering properties. We aimed to assess the relationship between vitamin D and cystic fibrosis...

  3. Inhalable Antimicrobials for Treatment of Bacterial Biofilm-Associated Sinusitis in Cystic Fibrosis Patients

    DEFF Research Database (Denmark)

    Klodzinska, Sylvia Natalie; Priemel, Petra Alexandra; Rades, Thomas

    2016-01-01

    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 infec...... and management of biofilm infections caused by P. aeruginosa and discusses critical issues related to novel antimicrobial drug formulation design approaches.......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....... 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...

  4. Vitamin A supplementation for cystic fibrosis.

    Science.gov (United States)

    Bonifant, Catherine M; Shevill, Elizabeth; Chang, Anne B

    2014-05-14

    People with cystic fibrosis and pancreatic insufficiency are at risk of fat soluble vitamin deficiency as these vitamins (A, D, E and K) are co-absorbed with fat. Thus, some cystic fibrosis centres routinely administer these vitamins as supplements but the centres vary in their approach of addressing the possible development of deficiencies in these vitamins. Vitamin A deficiency causes predominantly eye and skin problems while supplementation of vitamin A to excessive levels may cause harm to the respiratory and skeletal systems in children. Thus a systematic review on vitamin A supplementation in people with cystic fibrosis would help guide clinical practice. To determine if vitamin A supplementation in children and adults with cystic fibrosis:1. reduces the frequency of vitamin A deficiency disorders;2. improves general and respiratory health;3. increases the frequency of vitamin A toxicity. 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.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 07 April 2014. All randomised or quasi-randomised controlled trials comparing all preparations of oral vitamin A used as a supplement compared to either no supplementation (or placebo) at any dose and for any duration, in children or adults with cystic fibrosis (defined by sweat tests or genetic testing) with and without pancreatic insufficiency. No relevant studies for inclusion were identified in the search. No studies were included in this review. As there were no randomised or quasi-randomised controlled trials identified, we cannot draw any conclusions on the benefits (or otherwise) of regular administration of vitamin A in people with cystic fibrosis. Until further data are available, country or region specific guidelines on the use of

  5. Voice Disorder in Cystic Fibrosis Patients

    Science.gov (United States)

    Lourenço, Bruna Mendes; Costa, Kauê Machado; da Silva Filho, Manoel

    2014-01-01

    Cystic fibrosis is a common autosomal recessive disorder with drastic respiratory symptoms, including shortness of breath and chronic cough. While most of cystic fibrosis treatment is dedicated to mitigating the effects of respiratory dysfunction, the potential effects of this disease on vocal parameters have not been systematically studied. We hypothesized that cystic fibrosis patients, given their characteristic respiratory disorders, would also present dysphonic symptoms. Given that voice disorders can severely impair quality of life, the identification of a potential cystic fibrosis-related dysphonia could be of great value for the clinical evaluation and treatment of this disease. We tested our hypothesis by measuring vocal parameters, using both objective physical measures and the GRBAS subjective evaluation method, in male and female cystic fibrosis patients undergoing conventional treatment and compared them to age and sex matched controls. We found that cystic fibrosis patients had a significantly lower vocal intensity and harmonic to noise ratio, as well as increased levels of jitter and shimmer. In addition, cystic fibrosis patients also showed higher scores of roughness, breathiness and asthenia, as well as a significantly altered general grade of dysphonia. When we segregated the results according to sex, we observed that, as a group, only female cystic fibrosis patients had significantly lower values of harmonic to noise ratio and an abnormal general grade of dysphonia in relation to matched controls, suggesting that cystic fibrosis exerts a more pronounced effect on vocal parameters of women in relation to men. Overall, the dysphonic characteristics of CF patients can be explained by dysfunctions in vocal fold movement and partial upper airway obstruction, potentially caused by the accumulation of mucus and chronic cough characteristic of CF symptomatology. Our results show that CF patients exhibit significant dysphonia and suggest they may

  6. Inhaled mannitol for cystic fibrosis.

    Science.gov (United States)

    Nevitt, Sarah J; Thornton, Judith; Murray, Clare S; Dwyer, Tiffany

    2018-02-09

    Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action is unknown. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed and it is now available in Australia and some countries in Europe. This is an update of a previous review. To assess whether inhaled dry powder mannitol is well tolerated, whether it improves the quality of life and respiratory function in people with cystic fibrosis and which adverse events are associated with the treatment. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic databases, handsearching relevant journals and abstracts from conferences.Date of last search: 28 September 2017. All randomised controlled studies comparing mannitol with placebo, active inhaled comparators (for example, hypertonic saline or dornase alfa) or with no treatment. Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias in included studies. The quality of the evidence was assessed using GRADE. Six studies (reported in 50 publications) were included with a total of 784 participants.Duration of treatment in the included studies ranged from 12 days to six months, with open-label treatment for an additional six months in two of the studies. Five studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol) and the final study compared mannitol to dornase alfa alone and to mannitol plus dornase alfa. Two large studies had a similar parallel design and provided data for 600 participants, which could be pooled where data for a particular outcome and time point were

  7. European Cystic Fibrosis Society Standards of Care

    DEFF Research Database (Denmark)

    Stern, Martin; Bertrand, Dominique Pougheon; Bignamini, Elisabetta

    2014-01-01

    Since the earliest days of cystic fibrosis (CF) treatment, patient data have been recorded and reviewed in order to identify the factors that lead to more favourable outcomes. Large data repositories, such as the US Cystic Fibrosis Registry, which was established in the 1960s, enabled successful ...... to indicators of health, the role of CF Centres, regional networks, national health policy, and international data registration and comparisons.......Since the earliest days of cystic fibrosis (CF) treatment, patient data have been recorded and reviewed in order to identify the factors that lead to more favourable outcomes. Large data repositories, such as the US Cystic Fibrosis Registry, which was established in the 1960s, enabled successful...... therapies, approaches to care and indeed data recording. The quality of care for individuals with CF has become a focus at several levels: patient, centre, regional, national and international. This paper reviews the quality management and improvement issues at each of these levels with particular reference...

  8. Nutrition in Cystic Fibrosis: Macro- and Micronutrients

    NARCIS (Netherlands)

    Oudshoorn, Johanna Hermiena

    2006-01-01

    Cystic fibrosis (CF) is the most common life-threatening autosomal recessive inherited disease in Caucasians, and is characterized by progressive lung disease, pancreatic insufficiency, malnutrition, hepatobiliary disease and elevated sweat electrolyte levels. The increased survival of CF patients

  9. Festival food coma in cystic fibrosis.

    Science.gov (United States)

    Pandit, Chetan; Graham, Christie; Selvadurai, Hiran; Gaskin, Kevin; Cooper, Peter; van Asperen, Peter

    2013-07-01

    Children with cystic fibrosis liver disease and portal hypertension are at risk of developing acute hepatic encephalopathy. Even in the presence of normal synthetic liver function these children may have porto-systemic shunting. We report a case of an adolosecent who had cystic fibrosis liver disease and presented with life threatening hepatinc encephalopathy. This case illustrates that it is necessary to consider an appropriate dietary regimen in adolosecents with liver disease to prevent hepatic decompensation. Copyright © 2012 Wiley Periodicals, Inc.

  10. The effect of short-term, high-dose oral N-acetylcysteine treatment on oxidative stress markers in cystic fibrosis patients with chronic P. aeruginosa infection -- a pilot study.

    Science.gov (United States)

    Skov, Marianne; Pressler, Tacjana; Lykkesfeldt, Jens; Poulsen, Henrik Enghusen; Jensen, Peter Østrup; Johansen, Helle Krogh; Qvist, Tavs; Kræmer, Dorthe; Høiby, Niels; Ciofu, Oana

    2015-03-01

    Patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa lung infection have increased oxidative stress as a result of an imbalance between the production of reactive oxygen species caused by inflammation and their inactivation by the impaired antioxidant systems. Supplementation with anti-oxidants is potentially beneficial for CF patients. The effect of 4 weeks of oral N-acetylcysteine (NAC) treatment (2400 mg/day divided into two doses) on biochemical parameters of oxidative stress was investigated in an open-label, controlled, randomized trial on 21 patients; 11 patients in the NAC group and 10 in the control group. Biochemical parameters of oxidative burden and plasma levels of antioxidants were assessed at the end of the study and compared to the baseline values in the two groups. A significant increase in the plasma levels of the antioxidant ascorbic acid (p=0.037) and a significant decrease in the levels of the oxidized form of ascorbic acid (dehydroascorbate) (p=0.004) compared to baseline were achieved after NAC treatment. No significant differences were observed in the control group. The parameters of oxidative burden did not change significantly compared to baseline in either of the groups. A better lung function was observed in the NAC treated group with a mean (SD) change compared to baseline of FEV1% predicted of 2.11 (4.6), while a decrease was observed in the control group (change -1.4 (4.6)), though not statistically significant. Treatment with N-acetylcysteine 1200 mg×2/day for 30 days significantly decreased the level of oxidized vitamin C and increased the level of vitamin C (primary end-points) and a not statistically significant improvement of lung function was observed in this group of patients. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  11. Gene therapy in cystic fibrosis.

    Science.gov (United States)

    Flotte, T R; Laube, B L

    2001-09-01

    Theoretically, cystic fibrosis transmembrane conductance regulator (CFTR) gene replacement during the neonatal period can decrease morbidity and mortality from cystic fibrosis (CF). In vivo gene transfers have been accomplished in CF patients. Choice of vector, mode of delivery to airways, translocation of genetic information, and sufficient expression level of the normalized CFTR gene are issues that currently are being addressed in the field. The advantages and limitations of viral vectors are a function of the parent virus. Viral vectors used in this setting include adenovirus (Ad) and adeno-associated virus (AAV). Initial studies with Ad vectors resulted in a vector that was efficient for gene transfer with dose-limiting inflammatory effects due to the large amount of viral protein delivered. The next generation of Ad vectors, with more viral coding sequence deletions, has a longer duration of activity and elicits a lesser degree of cell-mediated immunity in mice. A more recent generation of Ad vectors has no viral genes remaining. Despite these changes, the problem of humoral immunity remains with Ad vectors. A variety of strategies such as vector systems requiring single, or widely spaced, administrations, pharmacologic immunosuppression at administration, creation of a stealth vector, modification of immunogenic epitopes, or tolerance induction are being considered to circumvent humoral immunity. AAV vectors have been studied in animal and human models. They do not appear to induce inflammatory changes over a wide range of doses. The level of CFTR messenger RNA expression is difficult to ascertain with AAV vectors since the small size of the vector relative to the CFTR gene leaves no space for vector-specific sequences on which to base assays to distinguish endogenous from vector-expressed messenger RNA. In general, AAV vectors appear to be safe and have superior duration profiles. Cationic liposomes are lipid-DNA complexes. These vectors generally have been

  12. Male fertility in cystic fibrosis.

    LENUS (Irish Health Repository)

    Chotirmall, S H

    2011-04-05

    Infertility rates among males with cystic fibrosis (CF) approximate 97%. No information is currently available within Ireland determining an understanding of fertility issues and the best methods of information provision to this specialized group. This study aimed to determine understanding and preferred approaches to information provision on fertility issues to Irish CF males. A Descriptive Study utilizing prospective coded questionnaires was mailed to a male CF cohort (n=50). Sections included demographics, fertility knowledge & investigation. Response rate was 16\\/50 (32%). All were aware that CF affected their fertility. More than two-thirds (n=11) were able to provide explanations whilst only one-third (n=5) provided the correct explanation. Significant numbers stated thoughts of marriage and a future family. Half have discussed fertility with a healthcare professional (HCP). Mean age of discussion was 21.9 years. One third preferred an earlier discussion. The commonest first source for information was written material which was also the preferred source. Three-quarters requested further information preferring again, written material. Significant gaps in sex education of Irish CF males exist. Discussion should be initiated by HCPs and centre-directed written material devised to address deficiencies.

  13. Cystic fibrosis: a clinical view.

    Science.gov (United States)

    Castellani, Carlo; Assael, Baroukh M

    2017-01-01

    Cystic fibrosis (CF), a monogenic disease caused by mutations in the CFTR gene on chromosome 7, is complex and greatly variable in clinical expression. Airways, pancreas, male genital system, intestine, liver, bone, and kidney are involved. The lack of CFTR or its impaired function causes fat malabsorption and chronic pulmonary infections leading to bronchiectasis and progressive lung damage. Previously considered lethal in infancy and childhood, CF has now attained median survivals of 50 years of age, mainly thanks to the early diagnosis through neonatal screening, recognition of mild forms, and an aggressive therapeutic attitude. Classical treatment includes pancreatic enzyme replacement, respiratory physiotherapy, mucolitics, and aggressive antibiotic therapy. A significant proportion of patients with severe symptoms still requires lung or, less frequently, liver transplantation. The great number of mutations and their diverse effects on the CFTR protein account only partially for CF clinical variability, and modifier genes have a role in modulating the clinical expression of the disease. Despite the increasing understanding of CFTR functioning, several aspects of CF need still to be clarified, e.g., the worse outcome in females, the risk of malignancies, the pathophysiology, and best treatment of comorbidities, such as CF-related diabetes or CF-related bone disorder. Research is focusing on new drugs restoring CFTR function, some already available and with good clinical impact, others showing promising preliminary results that need to be confirmed in phase III clinical trials.

  14. Ursodeoxycholic acid treatment in patients with cystic fibrosis at risk for liver disease.

    Science.gov (United States)

    Siano, Maria; De Gregorio, Fabiola; Boggia, Bartolo; Sepe, Angela; Ferri, Pasqualina; Buonpensiero, Paolo; Di Pasqua, Antonio; Raia, Valeria

    2010-06-01

    Meconium ileus has been detected as a risk factor for development of liver disease in cystic fibrosis, with influence on morbidity and mortality. To evaluate the effect of early treatment with ursodeoxycholic acid in patients with cystic fibrosis and meconium ileus to prevent chronic hepatic involvement and to explore the potential role of therapy on clinical outcomes. 26 cystic fibrosis patients with meconium ileus (16 M, mean age 8,4 years, range 3,5-9) were assigned to two groups: group 1 (14 patients) treated early with ursodeoxycholic acid (UDCAe); group 2 (12 patients) treated with ursodeoxycholic acid at the onset of cystic fibrosis liver disease (UDCAd). Anthropometric data, pulmonary function tests, pancreatic status, complications such as diabetes, hepatic involvement and Pseudomonas aeruginosa colonisation were compared among groups. A higher prevalence of cystic fibrosis chronic liver disease was observed in the UDCAd group with a statistically significant difference at 9 years of age (p<0.05). Chronic infection by P. aeruginosa was found in 7% of UDCAe and 33% of UDCAd (p<0.05). No differences were observed in nutritional status and other complications. Early treatment with ursodeoxycholic acid may be beneficial in patients at risk of developing cystic fibrosis chronic liver disease such as those with meconium ileus. Multicentre studies should be encouraged to confirm these data. Copyright 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  15. Cystic Fibrosis-Related Diabetes (CFRD): Daily Management

    Science.gov (United States)

    Cystic Fibrosis-Related Diabetes (CFRD): Daily Management September 20, 2011 This Web cast is supported by an unrestricted ... Moran, MD Professor, Pediatric Endocrinology University of Minnesota Cystic Fibrosis-Related Diabetes (CFRD): Daily Management September 20, 2011 ...

  16. Gastroenterological endpoints in drug trials for cystic fibrosis

    NARCIS (Netherlands)

    Bodewes, Frank A. J. A.; Verkade, Henkjan J.; Wilschanski, Micheal

    2016-01-01

    The phenotype of cystic fibrosis includes a wide variety of clinical and biochemical gastrointestinal presentations. These gastrointestinal characteristics of the disease have come under renewed interest as potential outcome measures and clinical endpoints for therapeutic trials in cystic fibrosis.

  17. Innovating cystic fibrosis clinical trial designs in an era of successful standard of care therapies.

    Science.gov (United States)

    VanDevanter, Donald R; Mayer-Hamblett, Nicole

    2017-11-01

    Evolving cystic fibrosis 'standards of care' have influenced recent cystic fibrosis clinical trial designs for new therapies; care additions/improvements will require innovative trial designs to maximize feasibility and efficacy detection. Three cystic fibrosis therapeutic areas (pulmonary exacerbations, Pseudomonas aeruginosa airway infections, and reduced cystic fibrosis transmembrane conductance regulator [CFTR] protein function) differ with respect to the duration for which recognized 'standards of care' have been available. However, developers of new therapies in all the three areas are affected by similar challenges: standards of care have become so strongly entrenched that traditional placebo-controlled studies in cystic fibrosis populations likely to benefit from newer therapies have become less and less feasible. Today, patients/clinicians are more likely to entertain participation in active-comparator trial designs, that have substantial challenges of their own. Foremost among these are the selection of 'valid' active comparator(s), estimation of a comparator's current clinical efficacy (required for testing noninferiority hypotheses), and effective blinding of commercially available comparators. Recent and future cystic fibrosis clinical trial designs will have to creatively address this collateral result of successful past development of effective cystic fibrosis therapies: patients and clinicians are much less likely to accept simple, placebo-controlled studies to evaluate future therapies.

  18. Liver Disease in Cystic Fibrosis: an Update

    Science.gov (United States)

    Parisi, Giuseppe Fabio; Di Dio, Giovanna; Franzonello, Chiara; Gennaro, Alessia; Rotolo, Novella; Lionetti, Elena; Leonardi, Salvatore

    2013-01-01

    Context Cystic fibrosis (CF) is the most widespread autosomal recessive genetic disorder that limits life expectation amongst the Caucasian population. As the median survival has increased related to early multidisciplinary intervention, other manifestations of CF have emergedespecially for the broad spectrum of hepatobiliary involvement. The present study reviews the existing literature on liver disease in cystic fibrosis and describes the key issues for an adequate clinical evaluation and management of patients, with a focus on the pathogenetic, clinical and diagnostic-therapeutic aspects of liver disease in CF. Evidence Acquisition A literature search of electronic databases was undertaken for relevant studies published from 1990 about liver disease in cystic fibrosis. The databases searched were: EMBASE, PubMed and Cochrane Library. Results CF is due to mutations in the gene on chromosome 7 that encodes an amino acidic polypeptide named CFTR (cystic fibrosis transmembrane regulator). The hepatic manifestations include particular changes referring to the basic CFTR defect, iatrogenic lesions or consequences of the multisystem disease. Even though hepatobiliary disease is the most common non-pulmonary cause ofmortalityin CF (the third after pulmonary disease and transplant complications), only about the 33%ofCF patients presents clinically significant hepatobiliary disease. Conclusions Liver disease will have a growing impact on survival and quality of life of cystic fibrosis patients because a longer life expectancy and for this it is important its early recognition and a correct clinical management aimed atdelaying the onset of complications. This review could represent an opportunity to encourage researchers to better investigate genotype-phenotype correlation associated with the development of cystic fibrosis liver disease, especially for non-CFTR genetic polymorphisms, and detect predisposed individuals. Therapeutic trials are needed to find strategies of

  19. Bacteriocin-mediated competition in cystic fibrosis lung infections

    DEFF Research Database (Denmark)

    Ghoul, Melanie; West, Stuart A.; Johansen, Helle Krogh

    2015-01-01

    Bacteriocins are toxins produced by bacteria to kill competitors of the same species. Theory and laboratory experiments suggest that bacteriocin production and immunity play a key role in the competitive dynamics of bacterial strains. The extent to which this is the case in natural populations......, especially human pathogens, remains to be tested. We examined the role of bacteriocins in competition using Pseudomonas aeruginosa strains infecting lungs of humans with cystic fibrosis (CF). We assessed the ability of different strains to kill each other using phenotypic assays, and sequenced their genomes...

  20. Endocytosis and intracellular protein degradation in cystic fibrosis fibroblasts

    International Nuclear Information System (INIS)

    Jessup, W.; Dean, R.T.

    1983-01-01

    Normal rates of pinocytosis of [ 3 H]sucrose were measured in cystic fibrosis fibroblasts, and were not affected by the addition of cystic fibrosis serum. Bulk protein degradation (a significant proportion of which occurs intralysosomally following autophagy) and its regulation by growth state were apparently identical in normal and cystic fibrosis cultures. (Auth.)

  1. Living with Cystic Fibrosis: A Guide for the Young Adult.

    Science.gov (United States)

    Cystic Fibrosis Foundation, Atlanta, GA.

    Intended for the young adult with cystic fibrosis, the booklet provides information on dealing with problems and on advances in treatment and detection related to the disease. Addressed are the following topics: description of cystic fibrosis; inheritance of cystic fibrosis; early diagnosis; friends, careers, and other matters; treatment;…

  2. Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function Reduces Airway Bacteria and Inflammation in People with Cystic Fibrosis and Chronic Lung Infections.

    Science.gov (United States)

    Hisert, Katherine B; Heltshe, Sonya L; Pope, Christopher; Jorth, Peter; Wu, Xia; Edwards, Rachael M; Radey, Matthew; Accurso, Frank J; Wolter, Daniel J; Cooke, Gordon; Adam, Ryan J; Carter, Suzanne; Grogan, Brenda; Launspach, Janice L; Donnelly, Seamas C; Gallagher, Charles G; Bruce, James E; Stoltz, David A; Welsh, Michael J; Hoffman, Lucas R; McKone, Edward F; Singh, Pradeep K

    2017-06-15

    Previous work indicates that ivacaftor improves cystic fibrosis transmembrane conductance regulator (CFTR) activity and lung function in people with cystic fibrosis and G551D-CFTR mutations but does not reduce density of bacteria or markers of inflammation in the airway. These findings raise the possibility that infection and inflammation may progress independently of CFTR activity once cystic fibrosis lung disease is established. To better understand the relationship between CFTR activity, airway microbiology and inflammation, and lung function in subjects with cystic fibrosis and chronic airway infections. We studied 12 subjects with G551D-CFTR mutations and chronic airway infections before and after ivacaftor. We measured lung function, sputum bacterial content, and inflammation, and obtained chest computed tomography scans. Ivacaftor produced rapid decreases in sputum Pseudomonas aeruginosa density that began within 48 hours and continued in the first year of treatment. However, no subject eradicated their infecting P. aeruginosa strain, and after the first year P. aeruginosa densities rebounded. Sputum total bacterial concentrations also decreased, but less than P. aeruginosa. Sputum inflammatory measures decreased significantly in the first week of treatment and continued to decline over 2 years. Computed tomography scans obtained before and 1 year after ivacaftor treatment revealed that ivacaftor decreased airway mucous plugging. Ivacaftor caused marked reductions in sputum P. aeruginosa density and airway inflammation and produced modest improvements in radiographic lung disease in subjects with G551D-CFTR mutations. However, P. aeruginosa airway infection persisted. Thus, measures that control infection may be required to realize the full benefits of CFTR-targeting treatments.

  3. Appetite stimulants for people with cystic fibrosis.

    Science.gov (United States)

    Chinuck, Ruth; Dewar, Jane; Baldwin, David R; Hendron, Elizabeth

    2014-07-27

    Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic anorexia attain optimal body mass index and nutritional status. However, these may have adverse effects on clinical status. The aim of this review is to systematically search for and evaluate evidence on the beneficial effects of appetite stimulants in the management of CF-related anorexia and synthesize reports of any side-effects. Trials were identified by searching the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, MEDLINE, Embase, CINAHL, handsearching reference lists and contacting local and international experts.Last search of online databases: 01 April 2014.Last search of the Cystic Fibrosis Trials Register: 08 April 2014. Randomised and quasi-randomised controlled trials of appetite stimulants, compared to placebo or no treatment for at least one month in adults and children with cystic fibrosis. Authors independently extracted data and assessed the risk of bias within eligible trials. Meta-analyses were performed. Three trials (total of 47 recruited patients) comparing appetite stimulants (cyproheptadine hydrochloride and megesterol acetate) to placebo were included; the numbers of adults or children within each trial were not always reported. The risk of bias of the included trials was graded as moderate.A meta-analysis of all three trials showed appetite stimulants produced a larger increase in weight z score at three months compared to placebo, mean difference 0.61 (95% confidence interval 0.29 to 0.93) (P children, appetite stimulants improved only two of the outcomes in this review - weight (or weight z score) and appetite; and side effects were insufficiently reported to determine the full extent of their impact. Whilst the data may suggest the potential use of appetite stimulants in treating anorexia in adults and children with cystic fibrosis

  4. Antimicrobial resistance, respiratory tract infections and role of biofilms in lung infections in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Ciofu, Oana; Tolker-Nielsen, Tim; Jensen, Peter Østrup

    2015-01-01

    Lung infection is the main cause of morbidity and mortality in patients with cystic fibrosis and is mainly dominated by Pseudomonas aeruginosa. The biofilm mode of growth makes eradication of the infection impossible, and it causes a chronic inflammation in the airways. The general mechanisms...

  5. Decreased mucosal oxygen tension in the maxillary sinuses in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Aanæs, Kasper; Rickelt, Lars Fledelius; Johansen, Helle Krogh

    2011-01-01

    Pseudomonas aeruginosa in the sinuses plays a role in the lungs in cystic fibrosis (CF) patients, but little is known about the sinus environment where the bacteria adapt. Anoxic areas are found in the lower respiratory airways but it is unknown if the same conditions exist in the sinuses....

  6. Psychological interventions for cystic fibrosis.

    Science.gov (United States)

    Glasscoe, C A; Quittner, A L

    2003-01-01

    As survival estimates for cystic fibrosis (CF) steadily increase long-term management has become an important focus for intervention. Psychological interventions are largely concerned with emotional and social adjustments, adherence to treatment and quality of life, however no systematic review of such interventions has been undertaken for this disease. To describe the extent and quality of effectiveness studies utilising psychological interventions for CF and whether these interventions provide significant psychosocial and physical benefits in addition to standard care. Relevant trials were identified from searches of Ovid MEDLINE, the Cochrane trial registers for CF and Depression, Anxiety and Neurosis Groups and PsychINFO; unpublished trials were located through professional networks and Listserves. Most recent search: April 2003. This review included RCTs and quasi-randomised trials. Study participants were children and adults diagnosed with CF, and their immediate family members. Psychological interventions were from a broad range of modalities and outcomes were primarily psychosocial, although physical outcomes and cost effectiveness were also considered. Two reviewers independently selected relevant trials and assessed their methodological quality. For binary and continuous outcomes a pooled estimate of treatment effect was calculated for each outcome. This review is based on the findings of eight studies, representing data from a total of 358 participants. Studies fell into four conceptually similar groups: (1) gene pre-test education counselling for relatives of those with CF (one study); (2) biofeedback, massage and music therapy to assist physiotherapy (three studies); (3) behavioural intervention to improve dietary intake in children up to 12 years (three studies); and (4) self-administration of treatments to improve quality of life in adults (one study). Interventions were largely educational or behavioural, targeted at specific treatment concerns

  7. Immunoreactive trypsin and neonatalscreening for cystic fibrosis

    International Nuclear Information System (INIS)

    Travert, G.; Laroche, D.; Blandin, C.; Pasquet, C.

    1988-01-01

    Immunoreactive trypsin (IRT) was measured in dried blood spots from 160.822 five-day-old babies as a part of a regionwide neonatal screening program for cystic fibrosis. A second test was performed for 492 babies in whom blood IRT levels were found greater than 900 μg/l; retesting revealed persistent elevation in 55. Sweat testing confirmed cystic fibrosis in 43 babies, but results were normal in 12. During the course of this study, a total of 51 cystic fibrosis babies were identified: 43 by newborn screening, 6 because they had meconium ileus; so, early diagnosis was achieved in 49 cases out of 51. Two newborn babies did not have elevated IRT and they were missed by the screening test. Our results confirm that elevated blood IRT is characteristic of newborn babies with cystic fibrosis and show that this test has an excellent specificity (99.7%) and a good sensitivity (95%) when used as a neonatal screening test [fr

  8. Barriers to adherence in cystic fibrosis

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke; Schiøtz, Peter Oluf

    2012-01-01

    Danish patients with cystic fibrosis aged 14 to 25 years and their parents. Conclusions: The present study showed that the majority of adolescents with CF and their parents experienced barriers to treatment adherence. Patients and parents agreed that the three most common barriers encountered lack...

  9. Cystic fibrosis year in review 2016.

    Science.gov (United States)

    Savant, Adrienne P; McColley, Susanna A

    2017-08-01

    In this article, we highlight cystic fibrosis (CF) research and case reports published in Pediatric Pulmonology during 2016. We also include articles from a variety of journals that are thematically related to these articles, or are of special interest to clinicians. © 2017 Wiley Periodicals, Inc.

  10. Inhalation of antibiotics in cystic fibrosis

    NARCIS (Netherlands)

    Touw, D J; Brimicombe, R W; Hodson, M E; Heijerman, H G; Bakker, W

    Aerosol administration of antipseudomonal antibiotics is commonly used in cystic fibrosis. However, its contribution to the improvement of lung function, infection and quality of life is not well-established. All articles published from 1965 until the present time concerning the inhalation of

  11. The cystic fibrosis of exocrine pancreas

    DEFF Research Database (Denmark)

    Wilschanski, Michael; Novak, Ivana

    2013-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) protein is highly expressed in the pancreatic duct epithelia and permits anions and water to enter the ductal lumen. This results in an increased volume of alkaline fluid allowing the highly concentrated proteins secreted by the acina...... (CF) and pancreatitis, and outline present and potential therapeutic approaches in CF treatment relevant to the pancreas....

  12. Nutrient Status of Adults with Cystic Fibrosis

    Science.gov (United States)

    GORDON, CATHERINE M.; ANDERSON, ELLEN J.; HERLYN, KAREN; HUBBARD, JANE L.; PIZZO, ANGELA; GELBARD, RONDI; LAPEY, ALLEN; MERKEL, PETER A.

    2011-01-01

    Nutrition is thought to influence disease status in patients with cystic fibrosis (CF). This cross-sectional study sought to evaluate nutrient intake and anthropometric data from 64 adult outpatients with cystic fibrosis. Nutrient intake from food and supplements was compared with the Dietary Reference Intakes for 16 nutrients and outcomes influenced by nutritional status. Attention was given to vitamin D and calcium given potential skeletal implications due to cystic fibrosis. Measurements included weight, height, body composition, pulmonary function, and serum metabolic parameters. Participants were interviewed about dietary intake, supplement use, pulmonary function, sunlight exposure, and pain. The participants’ mean body mass index (±standard deviation) was 21.8±4.9 and pulmonary function tests were normal. Seventy-eight percent used pancreatic enzyme replacement for malabsorption. Vitamin D deficiency [25-hydroxyvitamin D (25OHD)<37.5 nmol/L] was common: 25 (39%) were deficient despite adequate vitamin D intake. Lipid profiles were normal in the majority, even though total and saturated fat consumption represented 33.0% and 16.8% of energy intake, respectively. Reported protein intake represented 16.9% of total energy intake (range 10%–25%). For several nutrients, including vitamin D and calcium, intake from food and supplements in many participants exceeded recommended Tolerable Upper Intake Levels. Among adults with cystic fibrosis, vitamin D deficiency was common despite reported adequate intake, and lipid profiles were normal despite a relatively high fat intake. Mean protein consumption was adequate, but the range of intake was concerning, as both inadequate or excessive intake may have deleterious skeletal effects. These findings call into question the applicability of established nutrient thresholds for patients with cystic fibrosis. PMID:18060897

  13. PhoQ mutations promote lipid A modification and polymyxin resistance of Pseudomonas aeruginosa found in colistin-treated cystic fibrosis patients

    DEFF Research Database (Denmark)

    Miller, Amanda K; Brannon, Mark K; Stevens, Laurel

    2011-01-01

    Pseudomonas aeruginosa can develop resistance to polymyxin and other cationic antimicrobial peptides. Previous work has shown that mutations in the PmrAB and PhoPQ regulatory systems can confer low to moderate levels of polymyxin resistance (MICs of 8 - 64 mg/L) in laboratory and clinical strains...

  14. [Italian Cystic Fibrosis Register - Report 2010].

    Science.gov (United States)

    Amato, Annalisa; Ferrigno, Luigina; Salvatore, Marco; Toccaceli, Virgilia

    2016-01-01

    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

  15. INHALATION ANTIBIOTICS ARE ESSENTIAL FOR THE CONTROL OF INFECTION IN CHILDREN WITH CYSTIC FIBROSIS

    Directory of Open Access Journals (Sweden)

    O.I. Simonova

    2011-01-01

    Full Text Available The article discusses the problem of basis therapy in patients with chronic Pseudomonas aeruginosa infection and cystic fibrosis. Authors showed the safety, good tolerance and high efficacy of constant treatment with special tobramycin solution delivered by nebulizer (Tobi in children including ones under 6 years old. Even first inhalations of tobramycin result in decrease of Pseudomonas aeruginosa rate in bacterial inoculation or to it complete removal. The drug helps stabilization of clinical and functional state of patients, improvement of airflow and common state, and to clinical remission.Key words: children, cystic fibrosis, chronic Pseudomonas aeruginosa infection, tobramycin, nebulizer therapy.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (3: 119–123

  16. Pseudomonas aeruginosa chromosomal beta-lactamase in patients with cystic fibrosis and chronic lung infection. Mechanism of antibiotic resistance and target of the humoral immune response

    DEFF Research Database (Denmark)

    Ciofu, Oana

    2003-01-01

    the development of resistance to beta-lactam antibiotics and the occurrence of high beta-lactamase producing strains and between the MIC of the beta-lactams and the levels of beta-lactamase expression. Partially derepressed mutants, characterized by high basal levels of beta-lactamase with the possibility...... of induction to even higher levels during treatment with beta-lactam antibiotics, were the most frequent phenotype found among resistant Danish P. aeruginosa CF isolates. We have also shown that the high alginate producing P. aeruginosa isolates, that characterize the chronic lung infection in CF patients......, are more susceptible to antibiotics and produce less beta-lactamase than the non-mucoid paired isolates. We propose that the non-mucoid isolates are exposed to a relatively higher antibiotic pressure than the mucoid isolates and therefore, they become easily antibiotic resistant and in consequence produce...

  17. Quantification of methyl thiocyanate in the headspace of Pseudomonas aeruginosa cultures and in the breath of cystic fibrosis patients by selected ion flow tube mass spectrometry

    Czech Academy of Sciences Publication Activity Database

    Shestivska, Violetta; Němec, A.; Dřevínek, P.; Sovová, Kristýna; Dryahina, Kseniya; Španěl, Patrik

    2011-01-01

    Roč. 25, č. 18 (2011), s. 2459-2467 ISSN 0951-4198 R&D Projects: GA ČR GA203/09/0256; GA ČR GP203/09/P172 Institutional research plan: CEZ:AV0Z40400503 Keywords : pseudomonas aeruginosa cultures * flow tube mass spectrometry * methyl thiocyanate Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.790, year: 2011

  18. Physical exercise training for cystic fibrosis.

    Science.gov (United States)

    Radtke, Thomas; Nevitt, Sarah J; Hebestreit, Helge; Kriemler, Susi

    2017-11-01

    Physical exercise training may form an important part of regular care for people with cystic fibrosis. This is an update of a previously published review. To assess the effects of physical exercise training on exercise capacity by peak oxygen consumption, pulmonary function by forced expiratory volume in one second, health-related quality of life and further important patient-relevant outcomes in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 04 May 2017.We searched ongoing trials registers (clinicaltrials.gov and the WHO ICTRP). Date of most recent search: 10 August 2017. All randomised and quasi-randomised controlled clinical trials comparing exercise training of any type and a minimum duration of two weeks with conventional care (no training) in people with cystic fibrosis. Two authors independently selected studies for inclusion, assessed methodological quality and extracted data. The quality of the evidence was assessed using the GRADE system. Of the 83 studies identified, 15 studies which included 487 participants, met the inclusion criteria. The numbers in each study ranged from nine up to 72 participants; two studies were in adults, seven were in children and adolescents and six studies included all age ranges. Four studies of hospitalised participants lasted less than one month and 11 studies were outpatient-based, lasting between two months and three years. The studies included participants with a wide range of disease severity and employed differing levels of supervision with a mixture of types of training. There was also wide variation in the quality of the included studies.This systematic review shows very low- to low-quality evidence from both short- and long-term studies that in people

  19. Cystic fibrosis Delta F508 heterozygotes, smoking, and reproduction

    DEFF Research Database (Denmark)

    Dahl, Morten; Tybjaerg-Hansen, A; Wittrup, H H

    1998-01-01

    Cystic fibrosis is the most common fatal autosomal recessive disease affecting Caucasian populations. It remains a puzzle how this disease is maintained at such a remarkably high incidence, however, it could be due to a reproductive advantage in cystic fibrosis heterozygotes. We tested this hypot......Cystic fibrosis is the most common fatal autosomal recessive disease affecting Caucasian populations. It remains a puzzle how this disease is maintained at such a remarkably high incidence, however, it could be due to a reproductive advantage in cystic fibrosis heterozygotes. We tested.......001). In conclusion, overall these results do not support a reproductive advantage for cystic fibrosis DeltaF508 heterozygotes. However, the data cannot totally exclude the possibility that nonsmoking DeltaF508 heterozygotes experience a reproductive advantage while smoking DeltaF508 heterozygotes experience...... the opposite, a reproductive disadvantage. Accordingly, the data suggest a previously undocumented role of smoking on fecundity among cystic fibrosis heterozygotes....

  20. Pregnancy and cystic fibrosis: Approach to contemporary management

    Science.gov (United States)

    Tay, George; Callaway, Leonie; Bell, Scott C

    2014-01-01

    Over the previous 50 years survival of patients with cystic fibrosis has progressively increased. As a result of improvements in health care, increasing numbers of patients with cystic fibrosis are now considering starting families of their own. For the health care professionals who look after these patients, the assessment of the potential risks, and the process of guiding prospective parents through pregnancy and beyond can be both challenging and rewarding. To facilitate appropriate discussions about pregnancy, health care workers must have a detailed understanding of the various important issues that will ultimately need to be considered for any patient with cystic fibrosis considering parenthood. This review will address these issues. In particular, it will outline pregnancy outcomes for mothers with cystic fibrosis, issues that need to be taken into account when planning a pregnancy and the management of pregnancy for mothers with cystic fibrosis or mothers who have undergone organ transplantation as a result of cystic fibrosis. PMID:27512443

  1. Respiratory muscle training for cystic fibrosis.

    Science.gov (United States)

    Hilton, Nathan; Solis-Moya, Arturo

    2018-05-24

    Cystic fibrosis is the most common autosomal recessive disease in white populations, and causes respiratory dysfunction in the majority of individuals. Numerous types of respiratory muscle training to improve respiratory function and health-related quality of life in people with cystic fibrosis have been reported in the literature. Hence a systematic review of the literature is needed to establish the effectiveness of respiratory muscle training (either inspiratory or expiratory muscle training) on clinical outcomes in cystic fibrosis. This is an update of a previously published review. To determine the effectiveness of respiratory muscle training on clinical outcomes in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials register comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of most recent search: 17 April 2018.A hand search of the Journal of Cystic Fibrosis and Pediatric Pulmonology was performed, along with an electronic search of online trial databases up until 07 May 2018. Randomised controlled studies comparing respiratory muscle training with a control group in people with cystic fibrosis. Review authors independently selected articles for inclusion, evaluated the methodological quality of the studies, and extracted data. Additional information was sought from trial authors where necessary. The quality of the evidence was assessed using the GRADE system MAIN RESULTS: Authors identified 19 studies, of which nine studies with 202 participants met the review's inclusion criteria. There was wide variation in the methodological and written quality of the included studies. Four of the nine included studies were published as abstracts only and lacking concise details, thus limiting the information available. Seven studies were parallel studies and two of a cross-over design. Respiratory

  2. MR imaging of pancreas in cystic fibrosis

    International Nuclear Information System (INIS)

    Murayama, S.; Robinson, A.E.; Mulvihill, D.M.; Stallworth, J.M.; Goyco, P.G.; Beckerman, R.C.; Hines, M.R.

    1990-01-01

    The pancreatic regions of 18 patients with cystic fibrosis were analyzed with a 1.5 Tesla MR unit. Signal intensity of the pancreas was correlated with clinical data and ultrasound. A hyperintense pancreas on T1-weighted image was consistent with fatty replacement of pancreatic insufficiency. A pancreas of normal soft tissue intensity was found in two asymptomatic and one symptomatic patient. A very hypointense pancreas on any pulse sequence was considered to be an intermediate stage of pancreatic degeneration. (orig.)

  3. Meropenem in cystic fibrosis patients infected with resistant Pseudomonas aeruginosa or Burkholderia cepacia and with hypersensitivity to beta-lactam antibiotics

    DEFF Research Database (Denmark)

    Ciofu, Oana; Jensen, Tim; Pressler, Tacjana

    1996-01-01

    in pulmonary function (as a percentage of the predictive values) was 5.6% for FEV1 (forced expiratory volume in the first second) and 8.6% for FVC (forced vital capacity). C-reactive protein and erythrocyte sedimentation rate (ESR) and leukocyte count decreased significantly. In courses administered...... for chronic infection with B. cepacia the post treatment FEV1 and FVC values were higher than the pre-treatment values, and all the inflammatory parameters decreased. The geometric means of minimal inhibitory concentration (MICs) (microg/mL) for P. aeruginosa (B. cepacia) were: tobramycin 6 (59......), ciprofloxacin 1.2 (9.7), piperacillin 49 (16.3), ceftazidime 26 (23), aztreonam 26 (35), imipenem 6.4 (not determined) and meropenem 5.1 (4.8). No statistically significant increase in the MICs of meropenem for either pathogen occurred during therapy. Of the 124 courses, 115 were tolerated without any clinical...

  4. Physiological levels of nitrate support anoxic growth by denitrification of Pseudomonas aeruginosa at growth rates reported in cystic fibrosis lungs and sputum

    DEFF Research Database (Denmark)

    Line, Laura; Alhede, Morten; Kolpen, Mette

    2014-01-01

    denitrification. The growth rate of P. aeruginosa achieved by denitrification at physiological levels (~400 μM) of nitrate (NO(-) 3) is however, not known. Therefore, we have measured growth rates of anoxic cultures of PAO1 and clinical isolates (n = 12) in LB media supplemented with NO(-) 3 and found...... a significant increase of growth when supplementing PAO1 and clinical isolates with ≥150 μM NO(-) 3 and 100 μM NO(-) 3, respectively. An essential contribution to growth by denitrification was demonstrated by the inability to establish a significantly increased growth rate by a denitrification deficient Δnir...... of the four N-oxide reductases in PAO1 (Nar, Nir, Nor, Nos) further verified the engagement of denitrification, showing a transient increase in activation and expression and rapid consumption of NO(-) 3 followed by a transient increase of NO(-) 2. Growth rates obtained by denitrification in this study were...

  5. Cystic fibrosis: a mucosal immunodeficiency syndrome

    Science.gov (United States)

    Cohen, Taylor Sitarik; Prince, Alice

    2013-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) functions as a channel that regulates the transport of ions and the movement of water across the epithelial barrier. Mutations in CFTR, which form the basis for the clinical manifestations of cystic fibrosis, affect the epithelial innate immune function in the lung, resulting in exaggerated and ineffective airway inflammation that fails to eradicate pulmonary pathogens. Compounding the effects of excessive neutrophil recruitment, the mutant CFTR channel does not transport antioxidants to counteract neutrophil-associated oxidative stress. Whereas mutant CFTR expression in leukocytes outside of the lung does not markedly impair their function, the expected regulation of inflammation in the airways is clearly deficient in cystic fibrosis. The resulting bacterial infections, which are caused by organisms that have substantial genetic and metabolic flexibility, can resist multiple classes of antibiotics and evade phagocytic clearance. The development of animal models that approximate the human pulmonary phenotypes—airway inflammation and spontaneous infection—may provide the much-needed tools to establish how CFTR regulates mucosal immunity and to test directly the effect of pharmacologic potentiation and correction of mutant CFTR function on bacterial clearance. PMID:22481418

  6. [Endocrine complications of cystic fibrosis in childhood].

    Science.gov (United States)

    Castanet, M; Wieliczko, M-C

    2012-05-01

    Since the 20 last years, the median age of survival has dramatically improved in children suffering from cystic fibrosis and complications such as growth retardation, pubertal delay and low bone mineral density are now more often than not observed in affected adolescents. The severity of the disease and the poor nutritional status due to pancreatic insufficiency and malabsorption are commonly implicated but recent data suggest that the disease could also play a role though the alteration of the chlore chanel (CFTR). Furthermore an increase prevalence of glucose intolerance and diabetes due to the progressive β cells destruction is observed in these children that make the life sometimes difficult for these adolescents already affected by an heavy chronic disease. The monitoring of the children should thus now become pluridisciplinary and include regular clinical evaluation of height and pubertal status, mineral bone density by DEXA and OGTT every two years since 10 years of age. Therefore, in addition to the standard treatment of cystic fibrosis is now added the vitamin D supplementation, the subcutaneous insulin therapy and may be the growth hormone that could be a new therapeutic demonstrating beneficial effects in these chronic disease. However further studies need to be performed to improve the management of these new endocrine complications more and more frequent in children and adolescents suffering from cystic fibrosis. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  7. Cyanide levels found in infected cystic fibrosis sputum inhibit airway ciliary function.

    Science.gov (United States)

    Nair, Chandrika; Shoemark, Amelia; Chan, Mario; Ollosson, Sarah; Dixon, Mellissa; Hogg, Claire; Alton, Eric W F W; Davies, Jane C; Williams, Huw D

    2014-11-01

    We have previously reported cyanide at concentrations of up to 150 μM in the sputum of cystic fibrosis patients infected with Pseudomonas aeruginosa and a negative correlation with lung function. Our aim was to investigate possible mechanisms for this association, focusing on the effect of pathophysiologically relevant cyanide levels on human respiratory cell function. Ciliary beat frequency measurements were performed on nasal brushings and nasal air-liquid interface (ALI) cultures obtained from healthy volunteers and cystic fibrosis patients. Potassium cyanide decreased ciliary beat frequency in healthy nasal brushings (n = 6) after 60 min (150 μM: 47% fall, pcyanide as a key component inhibiting the ciliary beat frequency. If cyanide production similarly impairs mucocilliary clearance in vivo, it could explain the link with increased disease severity observed in cystic fibrosis patients with detectable cyanide in their airway. ©ERS 2014.

  8. Genetic modifiers of nutritional status in cystic fibrosis1234

    OpenAIRE

    Bradley, Gia M; Blackman, Scott M; Watson, Christopher P; Doshi, Vishal K; Cutting, Garry R

    2012-01-01

    Background: Improved nutrition early in life is associated with better pulmonary function for patients with cystic fibrosis (CF). However, nutritional status is poorly correlated with the CFTR genotype.

  9. Oral calorie supplements for cystic fibrosis.

    Science.gov (United States)

    Smyth, Rosalind L; Rayner, Oli

    2017-05-04

    Poor nutrition occurs frequently in people with cystic fibrosis and is associated with other adverse outcomes. Oral calorie supplements are used to increase total daily calorie intake and improve weight gain. However, they are expensive and there are concerns they may reduce the amount of food eaten and not improve overall energy intake. This is an update of a previously published review. To establish whether in people with cystic fibrosis, oral calorie supplements: increase daily calorie intake; and improve overall nutritional intake, nutritional indices, lung function, survival and quality of life. To assess adverse effects associated with using these supplements. We searched the Cochrane Cystic Fibrosis Trials Register comprising references from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We contacted companies marketing oral calorie supplements.Last search: 18 October 2016. Randomised or quasi-randomised controlled trials comparing use of oral calorie supplements for at least one month to increase calorie intake with no specific intervention or additional nutritional advice in people with cystic fibrosis. We independently selected the included trials, assessed risk of bias and extracted data. We contacted the authors of included trials and obtained additional information for two trials. We identified 21 trials and included three, reporting results from 131 participants lasting between three months and one year. Two trials compared supplements to additional nutritional advice and one to no intervention. Two of the included trials recruited only children. In one trial the risk of bias was low across all domains, in a second trial the risk of bias was largely unclear and in the third mainly low. Blinding of participants was unclear in two of the trials. Also, in one trial the clinical condition of groups appeared to be unevenly balanced at baseline and in another trial there were

  10. Alveolar inflammation in cystic fibrosis

    DEFF Research Database (Denmark)

    Ulrich, Martina; Worlitzsch, Dieter; Viglio, Simona

    2010-01-01

    and ceramide accumulation. We sought to investigate CF lung inflammation in the alveoli. METHODS: Lung tissue from 14 CF patients and four healthy individuals was analyzed for numbers of effector cells, elastin and collagen concentrations, inflammatory markers and density of Pseudomonas aeruginosa....... Additionally, desmosine and isodesmosine concentrations were determined in 52 urine specimens from CF patients to estimate the burden of elastase activities in respiratory secretions. RESULTS: Elastin concentration was significantly decreased and collagen significantly increased in CF alveolar tissues...... as compared to age-matched, healthy individuals. Elastin split products were significantly increased in urine samples from patients with CF and correlated inversely with age, indicating local tissue remodelling due to elastin degradation by unopposed proteolytic enzymes. Alveolar inflammation was also...

  11. Co-morbidity of cystic fibrosis and celiac disease in Scandinavian cystic fibrosis patients

    DEFF Research Database (Denmark)

    Fluge, Gjermund; Olesen, Hanne Vebert; Giljam, Marita

    2009-01-01

    Background: The co-morbidity of cystic fibrosis (CF) and celiac disease (CD) has been reported sporadically since the 1960s. To our knowledge, this is the first time a systematic screening is performed in a large cohort of CF patients. Methods: Transglutaminase-IgA (TGA), endomysium-IgA (EMA...

  12. Intracerebral abscess: A complication of severe cystic fibrosis lung disease

    OpenAIRE

    Fenton, Mark E; Cockcroft, Donald W; Gjevre, John A

    2008-01-01

    Intracerebral abscess is an uncommon complication of severe cystic fibrosis lung disease. The present report describes a case of fatal multiple intracerebral abscesses in a patient with a severely bronchiectatic, nonfunctioning right lung and chronic low-grade infection. The patient was previously turned down for pneumonectomy. Intracerebral abscess in cystic fibrosis and the potential role of pneumonectomy in the present patient are discussed.

  13. SERS detection of pneumonia in breath of children with cystic fibrosis

    DEFF Research Database (Denmark)

    Lauridsen, Rikke Kragh; Molin, Søren

    Cystic fibrosis (CF) is the most frequently inherited disease in the Western world, and also the one with the highest morbidity and mortality. The main reason is chronic lung infections caused by the pathogenic bacterium Pseudomonas aeruginosa, which is well-adapted to the thick and dehydrated mu...... exposed to passive smoking at home. The SERS substrate has a background peak in the Raman spectrum, which needs to be addressed, because it is located very close to the cyanide peak....

  14. Vitamin K supplementation for cystic fibrosis.

    Science.gov (United States)

    Jagannath, Vanitha A; Thaker, Vidhu; Chang, Anne B; Price, Amy I

    2017-08-22

    Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. This is an updated version of the review. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 30 January 2017. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). Two authors independently screened papers, extracted trial details and assessed their risk of bias. Two trials (total of 32 participants) each lasting one month were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial in children (aged 8 to 18 years); and the other (with an older cohort) had a cross-over design comparing supplements to no treatment, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin

  15. CYSTIC FIBROSIS: MICROBIOLOGY AND HOST RESPONSE

    Science.gov (United States)

    Zemanick, Edith T.

    2016-01-01

    THE EARLIEST DESCRIPTIONS OF LUNG DISEASE IN PEOPLE WITH CYSTIC FIBROSIS (CF) DEMONSTRATED THE INVOLVEMENT OF THREE INTERACTING PATHOPHYSIOLOGICAL ELEMENTS IN CF AIRWAYS: MUCUS OBSTRUCTION, INFLAMMATION, AND INFECTION. OVER THE PAST 7 DECADES, OUR UNDERSTANDING OF CF RESPIRATORY MICROBIOLOGY AND INFLAMMATION HAS EVOLVED WITH THE INTRODUCTION OF NEW TREATMENTS, WITH INCREASED LONGEVITY, AND WITH INCREASINGLY SOPHISTICATED LABORATORY TECHNIQUES. IN THIS CHAPTER, WE WILL REVIEW THE CURRENT STATE OF UNDERSTANDING OF THE ROLES OF INFECTION AND INFLAMMATION AND THEIR ROLES IN DRIVING LUNG DISEASE. WE WILL ALSO DISCUSS HOW THIS CONSTANTLY EVOLVING INFORMATION IS USED TO INFORM CURRENT THERAPEUTIC STRATEGIES, MEASURES AND PREDICTORS OF DISEASE SEVERITY, AND RESEARCH PRIORITIES. PMID:27469179

  16. Patient-reported Outcomes in Cystic Fibrosis

    OpenAIRE

    Goss, Christopher H.; Quittner, Alexandra L.

    2007-01-01

    Over the past 20 years, there has been tremendous progress in the area of patient-reported outcomes (PROs). A PRO instrument is defined as any measure of a patient's health status that is elicited directly from the patient and assesses how the patient “feels or functions with respect to his or her health condition.” The advances seen in clinical research regarding PROs has been mirrored in research in cystic fibrosis (CF). A large number of instruments have been used for both therapeutic and ...

  17. Prenatal intestinal volvulus: look for cystic fibrosis.

    Science.gov (United States)

    Chouikh, Taieb; Mottet, Nicolas; Cabrol, Christelle; Chaussy, Yann

    2016-12-21

    Intestinal volvulus is a life-threatening emergency requiring prompt surgical management. Prenatal intestinal volvulus is rare, and most are secondary to intestinal atresia, mesenteric defect or without any underlying cause. Cystic fibrosis (CF) is known to cause digestive tract disorders. After birth, 10-15% of newborns with CF may develop intestinal obstruction within a few days of birth because of meconial ileus. 1 This obstruction is a result of dehydrated thickened meconium obstructing the intestinal lumen. We report two cases of fetuses with prenatal diagnosis of segmental volvulus in whom CF was diagnosed. 2016 BMJ Publishing Group Ltd.

  18. Home intravenous antibiotic therapy in children with cystic fibrosis: clinical outcome, quality of life and economic benefit

    OpenAIRE

    Chrysochoou, EA; Hatziagorou, E; Kirvassilis, F; Tsanakas, J

    2016-01-01

    Background: Pediatric home care has improved therapeutic options for children with chronic disease. Home intravenous (IV) antibiotic treatment against Pseudomonas aeruginosa (PsA) in cystic fibrosis (CF) patients has offered increased flexibility to these patients and family life. A prospective clinical study was conducted to compare safety, efficacy, and cost benefits of home versus hospital IV antibiotic treatment among CF children and adolescents.

  19. Imaging the Abdominal Manifestations of Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    C. D. Gillespie

    2017-01-01

    Full Text Available Cystic fibrosis (CF is a multisystem disease with a range of abdominal manifestations including those involving the liver, pancreas, and kidneys. Recent advances in management of the respiratory complications of the disease has led to a greater life expectancy in patients with CF. Subsequently, there is increasing focus on the impact of abdominal disease on quality of life and survival. Liver cirrhosis is the most important extrapulmonary cause of death in CF, yet significant challenges remain in the diagnosis of CF related liver disease. The capacity to predict those patients at risk of developing cirrhosis remains a significant challenge. We review representative abdominal imaging findings in patients with CF selected from the records of two academic health centres, with a view to increasing familiarity with the abdominal manifestations of the disease. We review their presentation and expected imaging findings, with a focus on the challenges facing diagnosis of the hepatic manifestations of the disease. An increased familiarity with these abdominal manifestations will facilitate timely diagnosis and management, which is paramount to further improving outcomes for patients with cystic fibrosis.

  20. Global impact of bronchiectasis and cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Margarida Redondo

    2016-09-01

    To understand variation in the aetiology, microbiology and burden of bronchiectasis and cystic fibrosis across different global healthcare systems.; Bronchiectasis is the term used to refer to dilatation of the bronchi that is usually permanent and is associated with a clinical syndrome of cough, sputum production and recurrent respiratory infections. It can be caused by a range of inherited and acquired disorders, or may be idiopathic in nature. The most well recognised inherited disorder in Western countries is cystic fibrosis (CF, an autosomal recessive condition that leads to progressive bronchiectasis, bacterial infection and premature mortality. Both bronchiectasis due to CF and bronchiectasis due to other conditions are placing an increasing burden on healthcare systems internationally. Treatments for CF are becoming more effective leading to more adult patients with complex healthcare needs. Bronchiectasis not due to CF is becoming increasingly recognised, particularly in the elderly population. Recognition is important and can lead to identification of the underlying cause, appropriate treatment and improved quality of life. The disease is highly diverse in its presentation, requiring all respiratory physicians to have knowledge of the different “bronchiectasis syndromes”. The most common aetiologies and presenting syndromes vary depending on geography, with nontuberculous mycobacterial disease predominating in some parts of North America, post-infectious and idiopathic disease predominating in Western Europe, and post-tuberculosis bronchiectasis dominating in South Asia and Eastern Europe. Ongoing global collaborative studies will greatly advance our understanding of the international impact of bronchiectasis and CF.

  1. Cystic fibrosis chronic rhinosinusitis: A comprehensive review

    Science.gov (United States)

    Chaaban, Mohamad R.; Kejner, Alexandra; Rowe, Steven M.

    2013-01-01

    Background: Advances in the care of patients with cystic fibrosis (CF) have improved pulmonary outcomes and survival. In addition, rapid developments regarding the underlying genetic and molecular basis of the disease have led to numerous novel targets for treatment. However, clinical and basic scientific research focusing on therapeutic strategies for CF-associated chronic rhinosinusitis (CRS) lags behind the evidence-based approaches currently used for pulmonary disease. Methods: This review evaluates the available literature and provides an update concerning the pathophysiology, current treatment approaches, and future pharmaceutical tactics in the management of CRS in patients with CF. Results: Optimal medical and surgical strategies for CF CRS are lacking because of a dearth of well-performed clinical trials. Medical and surgical interventions are supported primarily by level 2 or 3 evidence and are aimed at improving clearance of mucus, infection, and inflammation. A number of novel therapeutics that target the basic defect in the cystic fibrosis transmembrane conductance regulator channel are currently under investigation. Ivacaftor, a corrector of the G551D mutation, was recently approved by the Food and Drug Administration. However, sinonasal outcomes using this and other novel drugs are pending. Conclusion: CRS is a lifelong disease in CF patients that can lead to substantial morbidity and decreased quality of life. A multidisciplinary approach will be necessary to develop consistent and evidence-based treatment paradigms. PMID:24119602

  2. Urinary incontinence in patients with cystic fibrosis.

    Science.gov (United States)

    Reichman, Gina; De Boe, Veerle; Braeckman, Johan; Michielsen, Dirk

    2016-01-01

    Owing to evolution in treatment, the average life expectancy of patients with cystic fibrosis (CF) has increased. This has been followed by an increase in urological complications such as urinary incontinence. As stress incontinence occurs during exercise, it may have a negative effect on the implementation of respiratory physiotherapy. The purpose of this study is to determine the prevalence of urinary incontinence and its effect on the quality of life and physiotherapy in a population with CF. Questionnaires were used to determine the prevalence of incontinence in patients of the Cystic Fibrosis Clinic of the University Hospital in Brussels. Two different surveys were used, depending on the age of the patients (incontinence were emphasized. Questionnaires were completed by 122 participants aged 6-59 years, showing an overall prevalence of 27% for urinary incontinence. Mainly adults reported urinary incontinence, with a prevalence of 11% in men and 68% in women aged 12 and above. The amount of urinary leakage was usually only a few drops and it was mainly triggered by coughing. Many of the participants had never mentioned this symptom to anyone. Doctors' and physical therapists' attention should be drawn to the fact that urinary incontinence is part of the complication spectrum of CF. A quarter of the study population refrained from coughing up phlegm and from physiotherapy. It is important to actively question and inform about this problem, to enable its detection and treatment.

  3. Psychosocial problems in children with cystic fibrosis

    DEFF Research Database (Denmark)

    Bregnballe, V; Thastum, M; Schiøtz, P O

    2007-01-01

    AIM: To compare the well-being of children (7-14 years) with cystic fibrosis (CF) (n = 43) with the well-being of healthy controls (n = 1121). METHODS: The self-report questionnaire Beck Youth Inventories (BYI) was used to study depression, anxiety, anger, disruptive behaviour and self-concept in......AIM: To compare the well-being of children (7-14 years) with cystic fibrosis (CF) (n = 43) with the well-being of healthy controls (n = 1121). METHODS: The self-report questionnaire Beck Youth Inventories (BYI) was used to study depression, anxiety, anger, disruptive behaviour and self......-concept in children with CF. A measure of social desirability was included as well as body mass index (BMI) and percentage of predicted forced expiratory volume in one second (FEV(1)) as measures of health status. RESULTS: The children with CF did not differ from the norm group concerning depression, disruptive...... behaviour and self-concept. Young children with CF (7-10 years) and boys with CF scored significantly higher on anxiety. Girls with CF scored significantly lower on anger than controls. BMI was not associated with any of the BYI subscales. In patients aged 11-14 years, there was a significant correlation...

  4. [Italian Cystic Fibrosis Registry. Report 2011-2014].

    Science.gov (United States)

    Giordani, Barbara; Amato, Annalisa; Majo, Fabio; Ferrari, Gianluca; Quattrucci, Serena; Minicucci, Laura; Padoan, Rita; Floridia, Giovanna; Puppo Fornaro, Gianna; Taruscio, Domenica; Salvatore, Marco

    2018-01-01

    The Italian Cystic Fibrosis Registry (ICFR) is based on a new agreement about the data flow towards the Registry signed on October, 4th 2016 by the Centre for Rare Diseases of the Italian National Institute of Health (NIH), the clinicians of the Italian National Referral and Support Centres for Cystic Fibrosis, the Paediatric Hospital "Bambino Gesù" (Rome), the Italian Cystic Fibrosis Society, and the Italian League for Cystic Fibrosis. The aim of the present Report is to improve the knowledge on cystic fibrosis (CF) through the epidemiological description of Italian patients. The members of the Scientific and Technical Committee have to write a report on data collected by ICFR, in order to contribute to achieve the aims of ICFR itself, i.e., to improve the care of CF patients. In particular, the Report should contribute to the following objectives: - to analyze the medium and long-term clinical and epidemiological trends of the disease; - to identify the main healthcare needs at regional and national level in order to contribute to the healthcare programmes and to the distribution of resources; - to compare Italian data with the international ones. Analyses and results described in the present Report are referred to patients in charge to the Italian National Referral and Support Centres for Cystic Fibrosis in the period 2011-2014. Data were sent by Centres by means of a specific software (Camilla, Ibis Informatica) and has undergone a double quality control (QC): the first by NIH and the second at a European level (before the inclusion of the Italian data within the European Cystic Fibrosis Registry). These QCs assure the completeness and accuracy of data as well as their consistency with European core data. A total of 29 different CF centres (referral, support, and Paediatric Hospital "Bambino Gesù") sent their data to ICFR; data referred to the period 2011-2014. Data regarding Sardinia Region (Southern Italy) are missing; data from Molise (Southern Italy) CF

  5. Quantitative immunoassays for diagnosis and carrier detection in cystic fibrosis

    International Nuclear Information System (INIS)

    Bullock, S.; Hayward, C.; Manson, J.; Brock, D.J.H.; Raeburn, J.A.

    1982-01-01

    Quantitative immunoprecipitation and immunoradiometric assays have been developed for a protein present in the serum of cystic fibrosis homozygotes, and to a lesser extent in the serum of heterozygotes. When tested on a panel of sera from 14 cystic fibrosis patients, 29 heterozygotes and 23 controls, the immunoprecipitation assay allowed correct assignments to be made on 94% of occasions with one batch of antiserum and 95% with another. With the same panel of sera, the immunoradiometric assay allowed 94% correct assignments. It is suggested that such accuracy is the maximum that can be expected in the present state of knowledge of cystic fibrosis. (author)

  6. Therapeutic flexible bronchoscopy in child with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Amina Selimović

    2008-05-01

    Full Text Available The report deals with the case of a 10-year-old girl with chronic cystic fibrosis. She has been repeatedly treated at the hospital. She has been hospitalized due to respiratory deterioration. Cystic fibrosis is a rare disease, inherited autosomaly recessively, but is very complex in terms of diagnostic and treatment (2. The diagnosis is confirmed based on a clinical picture of the child, measure of Chloride in the sweat, chest X-ray, CT thorax, laboratory findings--genetic confirmation CFTR ( cystic fibrosis transmembrane conductance regulator genes (3, which result in the production of hyper-viscous mucus and chloride malabsorption in the sweat glands ducts (5,6. Bronchial thickening and plugging and ring shadows suggesting bronchiectasis, segmental or lobar atelectasis are often. Computer tomography of the chest can be used to detect and localize thickening of bronchial airways walls, mucus plugging, hyperinflation and early bronchieactasiae. Pulmonary therapy: the object is to clear secretions from airways and to control infection (7. The diagnosis is originally set when she was 4 years old. She is now admitted due to a deterioration of the main disease. Day before admission in the hospital had a higher bodily temperature, cough and difficult breathing. She already treated conservatively (Ceftazidim, Ceftriakson, Kloksacillin Since the girl is a chronic patient with bronchiectasie chronic walls of bronchi changes full of the mucus, who is not responding to conservative treatment (antibiotics, therapeutic and diagnostic flexible bronchoscopy had to be performed, resulting in a gram-negative bacteria pseudomonas aeruginosa--a typical bacteria for chronically sick C. F.PATIENT:A pseudomonas therapy was prescribed according to the sensitive antibiogram, during which bronchoscopy was given locally on changes mucous pulmozyme and garamycin. Flexible bronchoscopy was performed as therapeutic. Local

  7. Pulmonary bacterial pathogens in cystic fibrosis patients and antibiotic therapy: a tool for the health workers

    Directory of Open Access Journals (Sweden)

    Coutinho Henrique

    2008-11-01

    Full Text Available Abstract Cystic fibrosis is the most common and best known genetic disease involving a defect in transepithelial Cl- transport by mutations in the CF gene on chromosome 7, which codes for the cystic fibrosis transmembrane conductance regulator protein (CFTR. The most serious symptoms are observed in the lungs, augmenting the risk of bacterial infection. The objective of this review was to describe the bacterial pathogens colonizing patients with cystic fibrosis. A systematic search was conducted using the international bibliographic databanks SCIELO, HIGHWIRE, PUBMED, SCIRUS and LILACS to provide a useful and practical review for healthcare workers to make them aware of these microorganisms. Today, B. cepacia, P. aeruginosa and S. aureus are the most important infectious agents in cystic fibrosis patients. However, healthcare professionals must pay attention to emerging infectious agents in these patients, because they represent a potentially serious future problem. Therefore, these pathogens should be pointed out as a risk to these patients, and hospitals all over the world must be prepared to detect and combat these bacteria.

  8. Possibilities of computed bronchophonography in the diagnosis of external respiratory dysfunction in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    E. B. Pavlinova

    2016-01-01

    Full Text Available The degree of respiratory organ injury in cystic fibrosis determines the prognosis of the disease. Objective: to evaluate external respiratory function in children with cystic fibrosis. The study enrolled 48 children followed up at the Omsk Cystic Fibrosis Center. A control group consisted of 42 non-addicted smoking children with no evidence for respiratory diseases in the history. External respiratory function was evaluated using computed bronchophonography; spirography was additionally carried out in children over 6 years of age. Computed bronchophonography revealed obstructive respiratory failure in all children with severe cystic fibrosis. Chronic respiratory tract infection with Pseudomonas aeruginosa and bronchiectasis were associated with the higher values of the acoustic work of breathing at frequencies over 5000 Hz. It was established that there was a moderate negative correlation between the value of the acoustic work of breathing in the high frequency range and the forced expiratory volume in 1 second in %. Conclusion. Computed bronchophonography could reveal obstructive external respiratory dysfunction in children less than 6 years of age. 

  9. Diabetes mellitus in childhood cystic fibrosis.

    LENUS (Irish Health Repository)

    Rauf, F

    2012-02-03

    Since 1984, five patients in the cystic fibrosis (CF) clinic at Cork Regional Hospital have developed diabetes mellitus (DM) and were treated with Insulin. None had received systemic corticosteroids but two had high calorie naso-gastric feeding regimes. Two died from lung disease. A fifteen year old boy developed bilateral cataracts. In nine other paediatric CF clinics in the Republic of Ireland (total: 420 patients), three patients have DM, two receiving Insulin. Abnormal glucose tolerance is becoming more common in CF as patients survive longer. The possible role of corticosteroid treatment and intensive carbohydrate feeding regimes in development of glucose intolerance must be considered. DM in CF differs from the usual childhood DM. Regular screening and early Insulin supplementation may be beneficial.

  10. Maintaining Respiratory Health in Cystic Fibrosis Patients

    Directory of Open Access Journals (Sweden)

    MR Modaresi

    2014-04-01

    Full Text Available Cystic fibrosis (CF is an inherited disease that primarily affects the lungs and the digestive system, however, it also affects a number of other organs and systems. More than 90% of mortality of  CF patients is due to lung complications.  Healthy lungs are important for a long life for people with CF, We will discuss two important topics for maintaining respiratory health. Chronic use of drugs for maintaining respiratory health There are a number of drugs available to keep CF lungs healthy. We will discuss the science behind the recommendations for use of: Inhaled antibiotics Dornase alfa Azithromycin Hypertonic saline High-dose ibuprofen Ivacaftor CF Airway Clearance Therapies Airway Clearance therapy is very important to keeping CF lungs healthy. Our discussions cover the following topics such as the: Daily airway clearance Different techniques of airway clearance Effect of aerobic exercise on airway clearance  

  11. South African adolescents with cystic fibrosis: a qualitative ...

    African Journals Online (AJOL)

    South African adolescents with cystic fibrosis: a qualitative exploration of their ... years) who had the defining characteristics of CF and were living in Gauteng province. ... The fundamental human need to be understood and to understand was ...

  12. Glucose 6-phosphate dehydrogenase deficiency and cystic fibrosis

    OpenAIRE

    Congdon, P. J.; Aggarwal, R. K.; Littlewood, J. M.; Shapiro, H.

    1981-01-01

    A child born to Pakistani parents is described. He had both cystic fibrosis and G-6PD-deficiency. So far as can be ascertained, the occurrence of both these conditions in the same individual has not previously been reported.

  13. Cystic fibrosis-related diabetes: a distinct condition.

    Science.gov (United States)

    Cano Megías, Marta; González Albarrán, Olga

    2015-01-01

    Cystic fibrosis is the most common fatal inherited autosomal recessive disease in Caucasians, affecting approximately one out of every 2,000 births. Survival of patients with cystic fibrosis has significantly improved due to advances in respiratory and nutritional care, and their current average life expectancy is 30-40 years. Development of cystic fibrosis-related diabetes is a comorbidity that increases with age and may reach a prevalence up to 50% in adults. Its development is associated to impaired lung function and nutritional status, and early diagnosis and treatment are therefore essential to improve quality of life and performance status. Insulin therapy for diabetes and other early carbohydrate metabolism disorders may improve lung function and nutritional status of patients with cystic fibrosis. Copyright © 2014 SEEN. Published by Elsevier Espana. All rights reserved.

  14. Complementary and alternative medicine use in children with cystic fibrosis.

    Science.gov (United States)

    Giangioppo, Sandra; Kalaci, Odion; Radhakrishnan, Arun; Fleischer, Erin; Itterman, Jennifer; Lyttle, Brian; Price, April; Radhakrishnan, Dhenuka

    2016-11-01

    To estimate the overall prevalence of complementary and alternative medicine use among children with cystic fibrosis, determine specific modalities used, predictors of use and subjective helpfulness or harm from individual modalities. Of 53 children attending the cystic fibrosis clinic in London, Ontario (100% recruitment), 79% had used complementary and alternative medicine. The most commonly used modalities were air purifiers, humidifiers, probiotics, and omega-3 fatty acids. Family complementary and alternative medicine use was the only independent predictor of overall use. The majority of patients perceived benefit from specific modalities for cystic fibrosis symptoms. Given the high frequency and number of modalities used and lack of patient and disease characteristics predicting use, we recommend that health care providers should routinely ask about complementary and alternative medicine among all pediatric cystic fibrosis patients and assist patients in understanding the potential benefits and risks to make informed decisions about its use. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Adeno-associated virus for cystic fibrosis gene therapy

    Directory of Open Access Journals (Sweden)

    S.V. Martini

    2011-11-01

    Full Text Available Gene therapy is an alternative treatment for genetic lung disease, especially monogenic disorders such as cystic fibrosis. Cystic fibrosis is a severe autosomal recessive disease affecting one in 2500 live births in the white population, caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR. The disease is classically characterized by pancreatic enzyme insufficiency, an increased concentration of chloride in sweat, and varying severity of chronic obstructive lung disease. Currently, the greatest challenge for gene therapy is finding an ideal vector to deliver the transgene (CFTR to the affected organ (lung. Adeno-associated virus is the most promising viral vector system for the treatment of respiratory disease because it has natural tropism for airway epithelial cells and does not cause any human disease. This review focuses on the basic properties of adeno-associated virus and its use as a vector for cystic fibrosis gene therapy.

  16. Modular microfluidic system as a model of cystic fibrosis airways

    DEFF Research Database (Denmark)

    Skolimowski, Maciej; Weiss Nielsen, Martin; Abeille, Fabien

    2012-01-01

    A modular microfluidic airways model system that can simulate the changes in oxygen tension in different compartments of the cystic fibrosis (CF) airways was designed, developed, and tested. The fully reconfigurable system composed of modules with different functionalities: multichannel peristalt...

  17. Abdominal manifestations of cystic fibrosis in children

    International Nuclear Information System (INIS)

    Chaudry, Gulraiz; Navarro, Oscar M.; Levine, Daniel S.; Oudjhane, Kamaldine

    2006-01-01

    Pulmonary complications remain the main cause of mortality in cystic fibrosis, but the presenting symptoms in children are often related to gastrointestinal or pancreaticobiliary disease. Furthermore, abdominal manifestations are now seen throughout childhood, from infancy to adolescence. The child might present in the neonatal period with meconium ileus or its attendant complications. The older child might present with distal intestinal obstruction syndrome or colonic stricture secondary to high doses of pancreatic enzyme replacement. Less-common gastrointestinal manifestations include intussusception, duodenitis and fecal impaction of the appendix. Most children also show evidence of exocrine pancreatic deficiency. Radiologically, the combination of fat deposition and pancreatic fibrosis leads to varying CT and MR appearances. A higher than normal incidence of pancreatic cysts and calcification is also seen. Decreased transport of water and chloride also increases the viscosity of bile, with subsequent obstruction of the biliary ductules. If extensive, this can progress to obstructive cirrhosis, portal hypertension and esophageal varices. Diffuse fatty infiltration, hypersplenism and gallstones are also commonly seen in these patients. We present a pictorial review of the radiological appearance of these abdominal manifestations. The conditions are dealt with individually, together with typical appearances in various imaging modalities. (orig.)

  18. Abdominal manifestations of cystic fibrosis in children

    Energy Technology Data Exchange (ETDEWEB)

    Chaudry, Gulraiz; Navarro, Oscar M.; Levine, Daniel S.; Oudjhane, Kamaldine [University of Toronto, Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, ON (Canada)

    2006-03-15

    Pulmonary complications remain the main cause of mortality in cystic fibrosis, but the presenting symptoms in children are often related to gastrointestinal or pancreaticobiliary disease. Furthermore, abdominal manifestations are now seen throughout childhood, from infancy to adolescence. The child might present in the neonatal period with meconium ileus or its attendant complications. The older child might present with distal intestinal obstruction syndrome or colonic stricture secondary to high doses of pancreatic enzyme replacement. Less-common gastrointestinal manifestations include intussusception, duodenitis and fecal impaction of the appendix. Most children also show evidence of exocrine pancreatic deficiency. Radiologically, the combination of fat deposition and pancreatic fibrosis leads to varying CT and MR appearances. A higher than normal incidence of pancreatic cysts and calcification is also seen. Decreased transport of water and chloride also increases the viscosity of bile, with subsequent obstruction of the biliary ductules. If extensive, this can progress to obstructive cirrhosis, portal hypertension and esophageal varices. Diffuse fatty infiltration, hypersplenism and gallstones are also commonly seen in these patients. We present a pictorial review of the radiological appearance of these abdominal manifestations. The conditions are dealt with individually, together with typical appearances in various imaging modalities. (orig.)

  19. Abdominal manifestations of cystic fibrosis in adults: a review

    International Nuclear Information System (INIS)

    Constantine, S.; Au, V.W.K.; Slavotinek, J.P.

    2004-01-01

    Gastrointestinal manifestations of disease are present in most adults with cystic fibrosis. Radiologists are familiar with the classical imaging characteristics of end-stage pulmonary disease and the radiological findings of meconium ileus in neonates. As most patients now live into adulthood, recognition of the imaging appearances of abdominal disease is important to enable prompt diagnosis and treatment. Accordingly, this article presents typical imaging appearances of the adult gastrointestinal manifestations of cystic fibrosis. Copyright (2004) Blackwell Science Pty Ltd

  20. Laboratory confirmation of the diagnosis of cystic fibrosis.

    Science.gov (United States)

    Tocci, P M; McKey, R M

    1976-11-01

    The recent commercial introduction of a method for detecting albumin in meconium makes screening for cystic fibrosis feasible for many hospitals. If the tests is adopted, confirmatory tests should be available. Quantitative analyses of sweat for sodium by flame photometry and for chloride by silver titration and ion-sleective electrodes are now used as confirmatory tests. We compare results of these confirmatory methods applied to presons with cystic fibrosis, respiratory disorders, or digestive disorders, and to control subjects.

  1. PECULIARITIES OF ENT-DAMAGE IN CHILDREN WITH CYSTIC FIBROSIS

    Directory of Open Access Journals (Sweden)

    I.V. Martynova

    2011-01-01

    Full Text Available Traditional approach to cystic fibrosis patients treatment doesn’t involve upper respiratory tract assessment, though abnormal changes — consequences of the cystic fibrosis transmembrane conductivity regulator gene mutation- do affect nasal and paranasal mucosa to the same extent. Approximately half of cystic fibrosis patients suffer from chronic rhinosinusitis and/or nasal polyposis that worsens the clinical course of already severe disease. Chronic hyperplasia in paranasal cavities can be quite extensive, recurrent and can lead to destruction of osseous walls of the cavity and of nasal septum. Thus increasing the amount of hospital admissions and and their duration. Low awareness of ENT-specialists working in polyclinics and in hospitals of ENT-pathology in cystic fibrosis patients leads to belated diagnostics, excessive manipulations, ineffective treatment, including surgery. All these lays grounds to implication of the early screening diagnostic program and development of proper treatment methods of ENT-complications of cystic fibrosis — therapeutic as well as surgical, with strict specification of indications and contraindications. Key words: cystic fibrosis, chronic rhino sinusitis, nasal polyposis. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (5: 49–53.

  2. Management of the Upper Airway in Cystic Fibrosis

    Science.gov (United States)

    Illing, Elisa A.; Woodworth, Bradford A.

    2015-01-01

    Purpose of Review Upper airway disease engenders significant morbidity for patients with cystic fibrosis and is increasingly recognized as having a much greater role in pulmonary outcomes and quality of life than originally believed. Widespread disparate therapeutic strategies for cystic fibrosis chronic rhinosinusitis underscore the absence of a standardized treatment paradigm. This review outlines the most recent evidence-based trends in the management of upper airway disease in cystic fibrosis. Recent Findings The unified airway theory proposes that the sinuses are a focus of initial bacterial colonization which seeds the lower airway and may play a large role in maintaining lung infections. Mounting evidence suggests more aggressive treatment of the sinuses may confer significant improvement in pulmonary disease and quality of life outcomes in cystic fibrosis patients. However, there is a lack of high-level evidence regarding medical and surgical management of cystic fibrosis chronic rhinosinusitis that makes generalizations difficult. Summary Well designed clinical trials with long-term follow-up concerning medical and surgical interventions for cystic fibrosis sinus disease are required to establish standardized treatment protocols, but increased interest in the sinuses as a bacterial reservoir for pulmonary infections has generated considerable attention. PMID:25250804

  3. The role of anaerobic bacteria in the cystic fibrosis airway.

    Science.gov (United States)

    Sherrard, Laura J; Bell, Scott C; Tunney, Michael M

    2016-11-01

    Anaerobic bacteria are not only normal commensals, but are also considered opportunistic pathogens and have been identified as persistent members of the lower airway community in people with cystic fibrosis of all ages and stages of disease. Currently, the role of anaerobic bacteria in cystic fibrosis lower airway disease is not well understood. Therefore, this review describes the recent studies relating to the potential pathophysiological role(s) of anaerobes within the cystic fibrosis lungs. The most frequently identified anaerobic bacteria in the lower airways are common to both cystic fibrosis and healthy lungs. Studies have shown that in cystic fibrosis, the relative abundance of anaerobes fluctuates in the lower airways with reduced lung function and increased inflammation associated with a decreased anaerobic load. However, anaerobes found within the lower airways also produce virulence factors, may cause a host inflammatory response and interact synergistically with recognized pathogens. Anaerobic bacteria are potentially members of the airway microbiota in health but could also contribute to the pathogenesis of lower airway disease in cystic fibrosis via both direct and indirect mechanisms. A personalized treatment strategy that maintains a normal microbial community may be possible in the future.

  4. Environmental allergies and respiratory morbidities in cystic fibrosis.

    Science.gov (United States)

    Collaco, Joseph M; Morrow, Christopher B; Green, Deanna M; Cutting, Garry R; Mogayzel, Peter J

    2013-09-01

    Cystic fibrosis (CF) is characterized by recurrent respiratory infections and progressive lung disease. Although environmental factors account for 50% of the variation in CF lung function, few specific exposures have been identified. Studies using small study samples focusing on environmental allergies in CF have had inconsistent results. Our objective was to examine the role of environmental allergies in upper and lower respiratory tract morbidities in CF. A total of 1,321 subjects with CF were recruited through the U.S. CF Twin-Sibling Study. Questionnaires were used to determine the presence/absence of environmental allergies. Questionnaires, chart review, and U.S. CF Foundation Patient Registry data were used to track outcomes. Within the study sample 14% reported environmental allergies. Environmental allergies were associated with a higher risk of sinus disease (adjusted OR: 2.68; P allergies were also associated with a more rapid decline in lung function (additional -1.1%/year; P = 0.001). However, allergies were associated with a later median age of acquisition of Pseudomonas aeruginosa (6.6 years vs. 4.4 years; log rank P = 0.027). The reported use of common allergy medications, anti-histamines and leukotriene inhibitors, did not alter the frequency of respiratory morbidities. Environmental allergies are associated with an increased risk of sinus disease and nasal polyps and a more rapid decline in CF lung function, but may have a protective effect against the acquisition of P. aeruginosa. Prospective studies are needed to confirm these associations which have implications for more aggressive management of allergies. Copyright © 2012 Wiley Periodicals, Inc.

  5. Immune Recognition of the Epidemic Cystic Fibrosis Pathogen Burkholderia dolosa.

    Science.gov (United States)

    Roux, Damien; Weatherholt, Molly; Clark, Bradley; Gadjeva, Mihaela; Renaud, Diane; Scott, David; Skurnik, David; Priebe, Gregory P; Pier, Gerald; Gerard, Craig; Yoder-Himes, Deborah R

    2017-06-01

    Burkholderia dolosa caused an outbreak in the cystic fibrosis (CF) clinic at Boston Children's Hospital from 1998 to 2005 and led to the infection of over 40 patients, many of whom died due to complications from infection by this organism. To assess whether B. dolosa significantly contributes to disease or is recognized by the host immune response, mice were infected with a sequenced outbreak B. dolosa strain, AU0158, and responses were compared to those to the well-studied CF pathogen Pseudomonas aeruginosa In parallel, mice were also infected with a polar flagellin mutant of B. dolosa to examine the role of flagella in B. dolosa lung colonization. The results showed a higher persistence in the host by B. dolosa strains, and yet, neutrophil recruitment and cytokine production were lower than those with P. aeruginosa The ability of host immune cells to recognize B. dolosa was then assessed, B. dolosa induced a robust cytokine response in cultured cells, and this effect was dependent on the flagella only when bacteria were dead. Together, these results suggest that B. dolosa can be recognized by host cells in vitro but may avoid or suppress the host immune response in vivo through unknown mechanisms. B. dolosa was then compared to other Burkholderia species and found to induce similar levels of cytokine production despite being internalized by macrophages more than Burkholderia cenocepacia strains. These data suggest that B. dolosa AU0158 may act differently with host cells and is recognized differently by immune systems than are other Burkholderia strains or species. Copyright © 2017 American Society for Microbiology.

  6. Co-morbidity of cystic fibrosis and celiac disease in Scandinavian cystic fibrosis patients

    DEFF Research Database (Denmark)

    Fluge, G; Olesen, H V; Gilljam, M

    2009-01-01

    BACKGROUND: The co-morbidity of cystic fibrosis (CF) and celiac disease (CD) has been reported sporadically since the 1960s. To our knowledge, this is the first time a systematic screening is performed in a large cohort of CF patients. METHODS: Transglutaminase-IgA (TGA), endomysium-IgA (EMA...... patients were detected in the Danish CF cohort. Patients diagnosed with untreated CD reported symptoms typical of both CF and CD (poor weight gain, loose and/or fatty stools, fatigue, irritability, abdominal pain). They improved after introduction of a gluten-free diet. CONCLUSIONS: Systematic screening...

  7. Isolation of Pseudomonas cepacia in cystic fibrosis patient

    Directory of Open Access Journals (Sweden)

    Elizabeth de Andrade Marques

    1993-03-01

    Full Text Available Pulmonary infection on cystic fibrosis (CF patients are associated with a limited qualitative number of microorganisms. During the colonization process, Staphylococcus aureus usually preceedes Pseudomonas aeruginosa. This latter is at first non-mucoid, being replaced or associated to a mucoid morphotype which is rare in other diseases. In 1980, Pseudomonas cepacia appeared as an important agent in CF pulmonary infections with a mean frequency of about 6.1% isolations in different parts of the world. The primus colonization mainly occurs in the presence of pre-existent tissue lesions and the clinical progress of the disease is variable. In some patients it can be fulminant; in others it can cause a gradual and slow decrease in their pulmonary functions. The concern with this germ isolation is justified by its antibiotic multiple resistence and the possibility of direct transmission from a colonized patient to a non-colonized one. We reported the first case of P. cepacia infection in a CF patient in our area. The microbiological attendance to this patient had been made from 1986 to 1991 and the first positive culture appeared in 1988. The sensitivity profile showed that the primus colonization strain was sensitive to 9 of 17 tested antibiotics, however in the last culture the strain was resistent to all antibiotics. These data corroborate the need for monitoring the bacterial flora on CF patients respiratory system.

  8. Structure and function of the cystic fibrosis transmembrane conductance regulator

    Directory of Open Access Journals (Sweden)

    M.M. Morales

    1999-08-01

    Full Text Available Cystic fibrosis (CF is a lethal autosomal recessive genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR. Mutations in the CFTR gene may result in a defective processing of its protein and alter the function and regulation of this channel. Mutations are associated with different symptoms, including pancreatic insufficiency, bile duct obstruction, infertility in males, high sweat Cl-, intestinal obstruction, nasal polyp formation, chronic sinusitis, mucus dehydration, and chronic Pseudomonas aeruginosa and Staphylococcus aureus lung infection, responsible for 90% of the mortality of CF patients. The gene responsible for the cellular defect in CF was cloned in 1989 and its protein product CFTR is activated by an increase of intracellular cAMP. The CFTR contains two membrane domains, each with six transmembrane domain segments, two nucleotide-binding domains (NBDs, and a cytoplasmic domain. In this review we discuss the studies that have correlated the role of each CFTR domain in the protein function as a chloride channel and as a regulator of the outwardly rectifying Cl- channels (ORCCs.

  9. Microbiology of airway disease in a cohort of patients with Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Carnovale Vincenzo

    2006-01-01

    Full Text Available Abstract Background Recent reports document an increasing incidence of new Gram-negative pathogens such as Stenotrophomonas maltophilia and Alcaligenes xylosoxidans isolated from patients with Cystic Fibrosis, along with an increase in common Gram-negative pathogens such as Pseudomonas aeruginosa and Burkholderia cepacia complex. Furthermore, the increase in multidrug-resistance of such organisms makes the therapeutic management of these patients more problematic. Therefore, careful isolation and identification, and accurate studies of susceptibility to antibiotics are critical for predicting the spread of strains, improving therapeutic measures and facilitating our understanding of the epidemiology of emerging pathogens. The first aim of this study was to determine the incidence and the prevalence of colonization by Gram-negative organisms isolated from respiratory samples of Cystic Fibrosis patients in the Regional Referral Cystic Fibrosis Centre of Naples; the second was to evaluate the spectrum of multidrug-resistance of these organisms. Methods Patients (n = 300 attending the Regional Cystic Fibrosis Unit were enrolled in this study over 3 years. Sputum was processed for microscopic tests and culture. An automated system, Phoenix (Becton Dickinson, Sparks, Maryland, USA, was used for phenotypic identification of all strains; the API 20 NE identification system (bioMérieux, Marcy l'Etoile, France was used when the identification with the Phoenix system was inaccurate. A PCR-RFLP method was used to characterize the organisms in the Burkholderia cepacia complex. A chemosusceptibility test on microbroth dilutions (Phoenix was used. Primary outcomes such as FEV1 were correlate with different pathogens. Results During the period of study, 40% of patients was infected by Pseudomonas aeruginosa, 7% by Burkholderia cepacia complex, 11% by Stenotrophomonas maltophilia and 7% by Alcaligenes xylosoxidans. Of the strains isolated, 460 were multidrug

  10. Computed Tomography in pulmonary cystic fibrosis

    International Nuclear Information System (INIS)

    Taccone, A.; Marzoli, A.; Romano, L.; Girosi, D.

    1991-01-01

    This study was aimed at evaluating CT sensitivity in identifying the signs of pulmonary cystic fibrosis (CF). The chests of 39 patients (16 males and 23 females, mean age 19.1 years) were examined by CT: all patients had been given a clinical score according to Schwachman and Kulckzycki criteria. Thickened bronchial walls were observed in all cases, which are typical of peribronchitis. Bronchiectases were present in 87% of cases; their extent, pattern and localization were exactly shown on CT scans. Bronchoceles were seen on CT scans in 64% of patients; less frequent was the finding of atelectases and subpleural bullous emphysema. In a great number of patients (64% and 82%, respectively) pleural thickening and hilar adenopathy were demonstrated on CT scans. In conclusion, our results confirm CT as a more sensitive method than conventional radiography to identify and locate the signs of pulmonary CF. The early identification of the lesions of high prognostic value, since the early detection and treatment of bronchoceles may prevent permanent bronchiectasis

  11. Cystic fibrosis: myths. mistakes, and dogma.

    Science.gov (United States)

    Rubin, Bruce K

    2014-03-01

    As a student I recall being told that half of what we would learn in medical school would be proven to be wrong. The challenges were to identify the incorrect half and, often more challenging, be willing to give up our entrenched ideas. Myths have been defined as traditional concepts or practice with no basis in fact. A misunderstanding is a mistaken approach or incomplete knowledge that can be resolved with better evidence, while firmly established misunderstandings can become dogma; a point of view put forth as authoritative without basis in fact. In this paper, I explore a number of myths, mistakes, and dogma related to cystic fibrosis disease and care. Many of these are myths that have long been vanquished and even forgotten, while others are controversial. In the future, many things taken as either fact or "clinical experience" today will be proven wrong. Let us examine these myths with an open mind and willingness to change our beliefs when justified. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. A millennial view of cystic fibrosis.

    Science.gov (United States)

    Dodge, John A

    2015-01-01

    Although only identified as a distinct disease in the 1930s, it was soon apparent that Cystic Fibrosis (CF) had been present, but unrecognised, in European populations for many years - perhaps even centuries [1] . Within a decade of the early descriptions, the autosomal recessive nature of this genetic disease had been clarified, and its clinical features had been expanded. Secondary nutritional deficiencies complicated the underlying condition: the first clear description of CF as "a new disease", which included a speculation about its genetic basis (because there were 2 pairs of sibs in the case series) was published as Vitamin A deficiency in children [2]. The diagnosis was most often made at autopsy. When it was suspected in life, the diagnostic tests used included duodenal intubation to obtain fluid which would show impaired tryptic digestion of the coating of X-Ray film in CF children, and measurement of vitamin A in the blood. Some nutritional improvement could be expected with simple, rather inefficient pancreatic enzyme preparations, but it was not until mid-century that antibiotics began to treat pulmonary infections effectively. As a young doctor in the 1950s I soon became aware that the median age at death for affected children was about one year, and most died before reaching school age. .

  13. Infection, inflammation and exercise in cystic fibrosis

    Science.gov (United States)

    2013-01-01

    Regular exercise is positively associated with health. It has also been suggested to exert anti-inflammatory effects. In healthy subjects, a single exercise session results in immune cell activation, which is characterized by production of immune modulatory peptides (e.g. IL-6, IL-8), a leukocytosis and enhanced immune cell functions. Upon cessation of exercise, immune activation is followed by a tolerizing phase, characterized by a reduced responsiveness of immune cells. Regular exercise of moderate intensity and duration has been shown to exert anti-inflammatory effects and is associated with a reduced disease incidence and viral infection susceptibility. Specific exercise programs may therefore be used to modify the course of chronic inflammatory and infectious diseases such as cystic fibrosis (CF). Patients with CF suffer from severe and chronic pulmonary infections and inflammation, leading to obstructive and restrictive pulmonary disease, exercise intolerance and muscle cachexia. Inflammation is characterized by a hyper-inflammatory phenotype. Patients are encouraged to engage in exercise programs to maintain physical fitness, quality of life, pulmonary function and health. In this review, we present an overview of available literature describing the association between regular exercise, inflammation and infection susceptibility and discuss the implications of these observations for prevention and treatment of inflammation and infection susceptibility in patients with CF. PMID:23497303

  14. Asthma and cystic fibrosis: a tangled web.

    Science.gov (United States)

    Kent, Brian D; Lane, Stephen J; van Beek, Edwin J; Dodd, Jonathan D; Costello, Richard W; Tiddens, Harm A W M

    2014-03-01

    Successfully diagnosing concomitant asthma in people with cystic fibrosis (CF) is a challenging proposition, and the utility of conventional diagnostic criteria of asthma in CF populations remains uncertain. Nonetheless, the accurate identification of individuals with CF and asthma allows appropriate tailoring of therapy, and should reduce the unnecessary use of asthma medication in broader CF cohorts. In this review, we discuss the diagnostic challenge posed by asthma in CF, both in terms of clinical evaluation, and of interpretation of pulmonary function testing and non-invasive markers of airway inflammation. We also examine how the role of cross-sectional thoracic imaging in CF and asthma can assist in the diagnosis of asthma in these patients. Finally, we critically appraise the evidence base behind the use of asthma medications in CF populations, with a particular focus on the use of inhaled corticosteroids and bronchodilators. As shall be discussed, the gaps in the current literature make further high-quality research in this field imperative. © 2014 Wiley Periodicals, Inc.

  15. Viruses in cystic fibrosis patients' airways.

    Science.gov (United States)

    Billard, Lisa; Le Berre, Rozenn; Pilorgé, Léa; Payan, Christopher; Héry-Arnaud, Geneviève; Vallet, Sophie

    2017-11-01

    Although bacteria have historically been considered to play a major role in cystic fibrosis (CF) airway damage, a strong impact of respiratory viral infections (RVI) is also now recognized. Emerging evidence confirms that respiratory viruses are associated with deterioration of pulmonary function and exacerbation and facilitation of bacterial colonization in CF patients. The aim of this review is to provide an overview of the current knowledge on respiratory viruses in CF airways, to discuss the resulting inflammation and RVI response, to determine how to detect the viruses, and to assess their clinical consequences, prevalence, and interactions with bacteria. The most predominant are Rhinoviruses (RVs), significantly associated with CF exacerbation. Molecular techniques, and especially multiplex PCR, help to diagnose viral infections, and the coming rise of metagenomics will extend knowledge of viral populations in the complex ecosystem of CF airways. Prophylaxis and vaccination are currently available only for Respiratory syncytial and Influenza virus (IV), but antiviral molecules are being tested to improve CF patients' care. All the points raised in this review highlight the importance of taking account of RVIs and their potential impact on the CF airway ecosystem.

  16. Asthma and cystic fibrosis: A tangled web.

    LENUS (Irish Health Repository)

    Kent, Brian D

    2014-03-01

    Successfully diagnosing concomitant asthma in people with cystic fibrosis (CF) is a challenging proposition, and the utility of conventional diagnostic criteria of asthma in CF populations remains uncertain. Nonetheless, the accurate identification of individuals with CF and asthma allows appropriate tailoring of therapy, and should reduce the unnecessary use of asthma medication in broader CF cohorts. In this review, we discuss the diagnostic challenge posed by asthma in CF, both in terms of clinical evaluation, and of interpretation of pulmonary function testing and non-invasive markers of airway inflammation. We also examine how the role of cross-sectional thoracic imaging in CF and asthma can assist in the diagnosis of asthma in these patients. Finally, we critically appraise the evidence base behind the use of asthma medications in CF populations, with a particular focus on the use of inhaled corticosteroids and bronchodilators. As shall be discussed, the gaps in the current literature make further high-quality research in this field imperative. Pediatr Pulmonol. 2014; 49:205-213. © 2014 Wiley Periodicals, Inc.

  17. Targeting a genetic defect: cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Nico Derichs

    2013-03-01

    Full Text Available Cystic fibrosis (CF is caused by genetic mutations that affect the cystic fibrosis transmembrane conductance regulator (CFTR protein. These mutations can impact the synthesis and transfer of the CFTR protein to the apical membrane of epithelial cells, as well as influencing the gating or conductance of chloride and bicarbonate ions through the channel. CFTR dysfunction results in ionic imbalance of epithelial secretions in several organ systems, such as the pancreas, gastrointestinal tract, liver and the respiratory system. Since discovery of the CFTR gene in 1989, research has focussed on targeting the underlying genetic defect to identify a disease-modifying treatment for CF. Investigated management strategies have included gene therapy and the development of small molecules that target CFTR mutations, known as CFTR modulators. CFTR modulators are typically identified by high-throughput screening assays, followed by preclinical validation using cell culture systems. Recently, one such modulator, the CFTR potentiator ivacaftor, was approved as an oral therapy for CF patients with the G551D-CFTR mutation. The clinical development of ivacaftor not only represents a breakthrough in CF care but also serves as a noteworthy example of personalised medicine.

  18. Lung function imaging methods in Cystic Fibrosis pulmonary disease.

    Science.gov (United States)

    Kołodziej, Magdalena; de Veer, Michael J; Cholewa, Marian; Egan, Gary F; Thompson, Bruce R

    2017-05-17

    Monitoring of pulmonary physiology is fundamental to the clinical management of patients with Cystic Fibrosis. The current standard clinical practise uses spirometry to assess lung function which delivers a clinically relevant functional readout of total lung function, however does not supply any visible or localised information. High Resolution Computed Tomography (HRCT) is a well-established current 'gold standard' method for monitoring lung anatomical changes in Cystic Fibrosis patients. HRCT provides excellent morphological information, however, the X-ray radiation dose can become significant if multiple scans are required to monitor chronic diseases such as cystic fibrosis. X-ray phase-contrast imaging is another emerging X-ray based methodology for Cystic Fibrosis lung assessment which provides dynamic morphological and functional information, albeit with even higher X-ray doses than HRCT. Magnetic Resonance Imaging (MRI) is a non-ionising radiation imaging method that is garnering growing interest among researchers and clinicians working with Cystic Fibrosis patients. Recent advances in MRI have opened up the possibilities to observe lung function in real time to potentially allow sensitive and accurate assessment of disease progression. The use of hyperpolarized gas or non-contrast enhanced MRI can be tailored to clinical needs. While MRI offers significant promise it still suffers from poor spatial resolution and the development of an objective scoring system especially for ventilation assessment.

  19. Caratterizzazione di isolati di Pseudomonas aeruginosa provenienti da pazienti affetti da fibrosi cistica

    Directory of Open Access Journals (Sweden)

    Giovanna Pulcrano

    2007-06-01

    Full Text Available Pseudomonas aeruginosa is the major pulmonary pathogen that causes morbidity and mortality in burned, immunocompromised and cystic fibrosis patients. Among the various virulence factors, type IV-pili, play a major role in mediating bacteria-host cells interactions, in formation of biofilm and for twiching motility.These pili are composed of pilin, 15000-16000 molecular weight monomeric subunit, synthesized from pilA gene. The N-terminal region of pilin protein is strong conserved and is important for the oligomerization.The C-terminal region is less conserved and contains a disulfide-bonded loop (DSL structure that is thought to interact with the eukaryotic glycolipid receptor “asialo GM1”. Analysis of pilin allele distribution among isolates from various sources revealed the presence of six groups of pilin allels characterized by different DSL sequence and different associated accessory genes in pilA chromosomal locus. 81 P. aeruginosa isolates were recovered from cystic fibrosis patients during a 3 years period. 30 of these strains were grown and their genomic DNA was prepared using a rapid method for gram-negative bacteria. PCR primers were used for amplification of pilA and adjacent sequences revealing the presence of three different amplification products. One of these is highly homologous with pilA gene of PA14 strain, the others are identical to PA103 and PAK pilA genes. Our study revealed in the prevalence of isolates with group II pilin genes from Cystic Fibrosis compared with other groups that are predominant in previous studies.

  20. Cedecea davisae’s Role in a Polymicrobial Lung Infection in a Cystic Fibrosis Patient

    Directory of Open Access Journals (Sweden)

    Thayer G. Ismaael

    2012-01-01

    Full Text Available Chronic airway colonization and infection are the hallmark of cystic fibrosis (CF. Staphylococcus aureus, Pseudomonas aeruginosa, and Burkholderia cepacia are well-documented bacterial culprits in this chronic suppurative airway disease. Advanced molecular diagnostics have uncovered a possible role of a larger group of microorganisms in CF. Cedecea is a member of the family Enterobacteriaceae and is an emerging pathogen. We present a case of a polymicrobial healthcare-associated pneumonia in a CF patient caused by Cedecea davisae, among other bacteria.

  1. DeltaF508 heterozygosity in cystic fibrosis and susceptibility to asthma

    DEFF Research Database (Denmark)

    Dahl, Morten; Tybjaerg-Hansen, A; Lange, P

    1998-01-01

    Cystic fibrosis is a recessive disorder mainly characterised by lung disease. We tested the hypothesis that individuals heterozygous for the common cystic fibrosis deltaF508 mutation are at risk of obstructive pulmonary disease.......Cystic fibrosis is a recessive disorder mainly characterised by lung disease. We tested the hypothesis that individuals heterozygous for the common cystic fibrosis deltaF508 mutation are at risk of obstructive pulmonary disease....

  2. Ivacaftor: A Novel Gene-Based Therapeutic Approach for Cystic Fibrosis

    OpenAIRE

    Condren, Michelle E.; Bradshaw, Marquita D.

    2013-01-01

    Ivacaftor is a new therapeutic agent that acts at the cystic fibrosis transmembrane conductance regulator (CFTR) channel to alter activity. It is approved for use in patients 6 years and older with cystic fibrosis who have at least 1 G551D mutation in the CFTR gene. It is unlike any other current pharmacologic agent for cystic fibrosis in that it specifically targets the gene defect associated with cystic fibrosis as opposed to treating resulting symptomology. Mucoactive agents, antibiotics, ...

  3. Night blindness in a teenager with cystic fibrosis.

    LENUS (Irish Health Repository)

    Roddy, Marie Frances

    2011-12-01

    This article describes the case of a 16-year-old boy with cystic fibrosis who presented with difficulty seeing in the dark. He had a history of bowel surgery at birth, and he developed cystic fibrosis liver disease and osteopenia during his teenage years. He always had good lung function. When his serum vitamin A level was checked, it was undetectable in sample. He was diagnosed with night blindness and commenced on high-dose vitamin A. His symptoms resolved within 3 days. However, it took over 1 year for his vitamin A level to return to normal. This case emphasizes the importance of monitoring vitamin levels in cystic fibrosis to detect deficiency and prevent long-term consequences, and it highlights the challenges encountered during the course of night blindness treatment.

  4. Mechanisms of the noxious inflammatory cycle in cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Freyssinet Jean-Marie

    2009-03-01

    Full Text Available Abstract Multiple evidences indicate that inflammation is an event occurring prior to infection in patients with cystic fibrosis. The self-perpetuating inflammatory cycle may play a pathogenic part in this disease. The role of the NF-κB pathway in enhanced production of inflammatory mediators is well documented. The pathophysiologic mechanisms through which the intrinsic inflammatory response develops remain unclear. The unfolded mutated protein cystic fibrosis transmembrane conductance regulator (CFTRΔF508, accounting for this pathology, is retained in the endoplasmic reticulum (ER, induces a stress, and modifies calcium homeostasis. Furthermore, CFTR is implicated in the transport of glutathione, the major antioxidant element in cells. CFTR mutations can alter redox homeostasis and induce an oxidative stress. The disturbance of the redox balance may evoke NF-κB activation and, in addition, promote apoptosis. In this review, we examine the hypotheses of the integrated pathogenic processes leading to the intrinsic inflammatory response in cystic fibrosis.

  5. Hypertonic Saline in Treatment of Pulmonary Disease in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Emer P. Reeves

    2012-01-01

    Full Text Available The pathogenesis of lung disease in cystic fibrosis is characterised by decreased airway surface liquid volume and subsequent failure of normal mucociliary clearance. Mucus within the cystic fibrosis airways is enriched in negatively charged matrices composed of DNA released from colonizing bacteria or inflammatory cells, as well as F-actin and elevated concentrations of anionic glycosaminoglycans. Therapies acting against airway mucus in cystic fibrosis include aerosolized hypertonic saline. It has been shown that hypertonic saline possesses mucolytic properties and aids mucociliary clearance by restoring the liquid layer lining the airways. However, recent clinical and bench-top studies are beginning to broaden our view on the beneficial effects of hypertonic saline, which now extend to include anti-infective as well as anti-inflammatory properties. This review aims to discuss the described therapeutic benefits of hypertonic saline and specifically to identify novel models of hypertonic saline action independent of airway hydration.

  6. Parental care and overprotection of children with cystic fibrosis.

    Science.gov (United States)

    Cappelli, M; McGrath, P J; MacDonald, N E; Katsanis, J; Lascelles, M

    1989-09-01

    Parental overprotection has often been clinically associated with the psychological maladjustment of children with a chronic disease. The purpose of this study was to examine parental care and overprotection in children with cystic fibrosis compared to healthy controls. Results indicated no differences in the level of parental care or overprotection between controls and children with cystic fibrosis. However, a number of significant correlations were found between parental care and overprotection and children's psychosocial functioning. In particular, positive correlations were found between parental overprotection and poor psychosocial functioning in children with cystic fibrosis, whereas, poor psychosocial functioning in healthy children was associated with lack of parental care. Parental overprotection and care appear to play important roles in the emotional and psychological functioning of healthy and chronically ill children.

  7. Breakthrough Therapies: Cystic Fibrosis (CF) Potentiators and Correctors

    Science.gov (United States)

    Solomon, George M.; Marshall, Susan G.; Ramsey, Bonnie W.; Rowe, Steven M.

    2015-01-01

    Cystic Fibrosis is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene resulting in abnormal protein function. Recent advances of targeted molecular therapies and high throughput screening have resulted in multiple drug therapies that target many important mutations in the CFTR protein. In this review, we provide the latest results and current progress of CFTR modulators for the treatment of cystic fibrosis, focusing on potentiators of CFTR channel gating and Phe508del processing correctors for the Phe508del CFTR mutation. Special emphasis is placed on the molecular basis underlying these new therapies and emerging results from the latest clinical trials. The future directions for augmenting the rescue of Phe508del with CFTR modulators is also emphasized. PMID:26097168

  8. Preimplantation genetic diagnosis for cystic fibrosis: a case report

    Science.gov (United States)

    Biazotti, Maria Cristina Santoro; Pinto, Walter; de Albuquerque, Maria Cecília Romano Maciel; Fujihara, Litsuko Shimabukuro; Suganuma, Cláudia Haru; Reigota, Renata Bednar; Bertuzzo, Carmen Sílvia

    2015-01-01

    Cystic fibrosis is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene. This disorder produces a variable phenotype including lung disease, pancreatic insufficiency, and meconium ileus plus bilateral agenesis of the vas deferens causing obstructive azoospermia and male infertility. Preimplantation genetic diagnosis is an alternative that allows identification of embryos affected by this or other genetic diseases. We report a case of couple with cystic fibrosis; the woman had the I148 T mutation and the man had the Delta F508 gene mutation. The couple underwent in vitro fertilization, associated with preimplantation genetic diagnosis, and with subsequent selection of healthy embryos for uterine transfer. The result was an uneventful pregnancy and delivery of a healthy male baby. PMID:25993078

  9. An atypical presentation of cystic fibrosis: a case report

    Directory of Open Access Journals (Sweden)

    Joshi Deepak

    2008-06-01

    Full Text Available Abstract Introduction The presentation of cystic fibrosis is dependant upon which organs are affected. Common presentations include chronic respiratory infections and malabsorption. Patients with atypical disease tend to present late in childhood or as adults. Eye manifestations of cystic fibrosis are less well known. Case presentation A 14-year-old Caucasian boy presented with tiredness and difficulty seeing at night, over a period of 6 months. Good vision was only described in bright conditions. There was no history of jaundice, steatorrhea or diarrhoea. Conclusion This is the first reported case of newly diagnosed cystic fibrosis-related liver disease in a teenage boy, whose presenting symptom was night blindness secondary to vitamin A deficiency.

  10. Hypertonic saline in treatment of pulmonary disease in cystic fibrosis.

    LENUS (Irish Health Repository)

    Reeves, Emer P

    2012-01-01

    The pathogenesis of lung disease in cystic fibrosis is characterised by decreased airway surface liquid volume and subsequent failure of normal mucociliary clearance. Mucus within the cystic fibrosis airways is enriched in negatively charged matrices composed of DNA released from colonizing bacteria or inflammatory cells, as well as F-actin and elevated concentrations of anionic glycosaminoglycans. Therapies acting against airway mucus in cystic fibrosis include aerosolized hypertonic saline. It has been shown that hypertonic saline possesses mucolytic properties and aids mucociliary clearance by restoring the liquid layer lining the airways. However, recent clinical and bench-top studies are beginning to broaden our view on the beneficial effects of hypertonic saline, which now extend to include anti-infective as well as anti-inflammatory properties. This review aims to discuss the described therapeutic benefits of hypertonic saline and specifically to identify novel models of hypertonic saline action independent of airway hydration.

  11. Episodic seasonal Pseudo-Bartter syndrome in cystic fibrosis.

    Science.gov (United States)

    Kintu, Brett; Brightwell, Alex

    2014-06-01

    Pseudo-Bartter syndrome (PBS) describes an uncommon but well recognised complication of cystic fibrosis leading to hypochloraemic, hypokalaemic metabolic alkalosis. Pseudo-Bartter syndrome is usually seen at initial presentation or within the first two years of life in children with cystic fibrosis. Risk factors for development of PBS include warm weather conditions, severe respiratory or pancreatic disease and gastrointestinal losses (e.g. vomiting and diarrhoea). PBS is rare in older children and adolescents although epidemics have been associated with heat wave conditions in warmer climates. In this era of climate change, it is crucial that clinicians consider Pseudo-Bartter syndrome when patients with cystic fibrosis present unwell during summer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Cystic Fibrosis in the African Diaspora.

    Science.gov (United States)

    Stewart, Cheryl; Pepper, Michael S

    2017-01-01

    Identifying mutations that cause cystic fibrosis (CF) is important for making an early, unambiguous diagnosis, which, in turn, is linked to better health and a greater life expectancy. In patients of African descent, a molecular diagnosis is often confounded by the fact that the majority of investigations undertaken to identify causative mutations have been conducted on European populations, and CF-causing mutations tend to be population specific. We undertook a survey of published data with the aim of identifying causative CF mutations in patients of African descent in the Americas. We found that 1,584 chromosomes had been tested in only 6 countries, of which 876 alleles (55.3%) still remained unidentified. There were 59 mutations identified. Of those, 41 have been shown to cause CF, 17 have no associated functional studies, and one (R117H) is of varying clinical consequence. The most common mutations identified in the patients of African descent were: ΔF508 (29.4% identified in the United States, Colombia, Brazil, and Venezuela); 3120 + 1G>A (8.4% identified in Brazil, the United States, and Colombia); G85E (3.8% identified in Brazil); 1811 + 1.6kbA>G (3.7% identified in Colombia); and 1342 - 1G>C (3.1% identified in the United States). The majority of the mutations identified (81.4%) have been described in just one country. Our findings indicate that there is a need to fully characterize the spectrum of CF mutations in the diaspora to improve diagnostic accuracy for these patients and facilitate treatment.

  13. Raman spectroscopy as a new tool for early detection of bacteria in patients with cystic fibrosis

    International Nuclear Information System (INIS)

    Rusciano, Giulia; Capriglione, Paola; Pesce, Giuseppe; Sasso, Antonio; Abete, Pasquale; Carnovale, Vincenzo

    2013-01-01

    Respiratory infections represent a major threat for people affected by cystic fibrosis, leading to pulmonary deterioration and lung transplantation as a therapeutic option for end-stage patients. A fast and correct identification of pathogens in airway fluid of these patients is crucial to establish appropriate therapies, to prevent cross-infections and, ultimately, to preserve lung function. In this study, we used Raman spectroscopy to reveal bacteria in the sputa of patients such as Pseudomonas aeruginosa and Staphylococcus aureus, which are among the earliest and the most frequent bacteria affecting cystic fibrosis patients. We found that Raman analysis, combined with principal component analysis, is able to provide a correct identification of these bacteria, with a global accuracy higher than 95%. Interestingly, bacterial identification is performed by analysing patients’ sputa as a whole, avoiding, therefore, time-consuming procedures involving bacterial isolation or even bacterial cultures. This study suggests that Raman spectroscopy could be a suitable candidate for the development of innovative and non-invasive procedures for a fast and reliable identification of respiratory infections in cystic fibrosis patients. (letter)

  14. Raman spectroscopy as a new tool for early detection of bacteria in patients with cystic fibrosis

    Science.gov (United States)

    Rusciano, Giulia; Capriglione, Paola; Pesce, Giuseppe; Abete, Pasquale; Carnovale, Vincenzo; Sasso, Antonio

    2013-07-01

    Respiratory infections represent a major threat for people affected by cystic fibrosis, leading to pulmonary deterioration and lung transplantation as a therapeutic option for end-stage patients. A fast and correct identification of pathogens in airway fluid of these patients is crucial to establish appropriate therapies, to prevent cross-infections and, ultimately, to preserve lung function. In this study, we used Raman spectroscopy to reveal bacteria in the sputa of patients such as Pseudomonas aeruginosa and Staphylococcus aureus, which are among the earliest and the most frequent bacteria affecting cystic fibrosis patients. We found that Raman analysis, combined with principal component analysis, is able to provide a correct identification of these bacteria, with a global accuracy higher than 95%. Interestingly, bacterial identification is performed by analysing patients’ sputa as a whole, avoiding, therefore, time-consuming procedures involving bacterial isolation or even bacterial cultures. This study suggests that Raman spectroscopy could be a suitable candidate for the development of innovative and non-invasive procedures for a fast and reliable identification of respiratory infections in cystic fibrosis patients.

  15. Aerosol scintigraphy in the assessment of therapy for cystic fibrosis

    International Nuclear Information System (INIS)

    Kuni, C.C.; Regelmann, W.E.; Budd, J.R.; Cret, R.P. du; Boudreau, R.J.

    1990-01-01

    This paper evaluates respiration therapy, counselling, and antibiotic therapy in the treatment of exacerbations of cystic fibrosis. Thirteen patients with cystic fibrosis, aged 11-32 years, who were hospitalized for exacerbation and who had sputum cultures positive for Pseudomonas were treated initially for 3 days with respiration therapy and counselling followed by 14 days of therapy with antibiotics (n = 7) or placebo (n = 6). Tc-99m-DTPA aerosol scintigraphy was performed on days, 1, 4, and 17. Scintigrams were evaluated for change in number of nonventilated segments, change in number of bronchial deposits of aerosol, and subjective overall change

  16. The Role of Vitamin A in Patients with Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    N.V. Rogovyk

    2013-10-01

    Full Text Available Cystic fibrosis is hereditary monogenic exocrine disease, which manifests itself most often by disorders in bronchopulmonary and digestive systems. The affection of the latter leads to deficiency of liposoluble vitamins A, D, E and K in the body of the patient. The lack and excess of vitamin A in this disease may contribute to a number of pathological states and aggravate the disease. Therefore, in the records of all European centers of cystic fibrosis it is recommended to carry out annual determination of the levels of vitamin A, followed by individual dose adjustment.

  17. Computed tomography of the thorax in children with cystic fibrosis

    International Nuclear Information System (INIS)

    Parente Filho, Livio William Sales; Marchiori, Edson; Daltro, Pedro; Santos, Eloa Nunes

    1998-01-01

    We studied retrospectively the value of computed tomography of the thorax in patients suffering from cystic fibrosis. Twenty-six patients were studied, which showed as the most frequency pulmonary findings bronchial wall thickening in 22 patients (84.6), followed by bronchiectasis in 16 patients (61.5%). Less frequent finding were ill-defined patch consolidation, mucoid impaction, bullaes and atelectasis. We found a predominant distribution of bronchial wall thickening and bronchiectasis in the upper lobes of the lungs. Computed tomography is the more sensitive technique for early visualization and location of the manifestations of cystic fibrosis bronchopathy. (author)

  18. Plasma lactoferrin levels in pregnancy and cystic fibrosis

    International Nuclear Information System (INIS)

    Sykes, J.A.C.; Thomas, M.J.; Goldie, D.J.; Turner, G.M.

    1982-01-01

    Plasma lactoferrin levels have been determined by radioimmunoassay for the different weeks of normal pregnancy, in normal healthy adults and in children with and without cystic fibrosis. The lactoferrin levels were higher in pregnancy than in both male and female normal adults and showed a slight progressive increase up to week 29 and thereafter remained high. Five out of seven children with cystic fibrosis had markedly raised plasma lactoferrin levels from six to 16 times higher than the mean of a control group of children. (Auth.)

  19. Cystic fibrosis genetics: from molecular understanding to clinical application

    Science.gov (United States)

    Cutting, Garry R.

    2015-01-01

    The availability of the human genome sequence and tools for interrogating individual genomes provide an unprecedented opportunity to apply genetics to medicine. Mendelian conditions, which are caused by dysfunction of a single gene, offer powerful examples that illustrate how genetics can provide insights into disease. Cystic fibrosis, one of the more common lethalautosomal recessive Mendelian disorders, is presented here as an example. Recent progress in elucidating disease mechanism and causes of phenotypic variation, as well as in the development of treatments, demonstrates that genetics continues to play an important part in cystic fibrosis research 25 years after the d iscove1y of the disease-causing gene. PMID:25404111

  20. "Cystic fibrotics could survive cholera, choleraics could survive cystic fibrosis"; hypothesis that explores new horizons in treatment of cystic fibrosis.

    Science.gov (United States)

    Azimi, Arsalan

    2015-12-01

    Cystic fibrosis, the most common inherited disease of white population, is a disease of CFTR channels, in which mucosal function of many organs especially respiratory tract is impaired. Decreased mucociliary clearance and accumulation of mucus in airways facilitates colonization of infectious microorganisms, followed by infection. Following chronic infection, persistent inflammation ensues, which results in airway remodeling and deterioration of mucociliary clearance and result in a vicious cycle. Here, it is hypothesized that cholera toxin (CT) could ameliorate symptoms of cystic fibrosis as CT could dilute the thickened mucus, improve mucociliary clearance and alleviate airway obstruction. CT strengthens immunity of airway mucosa and it could attenuates bacterial growth and reduce persistency of infection. CT also modulates cellular immune response and it could decrease airway inflammation, hinder airway remodeling and prevent respiratory deterioration. Thereby it is hypothesized that CT could target and ameliorate many of pathophysiologic steps of the disease and it explores new horizons in treatment of CF. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Cystic fibrosis transmembrane regulator haplotypes in households of patients with cystic fibrosis.

    Science.gov (United States)

    Furgeri, Daniela Tenório; Marson, Fernando Augusto Lima; Correia, Cyntia Arivabeni Araújo; Ribeiro, José Dirceu; Bertuzzo, Carmen Sílvia

    2018-01-30

    Nearly 2000 mutations in the cystic fibrosis transmembrane regulator (CFTR) gene have been reported. The F508del mutation occurs in approximately 50-65% of patients with cystic fibrosis (CF). However, molecular diagnosis is not always possible. Therefore, silent polymorphisms can be used to label the mutant allele in households of patients with CF. To verify the haplotypes of four polymorphisms at the CFTR locus in households of patients with CF for pre-fertilization, pre-implantation, and prenatal indirect mutation diagnosis to provide better genetic counseling for families and patients with CF and to associate the genotypes/haplotypes with the F508del mutation screening. GATT polymorphism analysis was performed using direct polymerase chain reaction amplification, and the MP6-D9, TUB09 and TUB18 polymorphism analyses were performed using restriction fragment length polymorphism. Nine haplotypes were found in 37 CFTR alleles, and of those, 24 were linked with the F508del mutation and 13 with other CFTR mutations. The 6 (GATT), C (MP6-D9), G (TUB09), and C (TUB18) haplotypes showed the highest prevalence (48%) of the mutant CFTR allele and were linked to the F508del mutation (64%). In 43% of households analyzed, at least one informative polymorphism can be used for the indirect diagnostic test. CFTR polymorphisms are genetic markers that are useful for identifying the mutant CFTR alleles in households of patients with CF when it is not possible to establish the complete CFTR genotype. Moreover, the polymorphisms can be used for indirect CFTR mutation identification in cases of pre-fertilization, pre-implantation and prenatal analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Pancreatic changes in cystic fibrosis: CT and sonographic appearances

    International Nuclear Information System (INIS)

    Daneman, A.; Gaskin, K.; Martin, D.J.; Cutz, E.

    1983-01-01

    The computed tomographic (CT) and sonographic appearances of the late stages of pancreatic damage in three patients with cystic fibrosis are illustrated. All three had severe exocrine pancreatic insufficiency with steatorrhea. In two patients CT revealed complete fatty replacement of the entire pancreas. In the third, increased echogenicity of the pancreas on sonography and the inhomogeneous attenuation on CT were interpreted as being the result of a combination of fibrosis, fatty replacement, calcification, and probable cyst formation

  3. Cat and dog exposure and respiratory morbidities in cystic fibrosis.

    Science.gov (United States)

    Morrow, Christopher B; Raraigh, Karen S; Green, Deanna M; Blackman, Scott M; Cutting, Garry R; Collaco, Joseph M

    2014-10-01

    To understand the triggers that may impact respiratory health in cystic fibrosis (CF), including the effects of pets, because environmental factors contribute to one-half of the variation in lung function in patients with CF. A total of 703 subjects with CF were recruited through the US CF Twin-Sibling Study. Questionnaires were used to determine the presence/absence of cats and dogs in households with a child with CF. Questionnaires, chart review, and US CF Foundation Patient Registry data were used to track respiratory and infection outcomes. Within the sample, 47% of subjects reported owning a dog, and 28% reported owning a cat. After adjustment for demographic factors, dog ownership was not associated with any adverse clinical outcomes, and cat ownership was associated an increased risk in developing nasal polyps (aOR 1.66; P = .024) compared with noncat owners. Subjects who owned both cats and dogs were twice as likely to report wheezing compared with other subjects (aOR: 2.01; P = .009). There were no differences in prevalence and age of acquisition for the common CF respiratory pathogens Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus between cat/dog owners and noncat/dog owners. Cat ownership was associated with a greater frequency of developing nasal polyps and combined cat-dog ownership was associated with a greater rate of wheezing. Prospective studies are needed to confirm these associations and the potential psychosocial benefits of cat and/or dog ownership. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations.

    Directory of Open Access Journals (Sweden)

    Edith T Zemanick

    Full Text Available Pulmonary exacerbations (PEx, frequently associated with airway infection and inflammation, are the leading cause of morbidity in cystic fibrosis (CF. Molecular microbiologic approaches detect complex microbiota from CF airway samples taken during PEx. The relationship between airway microbiota, inflammation, and lung function during CF PEx is not well understood.To determine the relationships between airway microbiota, inflammation, and lung function in CF subjects treated for PEx.Expectorated sputum and blood were collected and lung function testing performed in CF subjects during early (0-3d. and late treatment (>7d. for PEx. Sputum was analyzed by culture, pyrosequencing of 16S rRNA amplicons, and quantitative PCR for total and specific bacteria. Sputum IL-8 and neutrophil elastase (NE; and circulating C-reactive protein (CRP were measured.Thirty-seven sputum samples were collected from 21 CF subjects. At early treatment, lower diversity was associated with high relative abundance (RA of Pseudomonas (r = -0.67, p<0.001, decreased FEV(1% predicted (r = 0.49, p = 0.03 and increased CRP (r = -0.58, p = 0.01. In contrast to Pseudomonas, obligate and facultative anaerobic genera were associated with less inflammation and higher FEV₁. With treatment, Pseudomonas RA and P. aeruginosa by qPCR decreased while anaerobic genera showed marked variability in response. Change in RA of Prevotella was associated with more variability in FEV₁ response to treatment than Pseudomonas or Staphylococcus.Anaerobes identified from sputum by sequencing are associated with less inflammation and higher lung function compared to Pseudomonas at early exacerbation. CF PEx treatment results in variable changes of anaerobic genera suggesting the need for larger studies particularly of patients without traditional CF pathogens.

  5. Cystic fibrosis, molecular genetics for all life

    Directory of Open Access Journals (Sweden)

    Ausilia Elce

    2015-10-01

    Full Text Available Cystic fibrosis (CF is the most frequent lethal autosomal recessive disorder among Caucasians (incidence: 1:2,500 newborn. In the last two decades CF prognosis considerably improved and many patients well survive into their adulthood. Furthermore, milder CF with a late onset was described. CF is a challenge for laboratory of molecular genetics that greatly contributes to the natural history of the disease since fetal age. Carrier screening and prenatal diagnosis, also by non-invasive analysis of maternal blood fetal DNA, are now available, and many labs offer preimplantation diagnosis. The major criticism in prenatal medicine is the lack of an effective multidisciplinary counseling that helps the couples to plan their reasoned reproductive choice. Most countries offer newborn screening that significantly reduce CF morbidity but different protocols based on blood trypsin, molecular analysis and sweat chloride cause a variable efficiency of the screening programs. Again, laboratory is crucial for CF diagnosis in symptomatic patients: sweat chloride is the diagnostic golden standard, but different methodologies and the lack of quality control in most labs reduce its effectiveness. Molecular analysis contributes to confirm diagnosis in symptomatic subjects; furthermore, it helps to predict the disease outcome on the basis of the mutation (genotype-phenotype correlation and mutations in a myriad of genes, inherited independently by CF transmembrane conductance regulator (CFTR, which may modulate the clinical expression of the disease in each single patient (modifier genes. More recently, the search of the CFTR mutations gained a role in selecting CF patients that may benefit from biological therapy based on correctors and potentiators that are effective in patients bearing specific mutations (personalized therapy. All such applications of molecular diagnostics confirm the “uniqueness” of each CF patient, offering to laboratory medicine the

  6. Cystic Fibrosis Colorectal Cancer Screening Consensus Recommendations.

    Science.gov (United States)

    Hadjiliadis, Denis; Khoruts, Alexander; Zauber, Ann G; Hempstead, Sarah E; Maisonneuve, Patrick; Lowenfels, Albert B

    2018-02-01

    Improved therapy has substantially increased survival of persons with cystic fibrosis (CF). But the risk of colorectal cancer (CRC) in adults with CF is 5-10 times greater compared to the general population, and 25-30 times greater in CF patients after an organ transplantation. To address this risk, the CF Foundation convened a multi-stakeholder task force to develop CRC screening recommendations. The 18-member task force consisted of experts including pulmonologists, gastroenterologists, a social worker, nurse coordinator, surgeon, epidemiologist, statistician, CF adult, and a parent. The committee comprised 3 workgroups: Cancer Risk, Transplant, and Procedure and Preparation. A guidelines specialist at the CF Foundation conducted an evidence synthesis February-March 2016 based on PubMed literature searches. Task force members conducted additional independent searches. A total of 1159 articles were retrieved. After initial screening, the committee read 198 articles in full and analyzed 123 articles to develop recommendation statements. An independent decision analysis evaluating the benefits of screening relative to harms and resources required was conducted by the Department of Public Health at Erasmus Medical Center, Netherlands using the Microsimulation Screening Analysis model from the Cancer Innervation and Surveillance Modeling Network. The task force included recommendation statements in the final guideline only if they reached an 80% acceptance threshold. The task force makes 10 CRC screening recommendations that emphasize shared, individualized decision-making and familiarity with CF-specific gastrointestinal challenges. We recommend colonoscopy as the preferred screening method, initiation of screening at age 40 years, 5-year re-screening and 3-year surveillance intervals (unless shorter interval is indicated by individual findings), and a CF-specific intensive bowel preparation. Organ transplant recipients with CF should initiate CRC screening

  7. Fungal atopy in adult cystic fibrosis.

    LENUS (Irish Health Repository)

    Henry, M

    2012-02-03

    This study set out to estimate the prevalence of atopy to a variety of common ubiquitous fungi, including A. fumigatus, in cystic fibrosis (CF), and to evaluate the investigations by which the diagnosis was made. Particular attention was paid to the usefulness of skin testing and immunoassays in detecting which patients had simple fungal atopy, and which patients were at high risk of developing allergic bronchopulmonary mycoses. This cross-sectional study included 21 adult CF patients and 20 matched controls. Serum samples were taken for the measurement of total serum IgE and specific serum IgE to nine common fungi. Immediate hypersensitivity skin prick testing to each of the fungi was also performed. Simple fungal atopy was described in subjects fulfilling the following criteria: total serum IgE > 100 KU l(-1) with specific radioimmunoassay > or = grade 1 to at least one fungus and a positive skin prick test (SPT) > or = 3 mm to the same fungus. \\'High risk\\' for developing allergic bronchopulmonary mycosis (ABPM) was described in subjects fulfilling the following criteria: total serum IgE > 200 KU l(-1) with specific radioimmunoassay > or = grade 2 to at least one fungus and a positive skin prick test (SPT) > or = 6 mm to the same fungus. The adult CF group had a significantly higher total SPT score (P=0.005) and mean total serum IgE (P<0.05) than controls. Forty-three percent of CF patients fulfilled the criteria for fungal atopy to at least a single fungus. Over half this group had an atopic tendency to more than one fungus. Nineteen percent of the CF group were at least \\'high risk\\' of developing ABPM. Skin prick testing is a better marker of fungal atopy and a better predictor of those adult CF patients at higher risk of developing ABPM than specific radioimmunoassay serum testing. There is a high prevalence of fungal atopy in the adult CF population. Total serum IgE and skin prick testing are good predictors of fungal atopy and help predict those at

  8. Technology evaluation: cystic fibrosis therapy, Genzyme.

    Science.gov (United States)

    Cockett, M I

    1999-04-01

    Genzyme is developing therapies to replace the defective forms of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein in CF patients. The company is developing a gene therapy, as well as a recombinant production of CFTR for protein replacement therapy. Both approaches have been granted orphan drug status by the FDA [156348]. The results of several clinical trials were discussed at the first annual meeting of the American Society of Gene Therapy in May 1998. A single dose nasal administration was well tolerated by volunteers, but had disappointing efficacy. In a study completed at the Royal Brompton Hospital, London, a single dose aerosol application of GL-67:DOPE was administered to eight patients, while another eight received GL-67:DOPE plus pCF1-CFTR. In the second group, a moderate increase in the potential difference in the lung was observed, with a slight trend towards bacterial adherence normalization in the airway cells. Seven of the patients in the second group, and three patients who received lipid alone, developed, flu-like symptoms within 24 h. A trial at the University of Alabama, using the same formulation, showed that flu-like symptoms developed in six of eight patients by day two, and in all patients by day seven [290120]. In 1995, the company began a clinical safety trial involving delivery of a normal CF gene to the patient's lungs via an adenovirus vector. The administration involves the inhalation of an aerosol containing the vector or, separately, delivery to one lobe of the patient's lung via a bronchoscope [191678]. To evaluate additional delivery methods for the gene, Genzyme has an exclusive research agreement for the use of Vical's cytofectins as non-viral delivery vectors for CFTR. Also under investigation are delivery systems for the nasal epithelium using liposomes or lipid-DNA complexes. These protocols are being developed in collaboration with the National Heart & Lung Institute, London, and an undisclosed

  9. Not All Children with Cystic Fibrosis Have Abnormal Esophageal Neutralization during Chemical Clearance of Acid Reflux.

    Science.gov (United States)

    Woodley, Frederick W; Moore-Clingenpeel, Melissa; Machado, Rodrigo Strehl; Nemastil, Christopher J; Jadcherla, Sudarshan R; Hayes, Don; Kopp, Benjamin T; Kaul, Ajay; Di Lorenzo, Carlo; Mousa, Hayat

    2017-09-01

    Acid neutralization during chemical clearance is significantly prolonged in children with cystic fibrosis, compared to symptomatic children without cystic fibrosis. The absence of available reference values impeded identification of abnormal findings within individual patients with and without cystic fibrosis. The present study aimed to test the hypothesis that significantly more children with cystic fibrosis have acid neutralization durations during chemical clearance that fall outside the physiological range. Published reference value for acid neutralization duration during chemical clearance (determined using combined impedance/pH monitoring) was used to assess esophageal acid neutralization efficiency during chemical clearance in 16 children with cystic fibrosis (3 to chemical clearance exceeded the upper end of the physiological range in 9 of 16 (56.3%) children with and in 3 of 16 (18.8%) children without cystic fibrosis ( p =0.0412). The likelihood ratio for duration indicated that children with cystic fibrosis are 2.1-times more likely to have abnormal acid neutralization during chemical clearance, and children with abnormal acid neutralization during chemical clearance are 1.5-times more likely to have cystic fibrosis. Significantly more (but not all) children with cystic fibrosis have abnormally prolonged esophageal clearance of acid. Children with cystic fibrosis are more likely to have abnormal acid neutralization during chemical clearance. Additional studies involving larger sample sizes are needed to address the importance of genotype, esophageal motility, composition and volume of saliva, and gastric acidity on acid neutralization efficiency in cystic fibrosis children.

  10. Sinus biofilms in patients with cystic fibrosis: is adjusted eradication therapy needed?

    DEFF Research Database (Denmark)

    Aanaes, Kasper; Eickhardt, Steffen; Johansen, Helle Krogh

    2015-01-01

    The paranasal sinuses can be a focus for colonisation of the cystic fibrosis (CF) lungs with pathogens. In the sinuses, bacteria can adapt to the lung environment and enhance their antibiotic resistance, with biofilm formation thought to be the most important adaptive mechanism, causing recalcitr......The paranasal sinuses can be a focus for colonisation of the cystic fibrosis (CF) lungs with pathogens. In the sinuses, bacteria can adapt to the lung environment and enhance their antibiotic resistance, with biofilm formation thought to be the most important adaptive mechanism, causing...... recalcitrant disease. The presence of biofilms in CF sinuses is sparsely described. In this descriptive cross-sectional study, the sinus mucosa from 16 CF patients were analysed by fluorescence in situ hybridization using specific peptide nucleic acid (PNA-FISH) probes for Pseudomonas aeruginosa...... and Staphylococcus aureus to demonstrate the presence of biofilms. Small clusters of biofilm were visualised lining the sinus mucosa of CF patients. Biofilms were found in 10 out of 18 cases; 7 with intermittent lung colonisation, 2 chronically infected, and one lung transplanted patient. Finding P. aeruginosa...

  11. Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment

    Directory of Open Access Journals (Sweden)

    Morgan T. Sutton

    2016-01-01

    Full Text Available Cystic fibrosis (CF is a genetic disease in which the battle between pulmonary infection and inflammation becomes the major cause of morbidity and mortality. We have previously shown that human MSCs (hMSCs decrease inflammation and infection in the in vivo murine model of CF. The studies in this paper focus on the specificity of the hMSC antimicrobial effectiveness using Pseudomonas aeruginosa (gram negative bacteria and Staphylococcus aureus (gram positive bacteria. Our studies show that hMSCs secrete bioactive molecules which are antimicrobial in vitro against Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumonia, impacting the rate of bacterial growth and transition into colony forming units regardless of the pathogen. Further, we show that the hMSCs have the capacity to enhance antibiotic sensitivity, improving the capacity to kill bacteria. We present data which suggests that the antimicrobial effectiveness is associated with the capacity to slow bacterial growth and the ability of the hMSCs to secrete the antimicrobial peptide LL-37. Lastly, our studies demonstrate that the tissue origin of the hMSCs (bone marrow or adipose tissue derived, the presence of functional cystic fibrosis transmembrane conductance regulator (CFTR: human, Cftr: mouse activity, and response to effector cytokines can impact both hMSC phenotype and antimicrobial potency and efficacy. These studies demonstrate, the unique capacity of the hMSCs to manage different pathogens and the significance of their phenotype in both the antimicrobial and antibiotic enhancing activities.

  12. Pharmacokinetics of aerosolized tobramycin in adult patients with cystic fibrosis

    NARCIS (Netherlands)

    Touw, D J; Jacobs, F A; Brimicombe, R W; Heijerman, H G; Bakker, W; Briemer, D D

    This study was performed to determine the clinical pharmacokinetics of tobramycin in six patients with cystic fibrosis (CF) after inhalation of 600 mg. Tobramycin was administered with an ultrasonic nebulizer (WISTO SENIOR). Blood and urine were sampled until 24 h after inhalation. Maximum

  13. Transcellular sodium transport in cultured cystic fibrosis human nasal epithelium

    DEFF Research Database (Denmark)

    Willumsen, Niels J.; Boucher, Richard C.

    1991-01-01

    Cystic fibrosis (CF) airway epithelia exhibit raised transepithelial Na+ transport rates, as determined by open-circuit isotope fluxes and estimates of the amiloride-sensitive equivalent short-circuit current (Ieq). To study the contribution of apical and basolateral membrane paths to raised Na+ ...

  14. New advances in cystic fibrosis - implications for developing countries

    African Journals Online (AJOL)

    New advances in cystic fibrosis - implications for developing countries. Heather J Zar, Eric Bateman, Michelle Ramsay. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Article Metrics. Metrics Loading ... Metrics powered by PLOS ALM.

  15. Risk of asthma in heterozygous carriers for cystic fibrosis

    DEFF Research Database (Denmark)

    Nielsen, Anne Orholm; Qayum, Sadaf; Bouchelouche, Pierre Nourdine

    2016-01-01

    Background Patients with cystic fibrosis (CF) have a higher prevalence of asthma than the background population, however, it is unclear whether heterozygous CF carriers are susceptible to asthma. Given this, a meta-analysis is necessary to determine the veracity of the association of CF...

  16. Students as Technicians: Screening Newborns for Cystic Fibrosis

    Science.gov (United States)

    Gusky, Sharon

    2014-01-01

    In this activity, freshman college students learn biotechnology techniques while playing the role of a laboratory technician. They perform simulations of three diagnostic tests used to screen newborns for cystic fibrosis. By performing an ELISA, a PCR analysis, and a conductivity test, students learn how biotechnology techniques can be used to…

  17. Uptake of genetic counselling services by patients with cystic fibrosis ...

    African Journals Online (AJOL)

    Background: Although cystic fibrosis (CF) is a common genetic condition, genetic counselling services appear to be underutilised by affected families. The aim of this study was to determine the uptake of genetic counselling and mutation testing for CF by relatives of affected individuals, and the impact of introducing ...

  18. Treatment of lung infection in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Döring, Gerd; Flume, Patrick; Heijerman, Harry

    2012-01-01

    In patients with cystic fibrosis (CF) lung damage secondary to chronic infection is the main cause of death. Treatment of lung disease to reduce the impact of infection, inflammation and subsequent lung injury is therefore of major importance. Here we discuss the present status of antibiotic...

  19. Diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis

    DEFF Research Database (Denmark)

    Skov, M; Koch, C; Reimert, C M

    2000-01-01

    The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients may be difficult to establish because ABPA shares many characteristics with coexisting atopy or other lung infections in these patients. This study aimed to evaluate the sensitivity and specificity...

  20. Systematic review of N-acetylcysteine in cystic fibrosis

    NARCIS (Netherlands)

    Duijvestijn, YCM; Brand, PLP

    A systematic review was carried out to evaluate whether the use of N-acetylcysteine to improve lung function in patients with cystic fibrosis is supported by published evidence. Medline and the Cochrane Library were searched and the reference lists of all retrieved papers and of relevant chapters of

  1. Cystic fibrosis heterozygotes do not have increased platelet activation

    DEFF Research Database (Denmark)

    Tarnow, Inge; Michelson, Alan D.; Frelinger III, Andrew L.

    2007-01-01

    Introduction: We have previously demonstrated platelet hyperreactivity in cystic fibrosis (CF) patients. Carriers of one CF m utation (heterozygotes) have been shown to have abnormalities related to the presence of only one-half the normal amount of CF transmembrane conductance regulator protein...

  2. The Adolescent With Cystic Fibrosis : A Psychosocial Perspective ...

    African Journals Online (AJOL)

    Objective: to provide an overview of the literature pertaining to the mental health of adolescents with Cystic Fibrosis (CF), a chronic physical disorder. Method: a Medline search and aditional hand searches were performed to identify key articles relating to the psychosocial impact of CF and other chronic disorders in ...

  3. Scandinavian Nurse Specialist Group/Cystic Fibrosis (SNSG/CF)

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke; Erwander, Inger

    2006-01-01

    /CF comprises one CF nurse from each of the centers. The board meets twice a year to plan workshops and courses. SNSG/CF is part of the International Nurse Specialist Group/Cystic Fibrosis (INSG/CF). Results: Within the framework of SNSG/CF a 2-day workshop is held every second year for approximately 40...

  4. 78 FR 26681 - Medical Criteria for Evaluating Cystic Fibrosis

    Science.gov (United States)

    2013-05-07

    ...-1213, or TTY 1-800-325-0778, or visit our Internet site, Social Security Online, at http://www... SOCIAL SECURITY ADMINISTRATION [Docket No. SSA-2006-0149] RIN 0960-AF58 Medical Criteria for Evaluating Cystic Fibrosis AGENCY: Social Security Administration. ACTION: Notice of teleconference. SUMMARY...

  5. Inspiratory muscle training in patients with cystic fibrosis

    NARCIS (Netherlands)

    de Jong, W.; van Aalderen, W.M.C.; Kraan, J.; Koeter, G.H.; van der Schans, C.P.

    Little information is available about the effects of inspiratory muscle training in patients with cystic fibrosis (CF). In this study the effects of inspiratory-threshold loading in patients with CF on strength and endurance of the inspiratory muscles, pulmonary function, exercise capacity, dyspnoea

  6. Dietary intake and body-growth in cystic fibrosis

    NARCIS (Netherlands)

    Woestenenk, J.W.

    2015-01-01

    Cystic fibrosis (CF) is a life-threatening genetic disorder that affects mostly the lungs but also the pancreas, liver and intestine. CF is characterised by chronic pulmonary inflammation resulting in a gradual, progressive decline in pulmonary function. The vast majority of CF patients also have an

  7. Clinical pharmacokinetics of antimicrobial drugs in cystic fibrosis

    NARCIS (Netherlands)

    Touw, D J

    The disposition of many drugs in cystic fibrosis is abnormal compared with healthy individuals. In general, changes include an increased volume of distribution expressed in liters per kg bodyweight for highly hydrophilic drugs such as aminoglycosides, and, to a lesser extent, for penicillins and

  8. Uptake of genetic counselling services by patients with cystic fibrosis ...

    African Journals Online (AJOL)

    2011-05-09

    May 9, 2011 ... Cystic fibrosis (CF) is a chronic, inherited disorder that affects the respiratory tract, pancreas, .... 18%) themselves and other individuals, such as nurses (20 out of 153, 13%), general practitioners (15 out of 153, 10%) .... considered to be rare in this ethnic group, it is likely that. CF is still under-recognised and ...

  9. Pregnancy outcome in women with cystic fibrosis-related diabetes.

    Science.gov (United States)

    Reynaud, Quitterie; Poupon-Bourdy, Stéphanie; Rabilloud, Muriel; Al Mufti, Lina; Rousset Jablonski, Christine; Lemonnier, Lydie; Nove-Josserand, Raphaële; Touzet, Sandrine; Durieu, Isabelle

    2017-10-01

    With increasing life expectancy, more women with cystic fibrosis and diabetes mellitus become pregnant. We investigated how pre-gestational diabetes (cystic fibrosis-related diabetes) influenced pregnancy outcome and the clinical status of these women. We analyzed all pregnancies reported to the French cystic fibrosis registry between 2001 and 2012, and compared forced expiratory volume (FEV 1 ) and body mass index before and after pregnancy in women with and without pre-gestational diabetes having a first delivery. A total 249 women delivered 314 infants. Among these, 189 women had a first delivery and 29 of these had pre-gestational diabetes. There was a trend towards a higher rate of assisted conception among diabetic women (53.8%) than non-diabetic women (34.5%, p = 0.06), and the rate of cesarean section was significantly higher in diabetic women (48% vs. 21.4%, p = 0.005). The rate of preterm birth and mean infant birthweight did not differ significantly between diabetic and non-diabetic women. Forced expiratory volume before pregnancy was significantly lower in the diabetic group. The decline in forced expiratory volume and body mass index following pregnancy did not differ between the women with and those without pre-gestational diabetes. Pre-gestational diabetes in women with cystic fibrosis is associated with a higher rate of cesarean section but does not seem to have a clinically significant impact on fetal growth or preterm delivery. The changes in maternal pulmonary and nutritional status following pregnancy in women with cystic fibrosis were not influenced by pre-gestational diabetes. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  10. Effect of Obstructive airway disease in patients with non-cystic fibrosis bronchiectasis

    International Nuclear Information System (INIS)

    Khalid, Mohammad; Saleemi, Sarfraz; Zeitouni, Mohammed; Al-Dammas, Saleh; Khaliq, Mohammad Rehan

    2004-01-01

    Extensive research has been devoted to cystic fibrosis-related brochiectasis compared with noncystic fibrosis brochiectasis but the latter is more common and results in significant morbidity and mortality. We assessed the relationship between pulmonary function test (PFT) findings and sputum bacteriology, blood gases, number of hospital admissions and mortality in patients with non-cystic fibrosis brochiectasis (NCFB). we conducted a retrospective review of 88 consecutive patients admitted with exacerbation of brochiectasis over 5 years from 1996 to 2001. Demographic and clinical data collected included gender, age, pulmonary functions, arterial blood gases, sputum bacteriology during stable and exacerbation periods and number of hospital admissions due to exacerbation of brochiectasis. A comparison was made between patients having obstructive airway disease (OAD group) and patients with normal or restrictive pulmonaru functions (non-OAD group). OAD patients with NCFB adversely affected clinical outcome.There was a significant increase in Pseuomonas colonization (60.3% vs. 16%; P<0.0003), hypercapnic respiratory failure (63.4% vs. 20%; P<0.0003) and mean number of admissons due to exacerbation (6 vs. 2; P<0.0001)in the OAD group as compared with the non OAD group, the difference was not statistically significant. Patients with NCFB who have OAD have a significantly higher rate of colonization with Pseuomonas aeruginosa (PSA) hypercapric respiratory failure, a greater number of hospital admissions due to exacerbation of brochiectasis and a a higher mortality compared with patients with restrictive or normal pulmonary functions. (author)

  11. Non-Invasive Evaluation of Cystic Fibrosis Related Liver Disease in Adults with ARFI, Transient Elastography and Different Fibrosis Scores

    OpenAIRE

    Karlas, Thomas; Neuschulz, Marie; Oltmanns, Annett; Güttler, Andrea; Petroff, David; Wirtz, Hubert; Mainz, Jochen G.; Mössner, Joachim; Berg, Thomas; Tröltzsch, Michael; Keim, Volker; Wiegand, Johannes

    2012-01-01

    BACKGROUND: Cystic fibrosis-related liver disease (CFLD) is present in up to 30% of cystic fibrosis patients and can result in progressive liver failure. Diagnosis of CFLD is challenging. Non-invasive methods for staging of liver fibrosis display an interesting diagnostic approach for CFLD detection. AIM: We evaluated transient elastography (TE), acoustic radiation force impulse imaging (ARFI), and fibrosis indices for CFLD detection. METHODS: TE and ARFI were performed in 55 adult CF patient...

  12. SPECIFIC DISORDERS OF THE RESPIRATORY SYSTEM IN CYSTIC FIBROSIS. CLINICAL EFFICACY OF THERAPY WITH DORNASE ALFA IN CHILDREN

    Directory of Open Access Journals (Sweden)

    T.V. Simanova

    2010-01-01

    Full Text Available The article is devoted to specific disorders of the respiratory system in cystic fibrosis. 64 patients with cystic fibrosis (CF aged 2 months to 32 years and residing in the Udmurtian Republic were studied. Epidemiological and genetic specifics of this disease in the mentioned region of the RF were examined. Clinical, X-ray, functional and microbiological studies of the CF patients’ respiratory system were conducted. It was found that genotype delF508 and chronic infection Pseudomonas aeruginosa, Staphylococcus aureus cause severe structural changes to the bronchopulmonary system more often. The obtained data suggest the advisability of identifying the groups of CF patients at the highest risk of severe respiratory system disorders in order to optimise therapeutic efforts. The article provides indicators of clinical efficacy of a dornase alfa therapy in CF children.Key words: cystic fibrosis, genotype, delF508 mutation, respiratory organs, pseudomonas aeruginosa infection, staphylococcal infection, respiratory function, mucolytic function, dornase alfa. (Pediatric Pharmacology. – 2010; 7(6:44-48

  13. Chest CT features of cystic fibrosis in Korea: Comparison with non-cystic fibrosis diseases

    International Nuclear Information System (INIS)

    Yang, So Yeon; Lee, Kyung Soo; Kim, Tae Jung; Kim, Tae Sung; Cha, Min Jae; Yoon, Hyun Jung

    2017-01-01

    Cystic fibrosis (CF) is a rare congenital disease in Korea, and its clinical and imaging findings are unclear. The objective of our study was to describe the clinical and CT features of CF in Korea and compare its features with those of other diseases mimicking CF. From November 1994 to December 2014, a presumptive diagnosis of CF was made in 23 patients based on clinical or radiological examination. After the exclusion of 10 patients without diagnostic confirmation, 13 patients were included in the study. A diagnosis of CF was made with the CF gene study. CT findings were evaluated for the presence and distribution of parenchymal abnormalities including bronchiectasis, tree-in-bud (TIB) pattern, mucus plugging, consolidation, and mosaic attenuation. Of the 13 patients, 7 (median age, 15 years) were confirmed as CF, 4 (median age, 19 years) had primary ciliary dyskinesia, 1 had bronchiectasis of unknown cause, and 1 had chronic asthma. CT of patients with CF showed bilateral bronchiectasis, TIB pattern, mosaic attenuation, and mucus plugging in all patients, with upper lung predominance (57%). In CT of the non-CF patients, bilateral bronchiectasis, TIB pattern, mosaic attenuation, and mucus plugging were also predominant features, with lower lung predominance (50%). Korean patients with CF showed bilateral bronchiectasis, cellular bronchiolitis, mucus plugging, and mosaic attenuation, which overlapped with those of non-CF patients. CF gene study is recommended for the definitive diagnosis of CF in patients with these clinical and imaging features

  14. Chest CT features of cystic fibrosis in Korea: Comparison with non-cystic fibrosis diseases

    Energy Technology Data Exchange (ETDEWEB)

    Yang, So Yeon; Lee, Kyung Soo; Kim, Tae Jung; Kim, Tae Sung [Dept. of Radiology, and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Cha, Min Jae [Dept. of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul (Korea, Republic of); Yoon, Hyun Jung [Dept. of Radiology, Hanyang University Hospital, Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2017-01-15

    Cystic fibrosis (CF) is a rare congenital disease in Korea, and its clinical and imaging findings are unclear. The objective of our study was to describe the clinical and CT features of CF in Korea and compare its features with those of other diseases mimicking CF. From November 1994 to December 2014, a presumptive diagnosis of CF was made in 23 patients based on clinical or radiological examination. After the exclusion of 10 patients without diagnostic confirmation, 13 patients were included in the study. A diagnosis of CF was made with the CF gene study. CT findings were evaluated for the presence and distribution of parenchymal abnormalities including bronchiectasis, tree-in-bud (TIB) pattern, mucus plugging, consolidation, and mosaic attenuation. Of the 13 patients, 7 (median age, 15 years) were confirmed as CF, 4 (median age, 19 years) had primary ciliary dyskinesia, 1 had bronchiectasis of unknown cause, and 1 had chronic asthma. CT of patients with CF showed bilateral bronchiectasis, TIB pattern, mosaic attenuation, and mucus plugging in all patients, with upper lung predominance (57%). In CT of the non-CF patients, bilateral bronchiectasis, TIB pattern, mosaic attenuation, and mucus plugging were also predominant features, with lower lung predominance (50%). Korean patients with CF showed bilateral bronchiectasis, cellular bronchiolitis, mucus plugging, and mosaic attenuation, which overlapped with those of non-CF patients. CF gene study is recommended for the definitive diagnosis of CF in patients with these clinical and imaging features.

  15. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis.

    Science.gov (United States)

    Floto, R Andres; Olivier, Kenneth N; Saiman, Lisa; Daley, Charles L; Herrmann, Jean-Louis; Nick, Jerry A; Noone, Peadar G; Bilton, Diana; Corris, Paul; Gibson, Ronald L; Hempstead, Sarah E; Koetz, Karsten; Sabadosa, Kathryn A; Sermet-Gaudelus, Isabelle; Smyth, Alan R; van Ingen, Jakko; Wallace, Richard J; Winthrop, Kevin L; Marshall, Bruce C; Haworth, Charles S

    2016-01-01

    Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with pre-existing inflammatory lung disease such as cystic fibrosis (CF). Pulmonary disease caused by NTM has emerged as a major threat to the health of individuals with CF but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened an expert panel of specialists to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM pulmonary disease in individuals with CF. Nineteen experts were invited to participate in the recommendation development process. Population, Intervention, Comparison, Outcome (PICO) methodology and systematic literature reviews were employed to inform draft recommendations. An anonymous voting process was used by the committee to reach consensus. All committee members were asked to rate each statement on a scale of: 0, completely disagree, to 9, completely agree; with 80% or more of scores between 7 and 9 being considered 'good' agreement. Additionally, the committee solicited feedback from the CF communities in the USA and Europe and considered the feedback in the development of the final recommendation statements. Three rounds of voting were conducted to achieve 80% consensus for each recommendation statement. Through this process, we have generated a series of pragmatic, evidence-based recommendations for the screening, investigation, diagnosis and treatment of NTM infection in individuals with CF as an initial step in optimising management for this challenging condition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  16. Multifunctional superparamagnetic nanoparticles for enhanced drug transport in cystic fibrosis

    Science.gov (United States)

    Armijo, Leisha M.; Brandt, Yekaterina I.; Rivera, Antonio C.; Cook, Nathaniel C.; Plumley, John B.; Withers, Nathan J.; Kopciuch, Michael; Smolyakov, Gennady A.; Huber, Dale L.; Smyth, Hugh D.; Osinski, Marek

    2012-10-01

    Iron oxide colloidal nanoparticles (ferrofluids) are investigated for application in the treatment of cystic fibrosis lung infections, the leading cause of mortality in cystic fibrosis patients. We investigate the use of iron oxide nanoparticles to increase the effectiveness of administering antibiotics through aerosol inhalation using two mechanisms: directed particle movement in the presence of an inhomogeneous static external magnetic field and magnetic hyperthermia. Magnetic hyperthermia is an effective method for decreasing the viscosity of the mucus and biofilm, thereby enhancing drug, immune cell, and antibody penetration to the affected area. Iron oxide nanoparticles of various sizes and morphologies were synthesized and tested for specific losses (heating power). Nanoparticles in the superparamagnetic to ferromagnetic size range exhibited excellent heating power. Additionally, iron oxide / zinc selenide core/shell nanoparticles were prepared, in order to enable imaging of the iron oxide nanoparticles. We also report on synthesis and characterization of MnSe/ZnSeS alloyed quantum dots.

  17. Psychological interventions for individuals with cystic fibrosis and their families.

    Science.gov (United States)

    Goldbeck, Lutz; Fidika, Astrid; Herle, Marion; Quittner, Alexandra L

    2014-06-18

    With increasing survival estimates for individuals with cystic fibrosis, long-term management has become an important focus. Psychological interventions are largely concerned with adherence to treatment, emotional and social adaptation and health-related quality of life. We are unaware of any relevant systematic reviews. To determine whether psychological interventions for people with cystic fibrosis provide significant psychosocial and physical benefits in addition to standard medical care. Studies were identified from two Cochrane trials registers (Cystic Fibrosis and Genetic Disorders Group; Depression, Anxiety and Neurosis Group), Ovid MEDLINE and PsychINFO; unpublished trials were located through professional networks and Listserves. Most recent search of the Cystic Fibrosis and Genetic Disorders Group's register: 19 December 2013.Most recent search of the Depression, Anxiety and Neurosis Group's register: 12 November 2013. Randomised controlled studies of a broad range of psychological interventions evaluating subjective and objective health outcomes, such as quality of life or pulmonary function, in individuals of all ages with cystic fibrosis and their immediate family. We were interested in psychological interventions, including psychological methods within the scope of psychotherapeutic or psychosomatic mechanism of action (e.g. cognitive behavioural, cognitive, family systems or systemic, psycho-dynamic, or other, e.g. supportive, relaxation, or biofeedback), which were aimed at improving psychological and psychosocial outcomes (e.g. quality of life, levels of stress or distress, psychopathology, etc.), adaptation to disease management and physiological outcomes. Three authors were involved in selecting the eligible studies and two of these authors assessed their risk of bias. The review includes 16 studies (eight new studies included in this update) representing data from 556 participants. Studies are diverse in their design and their methods. They

  18. "Bong lung" in cystic fibrosis: a case report

    Directory of Open Access Journals (Sweden)

    Hauser Jenny

    2010-11-01

    Full Text Available Abstract Introduction Marijuana or "bong" lung has been recently described. Subjects typically develop large peripheral paraseptal lung bullae and are predisposed to spontaneous pneumothoraces. The underlying mechanism for bullae formation is uncertain, but probably relates to direct lung toxicity and repeated barotrauma as the smoker performs frequent valsalva manoeuvres in an attempt to derive a greater drug effect. Case presentation We describe a case of probable "bong lung" occurring in a 23-year-old Caucasian man with cystic fibrosis who had a history of recurrent pneumothoraces and unusual findings on sputum cytology. Conclusion Our case highlights the importance of questioning young adult cystic fibrosis patients about illicit drug use and the utility of sputum cytology and computed tomography scanning when patients present with pneumothoraces and deteriorations in clinical status.

  19. [Inhaled treatments in cystic fibrosis: what's new in 2013?].

    Science.gov (United States)

    Dubus, J-C; Bassinet, L; Chedevergne, F; Delaisi, B; Desmazes-Dufeu, N; Reychler, G; Vecellio, L

    2014-04-01

    In the past few years some new inhaled drugs and inhalation devices have been proposed for the treatment of cystic fibrosis. Breath-controlled nebulizers allow increased pulmonary deposition, with a lower variability and a shorter delivery time. The new dry powder formulations of tobramycin, colistine and mannitol require a change in the inhalation technique which must be slow and deep. In the field of the inhaled mucolytic drugs, hypertonic saline and mannitol have an indication in some patients. With regard to antibiotics, dry-powder tobramycin and colistine can be substituted for the same drug delivered by nebulization. Nebulized aztreonam needs more studies to determine its place. These new treatments represent a definite advance for cystic fibrosis patients and need to be known by all practitioners. Their position in our therapeutic arsenal remains to be accurately defined. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  20. Vitamin D bioavailability in cystic fibrosis: a cause for concern?

    Science.gov (United States)

    Mailhot, Geneviève

    2012-05-01

    Despite the inclusion of extra vitamin D in their regimen of fat-soluble vitamin supplementation, cystic fibrosis patients remain chronically depleted of vitamin D. The persistence of suboptimal vitamin D status is often blamed on the maldigestion and malabsorption of fat. However, the mitigated success of recent clinical trials with high-dose vitamin D supplementation suggests that vitamin D bioavailability might be impaired in these patients. Given the growing understanding of the importance of this vitamin in the regulation of multiple biological functions beyond skeletal health, the present review analyzes the current literature by addressing each step of vitamin D metabolism and action in the context of this life-limiting pathology. In addition, it highlights the importance of vitamin D in relation to organs and or conditions affected by cystic fibrosis. © 2012 International Life Sciences Institute.

  1. Antioxidant supplementation for lung disease in cystic fibrosis

    DEFF Research Database (Denmark)

    Ciofu, Oana; Lykkesfeldt, Jens

    2014-01-01

    BACKGROUND: Airway infection leads to progressive damage of the lungs in cystic fibrosis and oxidative stress has been implicated in the etiology. Supplementation of antioxidant micronutrients (vitamin E, vitamin C, ß-carotene and selenium) or glutathione may therefore potentially help maintain...... COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data and assessed the risk of bias in the included studies. We contacted trial investigators to obtain missing information. Primary outcomes are lung function and quality of life; secondary outcomes are oxidative stress...... or by inhalation) appears to improve lung function in some cases and decrease oxidative stress; however, due to the very intensive antibiotic treatment and other treatments that cystic fibrosis patients receive, the beneficial effect of antioxidants is very difficult to assess in patients with chronic infection...

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

    Science.gov (United States)

    Santos, V; Cardoso, A V; Lopes, C; Azevedo, P; Gamboa, F; Amorim, A

    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. Evaluate the adult population with CF, comparing patients who were diagnosed before and after 18 years of age. 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. 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. 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. Copyright © 2016 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

  3. Aquagenic Wrinkling of the Palms in Patients with Cystic Fibrosis

    DEFF Research Database (Denmark)

    Kaiser, H; Brustad, N; Pressler, T

    2018-01-01

    Aquagenic wrinkling of the palms (AWP) is a condition characterized by oedema, confluent white papules and excessive wrinkling of the palms after few minutes exposure to water. The phenomenon may be associated with pain, numbness and pruritus1,2. It was first noticed and described in 1974 in chil...... in children with cystic fibrosis (CF) by a paediatrician R.B. Elliott3. This article is protected by copyright. All rights reserved....

  4. Adherence to treatment in adolescents with cystic fibrosis

    DEFF Research Database (Denmark)

    Bucks, Romola S.; Hawkins, Katharine; Skinner, T. C.

    2009-01-01

    ObjectivesThis study was conducted to explore the relationships between illness perceptions, emotional representations, treatment beliefs and reported adherence in adolescents with cystic fibrosis (CF). MethodsThirty-eight adolescents completed questionnaires assessing their perceptions of CF, be...... CF as a chronic condition. ConclusionsThe findings provide preliminary support for the self-regulatory model, using the necessity-concerns framework to operationalize treatment beliefs, in explaining adherence to treatment in adolescents with CF....

  5. Improving care at cystic fibrosis centers through quality improvement.

    Science.gov (United States)

    Kraynack, Nathan C; McBride, John T

    2009-10-01

    Quality improvement (QI) using a clinical microsystems approach provides cystic fibrosis (CF) centers the opportunity to make a significant positive impact on the health of their patients. The availability of center-specific outcomes data and the support of the Cystic Fibrosis Foundation are important advantages for these quality improvement efforts. This article illustrates how the clinical microsystems methodology can improve care delivery and outcomes by describing the gradual application of quality improvement principles over the past 5 years by the CF team at the Lewis Walker Cystic Fibrosis Center at Akron Children's Hospital in Akron, Ohio. Using the example of a project to improve the pulmonary function of the pediatric patients at our center as a framework, we describe the QI process from the initial team-building phase, through the assessment of care processes, standardization of care, and developing a culture of continuous improvement. We outline how enthusiastic commitment from physician leadership, clinical managers and central administration, the availability of coaches, and an appreciation of the importance of measurement, patient involvement, communication, and standardization are critical components for successful process improvement. Copyright Thieme Medical Publishers.

  6. Anaesthesia for parturients with severe cystic fibrosis: a case series.

    LENUS (Irish Health Repository)

    Deighan, M

    2014-02-01

    Cystic fibrosis affects 1 in 1600-2500 live births and is inherited in an autosomal recessive manner. It primarily involves the respiratory, gastrointestinal and reproductive tracts, with impaired clearance of, and obstruction by, increasingly viscous secretions. Severe respiratory disease, diabetes and gastro-oesophageal reflux may result. Improvements in medical management and survival of cystic fibrosis patients means more are committing to pregnancies. Although guidance for anaesthesia in this patient group is available, management and outcome data associated with more severe cases are sparse. Patients with severe cystic fibrosis require multidisciplinary input and should be managed in a tertiary referral centre. Close monitoring of respiratory function and preoperative optimisation during pregnancy are mandatory. The risk of preterm labour and delivery is increased. Pregnancy and delivery can be managed successfully, even in patients with FEV1 <40% predicted. Neuraxial anaesthesia and analgesia should be the technique of choice for delivery. Postoperative care should be carried out in a critical care setting with the provision of postoperative ventilation if necessary.

  7. Cystic Fibrosis Gene Therapy in the UK and Elsewhere

    Science.gov (United States)

    Pytel, Kamila M.; Alton, Eric W.F.W.

    2015-01-01

    Abstract The cystic fibrosis transmembrane conductance regulator (CFTR) gene was identified in 1989. This opened the door for the development of cystic fibrosis (CF) gene therapy, which has been actively pursued for the last 20 years. Although 26 clinical trials involving approximately 450 patients have been carried out, the vast majority of these trials were short and included small numbers of patients; they were not designed to assess clinical benefit, but to establish safety and proof-of-concept for gene transfer using molecular end points such as the detection of recombinant mRNA or correction of the ion transport defect. The only currently published trial designed and powered to assess clinical efficacy (defined as improvement in lung function) administered AAV2-CFTR to the lungs of patients with CF. The U.K. Cystic Fibrosis Gene Therapy Consortium completed, in the autumn of 2014, the first nonviral gene therapy trial designed to answer whether repeated nonviral gene transfer (12 doses over 12 months) can lead to clinical benefit. The demonstration that the molecular defect in CFTR can be corrected with small-molecule drugs, and the success of gene therapy in other monogenic diseases, is boosting interest in CF gene therapy. Developments are discussed here. PMID:25838137

  8. Exhaled nitric oxide in paediatric asthma and cystic fibrosis.

    Science.gov (United States)

    Lundberg, J O; Nordvall, S L; Weitzberg, E; Kollberg, H; Alving, K

    1996-01-01

    Nitric oxide (NO) is present in exhaled air of humans. This NO is mostly produced in the upper airways, whereas basal NO excretion in the lower airways is low. Children with Kartagener's syndrome have an almost total lack of NO in nasally derived air, whereas adult asthmatics have increased NO in orally exhaled air. NO excretion was measured in the nasal cavity and in orally exhaled air in 19 healthy children, in 36 age matched subjects with asthma, and in eight children with cystic fibrosis. NO levels in orally exhaled air were similar in controls and in children with cystic fibrosis, at 4.8 (SD 1.2) v 5.8 (0.8) parts per billion (ppb), but were increased in asthmatic children who were untreated or were being treated only with low doses of inhaled steroids (13.8 (2.5) ppb). Nasal NO levels were reduced by about 70% in children with cystic fibrosis compared to controls and asthmatics. Measurements of airway NO release in different parts of the airways may be useful in non-invasive diagnosis and monitoring of inflammatory airway diseases. PMID:8984919

  9. Personalized medicine for cystic fibrosis: establishing human model systems.

    Science.gov (United States)

    Mou, Hongmei; Brazauskas, Karissa; Rajagopal, Jayaraj

    2015-10-01

    With over 1,500 identifiable mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that result in distinct functional and phenotypical abnormalities, it is virtually impossible to perform randomized clinical trials to identify the best therapeutics for all patients. Therefore, a personalized medicine approach is essential. The only way to realistically accomplish this is through the development of improved in vitro human model systems. The lack of a readily available and infinite supply of human CFTR-expressing airway epithelial cells is a key bottleneck. We propose that a concerted two-pronged approach is necessary for patient-specific cystic fibrosis research to continue to prosper and realize its potential: (1) more effective culture and differentiation conditions for growing primary human airway and nasal epithelial cells and (2) the development of collective protocols for efficiently differentiating disease- and patient-specific induced pluripotent stem cells (iPSC) into pure populations of adult epithelial cells. Ultimately, we need a personalized human model system for cystic fibrosis with the capacity for uncomplicated bankability, widespread availability, and universal applicability for patient-specific disease modeling, novel pharmacotherapy investigation and screening, and readily executable genetic modification. © 2015 Wiley Periodicals, Inc.

  10. Association of body mass index with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Q.; Li, T. [Department of Respirology, Qilu Hospital of Shandong University, Jinan, Shandong Province (China); Li, J.C. [Neurosurgical Intensive Care Unit, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province (China); Li, Y. [Department of Respirology, Qilu Hospital of Shandong University, Jinan, Shandong Province (China)

    2015-07-10

    The objective of this observational, multicenter study was to evaluate the association of body mass index (BMI) with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis. A total of 339 patients (197 females, 142 males) diagnosed with non-cystic fibrosis bronchiectasis by high-resolution computed tomography were classified into four groups: underweight (BMI<18.5 kg/m{sup 2}), normal weight (18.5≤BMI<25.0 kg/m{sup 2}), overweight (25.0≤BMI<30.0 kg/m{sup 2}), and obese (BMI≥30.0 kg/m{sup 2}). Clinical variables expressing disease severity were recorded, and acute exacerbations, hospitalizations, and survival rates were estimated during the follow-up period. The mean BMI was 21.90 kg/m{sup 2}. The underweight group comprised 28.61% of all patients. BMI was negatively correlated with acute exacerbations, C-reactive protein, erythrocyte sedimentation rate, radiographic extent of bronchiectasis, and chronic colonization by P. aeruginosa and positively correlated with pulmonary function indices. BMI was a significant predictor of hospitalization risk independent of relevant covariates. The 1-, 2-, 3-, and 4-year cumulative survival rates were 94%, 86%, 81%, and 73%, respectively. Survival rates decreased with decreasing BMI (χ{sup 2}=35.16, P<0.001). The arterial carbon dioxide partial pressure, inspiratory capacity, age, BMI, and predicted percentage of forced expiratory volume in 1 s independently predicted survival in the Cox proportional hazard model. In conclusion, an underweight status was highly prevalent among patients with non-cystic fibrosis bronchiectasis. Patients with a lower BMI were prone to developing more acute exacerbations, worse pulmonary function, amplified systemic inflammation, and chronic colonization by P. aeruginosa. BMI was a major determinant of hospitalization and death risks. BMI should be considered in the routine assessment of patients with non-cystic fibrosis bronchiectasis.

  11. Association of body mass index with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis

    International Nuclear Information System (INIS)

    Qi, Q.; Li, T.; Li, J.C.; Li, Y.

    2015-01-01

    The objective of this observational, multicenter study was to evaluate the association of body mass index (BMI) with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis. A total of 339 patients (197 females, 142 males) diagnosed with non-cystic fibrosis bronchiectasis by high-resolution computed tomography were classified into four groups: underweight (BMI<18.5 kg/m 2 ), normal weight (18.5≤BMI<25.0 kg/m 2 ), overweight (25.0≤BMI<30.0 kg/m 2 ), and obese (BMI≥30.0 kg/m 2 ). Clinical variables expressing disease severity were recorded, and acute exacerbations, hospitalizations, and survival rates were estimated during the follow-up period. The mean BMI was 21.90 kg/m 2 . The underweight group comprised 28.61% of all patients. BMI was negatively correlated with acute exacerbations, C-reactive protein, erythrocyte sedimentation rate, radiographic extent of bronchiectasis, and chronic colonization by P. aeruginosa and positively correlated with pulmonary function indices. BMI was a significant predictor of hospitalization risk independent of relevant covariates. The 1-, 2-, 3-, and 4-year cumulative survival rates were 94%, 86%, 81%, and 73%, respectively. Survival rates decreased with decreasing BMI (χ 2 =35.16, P<0.001). The arterial carbon dioxide partial pressure, inspiratory capacity, age, BMI, and predicted percentage of forced expiratory volume in 1 s independently predicted survival in the Cox proportional hazard model. In conclusion, an underweight status was highly prevalent among patients with non-cystic fibrosis bronchiectasis. Patients with a lower BMI were prone to developing more acute exacerbations, worse pulmonary function, amplified systemic inflammation, and chronic colonization by P. aeruginosa. BMI was a major determinant of hospitalization and death risks. BMI should be considered in the routine assessment of patients with non-cystic fibrosis bronchiectasis

  12. Association of body mass index with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis

    Directory of Open Access Journals (Sweden)

    Q. Qi

    2015-08-01

    Full Text Available The objective of this observational, multicenter study was to evaluate the association of body mass index (BMI with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis. A total of 339 patients (197 females, 142 males diagnosed with non-cystic fibrosis bronchiectasis by high-resolution computed tomography were classified into four groups: underweight (BMI<18.5 kg/m2, normal weight (18.5≤BMI<25.0 kg/m2, overweight (25.0≤BMI<30.0 kg/m2, and obese (BMI≥30.0 kg/m2. Clinical variables expressing disease severity were recorded, and acute exacerbations, hospitalizations, and survival rates were estimated during the follow-up period. The mean BMI was 21.90 kg/m2. The underweight group comprised 28.61% of all patients. BMI was negatively correlated with acute exacerbations, C-reactive protein, erythrocyte sedimentation rate, radiographic extent of bronchiectasis, and chronic colonization by P. aeruginosa and positively correlated with pulmonary function indices. BMI was a significant predictor of hospitalization risk independent of relevant covariates. The 1-, 2-, 3-, and 4-year cumulative survival rates were 94%, 86%, 81%, and 73%, respectively. Survival rates decreased with decreasing BMI (χ2=35.16, P<0.001. The arterial carbon dioxide partial pressure, inspiratory capacity, age, BMI, and predicted percentage of forced expiratory volume in 1 s independently predicted survival in the Cox proportional hazard model. In conclusion, an underweight status was highly prevalent among patients with non-cystic fibrosis bronchiectasis. Patients with a lower BMI were prone to developing more acute exacerbations, worse pulmonary function, amplified systemic inflammation, and chronic colonization by P. aeruginosa. BMI was a major determinant of hospitalization and death risks. BMI should be considered in the routine assessment of patients with non-cystic fibrosis bronchiectasis.

  13. Airway Clearance Devices for Cystic Fibrosis

    Science.gov (United States)

    2009-01-01

    Executive Summary Objective The purpose of this evidence-based analysis is to examine the safety and efficacy of airway clearance devices (ACDs) for cystic fibrosis and attempt to differentiate between devices, where possible, on grounds of clinical efficacy, quality of life, safety and/or patient preference. Background Cystic fibrosis (CF) is a common, inherited, life-limiting disease that affects multiple systems of the human body. Respiratory dysfunction is the primary complication and leading cause of death due to CF. CF causes abnormal mucus secretion in the airways, leading to airway obstruction and mucus plugging, which in turn can lead to bacterial infection and further mucous production. Over time, this almost cyclical process contributes to severe airway damage and loss of respiratory function. Removal of airway secretions, termed airway clearance, is thus an integral component of the management of CF. A variety of methods are available for airway clearance, some requiring mechanical devices, others physical manipulation of the body (e.g. physiotherapy). Conventional chest physiotherapy (CCPT), through the assistance of a caregiver, is the current standard of care for achieving airway clearance, particularly in young patients up to the ages of six or seven. CF patients are, however, living much longer now than in decades past. The median age of survival in Canada has risen to 37.0 years for the period of 1998-2002 (5-year window), up from 22.8 years for the 5-year window ending in 1977. The prevalence has also risen accordingly, last recorded as 3,453 in Canada in 2002, up from 1,630 in 1977. With individuals living longer, there is a greater need for independent methods of airway clearance. Airway Clearance Devices There are at least three classes of airway clearance devices: positive expiratory pressure devices (PEP), airway oscillating devices (AOD; either handheld or stationary) and high frequency chest compression (HFCC)/mechanical percussion (MP

  14. Cystic Fibrosis Transmembrane Regulator Modulators: Implications for the Management of Depression and Anxiety in Cystic Fibrosis.

    Science.gov (United States)

    Talwalkar, Jaideep S; Koff, Jonathan L; Lee, Hochang B; Britto, Clemente J; Mulenos, Arielle M; Georgiopoulos, Anna M

    Individuals with cystic fibrosis (CF) are at high risk for depression and anxiety, which are associated with worse medical outcomes. Novel therapies for CF hold great promise for improving physical health, but the effects of these therapies on mental health remain poorly understood. This review aims to familiarize psychiatrists with the potential effect of novel CF therapies on depression and anxiety. We discuss novel therapies that directly target the mutant CF protein, the CF transmembrane regulator (CFTR), which are called CFTR modulators. We summarize depression and anxiety screening and treatment guidelines under implementation in accredited CF centers. Case vignettes highlight the complexities of caring for individuals with CF with comorbid depression and anxiety, including patients experiencing worsening depression and anxiety proximate to initiation of CFTR modulator therapy, and management of drug-drug interactions. Although CFTR modulator therapies provide hope for improving clinical outcomes, worsening depression and anxiety occurs in some patients when starting these novel agents. This phenomenon may be multifactorial, with hypothesized contributions from CFTR modulator-psychotropic medication interactions, direct effects of CFTR modulators on central nervous system function, the psychologic effect of starting a potentially life-altering drug, and typical triggers of depression and anxiety such as stress, pain, and inflammation. The medical and psychiatric complexity of many individuals with CF warrants more direct involvement of mental health specialists on the multidisciplinary CF team. Inclusion of mental health variables in patients with CF registries will facilitate further examination at an epidemiologic level. Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

  15. Risk factors for mortality before age 18 years in cystic fibrosis.

    Science.gov (United States)

    McColley, Susanna A; Schechter, Michael S; Morgan, Wayne J; Pasta, David J; Craib, Marcia L; Konstan, Michael W

    2017-07-01

    Understanding early-life risk factors for childhood death in cystic fibrosis (CF) is important for clinical care, including the identification of effective interventions. Data from the Epidemiologic Study of Cystic Fibrosis (ESCF) collected 1994-2005 were linked with the Cystic Fibrosis Foundation Patient Registry (CFFPR) demographic and mortality data from 2013. Inclusion criteria were ≥1 visit annually at age 3-5 years and ≥1 FEV 1 measurement at age 6-8 years. Demographic data, nutritional parameters, pulmonary signs and symptoms, microbiology, and FEV 1 were evaluated as risk factors for death before age 18 years. Multivariable Cox proportional hazards regression was used to model the simultaneous effects of risk factors associated with death before age 18 years. Among 5365 patients enrolled in ESCF who met inclusion criteria, 3880 (72%) were linked to the CFFPR. Among these, 191 (5.7%) died before age 18 years; median age at death was 13.4 ± 3.1 years. Multivariable regression showed clubbing, crackles, female sex, unknown CFTR genotype, minority race or ethnicity, Medicaid insurance (a proxy of low socioeconomic status), Pseudomonas aeruginosa on 2 or more cultures, and weight-for-age <50th percentile were significant risk factors for death regardless of inclusion of FEV 1 at age 6-8 years in the model. We identified multiple risk factors for childhood death of patients with CF, all of which remained important after incorporating FEV 1 at age 6-8 years. Among the factors identified were the presence of clubbing or crackles at age 3-5 years, signs which are not routinely collected in registries. © 2017 Wiley Periodicals, Inc.

  16. Comparative genomics of non-pseudomonal bacterial species colonising paediatric cystic fibrosis patients

    Directory of Open Access Journals (Sweden)

    Kate L. Ormerod

    2015-09-01

    Full Text Available The genetic disorder cystic fibrosis is a life-limiting condition affecting ∼70,000 people worldwide. Targeted, early, treatment of the dominant infecting species, Pseudomonas aeruginosa, has improved patient outcomes; however, there is concern that other species are now stepping in to take its place. In addition, the necessarily long-term antibiotic therapy received by these patients may be providing a suitable environment for the emergence of antibiotic resistance. To investigate these issues, we employed whole-genome sequencing of 28 non-Pseudomonas bacterial strains isolated from three paediatric patients. We did not find any trend of increasing antibiotic resistance (either by mutation or lateral gene transfer in these isolates in comparison with other examples of the same species. In addition, each isolate contained a virulence gene repertoire that was similar to other examples of the relevant species. These results support the impaired clearance of the CF lung not demanding extensive virulence for survival in this habitat. By analysing serial isolates of the same species we uncovered several examples of strain persistence. The same strain of Staphylococcus aureus persisted for nearly a year, despite administration of antibiotics to which it was shown to be sensitive. This is consistent with previous studies showing antibiotic therapy to be inadequate in cystic fibrosis patients, which may also explain the lack of increasing antibiotic resistance over time. Serial isolates of two naturally multi-drug resistant organisms, Achromobacter xylosoxidans and Stenotrophomonas maltophilia, revealed that while all S. maltophilia strains were unique, A. xylosoxidans persisted for nearly five years, making this a species of particular concern. The data generated by this study will assist in developing an understanding of the non-Pseudomonas species associated with cystic fibrosis.

  17. Early treatment with inhaled antibiotics postpones next occurrence of Achromobacter in cystic fibrosis

    DEFF Research Database (Denmark)

    Wang, Mikala; Ridderberg, W; Hansen, Christine Rønne

    2013-01-01

    In this nationwide retrospective study, we analysed species distribution, antimicrobial susceptibility and time to next occurrence of Achromobacter in Danish cystic fibrosis (CF) patients from 2000 to 2011....

  18. Deposição pulmonar de tobramicina inalatória antes e após fisioterapia respiratória e uso de salbutamol inalatório em pacientes com fibrose cística colonizados por Pseudomonas aeruginosa Pulmonary deposition of inhaled tobramycin prior to and after respiratory therapy and use of inhaled albuterol in cystic fibrosis patients colonized with Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Milena Baptistella Grotta

    2009-01-01

    Full Text Available OBJETIVO: Avaliar se a fisioterapia respiratória seguida do uso de salbutamol inalatório modifica a deposição pulmonar de tobramicina inalatória em pacientes com fibrose cística (FC e se a deposição pulmonar apresenta correlação com a gravidade da doença ou com o genótipo. MÉTODOS: Um estudo prospectivo foi realizado com pacientes com FC maiores de 6 anos e colonizados por Pseudomonas aeruginosa. Os critérios de exclusão foram exacerbação pulmonar, mudança terapêutica entre as fases do estudo e FEV1 OBJECTIVE: To evaluate whether respiratory therapy followed by the use of inhaled albuterol modifies the pulmonary deposition of inhaled tobramycin in patients with cystic fibrosis (CF and whether pulmonary deposition correlates with disease severity or genotype. METHODS: A prospective study was carried out including patients with CF older than 6 years of age and colonized with Pseudomonas aeruginosa. Exclusion criteria were pulmonary exacerbation, changes in therapy between the study phases and FEV1 < 25%. All patients were submitted to pulmonary scintigraphy by means of a scintillation camera equipped with a low energy all purpose collimator in order to evaluate drug penetration following the administration of inhaled 99mTc-tobramycin, as well as to pulmonary perfusion with 99mTc-macroaggregated albumin (phase 1. One month later, the same procedure was performed following respiratory therapy and administration of inhaled albuterol (phase 2. RESULTS: We included 24 patients (12 males aged 5-27 years (mean ± SD: 12.85 ± 6.64 years. The Shwachman score (SS was excellent/good in 8 patients, moderate/fair in 16 and poor in 0. Genotyping revealed that 7 patients were ΔF508 homozygotes, 13 were ΔF508 heterozygotes; and 4 presented other mutations. In all patients, lung deposition of tobramycin decreased in phase 2, especially in those with moderate/fair SS (p = 0.017 and in heterozygotes (p = 0.043. CONCLUSIONS: The use of a

  19. Non-invasive measurement of liver and pancreas fibrosis in patients with cystic fibrosis.

    Science.gov (United States)

    Friedrich-Rust, Mireen; Schlueter, Nina; Smaczny, Christina; Eickmeier, Olaf; Rosewich, Martin; Feifel, Kirstin; Herrmann, Eva; Poynard, Thierry; Gleiber, Wolfgang; Lais, Christoph; Zielen, Stefan; Wagner, Thomas O F; Zeuzem, Stefan; Bojunga, Joerg

    2013-09-01

    Patients with cystic fibrosis (CF) have a relevant morbidity and mortality caused by CF-related liver-disease. While transient elastography (TE) is an established elastography method in hepatology centers, Acoustic-Radiation-Force-Impulse (ARFI)-Imaging is a novel ultrasound-based elastography method which is integrated in a conventional ultrasound-system. The aim of the present study was to evaluate the prevalence of liver-fibrosis in patients with CF using TE, ARFI-imaging and fibrosis blood tests. 106 patients with CF were prospectively included in the present study and received ARFI-imaging of the left and right liver-lobe, ARFI of the pancreas TE of the liver and laboratory evaluation. The prevalence of liver-fibrosis according to recently published best practice guidelines for CFLD was 22.6%. Prevalence of significant liver-fibrosis assessed by TE, ARFI-right-liver-lobe, ARFI-left-liver-lobe, Fibrotest, Fibrotest-corrected-by-haptoglobin was 17%, 24%, 40%, 7%, and 16%, respectively. The best agreement was found for TE, ARFI-right-liver-lobe and Fibrotest-corrected-by-haptoglobin. Patients with pancreatic-insufficiency had significantly lower pancreas-ARFI-values as compared to patients without. ARFI-imaging and TE seem to be promising non-invasive methods for detection of liver-fibrosis in patients with CF. Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  20. Ursodeoxycholic acid for cystic fibrosis-related liver disease.

    Science.gov (United States)

    Cheng, Katharine; Ashby, Deborah; Smyth, Rosalind L

    2017-09-11

    Abnormal biliary secretion leads to the thickening of bile and the formation of plugs within the bile ducts; the consequent obstruction and abnormal bile flow ultimately results in the development of cystic fibrosis-related liver disease. This condition peaks in adolescence with up to 20% of adolescents with cystic fibrosis developing chronic liver disease. Early changes in the liver may ultimately result in end-stage liver disease with people needing transplantation. One therapeutic option currently used is ursodeoxycholic acid. This is an update of a previous review. To analyse evidence that ursodeoxycholic acid improves indices of liver function, reduces the risk of developing chronic liver disease and improves outcomes in general in cystic fibrosis. We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also contacted drug companies and searched online trial registries.Date of the most recent search of the Group's trials register: 09 April 2017. Randomised controlled trials of the use of ursodeoxycholic acid for at least three months compared with placebo or no additional treatment in people with cystic fibrosis. Two authors independently assessed trial eligibility and quality. The authors used GRADE to assess the quality of the evidence. Twelve trials have been identified, of which four trials involving 137 participants were included; data were only available from three of the trials (118 participants) since one cross-over trial did not report appropriate data. The dose of ursodeoxycholic acid ranged from 10 to 20 mg/kg/day for up to 12 months. The complex design used in two trials meant that data could only be analysed for subsets of participants. There was no significant difference in weight change, mean difference -0.90 kg (95% confidence interval -1.94 to 0.14) based on 30

  1. Antibiotic-resistant obligate anaerobes during exacerbations of cystic fibrosis patients.

    Science.gov (United States)

    Worlitzsch, D; Rintelen, C; Böhm, K; Wollschläger, B; Merkel, N; Borneff-Lipp, M; Döring, G

    2009-05-01

    Pseudomonas aeruginosa and Staphylococcus aureus are thought to cause the majority of lung infections in patients with cystic fibrosis (CF). However, other bacterial pathogens may contribute to the pathophysiology of lung disease. Here, obligate anaerobes were identified in a cross-sectional study, and cell numbers and antibiotic susceptibilities of facultative and obligate anaerobes from 114 sputum samples from nine children and 36 adults with CF were determined. Furthermore, in 12 CF patients, we investigated whether conventional intravenous antibiotic therapy, administered during acute exacerbations, would affect the numbers of obligate anaerobes. Fifteen genera of obligate anaerobes were identified in 91% of the CF patients. Cell numbers (mean: 2.2 x 10(7) +/- standard deviation 6.9 x 10(7) CFU/mL of sputum sample) were comparable to those of P. aeruginosa and S. aureus. Staphylococcus saccharolyticus and Peptostreptococcus prevotii were most prevalent. Infection with P. aeruginosa did not increase the likelihood that obligate anaerobes are present in sputum specimens. Single obligate anaerobic species persisted for up to 11 months in sputum plugs in vivo. Patients with and without obligate anaerobes in sputum specimens did not differ in lung function. Intravenous therapy directed against P. aeruginosa during acute exacerbations increased lung function, but did not reduce the numbers of obligate anaerobes. Obligate anaerobic species differed widely in their patterns of resistance against meropenem, piperacillin-tazobactam, clindamycin, metronidazole and ceftazidime. In 58% of patients with acute exacerbations, obligate anaerobes were detected that were resistant to the antibiotics used for treatment. Antibiotic therapy, optimized to target anaerobes in addition to P. aeruginosa, may improve the management of CF lung disease.

  2. Effectiveness of tobramycin conjugated to iron oxide nanoparticles in treating infection in cystic fibrosis

    Science.gov (United States)

    Brandt, Yekaterina I.; Armijo, Leisha M.; Rivera, Antonio C.; Plumley, John B.; Cook, Nathaniel C.; Smolyakov, Gennady A.; Smyth, Hugh D. C.; Osiński, Marek

    2013-02-01

    Cystic fibrosis (CF) is an inherited childhood-onset life-shortening disease. It is characterized by increased respiratory production, leading to airway obstruction, chronic lung infection and inflammatory reactions. The most common bacteria causing persisting infections in people with CF is Pseudomonas aeruginosa. Superparamagnetic Fe3O4 iron oxide nanoparticles (NPs) conjugated to the antibiotic (tobramycin), guided by a gradient of the magnetic field or subjected to an oscillating magnetic field, show promise in improving the drug delivery across the mucus and P. aeruginosa biofilm to the bacteria. The question remains whether tobramycin needs to be released from the NPs after the penetration of the mucus barrier in order to act upon the pathogenic bacteria. We used a zero-length 1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride (EDC) crosslinking agent to couple tobramycin, via its amine groups, to the carboxyl groups on Fe3O4 NPs capped with citric acid. The therapeutic efficiency of Fe3O4 NPs attached to the drug versus that of the free drug was investigated in P. aeruginosa culture.

  3. Siblings of children with cystic fibrosis: quality of life and the impact of illness.

    Science.gov (United States)

    Havermans, T; Wuytack, L; Deboel, J; Tijtgat, A; Malfroot, A; De Boeck, C; Proesmans, M

    2011-03-01

    To asses self-reported quality of life (QoL) and perception of impact of illness on siblings of children with cystic fibrosis (CF). The Child Health Questionnaire was used to assess QoL. The Sibling Perception Questionnaire was used to assess impact of illness. Siblings of children with CF (n= 39) rated their QoL higher than siblings of healthy children on most QoL domains (e.g. Physical Functioning, Behavior, Mental Health). Siblings older than the child with CF reported a higher impact of CF than younger siblings. Perceived impact of illness was higher when the child with CF had been hospitalized or was intermittent or chronically infected with Pseudomonas aeruginosa. Siblings of children with CF reported a good QoL. QoL and impact of illness were related to indices of CF severity. Insight into sibling-issues helps CF teams to provide family-oriented care. © 2010 Blackwell Publishing Ltd.

  4. Benchmark Evaluation of True Single Molecular Sequencing to Determine Cystic Fibrosis Airway Microbiome Diversity

    Directory of Open Access Journals (Sweden)

    Andrea Hahn

    2018-05-01

    Full Text Available Cystic fibrosis (CF is an autosomal recessive disease associated with recurrent lung infections that can lead to morbidity and mortality. The impact of antibiotics for treatment of acute pulmonary exacerbations on the CF airway microbiome remains unclear with prior studies giving conflicting results and being limited by their use of 16S ribosomal RNA sequencing. Our primary objective was to validate the use of true single molecular sequencing (tSMS and PathoScope in the analysis of the CF airway microbiome. Three control samples were created with differing amounts of Burkholderia cepacia, Pseudomonas aeruginosa, and Prevotella melaninogenica, three common bacteria found in cystic fibrosis lungs. Paired sputa were also obtained from three study participants with CF before and >6 days after initiation of antibiotics. Antibiotic resistant B. cepacia and P. aeruginosa were identified in concurrently obtained respiratory cultures. Direct sequencing was performed using tSMS, and filtered reads were aligned to reference genomes from NCBI using PathoScope and Kraken and unique clade-specific marker genes using MetaPhlAn. A total of 180–518 K of 6–12 million filtered reads were aligned for each sample. Detection of known pathogens in control samples was most successful using PathoScope. In the CF sputa, alpha diversity measures varied based on the alignment method used, but similar trends were found between pre- and post-antibiotic samples. PathoScope outperformed Kraken and MetaPhlAn in our validation study of artificial bacterial community controls and also has advantages over Kraken and MetaPhlAn of being able to determine bacterial strains and the presence of fungal organisms. PathoScope can be confidently used when evaluating metagenomic data to determine CF airway microbiome diversity.

  5. Pharmacokinetic variability of clarithromycin and differences in CYP3A4 activity in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Dalbøge, C S; Nielsen, X C; Dalhoff, K

    2014-01-01

    3A4-activity and clarithromycin metabolism was demonstrated (P cystic fibrosis patients may cause treatment failure. The Erythromycin Breath Test could be valuable in identifying cystic fibrosis patients in risk...

  6. Sodium and chlorine concentrations in mixed saliva of healthy and cystic fibrosis children

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez-Reyes, M. [Instituto Nacional de Investigaciones Nucleares, Mexico City (Mexico); Sanchez-Aguirre, F.J. [Instituto Mexicano del Seguro Social (Mexico). Dept. de Genetica

    1996-03-01

    Sodium and chlorine concentrations in mixed saliva were simultaneously measured by neutron activation analysis in nine normal children and in nine patients with cystic fibrosis. Sodium levels showed a significant difference (P < 0.01) between patients and controls. The concentration of chlorine was similar in both the control and the cystic fibrosis groups. (author).

  7. Short-term protein intake and stimulation of protein synthesis in stunted children with cystic fibrosis

    NARCIS (Netherlands)

    Geukers, Vincent G. M.; Oudshoorn, Johanna H.; Taminiau, Jan A. J. M.; van der Ent, Cornelis K.; Schilte, Piet; Ruiter, An F. C.; Ackermans, Mariëtte T.; Endert, Erik; Jonkers-Schuitema, Cora F.; Heymans, Hugo S. S.; Sauerwein, Hans P.

    2005-01-01

    Background: Stunted children with cystic fibrosis (CF) have less net protein anabolism than do children without CF, and the result is retarded growth in the CF patients. It is not known whether protein intake above that recommended by the Cystic Fibrosis Foundation would further stimulate whole-body

  8. False negative newborn screen and neonatal cholestasis in a premature child with cystic fibrosis

    NARCIS (Netherlands)

    Heidendael, J. F.; Tabbers, M. M.; de Vreede, I.

    2014-01-01

    Newborn screening for cystic fibrosis enables early diagnosis and treatment, leading to better outcomes for patients with cystic fibrosis. Although the sensitivity of several screening protocols is high, false negative screening results of the newborn patient still occur, which can lead to a

  9. Sodium and chlorine concentrations in mixed saliva of healthy and cystic fibrosis children

    International Nuclear Information System (INIS)

    Jimenez-Reyes, M.; Sanchez-Aguirre, F.J.

    1996-01-01

    Sodium and chlorine concentrations in mixed saliva were simultaneously measured by neutron activation analysis in nine normal children and in nine patients with cystic fibrosis. Sodium levels showed a significant difference (P < 0.01) between patients and controls. The concentration of chlorine was similar in both the control and the cystic fibrosis groups. (author)

  10. Clinical presentation of metabolic alkalosis in an adult patient with cystic fibrosis.

    Science.gov (United States)

    Sweetser, Lisel J; Douglas, James A; Riha, Renata L; Bell, Scott C

    2005-03-01

    In subtropical and tropical climates, dehydration is common in cystic fibrosis patients with respiratory exacerbations. This may lead to a clinical presentation of metabolic alkalosis with associated hyponatraemia and hypochloraemia. An adult cystic fibrosis patient who presented with a severe respiratory exacerbation accompanied by metabolic alkalosis is presented and the effects of volume correction are reported.

  11. Subclinical anaemia of chronic disease in adult patients with cystic fibrosis.

    LENUS (Irish Health Repository)

    O'connor, T M

    2012-02-03

    Patients with chronic hypoxaemia develop secondary polycythaemia that improves oxygen-carrying capacity. Therefore, normal haemoglobin and haematocrit values in the presence of chronic arterial hypoxaemia in cystic fibrosis constitute \\'relative anaemia\\'. We sought to determine the cause of this relative anaemia in patients with cystic fibrosis. We studied haematological indices and oxygen saturation in healthy volunteers (n=17) and in adult patients with cystic fibrosis (n=15). Patients with cystic fibrosis had lower resting arterial oxygen saturation when compared with normal volunteers (P<0.0001), and exercise led to a greater reduction in arterial oxygen saturation (P<0.0001). However, haemoglobin and haematocrit values in patients with cystic fibrosis did not significantly differ from normal volunteers. Serum iron (P=0.002), transferrin (P=0.02), and total iron-binding capacity (P=0.01) were lower in patients with cystic fibrosis. There were no significant differences in serum ferritin, percentage iron saturation, serum erythropoietin or red cell volume between the groups. The data presented demonstrate a characteristic picture of anaemia of chronic disease in adult patients with cystic fibrosis, except for normal haemoglobin and haematocrit values. Normal haemoglobin and haematocrit values in patients with cystic fibrosis appear to represent a combination of the effects of arterial hypoxaemia promoting polycythaemia, counterbalanced by chronic inflammation promoting anaemia of chronic disease.

  12. Epidemiological evaluation regarding the role of cystic fibrosis as a risk factor for child malnutrition.

    Science.gov (United States)

    Florescu, Laura; Paduraru, Dana Teodora Anton; Mîndru, Dana Elena; Temneanu, Oana Raluea; Petrariu, F D; Matei, Mioara Calipsoana

    2014-01-01

    Cystic fibrosis (CF) is the most common monogenic autosomal recessive disorder with progressive chronic evolution which is potentially lethal. Poor growth is a characteristic of children suffering from cystic fibrosis. A poor nutritional status is an independent risk factor for inadequate survival in cystic fibrosis and is associated with disease complications. The appropriate nutritional management is an important part of the treatment so that the patient with cystic fibrosis can achieve normal growth and development and maintain the best possible health status. A balanced diet supplemented with snacks high in fat and calories is necessary to increase the caloric intake in children with cystic fibrosis. Children with cystic fibrosis have higher caloric needs than healthy children of the same age and sex. Malnutrition in CF is multifactorial. Cystic fibrosis is a complex multisystem disorder affecting mainly the gastrointestinal tract and respiratory system. In the past, malnutrition was an inevitable consequence of disease progression, leading to poor growth, impaired respiratory muscle function, decreased exercise tolerance and immunological impairment. A positive association between body weight and height and survival has been widely reported. The energy requirements of patients with CF vary widely and generally increase with age and disease severity. Cystic fibrosis remains a paediatric disorder which is often underdiagnosed but which, if therapeutically managed properly (by means of drug therapy as well as by appropriate physiotherapy techniques), can lead to improved quality of life and, thus, to a bigger life expectancy.

  13. Vitamin E supplementation in people with cystic fibrosis.

    Science.gov (United States)

    Okebukola, Peter O; Kansra, Sonal; Barrett, Joanne

    2017-03-06

    People with cystic fibrosis are at an increased risk of fat-soluble vitamin deficiency including vitamin E. Vitamin E deficiency can cause a host of conditions such as haemolytic anaemia, cerebellar ataxia and cognitive difficulties. Vitamin E supplementation is widely recommended in cystic fibrosis and aims to ameliorate this deficiency. This is an updated version of the review. To determine the effects of any level of vitamin E supplementation on the frequency of vitamin E deficiency disorders in people with cystic fibrosis. We searched the Cochrane Group's Cystic Fibrosis Trials Register and also searched international trial registers for any ongoing clinical trials that were not identified during our register search.Date of last search of the Register: 10 October 2016. Date of last search of international trial registers: 15 February 2017. Randomised controlled trials and quasi-randomised controlled trials comparing any preparation of vitamin E supplementation to placebo or no supplement, regardless of dosage or duration. Two authors extracted outcome data from each study (published information) and assessed the risk of bias of each included study. Four studies with a total of 141 participants were included in the review, two of these were in children (aged six months to 14.5 years), and the other two did not specify participants' age. All studies used different formulations and doses of vitamin E for various durations of treatment (10 days to six months). Two studies compared the supplementation of fat-soluble as well as water-soluble formulations to no supplementation in different arms of the same study. A third study compared a water-soluble formulation to a placebo; and in the fourth study a fat-soluble formulation of vitamin E was assessed against placebo.At one month, three months and six months, water-soluble vitamin E significantly improved serum vitamin E levels compared with control: at one month, two studies, mean difference 17.66 (95% confidence

  14. Pancreatic enzyme replacement therapy for people with cystic fibrosis.

    Science.gov (United States)

    Somaraju, Usha Rani; Solis-Moya, Arturo

    2016-11-23

    Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review. To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 15 July 2016.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 22 July 2016. Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations. Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review. One

  15. Na and K dependence of the Na/K pump in cystic fibrosis fibroblasts.

    OpenAIRE

    Reznik, V M; Schneider, J A; Mendoza, S A

    1981-01-01

    The Na and K dependence of the Na/K pump was measured in skin fibroblasts from patients with cystic fibrosis and age/sex-matched controls. Under basal conditions, there was no difference between control and cystic fibrosis cells in protein per cell, intracellular Na and K content, or Na/K pump activity (measured as ouabain-sensitive 86Rb uptake). There was no difference in the Na dependence of the Na/K pump between cystic fibrosis cells and control cells. In cells from patients with cystic fi...

  16. Nutritional Assesment in Cystic Fibrosis Patients( Iran and Newzeland

    Directory of Open Access Journals (Sweden)

    V Moeeni

    2014-04-01

    Full Text Available Introduction: Patients with Cystic Fibrosis have increased risk of malnutrition. Early detection of nutritional deterioration enables prompt intervention and correction. The aims of this project were to: - Define the nutritional status of CF patients in Iran and New Zealand -    Compare and contrast the MacDonald Nutritional Screening tool  with the Australasian guidelines for Nutrition in Cystic Fibrosis -    Validate these results in comparison with patient’s evaluation by their CF clinical team.   Materials and Methods: 69 CF patients (2-18 years were assessed during routine outpatient visits over one year. Anthropometric measurements were obtained. Both tools were applied for each patient and the results compared to their clinical evaluation (as gold standard with calculation of specificity and sensitivity. Results: Under-nutrition was more frequent in Iranian than NZ patients (39% versus 0%, p=0.0001, whereas over-nutrition was more prevalent in NZ children (9% versus 17%, p=0.05. At the first visit, MacDonald and Australasian guidelines were able to recognize 77% and 61% of under-nourished Iranian patients, respectively. The mean sensitivity and specificity for all visits for the MacDonald tool were 83% & 73% (Iran and 65% & 86% (NZ. Sensitivity and specificity for the Australasian guidelines were 79% & 79% (Iran and 70% & 90% (NZ. Conclusions: Both tools successfully recognised patients at risk of malnutrition. The MacDonald tool had comparable sensitivity and specificity to that described previously, especially in Iranian patients. This tool may be helpful in recognizing at risk CF patients, particularly in developing countries with fewer resources. Key words: Iran, Cystic Fibrosis Patient, Newzeland, Nutritional Assesment.

  17. The Role of Computed Tomography in Monitoring Patients with Cystic Fibrosis

    International Nuclear Information System (INIS)

    Rybacka, Anna; Karmelita-Katulska, Katarzyna

    2016-01-01

    Cystic fibrosis is the most common lethal autosomal recessive disorder in the Caucasian population. Although the survival rate in patients constantly improves, lung damage is still the major cause of morbidity and mortality in patients with cystic fibrosis. In clinical practice, evaluation of patients’ pulmonary state is made by combination of monitoring of lung function and more directly by assessing the lung structure in imaging studies. Studies showed that computed tomography findings are more sensitive as compared to the pulmonary function tests. Computed tomography can identify a wide range of morphological abnormalities in patients with cystic fibrosis, such as bronchiectasis (which is progressive, irreversible and probably the most relevant structural change in cystic fibrosis) peribronchial thickening, mucous plugging and many other disorders that occur in the course of the disease. Computed tomography has a crucial role in the assessment of pulmonary damage over time, detecting complications and monitoring treatment effects in patients with cystic fibrosis

  18. Maintenance of nutritional status in patients with cystic fibrosis: new and emerging therapies

    Directory of Open Access Journals (Sweden)

    Kalnins D

    2012-06-01

    Full Text Available Daina Kalnins,1 Michael Wilschanski21Clinical Dietetics, Respiratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada; 2Pediatric Gastroenterology Unit, Hadassah University Hospitals, Jerusalem, IsraelAbstract: Poor clinical outcomes in cystic fibrosis are often associated with undernutrition. Normal growth and development should be achieved in cystic fibrosis, and nutritional counseling is paramount at all ages. Prevention and early detection of growth failure is the key to successful nutritional intervention. The advance in nutritional management is certainly one factor that has contributed to the improved survival in recent decades. This review outlines the major nutritional parameters in the management of the patient with cystic fibrosis, including recent advances in pancreatic enzyme replacement therapy and fat-soluble vitamin therapy. There are sections on complicated clinical situations which directly affect nutrition, for example, before and after lung transplantation, cystic fibrosis-related diabetes, and bone health.Keywords: cystic fibrosis, nutrition, fat-soluble vitamins, pancreatic enzymes

  19. Distinctly visible right upper lobe bronchus on the lateral chest: A clue to adolescent cystic fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Reinig, J.W.; Sanchez, F.W.; Thomason, D.M.; Gobien, R.P.

    1985-05-01

    Radiographic differentiation between cystic fibrosis and asthma presenting in teenagers and young adults can be difficult. Many patients with a late presentation of cystic fibrosis display minimal changes on a chest radiograph. However, a large majority (90%) of cystic fibrosis patients with an essentially normal PA chest radiograph will have a distinctly outlined orifice of right upper lobe bronchus on a lateral chest film as opposed to a small number of asthmatics (25%) or normal patients (18%). This observation correlates well with the pathologic finding that the initial pulmonary involvement in cystic fibrosis is typically in the right upper lobe in adolescents. Teenager or young adult patients presenting with a history of repeated respiratory infections, asthma-like symptoms and a distinctly visible right upper lobe bronchus on a lateral chest film should be sweat-tested to exclude cystic fibrosis.

  20. Within-Host Evolution of the Dutch High-Prevalent Pseudomonas aeruginosa Clone ST406 during Chronic Colonization of a Patient with Cystic Fibrosis

    DEFF Research Database (Denmark)

    Van Mansfeld, Rosa; De Been, Mark; Paganelli, Fernanda

    2016-01-01

    the MexE/F efflux pump, genes encoding the type six secretion system (T6SS) and type three secretion system (T3SS), which have also been previously implicated in adaptation of other P. aeruginosa strains during chronic infection of CF lungs. The observation that genetically different strains from...... genomic fragment only found in S2. Most SNPs and differentially expressed genes encoded proteins involved in metabolism, secretion and signal transduction or transcription. SNPs were identified in regulator genes mexT and exsA and coincided with differential gene expression of mexE and mexF, encoding......S during chronic colonization. These data suggest that the high-prevalent Dutch CF clone ST406 displays adaptation to the CF lung niche, which involves a limited number of mutations affecting regulators controlling biofilm formation and secretion and genes involved in metabolism. These genes could provide...

  1. Hepatocellular carcinoma complicating cystic fibrosis related liver disease.

    LENUS (Irish Health Repository)

    O'Donnell, D H

    2012-02-01

    Early diagnosis and treatment of the respiratory and gastrointestinal complications of cystic fibrosis (CF) have led to improved survival with many patients living beyond the fourth decade. Along with this increased life expectancy is the risk of further disease associated with the chronic manifestations of their condition. We report a patient with documented CF related liver disease for which he was under routine surveillance that presented with histologically proven hepatocellular carcinoma (HCC). It is important that physicians are aware of this association as increased vigilance may lead to earlier diagnosis and perhaps, a better outcome.

  2. Cystic fibrosis school for 10-year-olds

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke; Schiøtz, Peter Oluf

    2000-01-01

    the children about the respiratory system in CF. They take physiotherapi together and go to the swimmingpool. The dietician and the nurse teach the children about the digestive system in CF and they cook together. The children learn about genetics, liver problems, infertility etc from the doctor and the nurse......Compliance or rather lack of compliance has always been a problem when treating patients with cystic fibrosis. The patients tend to drop the treatment more or less if the treatment gets too complicated or laboured. We have attempted a systematical education of our patients in a CF school...

  3. Hypertonic saline for cystic fibrosis: worth its salt?

    Science.gov (United States)

    Goralski, Jennifer L; Donaldson, Scott H

    2014-06-01

    Airway dehydration in cystic fibrosis (CF) leads to chronic inflammation, ongoing infection and progressive lung disease. Restoration of airway hydration by inhalation of an osmotic agent (hypertonic saline) has been shown to be safe, effective and well-tolerated in adults with CF. Although the safety of hypertonic saline in infants and young children with CF has also been established, recent studies have reported inconclusive evidence about its efficacy. In this editorial, we discuss the evidence behind hypertonic saline use for adults, children and infants with CF.

  4. State of progress in treating cystic fibrosis respiratory disease

    Directory of Open Access Journals (Sweden)

    Flume Patrick A

    2012-08-01

    Full Text Available Abstract Since the discovery of the gene associated with cystic fibrosis (CF, there has been tremendous progress in the care of patients with this disease. New therapies have entered the market and are part of the standard treatment of patients with CF, and have been associated with marked improvement in survival. Now there are even more promising therapies directed at different components of the pathophysiology of this disease. In this review, our current knowledge of the pathophysiology of lung disease in patients with CF is described, along with the current treatment of CF lung disease, and the therapies in development that offer great promise to our patients.

  5. Life-threatening systemic symptoms in a cystic fibrosis patient

    OpenAIRE

    Gohy, Sophie; Froidure, Antoine; Lebecque, Patrick; ECFS

    2014-01-01

    Case report A 20-year-old male patient with cystic fibrosis (CF) (F508del/F508del, last FEV1: 92% predicted) was admitted for the sudden occurrence of high-grade fever, FEV1 drop (72% predicted) without increased cough, malaise, diffuse pain and generalized lymphadenopathies. Initial check-up revealed the presence of very recent bilateral hilar lymphadenopathies along with a marked inflammatory syndrome (WBC: 35,680/µl, neutrophils: 28,220/µl, CRP: 163mg/L). Within 24 hours, the patient devel...

  6. [Pancreatic infringement exocrine and endocrine in cystic fibrosis].

    Science.gov (United States)

    Kessler, L; Abély, M

    2016-12-01

    The exocrine pancreatic insufficiency affects more than 80% of cystic fibrosis (CF) infants. Pancreatic insufficiency is diagnosed by low levels of fecal elastase. An optimal caloric intake, a pancreatic enzyme treatment are the keys to maintain a good nutritional status. The fat soluble vitamins supplementation will be associated with pancreatic enzymes treatment and will be adapted to plasma levels. Iron and oligo-element deficiency such as zinc is common. The pancreatic enzymes function is not optimal in the proximal bowel: the intraluminal intestinal pH is low because of the absence of bicarbonate release by the pancreas. The use of proton pump inhibitors may improve the functionality of pancreatic enzymes treatment. New therapies such as ivacaftor in patients with a G551D mutation allows a weight gain in particular by restoring intestinal pH similar to controls. Lengthening of the life expectancy of patients with CF is accompanied by the emergence new aspects of the disease, especially diabetes, favored by pancreatic cystic fibrosis resulting in an anatomical destruction of pancreatic islets. Currently, diabetes affects a third of the patients after 20 years, and half after 30 years. Cystic fibrosis-related diabetes is a major factor of morbidity-mortality in all stages of the disease and is characterized by a preclinical phase of glucose intolerance particularly long reaching up to 10 years. Its pathophysiology combines a lack of insulin secretion, an insulin resistance secondary to chronic infection, and a decrease in the production of the GIP and GLP-1. The insulin secretion depending on the channel chlorine (Cystic Fibrosis Transmembrane conductance Regulator [CFTR]) activity at the membrane surface of insulin cell is reduced prior to the occurrence of pancreatic histological lesions. At the stage of diabetes, obtaining a normoglycemia by insulin treatment began very early allows to slow the decline of lung function and nutritional status. Given the silent

  7. Anabolic agent use in adults with cystic fibrosis.

    Science.gov (United States)

    Green, Heather D; Barry, Peter J; Jones, Andrew M

    2015-10-01

    The use of non-prescribed anabolic agents amongst non-athletes is increasing with young, adult males with cystic fibrosis (CF) in the highest risk demographic. There is evidence that anabolic agents increase weight and muscle mass in adults with a variety of catabolic conditions but there is no evidence for their use in hormone sufficient adults with CF. We report a case of anabolic agent use in a male adult with CF and review the clinical features of anabolic agent use with a focus on adults with CF. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. [Cystic Fibrosis Cloud database: An information system for storage and management of clinical and microbiological data of cystic fibrosis patients].

    Science.gov (United States)

    Prieto, Claudia I; Palau, María J; Martina, Pablo; Achiary, Carlos; Achiary, Andrés; Bettiol, Marisa; Montanaro, Patricia; Cazzola, María L; Leguizamón, Mariana; Massillo, Cintia; Figoli, Cecilia; Valeiras, Brenda; Perez, Silvia; Rentería, Fernando; Diez, Graciela; Yantorno, Osvaldo M; Bosch, Alejandra

    2016-01-01

    The epidemiological and clinical management of cystic fibrosis (CF) patients suffering from acute pulmonary exacerbations or chronic lung infections demands continuous updating of medical and microbiological processes associated with the constant evolution of pathogens during host colonization. In order to monitor the dynamics of these processes, it is essential to have expert systems capable of storing and subsequently extracting the information generated from different studies of the patients and microorganisms isolated from them. In this work we have designed and developed an on-line database based on an information system that allows to store, manage and visualize data from clinical studies and microbiological analysis of bacteria obtained from the respiratory tract of patients suffering from cystic fibrosis. The information system, named Cystic Fibrosis Cloud database is available on the http://servoy.infocomsa.com/cfc_database site and is composed of a main database and a web-based interface, which uses Servoy's product architecture based on Java technology. Although the CFC database system can be implemented as a local program for private use in CF centers, it can also be used, updated and shared by different users who can access the stored information in a systematic, practical and safe manner. The implementation of the CFC database could have a significant impact on the monitoring of respiratory infections, the prevention of exacerbations, the detection of emerging organisms, and the adequacy of control strategies for lung infections in CF patients. Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Serum concentrations of GM-CSF and G-CSF correlate with the Th1/Th2 cytokine response in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection

    DEFF Research Database (Denmark)

    Moser, Claus; Jensen, Peter Østrup; Pressler, Tacjana

    2005-01-01

    mobilizing monocytes and PMNs from the bone marrow, GM-CSF, G-CSF and IL-3 select subsets of dendritic cells, which subsequently induce distinct Th responses. Therefore, the present study examines the correlation between the mobilizing cytokines in serum and the Th responses. The IFN-gamma and IL-4...... production by peripheral blood mononuclear cells, and the concentrations of GM-CSF and G-CSF in serum as well as lung function, were determined in 37 CF patients with and 6 CF patients without chronic P. aeruginosa lung infection. The GM-CSF/G-CSF ratio correlated both with the IFN-gamma production and good...... lung function. In addition, an inverse correlation between IL-3 and IFN-gamma was observed. The results indicate involvement of endogenous GM-CSF, G-CSF and IL-3 in the skewed Th response in CF, and change to a Th1-dominated response might be achieved with GM-CSF treatment....

  10. Correlation between HRCT and pulmonary functional tests in cystic fibrosis

    International Nuclear Information System (INIS)

    Mastellari, Paola; Biggi, Simona; Lombardi, Alfonsa; Zompatori, Maurizio; Grzincich, Gianluigi; Pisi, Giovanna; Spaggiari, Cinzia

    2005-01-01

    Purpose. To compare the HRCT score by Oikonottlou and air trapping in expiratory scans with pulmonary functional tests and evaluate which radiological criteria are more useful to predict clinical impairment. Materials and methods. From January to September 2003, pulmonary HRCT study was performed in 37 patients (23 males), aged between 7 and 41 years, with cystic fibrosis. In the same day of CT examination they also received a complete functional evaluation. HRCT studies were evaluated by three radiologists blinded to the clinical data and were correlated with the lung function tests. Results. We obtained a high correlation (p=0.01) for two of the HRCT signs: extent of mucus plugging and mosaic perfusion pattern and all function tests. Discussion. Previous studies have demonstrated good correlation between lung function tests, in particular with FEV1 and HRCT signs. Our study differed from previous ones in that we analysed the correlation between lung function tests and with both single and combined CT criteria. Conclusion. Our results suggest that a simplified HRCT store could be useful to evaluate patients with cystic fibrosis [it

  11. Strategies for the etiological therapy of cystic fibrosis.

    Science.gov (United States)

    Maiuri, Luigi; Raia, Valeria; Kroemer, Guido

    2017-11-01

    Etiological therapies aim at repairing the underlying cause of cystic fibrosis (CF), which is the functional defect of the cystic fibrosis transmembrane conductance regulator (CFTR) protein owing to mutations in the CFTR gene. Among these, the F508del CFTR mutation accounts for more than two thirds of CF cases worldwide. Two somehow antinomic schools of thought conceive CFTR repair in a different manner. According to one vision, drugs should directly target the mutated CFTR protein to increase its plasma membrane expression (correctors) or improve its ion transport function (potentiators). An alternative strategy consists in modulating the cellular environment and proteostasis networks in which the mutated CFTR protein is synthesized, traffics to its final destination, the plasma membrane, and is turned over. We will analyze distinctive advantages and drawbacks of these strategies in terms of their scientific and clinical dimensions, and we will propose a global strategy for CF research and development based on a reconciliatory approach. Moreover, we will discuss the utility of preclinical biomarkers that may guide the personalized, patient-specific implementation of CF therapies.

  12. Two Qatari siblings with cystic fibrosis and apparent mineralocorticoid excess

    Directory of Open Access Journals (Sweden)

    Khalid Zahraldin

    2015-01-01

    Full Text Available Cystic fibrosis (CF and apparent mineralocorticoid excess (AME syndrome are both autosomal recessive disorders that result from mutations of specific identified genes for each condition. CF is caused by defects in the Cystic fibrosis trans membrane conductance regulator (CFTR gene which encodes for a protein that functions as a chloride channel and regulates the flow of other ions across the apical surface of epithelial cells. AME is due to the deficiency of 11β-hydroxysteroid dehydrogenase type 2 enzyme (11βHSD2, which is responsible for the peripheral inactivation of cortisol to cortisone. Cortisol excess stimulates the mineralocoritoid receptors (MR resulting in intense sodium retention, hypokalemia and hypertension. We report on a consanguineous Arab family, in which two sibs inherited both CF and AME. Gene testing for AME revealed previously unreported mutation in the 11βHSD2 gene. This report draws attention to the importance of recognizing the possibility of two recessive disorders in the same child in complex consanguineous families. Moreover, it provides a unique opportunity to highlight the implications of the coexistence of two genetic disorders on patient care and genetic counseling of the family.

  13. Defining palliative care in cystic fibrosis: A Delphi study.

    Science.gov (United States)

    Dellon, E P; Goggin, J; Chen, E; Sabadosa, K; Hempstead, S E; Faro, A; Homa, K

    2018-05-01

    The goal of palliative care is to improve quality of life for people with serious illness. We aimed to create a cystic fibrosis (CF)-specific definition of palliative care. A working group of 36 CF care providers, researchers, palliative care providers, quality improvement experts, individuals with CF, and CF caregivers completed a series of questionnaires to rate the value of each of 22 attributes of palliative care, rank top attributes to construct definitions of palliative care, and then rate proposed definitions. An average of 28 participants completed each of four questionnaires, with consistent distribution of stakeholder roles across questionnaires. Many identified overlaps in routine CF care and palliative care and highlighted the importance of a definition that feels relevant across the lifespan. Modified Delphi methodology was used to define palliative care in CF. The definition will be used as the foundation for development of CF-specific palliative care guidelines. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  14. Ethnicity impacts the cystic fibrosis diagnosis: A note of caution.

    Science.gov (United States)

    Bosch, Barbara; Bilton, Diana; Sosnay, Patrick; Raraigh, Karen S; Mak, Denise Y F; Ishiguro, Hiroshi; Gulmans, Vincent; Thomas, Muriel; Cuppens, Harry; Amaral, Margarida; De Boeck, Kris

    2017-07-01

    The diagnosis of Cystic Fibrosis (CF) is by consensus based on the same parameters in all patients, yet the influence of ethnicity has only scarcely been studied. We aimed at elucidating the impact of Asian descent on the diagnosis of CF. We performed a retrospective analysis of the CFTR2 and UK CF databases for clinical phenotype, sweat chloride values and CFTR mutations and compared the diagnostic characteristics of Asian to non-Asian patients with CF. Asian patients with CF do not have a worse clinical phenotype. The repeatedly reported lower FEV 1 of Asian patients with CF is attributable to the influence of ethnicity on lung function in general. However, pancreatic sufficiency is more common in Asian patients with CF. The diagnosis of CF in people with Asian ancestry is heterogeneous as mean sweat chloride values are lower (92±26 versus 99±22mmol/L in controls) and 14% have sweat chloride values below 60mmol/L (versus 6% in non-Asians). Also, CFTR mutations differ from those in Caucasians: 55% of British Asian patients with CF do not have one mutation included in the routine newborn screening panel. Bringing together the largest cohort of patients with CF and Asian ethnicity, we demonstrate that Asian roots impact on all three CF diagnostic pillars. These findings have implications for clinical practice in the increasingly ethnically diverse Western population. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  15. Practical Guidelines: Lung Transplantation in Patients with Cystic Fibrosis

    Science.gov (United States)

    Hirche, T. O.; Knoop, C.; Hebestreit, H.; Shimmin, D.; Solé, A.; Elborn, J. S.; Ellemunter, H.; Aurora, P.; Hogardt, M.; Wagner, T. O. F.; ECORN-CF Study Group

    2014-01-01

    There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation. PMID:24800072

  16. Molecular epidemiology of Aspergillus collected from cystic fibrosis patients.

    Science.gov (United States)

    Sabino, Raquel; Ferreira, Jose A G; Moss, Richard B; Valente, Joana; Veríssimo, Cristina; Carolino, Elisabete; Clemons, Karl V; Everson, Cassie; Banaei, Niaz; Penner, John; Stevens, David A

    2015-07-01

    Aspergillus respiratory infection is a common complication in cystic fibrosis (CF) and is associated with loss of pulmonary function and allergic disease. Fifty-three Aspergillus isolates recovered from CF patients were identified to species by Internal Transcribed Spacer Region (ITS), β-tubulin, and calmodulin sequencing. Three species complexes (Terrei, Nigri, and Fumigati) were found. Identification to species level gave a single Aspergillus terreus sensu stricto, one Aspergillus niger sensu stricto and 51 Aspergillus fumigatus sensu stricto isolates. No cryptic species were found. To our knowledge, this is the first prospective study of Aspergillus species in CF using molecular methods. The paucity of non-A. fumigatus and of cryptic species of A. fumigatus suggests a special association of A. fumigatus sensu stricto with CF airways, indicating it likely displays unique characteristics making it suitable for chronic residence in that milieu. These findings could refine an epidemiologic and therapeutic approach geared to this pathogen. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  17. Cysteamine-mediated clearance of antibiotic-resistant pathogens in human cystic fibrosis macrophages.

    Directory of Open Access Journals (Sweden)

    Chandra L Shrestha

    Full Text Available Members of the Burkholderia cepacia complex are virulent, multi-drug resistant pathogens that survive and replicate intracellularly in patients with cystic fibrosis (CF. We have discovered that B. cenocepacia cannot be cleared from CF macrophages due to defective autophagy, causing continued systemic inflammation and infection. Defective autophagy in CF is mediated through constitutive reactive oxygen species (ROS activation of transglutaminase-2 (TG2, which causes the sequestration (accumulation of essential autophagy initiating proteins. Cysteamine is a TG2 inhibitor and proteostasis regulator with the potential to restore autophagy. Therefore, we sought to examine the impact of cysteamine on CF macrophage autophagy and bacterial killing. Human peripheral blood monocyte-derived macrophages (MDMs and alveolar macrophages were isolated from CF and non-CF donors. Macrophages were infected with clinical isolates of relevant CF pathogens. Cysteamine caused direct bacterial growth killing of live B. cenocepacia, B. multivorans, P. aeruginosa and MRSA in the absence of cells. Additionally, B. cenocepacia, B. multivorans, and P. aeruginosa invasion were significantly decreased in CF MDMs treated with cysteamine. Finally, cysteamine decreased TG2, p62, and beclin-1 accumulation in CF, leading to increased Burkholderia uptake into autophagosomes, increased macrophage CFTR expression, and decreased ROS and IL-1β production. Cysteamine has direct anti-bacterial growth killing and improves human CF macrophage autophagy resulting in increased macrophage-mediated bacterial clearance, decreased inflammation, and reduced constitutive ROS production. Thus, cysteamine may be an effective adjunct to antibiotic regimens in CF.

  18. Inhaled antibiotics in non-cystic fibrosis bronchiectasis: A meta-analysis.

    Science.gov (United States)

    Xu, Li; Zhang, Fei; Du, Shuai; Yu, Qi; Chen, Lin; Long, Li-Hui; Li, Ya-Ming; Jia, Ai-Hua

    2016-09-01

    To evaluate the efficacy and safety of inhaled antibiotics for the treatment of non-cystic fibrosis bronchiectasis (NCFB). Pubmed, Cochrane library, Embase, Elsevier, OVID, Springerlink, Web of knowledge and NEJM were searched for randomized controlled trials (RCTs) on inhaled antibiotics in treatment of NCFB from inception until April 2015. Meta-analysis was conducted to assess the efficacy and safety of inhaled antibiotics in the treatment of NCFB. Twelve RCTs involving 1154 participants were included. They showed that inhaled antibiotics were more effective in reduction of sputum bacterial density, eradication of P. aeruginosa, prolonged time to exacerbation and reduction of new pathogens emergence with no significant difference in adverse events compared with control groups. However, we did not find significant benefits of inhaled antibiotics in reducing the risk of acute exacerbation, improving health-related quality of life and reduction of P. aeruginosa resistance. Moreover, inhaled antibiotics exerted a statistically significant reduction in FEV1%. Inhaled antibiotics may be an alternative pathway to inhibit airway inflammation with no more adverse events in patients with NCFB.

  19. The fate of inhaled antibiotics after deposition in cystic fibrosis: How to get drug to the bug?

    Science.gov (United States)

    Bos, Aukje C; Passé, Kimberly M; Mouton, Johan W; Janssens, Hettie M; Tiddens, Harm A W M

    2017-01-01

    Chronic airway infections in patients with cystic fibrosis (CF) are most often treated with inhaled antibiotics of which deposition patterns have been extensively studied. However, the journey of aerosol particles does not end after deposition within the bronchial tree. To review how local conditions affect the clinical efficacy of antibiotic aerosol particles after deposition in the airways of patients with CF. Electronic databases were searched from inception to September 2015. Original studies describing the effect of CF sputum or bacterial factors on antibiotic efficacy and formulations to increase efficacy were included. 35 articles were included which mostly described in vitro studies and mainly investigated aminoglycosides. After deposition, diffusion through the mucus layer was reduced for aminoglycosides, β-lactam antibiotics and fluoroquinolones. Within CF mucus, low oxygen tension adversely affected aminoglycosides, β-lactam antibiotics, and chloramphenicol; and molecules inactivated aminoglycosides but not β-lactam antibiotics. Finally, the alginate layer surrounding Pseudomonas aeruginosa was an important factor in the resistance against all antibiotics. After deposition in the airways, the local efficacy of inhaled antibiotics can be reduced by molecules within CF mucus and the alginate layer surrounding P. aeruginosa. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  20. Recent progress in translational cystic fibrosis research using precision medicine strategies.

    Science.gov (United States)

    Cholon, Deborah M; Gentzsch, Martina

    2018-03-01

    Significant progress has been achieved in developing precision therapies for cystic fibrosis; however, highly effective treatments that target the ion channel, CFTR, are not yet available for many patients. As numerous CFTR therapeutics are currently in the clinical pipeline, reliable screening tools capable of predicting drug efficacy to support individualized treatment plans and translational research are essential. The utilization of bronchial, nasal, and rectal tissues from individual cystic fibrosis patients for drug testing using in vitro assays such as electrophysiological measurements of CFTR activity and evaluation of fluid movement in spheroid cultures, has advanced the prediction of patient-specific responses. However, for precise prediction of drug effects, in vitro models of CFTR rescue should incorporate the inflamed cystic fibrosis airway environment and mimic the complex tissue structures of airway epithelia. Furthermore, novel assays that monitor other aspects of successful CFTR rescue such as restoration of mucus characteristics, which is important for predicting mucociliary clearance, will allow for better prognoses of successful therapies in vivo. Additional cystic fibrosis treatment strategies are being intensively explored, such as development of drugs that target other ion channels, and novel technologies including pluripotent stem cells, gene therapy, and gene editing. The multiple therapeutic approaches available to treat the basic defect in cystic fibrosis combined with relevant precision medicine models provide a framework for identifying optimal and sustained treatments that will benefit all cystic fibrosis patients. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  1. The evaluation of selected insomnia predictors in adolescents and young adults with cystic fibrosis.

    Science.gov (United States)

    Tomaszek, Lucyna; Cepuch, Grazyna; Pawlik, Lidia

    2018-03-21

    The purpose of the study was to assess the incidence of insomnia in adolescents and young adults with cystic fibrosis and its impact on the quality of life, and to examine whether demographic and clinical factors and negative emotional states are predictors of insomnia in these patients. The study was conducted among 95 cystic fibrosis patients aged 14-25 years. The study used a personal questionnaire survey, the Athens Insomnia Scale, the Cystic Fibrosis Quality of Life Questionnaire, the Hospital Anxiety and Depression Scale, and the Numeric Rating Scale. Insomnia was diagnosed in 38% of cystic fibrosis patients. In patients with insomnia, the level of anxiety (Me: 10 vs. 4; P=0.000) and depression (Me: 6.5 vs. 2; P=0.000) was significantly higher than in the good sleep quality group. The risk of insomnia increases as anxiety (OR: 4.31; 95% CI: 2.20 to 8.41) and depressive symptoms exacerbate (OR: 4.98; 95% CI: 1.84 to 13.43). Insomnia significantly worsens the quality of life in cystic fibrosis patients (ß =-0.5, P=0.000). Insomnia affects a large percentage of cystic fibrosis patients, and anxiety and depression are factors that increase the risk of insomnia. Insomnia decreases the quality of life in cystic fibrosis patients.

  2. Multiple-Breath Washout Outcomes Are Sensitive to Inflammation and Infection in Children with Cystic Fibrosis.

    Science.gov (United States)

    Ramsey, Kathryn A; Foong, Rachel E; Grdosic, Jasmine; Harper, Alana; Skoric, Billy; Clem, Charles; Davis, Miriam; Turkovic, Lidija; Stick, Stephen M; Davis, Stephanie D; Ranganathan, Sarath C; Hall, Graham L

    2017-09-01

    The lung clearance index is a measure of ventilation distribution derived from the multiple-breath washout technique. The lung clearance index is increased in the presence of lower respiratory tract inflammation and infection in infants with cystic fibrosis; however, the associations during the preschool years are unknown. We assessed the ability of the lung clearance index to detect the presence and extent of lower respiratory tract inflammation and infection in preschool children with cystic fibrosis. Ventilation distribution outcomes were assessed at 82 visits with 58 children with cystic fibrosis and at 38 visits with 31 healthy children aged 3-6 years. Children with cystic fibrosis also underwent bronchoalveolar lavage fluid collection for detection of lower respiratory tract inflammation and infection. Associations between multiple-breath washout indices and the presence and extent of airway inflammation and infection were assessed using linear mixed effects models. Lung clearance index was elevated in children with cystic fibrosis (mean [SD], 8.00 [1.45]) compared with healthy control subjects (6.67 [0.56]). In cystic fibrosis, the lung clearance index was elevated in individuals with lower respiratory tract infections (difference compared with uninfected [95% confidence interval], 0.62 [0.06, 1.18]) and correlated with the extent of airway inflammation. These data suggest that the lung clearance index may be a useful surveillance tool for monitoring the presence and extent of lower airway inflammation and infection in preschool children with cystic fibrosis.

  3. Variation in Cilia Protein Genes and Progression of Lung Disease in Cystic Fibrosis.

    Science.gov (United States)

    Blue, Elizabeth; Louie, Tin L; Chong, Jessica X; Hebbring, Scott J; Barnes, Kathleen C; Rafaels, Nicholas M; Knowles, Michael R; Gibson, Ronald L; Bamshad, Michael J; Emond, Mary J

    2018-04-01

    Cystic fibrosis, like primary ciliary dyskinesia, is an autosomal recessive disorder characterized by abnormal mucociliary clearance and obstructive lung disease. We hypothesized that genes underlying the development or function of cilia may modify lung disease severity in persons with cystic fibrosis. To test this hypothesis, we compared variants in 93 candidate genes in both upper and lower tertiles of lung function in a large cohort of children and adults with cystic fibrosis with those of a population control dataset. Variants within candidate genes were tested for association using the SKAT-O test, comparing cystic fibrosis cases defined by poor (n = 127) or preserved (n = 127) lung function with population controls (n = 3,269 or 3,148, respectively). Associated variants were then tested for association with related phenotypes in independent datasets. Variants in DNAH14 and DNAAF3 were associated with poor lung function in cystic fibrosis, whereas variants in DNAH14 and DNAH6 were associated with preserved lung function in cystic fibrosis. Associations between DNAH14 and lung function were replicated in disease-related phenotypes characterized by obstructive lung disease in adults. Genetic variants within DNAH6, DNAH14, and DNAAF3 are associated with variation in lung function among persons with cystic fibrosis.

  4. In silico search for modifier genes associated with pancreatic and liver disease in Cystic Fibrosis.

    Directory of Open Access Journals (Sweden)

    Pascal Trouvé

    Full Text Available Cystic Fibrosis is the most common lethal autosomal recessive disorder in the white population, affecting among other organs, the lung, the pancreas and the liver. Whereas Cystic Fibrosis is a monogenic disease, many studies reveal a very complex relationship between genotype and clinical phenotype. Indeed, the broad phenotypic spectrum observed in Cystic Fibrosis is far from being explained by obvious genotype-phenotype correlations and it is admitted that Cystic Fibrosis disease is the result of multiple factors, including effects of the environment as well as modifier genes. Our objective was to highlight new modifier genes with potential implications in the lung, pancreatic and liver outcomes of the disease. For this purpose we performed a system biology approach which combined, database mining, literature mining, gene expression study and network analysis as well as pathway enrichment analysis and protein-protein interactions. We found that IFI16, CCNE2 and IGFBP2 are potential modifiers in the altered lung function in Cystic Fibrosis. We also found that EPHX1, HLA-DQA1, HLA-DQB1, DSP and SLC33A1, GPNMB, NCF2, RASGRP1, LGALS3 and PTPN13, are potential modifiers in pancreas and liver, respectively. Associated pathways indicate that immune system is likely involved and that Ubiquitin C is probably a central node, linking Cystic Fibrosis to liver and pancreatic disease. We highlight here new modifier genes with potential implications in Cystic Fibrosis. Nevertheless, our in silico analysis requires functional analysis to give our results a physiological relevance.

  5. Dysregulated proinflammatory and fibrogenic phenotype of fibroblasts in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    François Huaux

    Full Text Available Morbi-mortality in cystic fibrosis (CF is mainly related to chronic lung infection and inflammation, uncontrolled tissue rearrangements and fibrosis, and yet the underlying mechanisms remain largely unknown. We evaluated inflammatory and fibrosis responses to bleomycin in F508del homozygous and wild-type mice, and phenotype of fibroblasts explanted from mouse lungs and skin. The effect of vardenafil, a cGMP-specific phosphodiesterase type 5 inhibitor, was tested in vivo and in culture. Responses of proinflammatory and fibrotic markers to bleomycin were enhanced in lungs and skin of CF mice and were prevented by treatment with vardenafil. Purified lung and skin fibroblasts from CF mice proliferated and differentiated into myofibroblasts more prominently and displayed higher sensitivity to growth factors than those recovered from wild-type littermates. Under inflammatory stimulation, mRNA and protein expression of proinflammatory mediators were higher in CF than in wild-type fibroblasts, in which CFTR expression reached similar levels to those observed in other non-epithelial cells, such as macrophages. Increased proinflammatory responses in CF fibroblasts were reduced by half with submicromolar concentrations of vardenafil. Proinflammatory and fibrogenic functions of fibroblasts are upregulated in CF and are reduced by vardenafil. This study provides compelling new support for targeting cGMP signaling pathway in CF pharmacotherapy.

  6. Autogenic drainage for airway clearance in cystic fibrosis.

    Science.gov (United States)

    McCormack, Pamela; Burnham, Paul; Southern, Kevin W

    2017-10-06

    Autogenic drainage is an airway clearance technique that was developed by Jean Chevaillier in 1967. The technique is characterised by breathing control using expiratory airflow to mobilise secretions from smaller to larger airways. Secretions are cleared independently by adjusting the depth and speed of respiration in a sequence of controlled breathing techniques during exhalation. The technique requires training, concentration and effort from the individual. It is important to systematically review the evidence demonstrating that autogenic drainage is an effective intervention for people with cystic fibrosis. To compare the clinical effectiveness of autogenic drainage in people with cystic fibrosis with other physiotherapy airway clearance techniques. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews, as well as two trials registers (31 August 2017).Dtae of most recent search of the Cochrane Cystic Fibrosis Trials Register: 25 September 2017. We identified randomised and quasi-randomised controlled studies comparing autogenic drainage to another airway clearance technique or no therapy in people with cystic fibrosis for at least two treatment sessions. Data extraction and assessments of risk of bias were independently performed by two authors. The authors assessed the quality of the evidence using the GRADE system. The authors contacted two investigators for further information pertinent to their published studies. Searches retrieved 35 references to 21 individual studies, of which seven (n = 208) were eligible for inclusion. One study was of parallel design with the remaining six being cross-over in design; participant numbers ranged from 17 to 75. The total study duration varied between four days and two years. The age of participants ranged between seven and 63 years with a wide

  7. Radiologic findings of cystic fibrosis in a Korean child at follow up study: case report

    International Nuclear Information System (INIS)

    Jang, Il Soo; Park, Choong Ki; Jeon, Seok Chol; Choi, Yo Won; Park, Dong Woo; Kim, Yong Soo; Kim, Young Sun; Ahn, You Hern

    2003-01-01

    Cystic fibrosis is a hereditary disease involving recessive transmission. The fundamental abnormality consists of the production of abnormal secretion from a variety of exocrine glands such as salivary and sweat glands and those of the pancreas, colon, and tracheobronchial trees. Cystic fibrosis is the most common lethal genetically transmitted disease among whites, but is uncommon in Asians, including Koreans. Although a case involving a Korean was reported in 1988, the focus was diagnosis rather than the radiological findings. In the case of cystic fibrosis we now describe, the focus is inverted: we emphasise the reported in 1988, focusing on radiologic findings

  8. Blunted perception of neural respiratory drive and breathlessness in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Charles C. Reilly

    2016-03-01

    Full Text Available The electromyogram recorded from the diaphragm (EMGdi and parasternal intercostal muscle using surface electrodes (sEMGpara provides a measure of neural respiratory drive (NRD, the magnitude of which reflects lung disease severity in stable cystic fibrosis. The aim of this study was to explore perception of NRD and breathlessness in both healthy individuals and patients with cystic fibrosis. Given chronic respiratory loading and increased NRD in cystic fibrosis, often in the absence of breathlessness at rest, we hypothesised that patients with cystic fibrosis would be able to tolerate higher levels of NRD for a given level of breathlessness compared to healthy individuals during exercise. 15 cystic fibrosis patients (mean forced expiratory volume in 1 s (FEV1 53.5% predicted and 15 age-matched, healthy controls were studied. Spirometry was measured in all subjects and lung volumes measured in the cystic fibrosis patients. EMGdi and sEMGpara were recorded at rest and during incremental cycle exercise to exhaustion and expressed as a percentage of maximum (% max obtained from maximum respiratory manoeuvres. Borg breathlessness scores were recorded at rest and during each minute of exercise. EMGdi % max and sEMGpara % max and associated Borg breathlessness scores differed significantly between healthy subjects and cystic fibrosis patients at rest and during exercise. The relationship between EMGdi % max and sEMGpara % max and Borg score was shifted to the right in the cystic fibrosis patients, such that at comparable levels of EMGdi % max and sEMGpara % max the cystic fibrosis patients reported significantly lower Borg breathlessness scores compared to the healthy individuals. At Borg score 1 (clinically significant increase in breathlessness from baseline corresponding levels of EMGdi % max (20.2±12% versus 32.15±15%, p=0.02 and sEMGpara % max (18.9±8% versus 29.2±15%, p=0.04 were lower in the healthy individuals compared to the cystic

  9. Anesthesia for Lobectomy in a Pediatric Patient` with Cystic Fibrosis: A Case Report

    Directory of Open Access Journals (Sweden)

    Seyedhejazi Mahin

    2014-07-01

    Full Text Available Cystic Fibrosis is the most common autosomal recessive disease which causes a lot of complications and there are some needed operations in lifelong of such patients. Anesthesia in these patients requires particular attention and a full cooperation of surgeon, anesthetist and pediatrician .We reported a case of lobectomy with lung separation in a 4.5 years old child with cystic fibrosis which was performed with minor complications in the hope that an awareness of such situations may turn up similar cases of study. Keywords: Cystic Fibrosis, Anesthesia, Pulmonic Lobectomy

  10. High Concentrations of Sodium Chloride Improve Microbicidal Activity of Ibuprofen against Common Cystic Fibrosis Pathogens

    Directory of Open Access Journals (Sweden)

    Adrián J. Muñoz

    2018-05-01

    Full Text Available Ibuprofen (IBU-H, a widely used anti-inflammatory, also shows a marked antimicrobial effect against several bacterial species, including those involved in cystic fibrosis such as Pseudomona aeruginosa, methicillin resistant Staphylococcus aureus and Burkholderia cepacia complex. Additionally, our results show significant synergy between water soluble Na-ibuprofen (IBU-Na and ionic strength. Salt concentrations above 0.5 M modify the zeta potential promoting the action of Na-IBU; thus, with 1 M sodium chloride, IBU-Na is ten times more efficient than in the absence of ionic strength, and the minimum effective contact time is reduced from hours to minutes. In short time periods, where neither IBU-Na nor controls with 1 M NaCl show activity, the combination of both leads to a reduction in the bacterial load. We also analyzed whether the changes caused by salt on the bacterial membrane also promoted the activity of other microbicide compounds used in cystic fibrosis like gentamicin, tobramycin and phosphomycin. The results show that the presence of ionic strength only enhanced the bactericidal activity of the amphipathic molecule of IBU-Na. In this respect, the effect of saline concentration was also reflected in the surface properties of IBU-Na, where, in addition to the clear differences observed between 145 mM and 1 M, singular behaviors were also found, different in each condition. The combination of anti-inflammatory activity and this improved bactericidal effect of Na-IBU in hypertonic solution provides a new alternative for the treatment of respiratory infections of fibrotic patients based on known and widely used compounds.

  11. Lung function comparison between two decades in cystic fibrosis children: A single centre study.

    Science.gov (United States)

    Tridello, Gloria; Volpi, Sonia; Assael, Baroukh M; Meneghelli, Ilaria; Passiu, Marianna; Circelli, Maria

    2015-12-01

    The purpose of this study was to compare two cohorts of cystic fibrosis (CF) patients born and treated in two different decades, diagnosed through a CF neonatal screening program. We compared pulmonary function decline from 10 to 15 years of age in patients with cystic fibrosis born between 1979 and 1984 (Cohort 1) and between 1991 and 1996 (Cohort 2). Forced expiratory volume in 1 sec (FEV1%) and forced expiratory flow from 25% to 75% (FEF 25-75%) were analyzed by a linear mixed model approach. The differences between the two cohorts were estimated and the overall cohort effect was tested. Ninety-two patients (51 males, 41 females) fulfilled the selection criteria. Pancreatic insufficiency and CF related diabetes were present in 91% and 20% of patients, respectively. The mean absolute decrement of FEV1% was 9.2 (standard deviation [SD] 11.2) in Cohort 1 and 0.6 (SD 10.4) in Cohort 2 (P decrement of FEF 25-75% was 16.3 (SD 19.5) in Cohort 1 and 1.3 (SD 16.8) in Cohort 2 (P < 0.001) and the Pseudomonas aeruginosa (Pa) colonization was 28% and 15% respectively (P = 0.1). Our results show that pulmonary function has clearly ameliorated over a decade in young CF patients, in a period during which several significant therapeutic changes have been introduced, such as dornase alfa, tobramycin and hypertonic saline. To our knowledge this is the first study showing a cohort effect in patients diagnosed after neonatal screening. © 2015 Wiley Periodicals, Inc.

  12. Exocrine cell-derived microparticles in response to lipopolysaccharide promote endocrine dysfunction in cystic fibrosis.

    Science.gov (United States)

    Constantinescu, Andrei Alexandru; Gleizes, Céline; Alhosin, Mahmoud; Yala, Elhassan; Zobairi, Fatiha; Leclercq, Alexandre; Stoian, Gheorghe; Mitrea, Ioan Liviu; Prévost, Gilles; Toti, Florence; Kessler, Laurence

    2014-03-01

    Diabetes in cystic fibrosis (CF) is a result of exocrine pancreas alteration followed by endocrine dysfunction at a later stage. Microparticles (MPs) are plasma membrane fragments shed from stimulated or damaged cells that act as cellular effectors. Our aim was to identify a new form of interaction between exocrine and endocrine pancreatic cells mediated by exocrine MPs, in the context of recurrent infection in CF. MPs from either human exocrine CFTRΔF508-mutated (CFPAC-1) cells or exocrine normal pancreatic (PANC-1) cells were collected after treatment by LPS from Pseudomonas aeruginosa and applied to rat endocrine normal insulin-secreting RIN-m5F cells. MP membrane integration in target cells was established by confocal microscopy and flow cytometry using PKH26 lipid probe. Apoptosis, lysosomal activity, insulin secretion were measured after 18 h. MP-mediated NF-κB activation was measured in HEK-Blue reporter cells by SEAP reporter gene system and in RIN-m5F cells by Western blot. In endocrine normal cells, CFTR inhibition was achieved using Inhibitor-172. Compared to PANC-1, MPs from CFPAC-1 significantly reduced insulin secretion and lysosomal activity in RIN-m5F. MPs induced NF-κB activation by increasing the level of IκB phosphorylation. Moreover, the inhibition of NF-κB activation using specific inhibitors was associated with a restored insulin secretion. Interestingly, CFTR inhibition in normal RIN-m5F cells promoted apoptosis and decreased insulin secretion. During recurrent infections associated with CF, exocrine MPs may contribute to endocrine cell dysfunction via NF-κB pathways. Membrane CFTR dysfunction is associated with decreased insulin secretion. © 2013. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. All rights reserved.

  13. A Roadmap to the Brittle Bones of Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Ashwini P. Gore

    2011-01-01

    Full Text Available Cystic fibrosis (CF is an autosomal recessive disorder which despite advances in medical care continues to be a life-limiting and often fatal disease. With increase in life expectancy of the CF population, bone disease has emerged as a common complication. Unlike the osteoporosis seen in postmenopausal population, bone disease in CF begins at a young age and is associated with significant morbidity due to fractures, kyphosis, increased pain, and decreased lung function. The maintenance of bone health is essential for the CF population during their lives to prevent pain and fractures but also as they approach lung transplantation since severe bone disease can lead to exclusion from lung transplantation. Early recognition, prevention, and treatment are key to maintaining optimal bone health in CF patients and often require a multidisciplinary approach. This article will review the pathophysiology, current clinical practice guidelines, and potential future therapies for treating CF-related bone disease.

  14. Serodiagnosis of Mycobacterium abscessus complex infection in cystic fibrosis

    DEFF Research Database (Denmark)

    Qvist, Tavs; Pressler, Tania; Taylor-Robinson, David

    2015-01-01

    Early signs of pulmonary disease with Mycobacterium abscessus complex (MABSC) can be missed in patients with cystic fibrosis (CF). A serological method could help stratify patients according to risk. The objective of this study was to test the diagnostic accuracy of a novel method for investigating...... and after culture conversion.307 patients had 3480 respiratory samples cultured and were then tested with the anti-MABSC IgG ELISA. Patients with MABSC pulmonary disease had median anti-MABSC IgG levels six-fold higher than patients with no history of infection (434 versus 64 ELISA units; p... sensitivity was 95% (95% CI 74-99%) and the specificity was 73% (95% CI 67-78%). A diagnostic algorithm was constructed to stratify patients according to risk.The test accurately identified patients with pulmonary disease caused by MABSC and was suited to be used as a complement to mycobacterial culture....

  15. Mucoid impaction presenting as multiple pulmonary nodules in cystic fibrosis

    International Nuclear Information System (INIS)

    Carpenter, L.D.; Lambie, N.K.; Wilsher, M.L.

    1996-01-01

    Mucoid impaction has been described as a complication of asthma and more commonly in patients with allergic bronchopulmonary aspergillosis. In such cases, the impacted pools of mucus may present as discrete nodules on chest X-ray and hence simulate the appearance of metastatic malignancy. A case of mucoid impaction presenting as multiple pulmonary nodules in a patient with cystic fibrosis is described. The chest X-ray showed hyperinfiltration and scattered changes consistent with bronchiectasis. Computed tomography scan confirmed these and additional intra-pulmonary nodular densities. This report illustrates that mucus impaction as a cause of pulmonary nodules should be considered in any patient with chronic lung disease characterised by excess mucus production. 6 refs., 3 figs

  16. Nutritional state and lung disease in cystic fibrosis.

    Science.gov (United States)

    Bakker, W

    1992-10-01

    The life expectancy of patients with cystic fibrosis (CF) is largely dependent on the severity and progress of the pulmonary involvement associated with the disease. Many data support the view that malnutrition and deterioration of lung function are closely interrelated and interdependent, with each affecting the other, leading to a spiral decline in both. The occurrence of malnutrition appears to be associated with poor lung function and poor survival, and conversely prevention of malnutrition appears to be associated with better lung function and improved survival. Nutritional intervention may lead to an improvement in body weight, lung function and exercise tolerance, provided that the intervention is combined with exercise training in order to increase both respiratory and other muscle mass. These improvements can be preserved when patients have the stamina to continue with a high-energy, high-fat diet and daily exercise training at home.

  17. The cystic fibrosis neutrophil: a specialized yet potentially defective cell.

    LENUS (Irish Health Repository)

    Hayes, Elaine

    2012-02-01

    Cystic fibrosis (CF) is one of the commonest genetically inherited diseases in the world. It is characterized by recurrent respiratory tract infections eventually leading to respiratory failure. One of the hallmarks of this disease is a persistent and predominantly neutrophil driven inflammation. Neutrophils provide the first line of defence by killing and digesting phagocytosed bacteria and fungi, yet despite advances in our understanding of the molecular and cellular basis of CF, there remains a paradox of why recruited CF neutrophils fail to eradicate bacterial infections in the lung. This review describes mechanisms involved in neutrophil migration, microbial killing and apoptosis leading to inflammatory resolution. We discuss dysregulated neutrophil activity and consider genetic versus inflammatory neutrophil reprogramming in CF and ultimately pharmacological modulation of the CF neutrophil for therapeutic intervention.

  18. The cystic fibrosis neutrophil: a specialized yet potentially defective cell.

    LENUS (Irish Health Repository)

    Hayes, Elaine

    2011-04-01

    Cystic fibrosis (CF) is one of the commonest genetically inherited diseases in the world. It is characterized by recurrent respiratory tract infections eventually leading to respiratory failure. One of the hallmarks of this disease is a persistent and predominantly neutrophil driven inflammation. Neutrophils provide the first line of defence by killing and digesting phagocytosed bacteria and fungi, yet despite advances in our understanding of the molecular and cellular basis of CF, there remains a paradox of why recruited CF neutrophils fail to eradicate bacterial infections in the lung. This review describes mechanisms involved in neutrophil migration, microbial killing and apoptosis leading to inflammatory resolution. We discuss dysregulated neutrophil activity and consider genetic versus inflammatory neutrophil reprogramming in CF and ultimately pharmacological modulation of the CF neutrophil for therapeutic intervention.

  19. The Influence of Genetics on Cystic Fibrosis Phenotypes

    Science.gov (United States)

    Knowles, Michael R.; Drumm, Mitchell

    2012-01-01

    Technological advances in genetics have made feasible and affordable large studies to identify genetic variants that cause or modify a trait. Genetic studies have been carried out to assess variants in candidate genes, as well as polymorphisms throughout the genome, for their associations with heritable clinical outcomes of cystic fibrosis (CF), such as lung disease, meconium ileus, and CF-related diabetes. The candidate gene approach has identified some predicted relationships, while genome-wide surveys have identified several genes that would not have been obvious disease-modifying candidates, such as a methionine sulfoxide transferase gene that influences intestinal obstruction, or a region on chromosome 11 proximate to genes encoding a transcription factor and an apoptosis controller that associates with lung function. These unforeseen associations thus provide novel insight into disease pathophysiology, as well as suggesting new therapeutic strategies for CF. PMID:23209180

  20. High resolution CT in children with cystic fibrosis

    International Nuclear Information System (INIS)

    Stiglbauer, R.; Schurawitzki, H.; Eichler, I.; Goetz, M.

    1992-01-01

    High resolution CT (HRCT) was performed in 24 children (median age 57.9 months) suffering from cystic fibrosis (CF). In 23 patients (one examination unacceptable because of motion artifacts) the most frequent finding was bronchial wall thickening, shown in 21 patients (91%), followed by bronchiectasis in 15 patients (65%). Less frequent findings were mucus plugging and patchy consolidations, which could be demonstrated in 11 patients each (48%). Findings were classified using a CT scoring system and including only irreversible pulmonary changes; a statistically significant correlation with lung function tests could be established. HRCT to date seems to be the most valuable method to determine extent and severity of lung involvement in children with CF and should therefore be routinely used for the staging of this disease. (orig.)

  1. The Use of Home Spirometry in Pediatric Cystic Fibrosis Patients

    Directory of Open Access Journals (Sweden)

    Aarti Shakkottai MD

    2017-02-01

    Full Text Available Medication adherence is poor among pediatric cystic fibrosis (CF patients, with adolescents having one of the lowest adherence rates. We wanted to identify an adherence intervention that would be acceptable to CF adolescents and assess its feasibility. We surveyed 40 adolescents with CF and asked about barriers to and motivators for their own adherence and to generate ideas for potential adherence interventions. Since most of the respondents chose frequent spirometry at home and medication reminders for interventions, we selected 5 subjects, 10 to 14 years of age, with CF to test the feasibility of home spirometry and medication reminders in pediatric CF patients. This article summarizes the results of both the survey and the feasibility pilot study.

  2. Toll-like receptors as therapeutic targets in cystic fibrosis.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2008-12-01

    Background: Toll-like receptors (TLRs) are pattern recognition receptors that act as a first-line of defence in the innate immune response by recognising and responding to conserved molecular patterns in microbial factors and endogenous danger signals. Cystic fibrosis (CF)-affected airways represent a milieu potentially rich in TLR agonists and the chronic inflammatory phenotype evident in CF airway epithelial cells is probably due in large part to activation of TLRs. Objective\\/methods: To examine the prospects of developing novel therapies for CF by targeting TLRs. We outline the expression and function of TLRs and explore the therapeutic potential of naturally-occurring and synthetic TLR inhibitors for CF. Results\\/conclusion: Modulation of TLRs has therapeutic potential for the inflammatory lung manifestations of CF.

  3. Cystic Fibrosis and Its Management Through Established and Emerging Therapies.

    Science.gov (United States)

    Spielberg, David R; Clancy, John P

    2016-08-31

    Cystic fibrosis (CF) is the most common life-shortening autosomal recessive disorder in the Caucasian population and occurs in many other ethnicities worldwide. The daily treatment burden is substantial for CF patients even when they are well, with numerous pharmacologic and physical therapies targeting lung disease requiring the greatest time commitment. CF treatments continue to advance with greater understanding of factors influencing long-term morbidity and mortality. In recent years, in-depth understanding of genetic and protein structure-function relationships has led to the introduction of targeted therapies for patients with specific CF genotypes. With these advances, CF has become a model of personalized or precision medicine. The near future will see greater access to targeted therapies for most patients carrying common mutations, which will mandate individualized bench-to-bedside methodologies for those with rare genotypes.

  4. Prevalence of dyslipidemia in adults with cystic fibrosis.

    Science.gov (United States)

    Rhodes, Bronwen; Nash, Edward F; Tullis, Elizabeth; Pencharz, Paul B; Brotherwood, Michelle; Dupuis, Annie; Stephenson, Anne

    2010-01-01

    A high fat calorie diet is advocated for patients with cystic fibrosis (CF) however the lipid profiles of individuals with CF, including those with CF-related diabetes (CFRD), are not well studied. We conducted a retrospective review of adult CF patients attending St Michael's Hospital between January 2005 and December 2007. 334 patients (77% pancreatic insufficient (PI)) were included in the study. Mean HDL cholesterol was significantly lower in males (p201mg/dL(5.2mmol/L) (p195mg/dL(2.2mmol/L). Diabetes was diagnosed in 23% of subjects. Lipid profiles were similar between diabetics and non-diabetics. Total cholesterol and triglycerides both increased with increasing age and increasing BMI (pdiabetes and those without. Fasting lipids should be monitored in CF patients, particularly those with PS, older age, and high BMI. As survival in CF increases, the prevalence of dyslipidemia may increase resulting in clinically important complications.

  5. Computed tomography dose optimisation in cystic fibrosis: A review.

    LENUS (Irish Health Repository)

    Ferris, Helena

    2016-04-28

    Cystic fibrosis (CF) is the most common autosomal recessive disease of the Caucasian population worldwide, with respiratory disease remaining the most relevant source of morbidity and mortality. Computed tomography (CT) is frequently used for monitoring disease complications and progression. Over the last fifteen years there has been a six-fold increase in the use of CT, which has lead to a growing concern in relation to cumulative radiation exposure. The challenge to the medical profession is to identify dose reduction strategies that meet acceptable image quality, but fulfil the requirements of a diagnostic quality CT. Dose-optimisation, particularly in CT, is essential as it reduces the chances of patients receiving cumulative radiation doses in excess of 100 mSv, a dose deemed significant by the United Nations Scientific Committee on the Effects of Atomic Radiation. This review article explores the current trends in imaging in CF with particular emphasis on new developments in dose optimisation.

  6. Cumulative radiation exposure in children with cystic fibrosis.

    LENUS (Irish Health Repository)

    O'Reilly, R

    2010-02-01

    This retrospective study calculated the cumulative radiation dose for children with cystic fibrosis (CF) attending a tertiary CF centre. Information on 77 children with a mean age of 9.5 years, a follow up time of 658 person years and 1757 studies including 1485 chest radiographs, 215 abdominal radiographs and 57 computed tomography (CT) scans, of which 51 were thoracic CT scans, were analysed. The average cumulative radiation dose was 6.2 (0.04-25) mSv per CF patient. Cumulative radiation dose increased with increasing age and number of CT scans and was greater in children who presented with meconium ileus. No correlation was identified between cumulative radiation dose and either lung function or patient microbiology cultures. Radiation carries a risk of malignancy and children are particularly susceptible. Every effort must be made to avoid unnecessary radiation exposure in these patients whose life expectancy is increasing.

  7. Neonatal Bartter syndrome associated with ileal atresia and cystic fibrosis

    Directory of Open Access Journals (Sweden)

    A O Akuma

    2013-01-01

    Full Text Available A rare case of neonatal Bartter syndrome presenting with severe hyperkalemia is reported in a preterm child born to consanguineous parents. This child also had ileal atresia, and meconium plugs were found at laparotomy. The diagnosis of cystic fibrosis was subsequently made on genetic testing. Despite full intensive care management and surgical interventions, he died of respiratory failure after 70 days. This is the first reported case of such conglomeration of pathologies in a newborn child. Second, in highlighting this case we want clinicians to be aware that a subtype of neonatal Bartter syndrome can present with initial hyperkalemia so that an erroneous diagnosis of pseudohypoaldosteronism is not made when this is seen in combination with hyperkalemia and hyperrenin hyperaldosteronism.

  8. Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

    Science.gov (United States)

    Chmiel, James F.; Konstan, Michael W.; Elborn, J. Stuart

    2013-01-01

    Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from 38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. PMID:23880054

  9. Thoracic findings in pediatric patiens with cystic fibrosis

    International Nuclear Information System (INIS)

    Wunsch, R.; Wunsch, C.

    2003-01-01

    Cystic fibrosis is the most common autosomal recessive metabolic disease in Europe with an incidence of 1:2500. The severity of the lung disease is the most important factor of morbidity and mortality in CF-patients. Because of the better diagnostic and therapeutic modalities life expectancy has increased significantly. The underlying pathology is a defect of chromosome 7, which encodes the regulation of the fluid balance across the cell membrane which effects chloride as well as sodium. The exocrine glands produce a viscous mucus which obstructs the airways and promotes infections. The result is the destruction of lung parenchyma. In daily routine, chest x-ray is still the most important radiological tool, although computed tomography depicts changes in morphology earlier and more exactly. Recent research studies show that MRI has - because of its additional functional options - interesting aspects for the future. (orig.) [de

  10. Genetic modifiers of nutritional status in cystic fibrosis1234

    Science.gov (United States)

    Bradley, Gia M; Blackman, Scott M; Watson, Christopher P; Doshi, Vishal K; Cutting, Garry R

    2012-01-01

    Background: Improved nutrition early in life is associated with better pulmonary function for patients with cystic fibrosis (CF). However, nutritional status is poorly correlated with the CFTR genotype. Objective: We investigated the extent to which modifier genes influence nutrition in children with CF. Design: BMI data were longitudinally collected from the CF Twin-Sibling Study and Cystic Fibrosis Foundation Patient Registry for twins and siblings from 2000 to 2010. A nutritional phenotype was derived for 1124 subjects by calculating the average BMI z score from 5–10 y of age (BMI-z5to10). The genetic contribution to the variation in BMI-z5to10 (ie, heritability) was estimated by comparing the similarity of the phenotype in monozygous twins to that in dizygous twins and siblings. Linkage analysis identified potential modifier-gene loci. Results: The median BMI-z5to10 was −0.07 (range: −3.89 to 2.30), which corresponded to the 47th CDC percentile. BMI-z5to10 was negatively correlated with pancreatic insufficiency, history of meconium ileus, and female sex but positively correlated with later birth cohorts and lung function. Monozygous twins showed greater concordance for BMI-z5to10 than did dizygous twins and siblings; heritability estimates from same-sex twin-only analyses ranged from 0.54 to 0.82. For 1010 subjects with pancreatic insufficiency, genome-wide significant linkage was identified on chromosomes 1p36.1 [log of odds (LOD): 5.3] and 5q14 (LOD: 5.1). These loci explained ≥16% and ≥15%, respectively, of the BMI variance. Conclusions: The analysis of twins and siblings with CF indicates a prominent role for genes other than CFTR to BMI variation. Specifically, regions on chromosomes 1 and 5 appear to harbor genetic modifiers of substantial effect. PMID:23134884

  11. Genetic modifiers of nutritional status in cystic fibrosis.

    Science.gov (United States)

    Bradley, Gia M; Blackman, Scott M; Watson, Christopher P; Doshi, Vishal K; Cutting, Garry R

    2012-12-01

    Improved nutrition early in life is associated with better pulmonary function for patients with cystic fibrosis (CF). However, nutritional status is poorly correlated with the CFTR genotype. We investigated the extent to which modifier genes influence nutrition in children with CF. BMI data were longitudinally collected from the CF Twin-Sibling Study and Cystic Fibrosis Foundation Patient Registry for twins and siblings from 2000 to 2010. A nutritional phenotype was derived for 1124 subjects by calculating the average BMI z score from 5-10 y of age (BMI-z(5to10)). The genetic contribution to the variation in BMI-z(5to10) (ie, heritability) was estimated by comparing the similarity of the phenotype in monozygous twins to that in dizygous twins and siblings. Linkage analysis identified potential modifier-gene loci. The median BMI-z(5to10) was -0.07 (range: -3.89 to 2.30), which corresponded to the 47th CDC percentile. BMI-z(5to10) was negatively correlated with pancreatic insufficiency, history of meconium ileus, and female sex but positively correlated with later birth cohorts and lung function. Monozygous twins showed greater concordance for BMI-z(5to10) than did dizygous twins and siblings; heritability estimates from same-sex twin-only analyses ranged from 0.54 to 0.82. For 1010 subjects with pancreatic insufficiency, genome-wide significant linkage was identified on chromosomes 1p36.1 [log of odds (LOD): 5.3] and 5q14 (LOD: 5.1). These loci explained ≥16% and ≥15%, respectively, of the BMI variance. The analysis of twins and siblings with CF indicates a prominent role for genes other than CFTR to BMI variation. Specifically, regions on chromosomes 1 and 5 appear to harbor genetic modifiers of substantial effect.

  12. CFTR, Mucins, and Mucus Obstruction in Cystic Fibrosis

    Science.gov (United States)

    Kreda, Silvia M.; Davis, C. William; Rose, Mary Callaghan

    2012-01-01

    Mucus pathology in cystic fibrosis (CF) has been known for as long as the disease has been recognized and is sometimes called mucoviscidosis. The disease is marked by mucus hyperproduction and plugging in many organs, which are usually most fatal in the airways of CF patients, once the problem of meconium ileus at birth is resolved. After the CF gene, CFTR, was cloned and its protein product identified as a cAMP-regulated Cl− channel, causal mechanisms underlying the strong mucus phenotype of the disease became obscure. Here we focus on mucin genes and polymeric mucin glycoproteins, examining their regulation and potential relationships to a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR). Detailed examination of CFTR expression in organs and different cell types indicates that changes in CFTR expression do not always correlate with the severity of CF disease or mucus accumulation. Thus, the mucus hyperproduction that typifies CF does not appear to be a direct cause of a defective CFTR but, rather, to be a downstream consequence. In organs like the lung, up-regulation of mucin gene expression by inflammation results from chronic infection; however, in other instances and organs, the inflammation may have a non-infectious origin. The mucus plugging phenotype of the β-subunit of the epithelial Na+ channel (βENaC)-overexpressing mouse is proving to be an archetypal example of this kind of inflammation, with a dehydrated airway surface/concentrated mucus gel apparently providing the inflammatory stimulus. Data indicate that the luminal HCO3 − deficiency recently described for CF epithelia may also provide such a stimulus, perhaps by causing a mal-maturation of mucins as they are released onto luminal surfaces. In any event, the path between CFTR dysfunction and mucus hyperproduction has proven tortuous, and its unraveling continues to offer its own twists and turns, along with fascinating glimpses into biology. PMID:22951447

  13. Genetic testing for cystic fibrosis in adult patients

    Directory of Open Access Journals (Sweden)

    Marina Mencinger

    2006-02-01

    Full Text Available Background: Cystic fibrosis (CF is an autosomal recessive disease caused by mutations in gene encoding cystic fibrosis transmembrane regulator (CFTR protein. Over 1400 mutations found in the gene contribute to the complexity of the CF phenotypes ranging from a classic multiorgan disease commonly involving respiratory, gastrointestinal and reproductive tract to mild and monosymptomatic presentations. Pilocarpine iontophoresis is considered as standard diagnostic test for CF, but it often fails in atypical forms of CF.Methods: In order to provide an additional diagnostic test to assure the diagnosis and provide patients with a proper medical care, we performed a genetic testing on 16 adults suspected to have atypical form of CF. Following counselling, parents of patients with possible homozygote variant of mutations were tested. On a personal request testing was also performed in an adult sibling of a patient with two known mutations to investigate possible carrier hood. The allele specific polymerase chain reaction method (PCR was used to detect 29 most common mutations in the cftr gene.Results: The diagnosis was proved in 3 individuals, a homozygote for Δ F508, and two compound heterozygotes Δ F508/R1162X and Δ F508/3849+10kbC>T. In three cases only one mutation was found: I148T, 2789+5G>A and Δ F508 in a heterozygote form.Conclusions: The genetic testing for CF is a valuable diagnostic tool in atypical forms of CF. Exclusion of possible differential diagnosis is warranted because of a variable CF phenotype. In cases where only one or no mutation was detected a necessity of whole gene sequencing is indicated to exclude rare mutations and polymorphisms that could be implicated in the pathogenesis of atypical CF.

  14. Multidimensional clinical phenotyping of an adult cystic fibrosis patient population.

    Directory of Open Access Journals (Sweden)

    Douglas J Conrad

    Full Text Available Cystic Fibrosis (CF is a multi-systemic disease resulting from mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR gene and has major manifestations in the sino-pulmonary, and gastro-intestinal tracts. Clinical phenotypes were generated using 26 common clinical variables to generate classes that overlapped quantiles of lung function and were based on multiple aspects of CF systemic disease.The variables included age, gender, CFTR mutations, FEV1% predicted, FVC% predicted, height, weight, Brasfield chest xray score, pancreatic sufficiency status and clinical microbiology results. Complete datasets were compiled on 211 subjects. Phenotypes were identified using a proximity matrix generated by the unsupervised Random Forests algorithm and subsequent clustering by the Partitioning around Medoids (PAM algorithm. The final phenotypic classes were then characterized and compared to a similar dataset obtained three years earlier.Clinical phenotypes were identified using a clustering strategy that generated four and five phenotypes. Each strategy identified 1 a low lung health scores phenotype, 2 a younger, well-nourished, male-dominated class, 3 various high lung health score phenotypes that varied in terms of age, gender and nutritional status. This multidimensional clinical phenotyping strategy identified classes with expected microbiology results and low risk clinical phenotypes with pancreatic sufficiency.This study demonstrated regional adult CF clinical phenotypes using non-parametric, continuous, ordinal and categorical data with a minimal amount of subjective data to identify clinically relevant phenotypes. These studies identified the relative stability of the phenotypes, demonstrated specific phenotypes consistent with published findings and identified others needing further study.

  15. Viral and atypical bacterial infections in the outpatient pediatric cystic fibrosis clinic

    DEFF Research Database (Denmark)

    Olesen, Hanne Vebert; Nielsen, Lars P; Schiotz, Peter Oluf

    2006-01-01

    BACKGROUND: Respiratory viral and atypical bacterial infections are associated with pulmonary exacerbations and hospitalisations in cystic fibrosis patients. We wanted to study the impact of such infections on children attending the outpatient clinic. METHODS: Seventy-five children were followed...

  16. Fat absorption in cystic fibrosis mice is impeded by defective lipolysis and post-lipolytic events

    NARCIS (Netherlands)

    Bijvelds, MJC; Bronsveld, [No Value; Havinga, R; Sinaasappel, M; de Jonge, HR; Verkade, HJ

    Cystic fibrosis (CF) is frequently associated with progressive loss of exocrine pancreas function, leading to incomplete digestion and absorption of dietary fat. Supplementing patients with pancreatic lipase reduces fat excretion, but it does not completely correct fat malabsorption, indicating that

  17. Hyponatremia-associated rhabdomyolysis following exercise in an adolescent with cystic fibrosis.

    Science.gov (United States)

    Kaskavage, Jillian; Sklansky, Daniel

    2012-07-01

    Adolescents with well-controlled cystic fibrosis, including good lung function and appropriate growth, commonly participate in competitive athletic activities. We present the case of an adolescent male with cystic fibrosis, hyponatremia, dehydration, and rhabdomyolysis after participating in football practice on a summer morning. The patient presented with severe myalgia and serum sodium of 129 mmol/L, chloride 90 mmol/L, and creatine phosphokinase 1146 U/L. Aggressive hydration with intravenous 0.9% saline resulted in clinical improvement with no renal or muscular sequelae. Health care providers need to educate patients with cystic fibrosis about maintaining adequate hydration and sodium repletion during exercise. Research is needed regarding the appropriate amount and composition of oral rehydration fluids in exercising individuals with cystic fibrosis, as the physiology encountered in these patients provides a unique challenge to maintaining electrolyte balance and stimulation of thirst.

  18. Iron accumulates in the lavage and explanted lungs of cystic fibrosis patients.

    Science.gov (United States)

    Abstract Oxidative stress participates in the pathophysiology of cystic fibrosis (CF). An underlying disruption in iron homeostasis can frequently be demonstrated in injuries and diseases associated with an oxidative stress. We tested the hypothesis that iron accumulation and ...

  19. Sodium and chlorine levels in hair and nails of healthy and cystic fibrosis children

    International Nuclear Information System (INIS)

    Olguin, M.T.; Jimenez-Reyes, M.; Pen-Aguilar, M.T.; Sanchez-Aguirre, F.J.

    1994-01-01

    Sodium and chlorine values are reported in μ/g, as determined by neutron activation analysis in washed hair and nails from healthy and cystic fibrosis children. The values thus determined in cystic fibrosis tended to be higher than those in controls, however statistical differences were not significant (p>0.01). Additional experiments were carried out for comparison between washed and unwashed samples of the cystic fibrosis and control group and only the differences between washed and unwashed cystic fibrosis nails were significant (p<0.01) in both sodium and chlorine values. Analysis of a standard reference milk sample, A-11 from IAEA, for the elements mentioned above gave a good agreement with the certified values. (author) 24 refs.; 6 figs.; 2 tabs

  20. Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum.

    Science.gov (United States)

    Shak, S; Capon, D J; Hellmiss, R; Marsters, S A; Baker, C L

    1990-12-01

    Respiratory distress and progressive lung destruction in cystic fibrosis can be attributed to bacterial persistence and the accumulation of viscous purulent secretions in the airways. More than 30 yr ago it was suggested that the large amounts of DNA in purulent secretions contribute to its viscosity and that bovine pancreatic DNase I could reduce the viscosity. To evaluate the potential clinical utility of recombinant human DNase I (rhDNase) in the treatment of cystic fibrosis, we have cloned, sequenced, and expressed rhDNase. Catalytic amounts of rhDNase greatly reduce the viscosity of purulent cystic fibrosis sputum, transforming it within minutes from a nonflowing viscous gel to a flowing liquid. The reduction in viscosity is associated with a decrease in size of DNA in the sputum. Inhalation of a rhDNase aerosol may be a simple direct approach that will help individuals with cystic fibrosis and other patients with pneumonia or bronchitis to clear their airways of purulent secretions.

  1. Pharmacoeconomic review of recombinant human DNase in the management of cystic fibrosis

    NARCIS (Netherlands)

    Zijlstra, Gerrit; Boersma, Cornelis; Frijlink, Henderik W.; Postma, Maarten J.

    For the treatment of patients with cystic fibrosis, recombinant human deoxyribonuclease I is widely used. Deoxyribonuclease I has a positive effect on lung function and the number of hospitalizations. Deoxyribonuclease I is currently administered by nebulization, which is an inefficient

  2. Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Larissa Lazzarini Furlan

    2017-11-01

    Conclusions: This study highlighted the importance of the rs4073 variant of the interleukin 8 gene, regarding response to inhaled bronchodilators, and of the assessment of mutations in the cystic fibrosis transmembrane conductance regulator gene.

  3. Vitamin A intake and serum retinol levels in children and adolescents with cystic fibrosis

    NARCIS (Netherlands)

    Woestenenk, JW; Broos, Nancy; Stellato, Rebecca K; Arets, Hubertus G M; van der Ent, Cornelis K.; Houwen, RHJ

    2016-01-01

    BACKGROUND: Pancreatic insufficient cystic fibrosis (CF) patients receive vitamin A supplementation according to CF-specific recommendations to prevent deficiencies. Whether current recommendations are optimal for preventing both deficiency and toxicity is a subject of debate. We assessed the

  4. [Cystic fibrosis--initial diagnosis in a 39-year-old patient].

    Science.gov (United States)

    Bargon, J; Rickmann, J; Jacobi, V; Straub, R; Arnemann, J; Wagner, T O

    2000-12-15

    Cystic fibrosis is the most common hereditary disorder among Caucasians. Most of the patients are diagnosed as children. However, some cases are going undiagnosed into adulthood and are then often misdiagnosed because the non-pediatricians do not know cystic fibrosis very well and do not consider this diagnosis in adult patients. We present the medical history of a woman, who was diagnosed with cystic fibrosis at the age of 39 years, although she had suffered from bronchiectasis, pancreatic insufficiency and liver cirrhosis since many years. Her medical history was long with some diagnosis, but because of her age nobody considered the final diagnosis. In adult patients with bronchiectasis, liver cirrhosis and pancreatic insufficiency in combination or with only one of these symptoms, cystic fibrosis should be included into the differential diagnosis.

  5. Influence of the cystic fibrosis transmembrane conductance regulator on expression of lipid metabolism-related genes in dendritic cells

    Directory of Open Access Journals (Sweden)

    Quadri Luis EN

    2009-04-01

    Full Text Available Abstract Background Cystic fibrosis (CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR gene. Infections of the respiratory tract are a hallmark in CF. The host immune responses in CF are not adequate to eradicate pathogens, such as P. aeruginosa. Dendritic cells (DC are crucial in initiation and regulation of immune responses. Changes in DC function could contribute to abnormal immune responses on multiple levels. The role of DC in CF lung disease remains unknown. Methods This study investigated the expression of CFTR gene in bone marrow-derived DC. We compared the differentiation and maturation profile of DC from CF and wild type (WT mice. We analyzed the gene expression levels in DC from naive CF and WT mice or following P. aeruginosa infection. Results CFTR is expressed in DC with lower level compared to lung tissue. DC from CF mice showed a delayed in the early phase of differentiation. Gene expression analysis in DC generated from naive CF and WT mice revealed decreased expression of Caveolin-1 (Cav1, a membrane lipid raft protein, in the CF DC compared to WT DC. Consistently, protein and activity levels of the sterol regulatory element binding protein (SREBP, a negative regulator of Cav1 expression, were increased in CF DC. Following exposure to P. aeruginosa, expression of 3β-hydroxysterol-Δ7 reductase (Dhcr7 and stearoyl-CoA desaturase 2 (Scd2, two enzymes involved in the lipid metabolism that are also regulated by SREBP, was less decreased in the CF DC compared to WT DC. Conclusion These results suggest that CFTR dysfunction in DC affects factors involved in membrane structure and lipid-metabolism, which may contribute to the abnormal inflammatory and immune response characteristic of CF.

  6. Tobramycin administered by the TOBI® Podhaler® for persons with cystic fibrosis: a review

    Directory of Open Access Journals (Sweden)

    VanDevanter DR

    2011-09-01

    Full Text Available Donald R VanDevanter1, David E Geller21Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, 2Nemours Children’s Clinic, Orlando, FL, USAAbstract: From its introduction, the antibiotic tobramycin has been an important tool in the management of persons with cystic fibrosis (CF and chronic Pseudomonas aeruginosa lung infections. Initially an intravenous rescue treatment for pulmonary exacerbations, tobramycin delivered by inhalation has become a mainstay of chronic suppressive CF infection management. Platforms for tobramycin aerosol delivery have steadily improved, with increased lung deposition complimented by decreased device complexities, loaded tobramycin doses, delivery times, and treatment burdens. Most recently, a unique tobramycin inhalation powder (TIP formulation with a portable delivery system, the TOBI® Podhaler® (Novartis AG, Basel, Switzerland has been developed and approved in Europe, Canada, and Chile. Four capsules, each containing 28 mg of TIP are successively pierced and inhaled via the T-326 Dry Powder Inhaler Device (Novartis AG, Basel, Switzerland. No external power source is required to deliver an efficacious tobramycin dose in minutes. By comparison, tobramycin inhalation solution (TIS (TOBI®; Novartis, is delivered by LC® Plus (PARI Respiratory Equipment Inc, Midlothian, VA jet nebulizer powered by an air compressor over 15–20 minutes. Comparative pharmacokinetics, safety, and efficacy studies of TIS and TIP in CF subjects with P. aeruginosa ≥ 6 years old demonstrate that: tobramycin lung deposition with 112 mg TIP is comparable to that attained with 300 mg TIS, TIP is more effective than placebo and not inferior to TIS with respect to pulmonary function benefit, and TIP has significantly faster treatment times and achieves higher patient satisfaction than TIS. TIP is associated with an increased frequency of mild to moderate local adverse events (cough, dysphonia, and

  7. Asthma and COPD in cystic fibrosis intron-8 5T carriers. A population-based study

    DEFF Research Database (Denmark)

    Dahl, Morten; Tybjaerg-Hansen, Anne; Lange, Peter

    2005-01-01

    Carriers of cystic fibrosis intron-8 5T alleles with high exon-9 skipping could have increased annual lung function decline and increased risk for asthma or chronic obstructive pulmonary disease (COPD).......Carriers of cystic fibrosis intron-8 5T alleles with high exon-9 skipping could have increased annual lung function decline and increased risk for asthma or chronic obstructive pulmonary disease (COPD)....

  8. Young patients with cystic fibrosis demonstrate subtle alterations of the cardiovascular system.

    Science.gov (United States)

    Eising, Jacobien B; van der Ent, Cornelis K; Teske, Arco J; Vanderschuren, Maaike M; Uiterwaal, Cuno S P M; Meijboom, Folkert J

    2018-02-02

    As life expectancy increases in patients with cystic fibrosis, it is important to pay attention to extra-pulmonary comorbidities. Several studies have shown signs of myocardial dysfunction in adult patients, but little is known about onset and development of these changes over time. In this prospective study, cardiac function in children with cystic fibrosis was compared to that of healthy children. 33 children, aged 3-12years, with cystic fibrosis were recruited from the Wilhelmina Children's hospital and 33 age-matched healthy children were selected from the WHISTLER study, a population-based cohort study. Measurements of lung function, arterial stiffness, and echocardiography (conventional measures and myocardial deformation imaging) were performed. There were no differences in anthropometrics, lung function and blood pressure between the two groups. The cystic fibrosis children had a higher arterial stiffness compared to the healthy children (pulse wave velocity respectively 5.76±0.57m/s versus 5.43±0.61m/s, p-value 0.049). Using conventional echocardiographic parameters for right ventricular function, Tricuspid Annular Plane Systolic Excursion) and Tissue Doppler Imaging, cystic fibrosis children had a reduced right ventricular systolic function when compared to the healthy children. After adjustment for lung function, global strains of both right and left ventricles were significantly lower in the cystic fibrosis group than in healthy children (linear regression coefficient 1.45% left ventricle, p-value 0.022 and 4.42% right ventricle, p-value cystic fibrosis children than in healthy controls. Our study suggests that already at a very young age, children with cystic fibrosis show an increased arterial stiffness and some signs of diminished both right and left ventricular function. Copyright © 2018. Published by Elsevier B.V.

  9. Cost Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.

    Science.gov (United States)

    Gini, Andrea; Zauber, Ann G; Cenin, Dayna R; Omidvari, Amir-Houshang; Hempstead, Sarah E; Fink, Aliza K; Lowenfels, Albert B; Lansdorp-Vogelaar, Iris

    2018-02-01

    Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared with the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. We adjusted the existing Microsimulation Screening Analysis-Colon model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess if optimal screening strategies would change. Colonoscopy every 5 years, starting at an age of 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in this population is not clear. Using a Microsimulation Screening Analysis-Colon model, we found screening of patients with cystic fibrosis for CRC to be cost effective. Because of the higher risk of CRC in these patients, screening should start at an earlier age with a shorter screening interval. The findings of this study (especially those on FIT

  10. Cost-Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.

    Science.gov (United States)

    Gini, Andrea; Zauber, Ann G; Cenin, Dayna R; Omidvari, Amir-Houshang; Hempstead, Sarah E; Fink, Aliza K; Lowenfels, Albert B; Lansdorp-Vogelaar, Iris

    2017-12-27

    Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared to the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. We adjusted the existing Microsimulation Screening Analysis-Colon microsimulation model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess whether optimal screening strategies would change. Colonoscopy every 5 years, starting at age 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in population is not clear. Using a Microsimulation Screening Analysis-Colon microsimulation model, we found screening of patients with cystic fibrosis for CRC to be cost-effective. Due to the higher risk in these patients for CRC, screening should start at an earlier age with a shorter screening interval. The findings of this study

  11. Cost Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer

    OpenAIRE

    Gini, A. (Andrea); Zauber, Ann; Cenin, Dayna R.; Omidvari, A.-H. (Amir-Houshang); Hempstead, S.E. (Sarah E.); Fink, A.K. (Aliza K.); Lowenfels, A.B. (Albert B.); Lansdorp-Vogelaar, Iris

    2018-01-01

    textabstractBackground & Aims: Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared with the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. Methods: We adjusted the existing Microsimulation Screening Analysis-Colon model to reflect increased CRC risk and lower life expectancy in patients with cys...

  12. Cystic Fibrosis-Related Diabetes in Adults: Where Can We Go From Here?

    OpenAIRE

    de Valk, Harold W.; van der Graaf, Eduard A.

    2007-01-01

    Cystic fibrosis (CF), a dysfunction of the exocrine glands, is one of the most frequently diagnosed genetic diseases. It is characterized by chronic pulmonary disease and pancreatic deficiency. Cystic fibrosis-related diabetes (CFRD) is a complication of CF and develops from impaired glucose tolerance via postprandial hyperglycemia with fasting normoglycemia to full-blown diabetes with fasting and postprandial hyperglycemia. CFRD is related to decreased life expectancy, most notably in female...

  13. A Fresh Shine onCystic Fibrosis Inhalation Therapy: Antimicrobial Synergy of Polymyxin B in Combination with Silver Nanoparticles.

    Science.gov (United States)

    Jasim, Raad; Schneider, Elena K; Han, Meiling; Azad, Mohammad A K; Hussein, Maytham; Nowell, Cameron; Baker, Mark A; Wang, Jiping; Li, Jian; Velkov, Tony

    2017-04-01

    This in vitro study aimed to investigate the synergistic antibacterial activity of polymyxin B in combination with 2 nm silver nanoparticles (NPs) against Gram-negative pathogens commonly isolated from the cystic fibrosis (CF) lung. The in vitro synergistic activity of polymyxin B with silver NPs was assessed using the checkerboard assay against polymyxinsusceptible and polymyxin-resistant Pseudomonas aeruginosa isolates from the lungs of CF patients. The combination was also examined against the Gram-negative species Haemophilus influenzae, Burkholderia cepacia, Burkholderia pseudomallei, Stenotrophomonas maltophilia, Klebsiella pneumoniae and Acinetobacter baumannii that are less common in the CF lung. The killing kinetics of the polymyxin B-silver NPs combinations was assessed against P. aeruginosa by static time-kill assays over 24 h. Polymyxin B and silver NPs alone were not active against polymyxin-resistant (MIC ≥4 mg/L) P. aeruginosa. Whereas, the combination of a clinically-relevant concentration of polymyxin B (2 mg/L) with silver NPs (4 mg/L) successfully inhibited the growth of polymyxin-resistant P. aeruginosa isolates from CF patients as demonstrated by ≥2 log10 decrease in bacterial count (CFU/mL) after 24 h. Treatment of P. aeruginosa cells with the combination induced cytosolic GFP release and an increase of cellular reactive oxygen species. In the nitrocefin assay, the combination displayed a membrane permeabilizing activity superior to each of the drugs alone. The combination of polymyxin B and silver NPs displays excellent synergistic activity against highly polymyxin-resistant P. aeruginosa and is potentially of considerable clinical utility for the treatment of problematic CF lung infections.

  14. Cystic fibrosis transmembrane conductance regulator (CFTR allelic variants relate to shifts in faecal microbiota of cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Serena Schippa

    Full Text Available INTRODUCTION: In this study we investigated the effects of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR gene variants on the composition of faecal microbiota, in patients affected by Cystic Fibrosis (CF. CFTR mutations (F508del is the most common lead to a decreased secretion of chloride/water, and to mucus sticky secretions, in pancreas, respiratory and gastrointestinal tracts. Intestinal manifestations are underestimated in CF, leading to ileum meconium at birth, or small bowel bacterial overgrowth in adult age. METHODS: Thirty-six CF patients, fasting and under no-antibiotic treatment, were CFTR genotyped on both alleles. Faecal samples were subjected to molecular microbial profiling through Temporal Temperature Gradient Electrophoresis and species-specific PCR. Ecological parameters and multivariate algorithms were employed to find out if CFTR variants could be related to the microbiota structure. RESULTS: Patients were classified by two different criteria: 1 presence/absence of F508del mutation; 2 disease severity in heterozygous and homozygous F508del patients. We found that homozygous-F508del and severe CF patients exhibited an enhanced dysbiotic faecal microbiota composition, even within the CF cohort itself, with higher biodiversity and evenness. We also found, by species-specific PCR, that potentially harmful species (Escherichia coli and Eubacterium biforme were abundant in homozygous-F508del and severe CF patients, while beneficial species (Faecalibacterium prausnitzii, Bifidobacterium spp., and Eubacterium limosum were reduced. CONCLUSIONS: This is the first report that establishes a link among CFTR variants and shifts in faecal microbiota, opening the way to studies that perceive CF as a 'systemic disease', linking the lung and the gut in a joined axis.

  15. Co-ordinate regulation of the cystic fibrosis and multidrug resistance genes in cystic fibrosis knockout mice.

    Science.gov (United States)

    Trezise, A E; Ratcliff, R; Hawkins, T E; Evans, M J; Freeman, T C; Romano, P R; Higgins, C F; Colledge, W H

    1997-04-01

    The cystic fibrosis (Cftr and multidrug resistance (Mdr1) genes encode structurally similar proteins which are members of the ABC transporter superfamily. These genes exhibit complementary patterns of expression in vivo, suggesting that the regulation of their expression may be co-ordinated. We have tested this hypothesis in vivo by examining Cftr and Mdr1 expression in cystic fibrosis knockout transgenic mice (Cftr(tm1CAM)). Cftr mRNA expression in Cftr(tm1CAM)/Cftr(tm1CAM) mice was 4-fold reduced in the intestine, as compared with littermate wild-type mice. All other Cftr(tm1CAM)/Cftr(tm1CAM) mouse tissues examined showed similar reductions in Cftr expression. In contrast, we observed a 4-fold increase in Mdr1 mRNA expression in the intestines of neonatal and 3- to 4-week-old Cftr(tm1CAM)/Cftr(tm1CAM) mice, as compared with age-matched +/+ mice, and an intermediate level of Mdr1 mRNA in heterozygous Cftr(tm1CAM) mice. In 10-week-old, Cftr(tm1CAM)/Cftr(tm1CAM) mice and in contrast to the younger mice, Mdr1 mRNA expression was reduced, by 3-fold. The expression of two control genes, Pgk-1 and Mdr2, was similar in all genotypes, suggesting that the changes in Mdr1 mRNA levels observed in the Cftr(tm1CAM)/Cftr(tm1CAM) mice are specific to the loss of Cftr expression and/or function. These data provide further evidence supporting the hypothesis that the regulation Cftr and Mdr1 expression is co-ordinated in vivo, and that this co-ordinate regulation is influenced by temporal factors.

  16. Cystic fibrosis transmembrane conductance regulator (CFTR) allelic variants relate to shifts in faecal microbiota of cystic fibrosis patients.

    Science.gov (United States)

    Schippa, Serena; Iebba, Valerio; Santangelo, Floriana; Gagliardi, Antonella; De Biase, Riccardo Valerio; Stamato, Antonella; Bertasi, Serenella; Lucarelli, Marco; Conte, Maria Pia; Quattrucci, Serena

    2013-01-01

    In this study we investigated the effects of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene variants on the composition of faecal microbiota, in patients affected by Cystic Fibrosis (CF). CFTR mutations (F508del is the most common) lead to a decreased secretion of chloride/water, and to mucus sticky secretions, in pancreas, respiratory and gastrointestinal tracts. Intestinal manifestations are underestimated in CF, leading to ileum meconium at birth, or small bowel bacterial overgrowth in adult age. Thirty-six CF patients, fasting and under no-antibiotic treatment, were CFTR genotyped on both alleles. Faecal samples were subjected to molecular microbial profiling through Temporal Temperature Gradient Electrophoresis and species-specific PCR. Ecological parameters and multivariate algorithms were employed to find out if CFTR variants could be related to the microbiota structure. Patients were classified by two different criteria: 1) presence/absence of F508del mutation; 2) disease severity in heterozygous and homozygous F508del patients. We found that homozygous-F508del and severe CF patients exhibited an enhanced dysbiotic faecal microbiota composition, even within the CF cohort itself, with higher biodiversity and evenness. We also found, by species-specific PCR, that potentially harmful species (Escherichia coli and Eubacterium biforme) were abundant in homozygous-F508del and severe CF patients, while beneficial species (Faecalibacterium prausnitzii, Bifidobacterium spp., and Eubacterium limosum) were reduced. This is the first report that establishes a link among CFTR variants and shifts in faecal microbiota, opening the way to studies that perceive CF as a 'systemic disease', linking the lung and the gut in a joined axis.

  17. Decreased coenzyme Q10 concentration in plasma of children with cystic fibrosis

    NARCIS (Netherlands)

    Oudshoorn, J.H.; Lecluse, A.L.Y.; Berg, R. van den; Vaes, W.H.J.; Laag, J. van der; Houwen, R.H.J.

    2006-01-01

    OBJECTIVES: Coenzyme Q10 (CoQ10) is an effective lipophilic antioxidant and protects against lipid peroxidation by scavenging radicals. Patients with cystic fibrosis generally have fat malabsorption; thus, we hypothesized that overall plasma CoQ10 concentration in pediatric patients with cystic

  18. Description and validation of a scoring system for tomosynthesis in pulmonary cystic fibrosis.

    Science.gov (United States)

    Vult von Steyern, Kristina; Björkman-Burtscher, Isabella M; Höglund, Peter; Bozovic, Gracijela; Wiklund, Marie; Geijer, Mats

    2012-12-01

    To design and validate a scoring system for tomosynthesis (digital tomography) in pulmonary cystic fibrosis. A scoring system dedicated to tomosynthesis in pulmonary cystic fibrosis was designed. Three radiologists independently scored 88 pairs of radiographs and tomosynthesis examinations of the chest in 60 patients with cystic fibrosis and 7 oncology patients. Radiographs were scored according to the Brasfield scoring system and tomosynthesis examinations were scored using the new scoring system. Observer agreements for the tomosynthesis score were almost perfect for the total score with square-weighted kappa >0.90, and generally substantial to almost perfect for subscores. Correlation between the tomosynthesis score and the Brasfield score was good for the three observers (Kendall's rank correlation tau 0.68, 0.77 and 0.78). Tomosynthesis was generally scored higher as a percentage of the maximum score. Observer agreements for the total score for Brasfield score were almost perfect (square-weighted kappa 0.80, 0.81 and 0.85). The tomosynthesis scoring system seems robust and correlates well with the Brasfield score. Compared with radiography, tomosynthesis is more sensitive to cystic fibrosis changes, especially bronchiectasis and mucus plugging, and the new tomosynthesis scoring system offers the possibility of more detailed and accurate scoring of disease severity. Tomosynthesis is more sensitive than conventional radiography for pulmonary cystic fibrosis changes. The radiation dose from chest tomosynthesis is low compared with computed tomography. Tomosynthesis may become useful in the regular follow-up of patients with cystic fibrosis.

  19. The role of daily physical activity and nutritional status on bone turnover in cystic fibrosis: a cross-sectional study

    OpenAIRE

    Tejero,Sergio; Cejudo,Pilar; Quintana-Gallego,E.; Sañudo,Borja; Oliva-Pascual-Vaca,A.

    2016-01-01

    ABSTRACT Background Nutritional status and daily physical activity (PA) may be an excellent tool for the maintenance of bone health in patients with cystic fibrosis (CF). Objective To evaluate the relationship between nutritional status, daily physical activity and bone turnover in cystic fibrosis patients. Method A cross-sectional study of adolescent and adult patients diagnosed with clinically stable cystic fibrosis was conducted. Total body, femoral neck, and lumbar spine bone mineral d...

  20. Nebuliser systems for drug delivery in cystic fibrosis.

    Science.gov (United States)

    Daniels, Tracey; Mills, Nicola; Whitaker, Paul

    2013-04-30

    Nebuliser systems are used to deliver medications to control the symptoms and the progression of lung disease in people with cystic fibrosis. Many types of nebuliser systems are available for use with various medications; however, there has been no previous systematic review which has evaluated these systems. To evaluate effectiveness, safety, burden of treatment and adherence to nebulised therapy using different nebuliser systems for people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching of relevant journals and abstract books of conference proceedings. We searched the reference lists of each study for additional publications and approached the manufacturers of both nebuliser systems and nebulised medications for published and unpublished data. Date of the most recent search: 15 Oct 2012. Randomised controlled trials or quasi-randomised controlled trials comparing nebuliser systems including conventional nebulisers, vibrating mesh technology systems, adaptive aerosol delivery systems and ultrasonic nebuliser systems. Two authors independently assessed studies for inclusion. They also independently extracted data and assessed the risk of bias. A third author assessed studies where agreement could not be reached. The search identified 40 studies with 20 of these (1936 participants) included in the review. These studies compared the delivery of tobramycin, colistin, dornase alfa, hypertonic sodium chloride and other solutions through the different nebuliser systems. This review demonstrates variability in the delivery of medication depending on the nebuliser system used. Conventional nebuliser systems providing higher flows, higher respirable fractions and smaller particles decrease treatment time, increase deposition and may be preferred by people with CF, as compared to conventional nebuliser systems providing

  1. Benign and Deleterious Cystic Fibrosis Transmembrane Conductance Regulator Mutations Identified by Sequencing in Positive Cystic Fibrosis Newborn Screen Children from California.

    Science.gov (United States)

    Salinas, Danieli B; Sosnay, Patrick R; Azen, Colleen; Young, Suzanne; Raraigh, Karen S; Keens, Thomas G; Kharrazi, Martin

    2016-01-01

    Of the 2007 Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutations, 202 have been assigned disease liability. California's racially diverse population, along with CFTR sequencing as part of newborn screening model, provides the opportunity to examine the phenotypes of children with uncategorized mutations to help inform disease liability and penetrance. We conducted a retrospective cohort study based on children screened from 2007 to 2011 and followed for two to six years. Newborns that screened positive were divided into three genotype groups: those with two CF-causing mutations (CF-C); those with one mutation of varying clinic consequence (VCC); and those with one mutation of unknown disease liability (Unknown). Sweat chloride tests, pancreatic sufficiency status, and Pseudomonas aeruginosa colonization were compared. Children with two CF-causing mutations had a classical CF phenotype, while 5% of VCC (4/78) and 11% of Unknown (27/244) met diagnostic criteria of CF. Children carrying Unknown mutations 2215insG with D836Y, and T1036N had early and classical CF phenotype, while others carrying 1525-42G>A, L320V, L967S, R170H, and 296+28A>G had a benign clinical presentation, suggesting that these are non-CF causing. While most infants with VCC and Unknown CFTR mutations do not meet diagnostic criteria for CF, a small proportion do. These findings highlight the range of genotypes and phenotypes in the first few years of life following CF newborn screening when CFTR sequencing is performed.

  2. Benign and Deleterious Cystic Fibrosis Transmembrane Conductance Regulator Mutations Identified by Sequencing in Positive Cystic Fibrosis Newborn Screen Children from California.

    Directory of Open Access Journals (Sweden)

    Danieli B Salinas

    Full Text Available Of the 2007 Cystic Fibrosis Transmembrane Conductance Regulator (CFTR mutations, 202 have been assigned disease liability. California's racially diverse population, along with CFTR sequencing as part of newborn screening model, provides the opportunity to examine the phenotypes of children with uncategorized mutations to help inform disease liability and penetrance.We conducted a retrospective cohort study based on children screened from 2007 to 2011 and followed for two to six years. Newborns that screened positive were divided into three genotype groups: those with two CF-causing mutations (CF-C; those with one mutation of varying clinic consequence (VCC; and those with one mutation of unknown disease liability (Unknown. Sweat chloride tests, pancreatic sufficiency status, and Pseudomonas aeruginosa colonization were compared.Children with two CF-causing mutations had a classical CF phenotype, while 5% of VCC (4/78 and 11% of Unknown (27/244 met diagnostic criteria of CF. Children carrying Unknown mutations 2215insG with D836Y, and T1036N had early and classical CF phenotype, while others carrying 1525-42G>A, L320V, L967S, R170H, and 296+28A>G had a benign clinical presentation, suggesting that these are non-CF causing.While most infants with VCC and Unknown CFTR mutations do not meet diagnostic criteria for CF, a small proportion do. These findings highlight the range of genotypes and phenotypes in the first few years of life following CF newborn screening when CFTR sequencing is performed.

  3. An adult cystic fibrosis patient presenting with persistent dyspnea: case report

    Directory of Open Access Journals (Sweden)

    Farinet Catherine L

    2006-05-01

    Full Text Available Abstract Background Persistent dyspnea is a common finding in the cystic fibrosis patient that typically leads to further work up of an alternative pulmonary etiology. Adult cystic fibrosis patients; however, are growing in numbers and they are living into the ages in which coronary artery disease becomes prevalent. Coronary disease should be included in the consideration of diagnostic possibilities. Case presentation A 52-year-old white male with cystic fibrosis was evaluated for exertional dyspnea associated with vague chest discomfort. Diagnostic testing revealed normal white blood cell, hemoglobin and platelet count, basic metabolic panel, fasting lipid profile, HbA1c, with chest radiograph confirming chronic cystic findings unchanged from prior radiographs and an electrocardiogram that revealed sinus rhythm with left anterior fascicular block. Stress thallium testing demonstrated a reversible anteroseptal perfusion defect with a 55% left ventricular ejection fraction. Heart catheterization found a 99% occlusion of the left anterior descending artery extending into the two diagonal branches, with 100% obstruction of the left anterior descending artery at the trifurcation and 70% lesion affecting the first posterior lateral branch of the circumflex artery. Conclusion This case report represents the first description in the medical literature of a cystic fibrosis patient diagnosed with symptomatic coronary artery disease. Applying a standard clinical practice guide proved useful toward evaluating a differential diagnosis for a cystic fibrosis patient presenting with dyspnea and chest discomfort.

  4. Presence of anxiety and depression in patients with bronchiectasis unrelated to cystic fibrosis.

    Science.gov (United States)

    Girón Moreno, Rosa María; Fernandes Vasconcelos, Gilda; Cisneros, Carolina; Gómez-Punter, Rosa Mar; Segrelles Calvo, Gonzalo; Ancochea, Julio

    2013-10-01

    Patients with chronic bronchiectasis (BQ) may suffer from psychological disorders. The objective of this study was to assess the presence of anxiety and depression in patients from a specialised BQ Unit, using validated questionnaires. We included patients consecutively diagnosed with BQ (unrelated to cystic fibrosis) by high resolution computed tomography in the study. Patients were clinically stable in the previous three weeks and voluntarily completed the Beck Depression Inventory, State-Trait Anxiety Inventory and St. George's Respiratory Questionnaire, after signing the informed consent. They were classified according to their scores on the psychological screening questionnaires, and their results were compared with the clinical, radiological and functional parameters and Quality of Life. Seventy patients were included, 48 women and 22 men, with a mean age of 64.19years. Thirty-four percent (34%) of patients showed symptoms of depression, and around 55% had scores above the 50th percentile in trait and state anxiety. The amount of sputum was associated with trait anxiety. Bacterial colonization was related to anxiety (trait and state), especially Pseudomonas aeruginosa colonization. Female patients showed a higher risk of depression. There was no relationship between the Quality of Life scores and the established classifications of anxiety and depression. A high percentage of patients with BQ presented anxiety (trait and state) and depression. The daily sputum production and bacterial colonization (especially with P. aeruginosa) were the variables most related to anxiety; depression was more common in women. We believe that the presence of psychological disorders should be evaluated, especially in patients with this profile. Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.

  5. Activity of innate antimicrobial peptides and ivacaftor against clinical cystic fibrosis respiratory pathogens.

    Science.gov (United States)

    Payne, Joanna E; Dubois, Alice V; Ingram, Rebecca J; Weldon, Sinead; Taggart, Clifford C; Elborn, J Stuart; Tunney, Michael M

    2017-09-01

    There is a clear need for new antimicrobials to improve current treatment of chronic lung infection in people with cystic fibrosis (CF). This study determined the activities of antimicrobial peptides (AMPs) and ivacaftor, a novel CF transmembrane conductance regulator potentiator, for CF treatment. Antimicrobial activities of AMPs [LL37, human β-defensins (HβD) 1-4 and SLPI] and ivacaftor against clinical respiratory isolates (Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus spp., Achromobacter spp. and Stenotrophomonas maltophilia) were determined using radial diffusion and time-kill assays, respectively. Synergy of LL37 and ivacaftor with tobramycin was determined by time-kill, with in vivo activity of ivacaftor and tobramycin compared using a murine infection model. LL37 and HβD3 were the most active AMPs tested, with MICs ranging from 3.2- ≥ 200 mg/L and 4.8- ≥ 200 mg/L, respectively, except for Achromobacter that was resistant. HβD1 and SLPI demonstrated no antimicrobial activity. LL37 demonstrated synergy with tobramycin against 4/5 S. aureus and 2/5 Streptococcus spp. isolates. Ivacaftor demonstrated bactericidal activity against Streptococcus spp. (mean log 10 decrease 3.31 CFU/mL) and bacteriostatic activity against S. aureus (mean log 10 change 0.13 CFU/mL), but no activity against other genera. Moreover, ivacaftor demonstrated synergy with tobramycin, with mean log 10 decreases of 5.72 CFU/mL and 5.53 CFU/mL at 24 h for S. aureus and Streptococcus spp., respectively. Ivacaftor demonstrated immunomodulatory but no antimicrobial activity in a P. aeruginosa in vivo murine infection model. Following further modulation to enhance activity, AMPs and ivacaftor offer real potential as therapeutics to augment antibiotic therapy of respiratory infection in CF. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  6. Elevated IgG4 serum levels in patients with cystic fibrosis.

    Science.gov (United States)

    Clerc, Axelle; Reynaud, Quitterie; Durupt, Stéphane; Chapuis-Cellier, Colette; Nové-Josserand, Raphaële; Durieu, Isabelle; Lega, Jean Christophe

    2017-01-01

    Serum immunoglobulin (Ig) G4 elevation has been associated with several pathological conditions other than IgG4-related disease (IgG4-RD). In cystic fibrosis (CF), an elevation of specific IgG4 has been associated with colonization and infection by Pseudomonas aeruginosa. IgG4 elevation may be a marker of chronic infection or inflammatory stimulation. The aim of this study was to explore the prevalence of elevated IgG4 levels in CF and its correlation with the major clinical and microbiological features found in CF patients. In a cross-sectional study, we analyzed data from a large cohort of adult CF patients attending the CF center of Lyon University Hospital. An elevated IgG4 level was defined as being above the cut-off value of 135 mg/dL. One hundred and sixty-five CF patients were analyzed. An IgG4 elevation was detected in 43 patients (26%). Compared with the control group (≤ 135 mg/dL), high IgG4 patients exhibited a greater prevalence of Staphylococcus aureus colonization and higher IgG, IgG1, IgG2 and IgE levels. No significant differences were observed in terms of pulmonary function, colonization with Pseudomonas aeruginosa, or the annual rate of bronchial exacerbations. An elevated IgG4 serum level was frequently detected in adult CF patients and did not appear to be associated with poor lung function. We suggest that IgG4 elevation is a marker of the activation of tolerance. Its clinical significance remains to be demonstrated.

  7. Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease

    Science.gov (United States)

    Flynn, Jeffrey M.; Niccum, David; Dunitz, Jordan M.

    2016-01-01

    Chronic lung infections in cystic fibrosis (CF) patients are composed of complex microbial communities that incite persistent inflammation and airway damage. Despite the high density of bacteria that colonize the lower airways, nutrient sources that sustain bacterial growth in vivo, and how those nutrients are derived, are not well characterized. In this study, we examined the possibility that mucins serve as an important carbon reservoir for the CF lung microbiota. While Pseudomonas aeruginosa was unable to efficiently utilize mucins in isolation, we found that anaerobic, mucin-fermenting bacteria could stimulate the robust growth of CF pathogens when provided intact mucins as a sole carbon source. 16S rRNA sequencing and enrichment culturing of sputum also identified that mucin-degrading anaerobes are ubiquitous in the airways of CF patients. The collective fermentative metabolism of these mucin-degrading communities in vitro generated amino acids and short chain fatty acids (propionate and acetate) during growth on mucin, and the same metabolites were also found in abundance within expectorated sputum. The significance of these findings was supported by in vivo P. aeruginosa gene expression, which revealed a heightened expression of genes required for the catabolism of propionate. Given that propionate is exclusively derived from bacterial fermentation, these data provide evidence for an important role of mucin fermenting bacteria in the carbon flux of the lower airways. More specifically, microorganisms typically defined as commensals may contribute to airway disease by degrading mucins, in turn providing nutrients for pathogens otherwise unable to efficiently obtain carbon in the lung. PMID:27548479

  8. Desensitization to inhaled aztreonam lysine in an allergic patient with cystic fibrosis using a novel approach.

    Science.gov (United States)

    Guglani, Lokesh; Abdulhamid, Ibrahim; Ditouras, Joanna; Montejo, Jenny

    2012-10-01

    To report the successful desensitization of a highly allergic patient with cystic fibrosis (CF) to inhaled aztreonam lysine using the novel approach of intravenous desensitization followed by full-dose inhaled therapy without any adverse reactions. A 19-year-old woman with CF had persistent Pseudomonas aeruginosa-positive cultures and a history of type I hypersensitivity reactions to multiple medications, including aztreonam and tobramycin (intravenous and inhaled). To start therapy with an inhaled antipseudomonal antibiotic on a chronic basis, she underwent rapid desensitization to intravenous aztreonam followed by initiation of inhaled aztreonam lysine. Following intravenous desensitization with aztreonam, there was no adverse reaction or decline in lung function noted with inhaled aztreonam lysine and the chronic therapy was continued at home, with a modified regimen to maintain desensitization. Aztreonam lysine has been used for treatment of patients with CF with chronic P. aeruginosa colonization. Previous allergic reaction to intravenous aztreonam is considered a contraindication for use of aztreonam lysine. Our patient had a history of hives and facial swelling following administration of intravenous aztreonam (type I hypersensitivity reaction) as well as hypersensitivity to tobramycin. Rapid desensitization can be done for drugs that mediate a type I hypersensitivity reaction, with mast cells and basophils being the cellular targets. There are a few case reports of desensitization to inhaled antibiotics such as tobramycin and colistin, but desensitization to aztreonam lysine has not previously been reported. Desensitization of a patient with CF who is allergic to intravenous aztreonam was successfully accomplished with the novel approach of rapid intravenous desensitization followed by inhaled therapy. As inhaled antibiotics are being increasingly used for patients with CF, this novel strategy can be used for desensitizing allergic patients with CF to

  9. Hemoglobin oxygen affinity in patients with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Dieter Böning

    Full Text Available In patients with cystic fibrosis lung damages cause arterial hypoxia. As a typical compensatory reaction one might expect changes in oxygen affinity of hemoglobin. Therefore position (standard half saturation pressure P50st and slope (Hill's n of the O2 dissociation curve as well as the Bohr coefficients (BC for CO2 and lactic acid were determined in blood of 14 adult patients (8 males, 6 females and 14 healthy controls (6 males, 8 females. While Hill's n amounted to approximately 2.6 in all subjects, P50st was slightly increased by 1 mmHg in both patient groups (controls male 26.7 ± 0.2, controls female 27.0 ± 0.1, patients male 27.7 ± 0.5, patients female 28.0 ± 0.3 mmHg; mean and standard error, overall p<0.01. Main cause was a rise of 1-2 µmol/g hemoglobin in erythrocytic 2,3-biphosphoglycerate concentration. One patient only, clearly identified as an outlier and with the mutation G551D, showed a reduction of both P50st (24.5 mmHg and [2,3-biphosphoglycerate] (9.8 µmol/g hemoglobin. There were no differences in BCCO2, but small sex differences in the BC for lactic acid in the controls which were not detectable in the patients. Causes for the right shift of the O2 dissociation curve might be hypoxic stimulation of erythrocytic glycolysis and an increased red cell turnover both causing increased [2,3-biphosphoglycerate]. However, for situations with additional hypercapnia as observed in exercising patients a left shift seems to be a more favourable adaptation in cystic fibrosis. Additionally when in vivo PO2 values were corrected to the standard conditions they mostly lay left of the in vitro O2 dissociation curve in both patients and controls. This hints to unknown fugitive factors influencing oxygen affinity.

  10. Sources of Variation in Sweat Chloride Measurements in Cystic Fibrosis

    Science.gov (United States)

    Blackman, Scott M.; Raraigh, Karen S.; Corvol, Harriet; Rommens, Johanna M.; Pace, Rhonda G.; Boelle, Pierre-Yves; McGready, John; Sosnay, Patrick R.; Strug, Lisa J.; Knowles, Michael R.; Cutting, Garry R.

    2016-01-01

    Rationale: Expanding the use of cystic fibrosis transmembrane conductance regulator (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. Objectives: To estimate potential sources of variation for sweat chloride measurements, including demographic factors, testing variability, recording biases, and CFTR genotype itself. Methods: A total of 2,639 sweat chloride measurements were obtained in 1,761 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 modeling. Measurements and Main 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%) (likelihood ratio test, P < 0.001). Twin analysis suggested that modifier genes did not play a significant role because the heritability estimate was negligible (H2 = 0; 95% confidence interval, 0.0–0.35). For an individual with CF, variation in sweat chloride was primarily caused by 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 caused by testing variability and unique environmental factors. If test precision and accuracy can be improved, sweat chloride measurement could be a valuable biomarker

  11. An Unusual Case of Cystic Fibrosis Associated Pneumocystis jiroveci Pneumonia in an Infant

    Directory of Open Access Journals (Sweden)

    Ravinder Kaur

    2016-01-01

    Full Text Available Pneumocystis jiroveci pneumonia (PJP is one of the major infections in patients with impaired immunity. The entity is common in HIV-seropositive individuals but quite very rare in HIV-seronegative individuals especially children. We report here a case of 16-week-old HIV-seronegative infant with chief complaint of chronic cough of one month of evolution. Sweat chloride test for diagnosis of cystic fibrosis was positive. Bronchoalveolar lavage (BAL fluid was collected and Pseudomonas aeruginosa was isolated on culture. Empirical antibiotic regimen comprising ceftriaxone and azithromycin was initiated that was switched to meropenem as per antimicrobial susceptibility report, but the patient did not improve. Subsequently, an immunofluorescence staining of BAL fluid was performed and P. jiroveci cysts were detected. Following a laboratory confirmation of Pneumocystis pneumonia, cotrimoxazole was added and the clinical condition of the patient significantly improved. This is an unusual case wherein unsuspected PJP occurred and since signs and symptoms of the patient persisted even after the initiation of antimicrobial therapy for Pseudomonas infection and resolved only after treatment for PJP was started, it suggests a causative role of P. jiroveci rather than colonization/contamination.

  12. Bronchial artery embolization for therapy of pulmonary bleeding in patients with cystic fibrosis

    International Nuclear Information System (INIS)

    Thalhammer, A.; Jacobi, V.; Balzer, J.; Straub, R.; Vogl, T.J.

    2002-01-01

    Introduction: Acute pulmonary emergencies in patient with cystic fibrosis (CF) can be found in cases of pneumothorax as well as hemoptysis. If the bleeding cannot be stopped by conservative methods, an embolization of the bronchial arteries should be done. Materials and Method: 11 patients were embolized using a combination of PVA particles and microcoils. Results: From January 1996 to June 2001 17 bronchial arteries in 11 patients were embolized. 7 patients suffered from chronical hemoptysis, 4 patients had an acute hemoptysis. In 4 patients both sides were embolized, in 3 patients only one side. The remaining 4 patients needed a second intervention, embolizing the other side. The primary embolizated bronchial artery was still closed in all 4 patients. In 1 patient the selective catheterization of a bronchial artery was not successful, thus the embolization could not be carried out. 1 patient died 5 days after the intervention due to a fulminant pneumonia (Pseudomonas aeruginosa) without recurrent bleeding. In two patients atypical branches from intercostal arteries feeding the bronchial arteries were detected and successfully embolized. All patients profited from the therapy, as bleeding could be stopped or at least be reduced. 3 patients suffered from back pain during or after intervention. There were no severe complications like neurological deficiencies or necroses. (orig.) [de

  13. Antibiotic management of lung infections in cystic fibrosis. II. Nontuberculous mycobacteria, anaerobic bacteria, and fungi.

    Science.gov (United States)

    Chmiel, James F; Aksamit, Timothy R; Chotirmall, Sanjay H; Dasenbrook, Elliott C; Elborn, J Stuart; LiPuma, John J; Ranganathan, Sarath C; Waters, Valerie J; Ratjen, Felix A

    2014-10-01

    Airway infections are a key component of cystic fibrosis (CF) lung disease. Whereas the approach to common pathogens such as Pseudomonas aeruginosa is guided by a significant body of evidence, other infections often pose a considerable challenge to treating physicians. In Part I of this series on the antibiotic management of difficult lung infections, we discussed bacterial organisms including methicillin-resistant Staphylococcus aureus, gram-negative bacterial infections, and treatment of multiple bacterial pathogens. Here, we summarize the approach to infections with nontuberculous mycobacteria, anaerobic bacteria, and fungi. Nontuberculous mycobacteria can significantly impact the course of lung disease in patients with CF, but differentiation between colonization and infection is difficult clinically as coinfection with other micro-organisms is common. Treatment consists of different classes of antibiotics, varies in intensity, and is best guided by a team of specialized clinicians and microbiologists. The ability of anaerobic bacteria to contribute to CF lung disease is less clear, even though clinical relevance has been reported in individual patients. Anaerobes detected in CF sputum are often resistant to multiple drugs, and treatment has not yet been shown to positively affect patient outcome. Fungi have gained significant interest as potential CF pathogens. Although the role of Candida is largely unclear, there is mounting evidence that Scedosporium species and Aspergillus fumigatus, beyond the classical presentation of allergic bronchopulmonary aspergillosis, can be relevant in patients with CF and treatment should be considered. At present, however there remains limited information on how best to select patients who could benefit from antifungal therapy.

  14. Intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells

    International Nuclear Information System (INIS)

    Verhaeghe, Catherine; Tabruyn, Sebastien P.; Oury, Cecile; Bours, Vincent; Griffioen, Arjan W.

    2007-01-01

    Cystic fibrosis is a common genetic disorder characterized by a severe lung inflammation and fibrosis leading to the patient's death. Enhanced angiogenesis in cystic fibrosis (CF) tissue has been suggested, probably caused by the process of inflammation, as similarly described in asthma and chronic bronchitis. The present study demonstrates an intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells. Microarray experiments showed that CF airway epithelial cells expressed several angiogenic factors such as VEGF-A, VEGF-C, bFGF, and PLGF at higher levels than control cells. These data were confirmed by real-time quantitative PCR and, at the protein level, by ELISA. Conditioned media of these cystic fibrosis cells were able to induce proliferation, migration and sprouting of cultured primary endothelial cells. This report describes for the first time that cystic fibrosis epithelial cells have an intrinsic angiogenic activity. Since excess of angiogenesis is correlated with more severe pulmonary disease, our results could lead to the development of new therapeutic applications

  15. The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis.

    Science.gov (United States)

    Frayman, Katherine B; Armstrong, David S; Carzino, Rosemary; Ferkol, Thomas W; Grimwood, Keith; Storch, Gregory A; Teo, Shu Mei; Wylie, Kristine M; Ranganathan, Sarath C

    2017-12-01

    In infants and young children with cystic fibrosis, lower airway infection and inflammation are associated with adverse respiratory outcomes. However, the role of lower airway microbiota in the pathogenesis of early cystic fibrosis lung disease remains uncertain. To assess the development of the lower airway microbiota over time in infants and young children with cystic fibrosis, and to explore its association with airway inflammation and pulmonary function at age 6 years. Serial, semi-annual bronchoscopies and bronchoalveolar lavage (BAL) procedures were performed in infants newly diagnosed with cystic fibrosis following newborn screening. Quantitative microbiological cultures and inflammatory marker (interleukin 8 and neutrophil elastase) measurements were undertaken contemporaneously. 16S ribosomal RNA gene sequencing was conducted on stored BAL samples. Spirometry results recorded at 6 years of age were extracted from medical records. Ninety-five BAL samples provided 16S ribosomal RNA gene data. These were collected from 48 subjects aged 1.2-78.3 months, including longitudinal samples from 27 subjects and 13 before age 6 months. The lower airway microbiota varied, but diversity decreased with advancing age. Detection of recognised cystic fibrosis bacterial pathogens was associated with reduced microbial diversity and greater lower airway inflammation. There was no association between the lower airway microbiota and pulmonary function at age 6 years. In infants with cystic fibrosis, the lower airway microbiota is dynamic. Dominance of the microbiota by recognised cystic fibrosis bacterial pathogens is associated with increased lower airway inflammation, however early microbial diversity is not associated with pulmonary function at 6 years of age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. Facilitating Positive Psychosocial Adaptation in Children with Cystic Fibrosis by Increasing Family Communication and Problem-Solving Skills. A Research Report to the Cystic Fibrosis Foundation.

    Science.gov (United States)

    Stabler, Brian; And Others

    This study tested the effects of two group-oriented supportive and educational approaches on the parents of children with cystic fibrosis (CF). Thirteen families were randomly assigned either to a group which received information on medical and technical aspects of CF or to a group which received instruction in communication skills in addition to…

  17. Long term prognosis of patients with cystic fibrosis in relation to early detection by neonatal screening and treatment in a cystic fibrosis centre

    NARCIS (Netherlands)

    Dankert-Roelse, J E; te Meerman, G J

    BACKGROUND: A study was undertaken to evaluate whether an early diagnosis by neonatal screening may improve the long term prognosis of patients with cystic fibrosis and to assess the influence of expert management started immediately after the diagnosis. METHODS: Comparative clinical follow up in

  18. Anti-Biofilm and Immunomodulatory Activities of Peptides That Inhibit Biofilms Formed by Pathogens Isolated from Cystic Fibrosis Patients

    Directory of Open Access Journals (Sweden)

    César de la Fuente-Núñez

    2014-10-01

    Full Text Available Cystic fibrosis (CF patients often acquire chronic respiratory tract infections due to Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc species. In the CF lung, these bacteria grow as multicellular aggregates termed biofilms. Biofilms demonstrate increased (adaptive resistance to conventional antibiotics, and there are currently no available biofilm-specific therapies. Using plastic adherent, hydroxyapatite and flow cell biofilm models coupled with confocal and scanning electron microscopy, it was demonstrated that an anti-biofilm peptide 1018 prevented biofilm formation, eradicated mature biofilms and killed biofilms formed by a wide range of P. aeruginosa and B. cenocepacia clinical isolates. New peptide derivatives were designed that, compared to their parent peptide 1018, showed similar or decreased anti-biofilm activity against P. aeruginosa biofilms, but increased activity against biofilms formed by the Gram-positive bacterium methicillin resistant Staphylococcus aureus. In addition, some of these new peptide derivatives retained the immunomodulatory activity of 1018 since they induced the production of the chemokine monocyte chemotactic protein-1 (MCP-1 and suppressed lipopolysaccharide-mediated tumor necrosis factor-α (TNF-α production by human peripheral blood mononuclear cells (PBMC and were non-toxic towards these cells. Peptide 1018 and its derivatives provide promising leads for the treatment of chronic biofilm infections and hyperinflammatory lung disease in CF patients.

  19. Glucose tolerance during pulmonary exacerbations in children with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    John Widger

    Full Text Available BACKGROUND: Patients with Cystic Fibrosis (CF are relatively insulinopenic and are at risk of diabetes, especially during times of stress. There is a paucity of data in the literature describing glucose tolerance during CF pulmonary exacerbations. We hypothesised that glucose tolerance would be worse during pulmonary exacerbations in children with CF than during clinical stability. METHODS: Patients with CF, 10 years or older, admitted with a pulmonary exacerbation underwent an OGTT within 48 hours of admission. A repeat OGTT was performed 4 to 6 weeks post discharge when the patients were well. RESULTS: Nine patients completed the study. Four patients were found to have normal glucose tolerance, 3 with impaired and 2 with CF related diabetes during the exacerbation. Mean change in 2-hour glucose was 1.1 mmol (SD = 0.77. At the follow up OGTT, 8 of 9 (89% remained within their respective glucose tolerance status groupings. CONCLUSION: The findings of this study show that there is little difference in glucose tolerance during CF exacerbations compared to clinical stability in the majority of patients.

  20. The airway microbiota in early cystic fibrosis lung disease.

    Science.gov (United States)

    Frayman, Katherine B; Armstrong, David S; Grimwood, Keith; Ranganathan, Sarath C

    2017-11-01

    Infection plays a critical role in the pathogenesis of cystic fibrosis (CF) lung disease. Over the past two decades, the application of molecular and extended culture-based techniques to microbial analysis has changed our understanding of the lungs in both health and disease. CF lung disease is a polymicrobial disorder, with obligate and facultative anaerobes recovered alongside traditional pathogens in varying proportions, with some differences observed to correlate with disease stage. While healthy lungs are not sterile, differences between the lower airway microbiota of individuals with CF and disease-controls are already apparent in childhood. Understanding the evolution of the CF airway microbiota, and its relationship with clinical treatments and outcome at each disease stage, will improve our understanding of the pathogenesis of CF lung disease and potentially inform clinical management. This review summarizes current knowledge of the early development of the respiratory microbiota in healthy children and then discusses what is known about the airway microbiota in individuals with CF, including how it evolves over time and where future research priorities lie. © 2017 Wiley Periodicals, Inc.

  1. Body composition and pulmonary function in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Saba eSheikh

    2014-04-01

    Full Text Available Background: Lower body mass index (BMI is associated with worse pulmonary function in cystic fibrosis (CF. Hypothesis: Lean body mass (LBM is more strongly associated with pulmonary function than BMI is.Methods: Anthropometrics, body composition by dual x-ray absorptiometry, and pulmonary function were determined in pancreatic insufficient CF (PI-CF youth. Sex and age-adjusted Z-scores (BMI-Z, LBMI-Z, FMI-Z were generated for CF and controls. 1 Associations of BMI-Z with LBMI-Z and FMI-Z and 2 age-adjusted associations of BMI-Z, LBMI-Z, and FMI-Z with FEV1%-predicted were tested. Results: 208 PI-CF subjects had lower BMI-Z, LBMI-Z, FMI-Z compared to 390 controls. BMI-Z was associated with lower LBMI-Z (pConclusions: In PI-CF youth, deficits in LBM were apparent. At lower BMI percentiles, BMI may not accurately depict LBM in PI-CF. In under-nourished PI-CF youth this preservation of FM in preference to LBM is relevant since LBMI-Z, but not FMI-Z, is positively associated with FEV1%-predicted. LBMI is more strongly associated with lung function compared to BMI, especially in the undernourished child and adolescent with PI-CF.

  2. Sphingobacterium respiratory tract infection in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    de Gregorio Fabiola

    2009-12-01

    Full Text Available Abstract Background Bacteria that belong to the genus Sphingobacterium are Gram-negative, non-fermentative bacilli, ubiquitous in nature and rarely involved in human infections. The aims of this study were to evaluate the epidemiology of infection by Sphingobacterium in a cohort of patients affected by Cystic Fibrosis (CF, the antibiotic susceptibility and the DNA fingerprinting of the isolated strains and to analyze some clinical outcomes of the infected patients. Findings Between January 2006 and June 2008, patients (n = 332 attending the Regional CF Unit in Naples, Italy, were enrolled. Sputum samples were processed for microscopic, cultural, phenotypic identification and antibiotic susceptibility testing. DNA fingerprinting was performed by pulsed-field gel electrophoresis (PFGE. A total of 21 strains of Sphingobacterium were isolated from 7 patients (13 of S. spiritovorum, 8 of S. multivorum. S. multivorum isolates were more resistant than those of S. spiritovorum. PFGE profiles were in general heterogeneous, which suggested independent circulation. Conclusions This is the first Italian report about respiratory tract infections by Sphingobacterium in CF patients. In our cohort, these infections were not associated with a deterioration of pulmonary function during the follow-up period. Although the exact role of this microorganism in CF lung disease is unknown and the number of infected patients was small, this study could represent an important starting-point for understanding the epidemiology and the possible pathogenic role of Sphingobacterium in CF patients.

  3. Pandoraea pnomenusa Isolated from an Australian Patient with Cystic Fibrosis.

    Science.gov (United States)

    Ambrose, Mark; Malley, Roslyn C; Warren, Sanchia J C; Beggs, Sean A; Swallow, Oliver F E; McEwan, Belinda; Stock, David; Roddam, Louise F

    2016-01-01

    Pandoraea species are considered as emerging pathogens in people with cystic fibrosis (CF). The contribution of these organisms to disease progression in CF patients is not fully understood owing in large measure to the scant reports in clinical and research literature describing their colonization of CF patients and their associated virulence determinants. In an effort to increase awareness and evidence for Pandoraea spp. infection in people with CF, and to stimulate research aimed at unraveling the pathogenic properties of Pandoraea, we report a case of a 26-year-old Australian (Tasmanian) man with CF who was chronically infected with Pandoraea pnomenusa for at least one year prior to his death from respiratory failure. In addition, we describe for the first time evidence suggesting that this bacterium is a facultative anaerobe and report on the availability of a whole genome sequence for this organism. To the best of our knowledge, this report represents only the second clinical case study of P. pnomenusa infection in the world, and the first in an Australian CF patient.

  4. Benchmarking to improve the quality of cystic fibrosis care.

    Science.gov (United States)

    Schechter, Michael S

    2012-11-01

    Benchmarking involves the ascertainment of healthcare programs with most favorable outcomes as a means to identify and spread effective strategies for delivery of care. The recent interest in the development of patient registries for patients with cystic fibrosis (CF) has been fueled in part by an interest in using them to facilitate benchmarking. This review summarizes reports of how benchmarking has been operationalized in attempts to improve CF care. Although certain goals of benchmarking can be accomplished with an exclusive focus on registry data analysis, benchmarking programs in Germany and the United States have supplemented these data analyses with exploratory interactions and discussions to better understand successful approaches to care and encourage their spread throughout the care network. Benchmarking allows the discovery and facilitates the spread of effective approaches to care. It provides a pragmatic alternative to traditional research methods such as randomized controlled trials, providing insights into methods that optimize delivery of care and allowing judgments about the relative effectiveness of different therapeutic approaches.

  5. CT characterization of inflammatory paranasal sinus disease in cystic fibrosis

    International Nuclear Information System (INIS)

    Eggesboe, H.B.

    2002-01-01

    Purpose: In patients with cystic fibrosis (CF) the prevalence of paranasal sinus affection approaches 100%. We hypothesized that the hyper viscous mucus reducing mucociliary clearance in CF patients could give sinonasal inflammatory patterns different from those in non-CF patients. We wanted to compare the extent and distribution of paranasal sinus disease and the inflammatory patterns in these two groups of patients. Material and Methods: One-hundred-and-eight CF patients (3-54 years old) and 79 controls (7-51 years old) with paranasal sinus disease confirmed at coronal CT were compared. The extent of disease was noted for each sinus and summed for all sinuses. Inflammatory patterns were identified and classified into: 1) routine surgery group (sporadic, infundibular and ostiomeatal complex (OMC) patterns) and 2) complex surgery group (sinonasal polyposis and sphenoethmoid recess (SER) patterns). Results: CF patients had more widespread sinonasal inflammatory changes and more advanced disease for each sinus. Most CF patients displayed sinonasal polyposis and SER patterns while most controls displayed sporadic, infundibular or OMC patterns. As a result, 67% of CF patients were classified to the complex surgery group, compared to only 19% of controls. Conclusion: The impaired mucociliary clearance in CF causes widespread inflammatory paranasal sinus disease, with inflammatory patterns more often requiring extensive surgery, with a higher risk of cerebrospinal fluid leak or bleeding, or involving areas that are more difficult to reach with the endoscope

  6. CFTR Modulators: Shedding Light on Precision Medicine for Cystic Fibrosis

    Science.gov (United States)

    Lopes-Pacheco, Miquéias

    2016-01-01

    Cystic fibrosis (CF) is the most common life-threatening monogenic disease afflicting Caucasian people. It affects the respiratory, gastrointestinal, glandular and reproductive systems. The major cause of morbidity and mortality in CF is the respiratory disorder caused by a vicious cycle of obstruction of the airways, inflammation and infection that leads to epithelial damage, tissue remodeling and end-stage lung disease. Over the past decades, life expectancy of CF patients has increased due to early diagnosis and improved treatments; however, these patients still present limited quality of life. Many attempts have been made to rescue CF transmembrane conductance regulator (CFTR) expression, function and stability, thereby overcoming the molecular basis of CF. Gene and protein variances caused by CFTR mutants lead to different CF phenotypes, which then require different treatments to quell the patients’ debilitating symptoms. In order to seek better approaches to treat CF patients and maximize therapeutic effects, CFTR mutants have been stratified into six groups (although several of these mutations present pleiotropic defects). The research with CFTR modulators (read-through agents, correctors, potentiators, stabilizers and amplifiers) has achieved remarkable progress, and these drugs are translating into pharmaceuticals and personalized treatments for CF patients. This review summarizes the main molecular and clinical features of CF, emphasizes the latest clinical trials using CFTR modulators, sheds light on the molecular mechanisms underlying these new and emerging treatments, and discusses the major breakthroughs and challenges to treating all CF patients. PMID:27656143

  7. Lung Transplantation for Cystic Fibrosis: Results, Indications, Complications, and Controversies

    Science.gov (United States)

    Lynch, Joseph P.; Sayah, David M.; Belperio, John A.; Weigt, S. Sam

    2016-01-01

    Survival in patients with cystic fibrosis (CF) has improved dramatically over the past 30 to 40 years, with mean survival now approximately 40 years. Nonetheless, progressive respiratory insufficiency remains the major cause of mortality in CF patients, and lung transplantation (LT) is eventually required. Timing of listing for LT is critical, because up to 25 to 41% of CF patients have died while awaiting LT. Globally, approximately 16.4% of lung transplants are performed in adults with CF. Survival rates for LT recipients with CF are superior to other indications, yet LT is associated with substantial morbidity and mortality (~50% at 5-year survival rates). Myriad complications of LT include allograft failure (acute or chronic), opportunistic infections, and complications of chronic immunosuppressive medications (including malignancy). Determining which patients are candidates for LT is difficult, and survival benefit remains uncertain. In this review, we discuss when LT should be considered, criteria for identifying candidates, contraindications to LT, results post-LT, and specific complications that may be associated with LT. Infectious complications that may complicate CF (particularly Burkholderia cepacia spp., opportunistic fungi, and nontuberculous mycobacteria) are discussed. PMID:25826595

  8. Proton MRI appearance of cystic fibrosis: Comparison to CT

    International Nuclear Information System (INIS)

    Puderbach, Michael; Eichinger, Monika; Kauczor, Hans-Ulrich; Gahr, Julie; Mueller, Frank-Michael; Ley, Sebastian; Tuengerthal, Siegfried; Schmaehl, Astrid; Fink, Christian; Plathow, Christian; Wiebel, Matthias

    2007-01-01

    Cystic fibrosis (CF) is the most frequent inherited disorder leading to premature death in the Caucasian population. As life expectancy is limited by pulmonary complications, repeated imaging [chest X-ray, multislice high-resolution computed tomography (MS-HRCT)] is required in the follow-up. Magnetic resonance imaging (MRI) of the lung parenchyma is a promising new diagnostic tool. Its value for imaging lung changes caused by CF compared with CT is demonstrated. MRI performs well when compared with CT, which serves as the gold standard. Its lack in spatial resolution is obvious, but advantages in contrast and functional assessment compensate for this limitation. Thus, MRI is a reasonable alternative for imaging the CF lung and should be introduced as a radiation-free modality for follow-up studies in CF patients. For further evaluation of the impact of MRI, systematic studies comparing MRI and conventional imaging modalities are necessary. Furthermore, the value of the additional functional MRI (fMRI) information has to be studied, and a scoring system for the morphological and functional aspect of MRI has to be established. (orig.)

  9. [The profile of caregivers to pediatric patients with cystic fibrosis].

    Science.gov (United States)

    Alves, Stella Pegoraro; Bueno, Denise

    2018-05-01

    The scope of this study was to establish the profile of caregivers of pediatric patients diagnosed with Cystic Fibrosis (CF). It was a cross-sectional, descriptive and prospective study in which the caregivers of fibrocystic patients were interviewed during pharmaceutical consultation in a reference center of a University Hospital in southern Brazil. General information was obtained about the caregivers and about their understanding of the disease, drug consumption and dynamics of treatment at home and at school. Seventy-five caregivers were interviewed. Most of them were female, 37.3 years old on average, mothers of the patients who did not work outside the home. Seventy-one caregivers declared difficulties in drug acquisition and patient support associations were highlighted as the main alternative to avoid the interruption of treatment. Another fact observed was the overload of the caregiving process on the shoulders of only one caregiver resulting in social and economic impacts and changes to the family's daily routine. This fact emphasizes the need of intervention by a qualified multidisciplinary team to identify and alleviate difficulties, investing in interpersonal relations and administering care.

  10. Personalized Drug Therapy in Cystic Fibrosis: From Fiction to Reality.

    Science.gov (United States)

    de Lima Marson, Fernando Augusto; Bertuzzo, Carmen Silvia; Ribeiro, Jose Dirceu

    2015-01-01

    Personalized drug therapy for cystic fibrosis (CF) is a long-term dream for CF patients, caregivers, physicians and researchers. After years of study, the fiction of personalized treatment has turned to hope. Basic information about CFTR mutations classes and new treatments is needed if we are to deal properly with the new CF era. The problems involved in this issue, however, should be evaluated with greater care and attention. VX-770 is a new drug available to treat CF patients with some class III CFTR mutations and other drugs are being studied regarding other classes. The scientific literature has constantly given information about each therapy, both in vitro and in vivo. The hope is increasing. Nevertheless the "scientific world" still lacks information about patients' reality and daily health related practical needs. Clinical trials have showed good evaluation of some drugs so far, but clinical response is a wide spectrum yet to be analyzed: CFTR mutations spectrum, costs related to the treatment with new drugs (for VX-770 therapy), variability of CF clinical expression, limitations to test in vitro drugs, absence of good clinical markers to evaluate drug response, absence of long-term studies and with patients below six years old, multidrug treatment used to improve the expression response, and finally, the most important problem, who will benefit from the new drugs therapy, are issues that constitute a barrier that should be overcome. Personalized drug therapy may not be a fiction anymore, but it is not yet a reality for all CF patients.

  11. [Peripherally inserted central catheter antibiotic therapy for cystic fibrosis patients].

    Science.gov (United States)

    Betegnie, A-L; Cracowski, C; Bedouch, P; Segond, C; Robein-Dobremez, M-J; Pin, I; Allenet, B

    2014-11-01

    Peripherally inserted central catheters (PICC) are more and more used for intravenous antibiotic infusions in cystic fibrosis (CF) patients in the Grenoble area (France). The aim of this study was to assess the use of this technique in this indication. 1. Retrospective evaluation of 102 consecutive PICC insertions over 3years and the incidence of adverse events during the therapy. 2. Prospective evaluation of 12 patient's satisfaction and their nurses over a 3-month period. 3. Comparative analysis of single domiciliary treatment costs using PICC versus peripheral catheter (PC). 102 PICC insertions were attempted in 31 patients. Seven failures and 7 complications occurred during the treatment requiring removal of the PICC, i.e. an overall success rate of 86.2% (88/102). Pain during PICC introduction was 4.2/10 (visual analogical scale). Mean satisfaction levels during therapy were 9.3/10 for patients and 8.7/10 for nurses. Compared with PC, all the patients said that PICC was "more comfortable". Differential costs of treatment with PC and with PICC at home were estimated at 57.15€ and 590.16€ respectively. PICC is an alternative to CP for intravenous antibiotherapy in CF patients, providing better safety and comfort. PICC use should be promoted in this indication. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  12. Emergence of respiratory Streptococcus agalactiae isolates in cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Vera Eickel

    Full Text Available Streptococcus agalactiae is a well-known pathogen for neonates and immunocompromized adults. Beyond the neonatal period, S. agalactiae is rarely found in the respiratory tract. During 2002-2008 we noticed S. agalactiae in respiratory secretions of 30/185 (16% of cystic fibrosis (CF patients. The median age of these patients was 3-6 years older than the median age CF patients not harboring S. agalactiae. To analyze, if the S. agalactiae isolates from CF patients were clonal, further characterization of the strains was achieved by capsular serotyping, surface protein determination and multilocus sequence typing (MLST. We found a variety of sequence types (ST among the isolates, which did not substantially differ from the MLST patterns of colonizing strains from Germany. However serotype III, which is often seen in colonizing strains and invasive infections was rare among CF patients. The emergence of S. agalactiae in the respiratory tract of CF patients may represent the adaptation to a novel host environment, supported by the altered surfactant composition in older CF patients.

  13. Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Ibrahim Ahmed Janahi

    2017-01-01

    Full Text Available Allergic bronchopulmonary aspergillosis (ABPA is a pulmonary disorder that often occurs in patients with asthma or cystic fibrosis (CF and is characterized by a hypersensitivity response to the allergens of the fungus Aspergillus fumigatus. In patients with CF, growth of A. fumigatus hyphae within the bronchial lumen triggers an immunoglobulin E (IgE-mediated hypersensitivity response that results in airway inflammation, bronchospasm, and bronchiectasis. In most published studies, the prevalence of ABPA is about 8.9% in patients with CF. Since the clinical features of this condition overlap significantly with that of CF, ABPA is challenging to diagnose and remains underdiagnosed in many patients. Diagnosis of ABPA in CF patients should be sought in those with evidence of clinical and radiologic deterioration that is not attributable to another etiology, a markedly elevated total serum IgE level (while off steroid therapy and evidence of A. fumigatus sensitization. Management of ABPA involves the use of systemic steroids to reduce inflammation and modulate the immune response. In patients who do not respond to steroids or cannot tolerate them, antifungal agents should be used to reduce the burden of A. fumigatus allergens. Recent studies suggest that omalizumab may be an effective option to reduce the frequency of ABPA exacerbations in patients with CF. Further randomized controlled trials are needed to better establish the efficacy of omalizumab in managing patients with CF and ABPA.

  14. L-ornithine derived polyamines in cystic fibrosis airways.

    Directory of Open Access Journals (Sweden)

    Hartmut Grasemann

    Full Text Available Increased arginase activity contributes to airway nitric oxide (NO deficiency in cystic fibrosis (CF. Whether down-stream products of arginase activity contribute to CF lung disease is currently unknown. The objective of this study was to test whether L-ornithine derived polyamines are present in CF airways and contribute to airway pathophysiology. Polyamine concentrations were measured in sputum of patients with CF and in healthy controls, using liquid chromatography-tandem mass spectrometry. The effect of spermine on airway smooth muscle mechanical properties was assessed in bronchial segments of murine airways, using a wire myograph. Sputum polyamine concentrations in stable CF patients were similar to healthy controls for putrescine and spermidine but significantly higher for spermine. Pulmonary exacerbations were associated with an increase in sputum and spermine levels. Treatment for pulmonary exacerbations resulted in decreases in arginase activity, L-ornithine and spermine concentrations in sputum. The changes in sputum spermine with treatment correlated significantly with changes in L-ornithine but not with sputum inflammatory markers. Incubation of mouse bronchi with spermine resulted in an increase in acetylcholine-induced force and significantly reduced nitric oxide-induced bronchial relaxation. The polyamine spermine is increased in CF airways. Spermine contributes to airways obstruction by reducing the NO-mediated smooth muscle relaxation.

  15. Imaging of cystic fibrosis lung disease and clinical interpretation

    Energy Technology Data Exchange (ETDEWEB)

    Wielpuetz, M.O.; Eichinger, M.; Kauczor, H.U. [Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology; Translational Lung Research Center Heidelberg (TLRC) (Germany); Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology with Nuclear Medicine; Biederer, J. [Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology; Translational Lung Research Center Heidelberg (TLRC) (Germany); Gross-Gerau Community Hospital (Germany). Radiologie Darmstadt; Wege, S. [Heidelberg University Hospital (Germany). Dept. of Pulmonology and Respiratory Medicine; Stahl, M.; Sommerburg, O. [Translational Lung Research Center Heidelberg (TLRC) (Germany); Heidelberg University Hospital (Germany). Div. of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center; Mall, M.A. [Translational Lung Research Center Heidelberg (TLRC) (Germany); Heidelberg University Hospital (Germany). Div. of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center; Heidelberg University Hospital (Germany). Dept. of Translational Pulmonology; Puderbach, M. [Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology; Translational Lung Research Center Heidelberg (TLRC) (Germany); Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology with Nuclear Medicine; Hufeland Hospital, Bad Langensalza (Germany). Dept. of Diagnostic and Interventional Radiology

    2016-09-15

    Progressive lung disease in cystic fibrosis (CF) is the life-limiting factor of this autosomal recessive genetic disorder. Increasing implementation of CF newborn screening allows for a diagnosis even in pre-symptomatic stages. Improvements in therapy have led to a significant improvement in survival, the majority now being of adult age. Imaging provides detailed information on the regional distribution of CF lung disease, hence longitudinal imaging is recommended for disease monitoring in the clinical routine. Chest X-ray (CXR), computed tomography (CT) and magnetic resonance imaging (MRI) are now available as routine modalities, each with individual strengths and drawbacks, which need to be considered when choosing the optimal modality adapted to the clinical situation of the patient. CT stands out with the highest morphological detail and has often been a substitute for CXR for regular severity monitoring at specialized centers. Multidetector CT data can be post-processed with dedicated software for a detailed measurement of airway dimensions and bronchiectasis and potentially a more objective and precise grading of disease severity. However, changing to CT was inseparably accompanied by an increase in radiation exposure of CF patients, a young population with high sensitivity to ionizing radiation and lifetime accumulation of dose. MRI as a cross-sectional imaging modality free of ionizing radiation can depict morphological hallmarks of CF lung disease at lower spatial resolution but excels with comprehensive functional lung imaging, with time-resolved perfusion imaging currently being most valuable.

  16. Ibuprofen regulation of microtubule dynamics in cystic fibrosis epithelial cells.

    Science.gov (United States)

    Rymut, Sharon M; Kampman, Claire M; Corey, Deborah A; Endres, Tori; Cotton, Calvin U; Kelley, Thomas J

    2016-08-01

    High-dose ibuprofen, an effective anti-inflammatory therapy for the treatment of cystic fibrosis (CF), has been shown to preserve lung function in a pediatric population. Despite its efficacy, few patients receive ibuprofen treatment due to potential renal and gastrointestinal toxicity. The mechanism of ibuprofen efficacy is also unclear. We have previously demonstrated that CF microtubules are slower to reform after depolymerization compared with respective wild-type controls. Slower microtubule dynamics in CF cells are responsible for impaired intracellular transport and are related to inflammatory signaling. Here, it is identified that high-dose ibuprofen treatment in both CF cell models and primary CF nasal epithelial cells restores microtubule reformation rates to wild-type levels, as well as induce extension of microtubules to the cell periphery. Ibuprofen treatment also restores microtubule-dependent intracellular transport monitored by measuring intracellular cholesterol transport. These effects are specific to ibuprofen as other cyclooxygenase inhibitors have no effect on these measures. Effects of ibuprofen are mimicked by stimulation of AMPK and blocked by the AMPK inhibitor compound C. We conclude that high-dose ibuprofen treatment enhances microtubule formation in CF cells likely through an AMPK-related pathway. These findings define a potential mechanism to explain the efficacy of ibuprofen therapy in CF. Copyright © 2016 the American Physiological Society.

  17. Fatty acyltranferases in serum in cystic fibrosis (CF) patients

    International Nuclear Information System (INIS)

    Zielenski, J.; Newman, L.J.; Slomiany, B.L.; Slomiany, A.

    1987-01-01

    Studies on serum and gastrointestinal secretion from CF patient is suggest that defective accumulation of mucus in gastrointestinal tract and excessive amount of a protease resistant peptides in serum are related to the abnormal activity of enzymes responsible for fatty acylation of proteins. Here, the authors investigated the fatty acyltransferase activities in serum of normal and CF patients. A 15μl of serum was mixed with 0.85 nmol [ 14 C]palmitoyl CoA, 200μg of serine and threonine and incubated at 37 0 C for 30 min. The incubates were immediately frozen, dried extracted with C/M and chromatographed in chloroform/methanol/water. The incorporation of [ 14 C]palmitate was determined using linear radioscanner and authoradiography. The results of HPTLC revealed that CF serum in addition of ACAT and LCAT contained enzymes responsible for the transfer of [ 14 C]palmitate to monoacylphosphoglycerides, and serine and threonine. In normal serum the formation of a small amount of palmitoyl serine and palmitoyl threonine was also observed but the acylation of monoacylphosphoglycerides was not detectable. The authors conclude that in cystic fibrosis the abnormal fatty acyltransferases are responsible for the occurrence of protease resistant glycoprotein, unusual peptides in serum and possibly for the modification of membrane proteins and lipids

  18. Sleep-disordered breathing in patients with cystic fibrosis *

    Science.gov (United States)

    Veronezi, Jefferson; Carvalho, Ana Paula; Ricachinewsky, Claudio; Hoffmann, Anneliese; Kobayashi, Danielle Yuka; Piltcher, Otavio Bejzman; Silva, Fernando Antonio Abreu e; Martinez, Denis

    2015-01-01

    Abstract Objective: To test the hypothesis that disease severity in patients with cystic fibrosis (CF) is correlated with an increased risk of sleep apnea. Methods: A total of 34 CF patients underwent clinical and functional evaluation, as well as portable polysomnography, spirometry, and determination of IL-1β levels. Results: Mean apnea-hypopnea index (AHI), SpO2 on room air, and Epworth Sleepiness Scale score were 4.8 ± 2.6, 95.9 ± 1.9%, and 7.6 ± 3.8 points, respectively. Of the 34 patients, 19 were well-nourished, 6 were at nutritional risk, and 9 were malnourished. In the multivariate model to predict the AHI, the following variables remained significant: nutritional status (β = −0.386; p = 0.014); SpO2 (β = −0.453; p = 0.005), and the Epworth Sleepiness Scale score (β = 0.429; p = 0.006). The model explained 51% of the variation in the AHI. Conclusions: The major determinants of sleep apnea were nutritional status, SpO2, and daytime sleepiness. This knowledge not only provides an opportunity to define the clinical risk of having sleep apnea but also creates an avenue for the treatment and prevention of the disease. PMID:26398755

  19. Exhaled breath analysis using electronic nose in cystic fibrosis and primary ciliary dyskinesia patients with chronic pulmonary infections

    DEFF Research Database (Denmark)

    Joensen, Odin; Paff, Tamara; Haarman, Eric G

    2014-01-01

    The current diagnostic work-up and monitoring of pulmonary infections may be perceived as invasive, is time consuming and expensive. In this explorative study, we investigated whether or not a non-invasive exhaled breath analysis using an electronic nose would discriminate between cystic fibrosis...... (CF) and primary ciliary dyskinesia (PCD) with or without various well characterized chronic pulmonary infections. We recruited 64 patients with CF and 21 with PCD based on known chronic infection status. 21 healthy volunteers served as controls. An electronic nose was employed to analyze exhaled......, this method significantly discriminates CF patients suffering from a chronic pulmonary P. aeruginosa (PA) infection from CF patients without a chronic pulmonary infection. Further studies are needed for verification and to investigate the role of electronic nose technology in the very early diagnostic workup...

  20. A theobromine derived silver N-heterocyclic carbene: synthesis, characterization, and antimicrobial efficacy studies on cystic fibrosis relevant pathogens.

    Science.gov (United States)

    Panzner, Matthew J; Hindi, Khadijah M; Wright, Brian D; Taylor, Jane B; Han, Daniel S; Youngs, Wiley J; Cannon, Carolyn L

    2009-09-21

    The increasing incidence of multidrug-resistant (MDR) pulmonary infections in the cystic fibrosis (CF) population has prompted the investigation of innovative silver based therapeutics. The functionalization of the naturally occurring xanthine theobromine at the N(1) nitrogen atom with an ethanol substituent followed by the methylation of the N(9) nitrogen atom gives the N-heterocyclic carbene precursor 1-(2-hydroxyethyl)-3,7,9-trimethylxanthinium iodide. The reaction of this xanthinium salt with silver acetate produces the highly hydrophilic silver carbene complex SCC8. The in vitro antimicrobial efficacy of this newly synthesized complex was evaluated with excellent results on a variety of virulent and MDR pathogens isolated from CF patients. A comparative in vivo study between the known caffeine derived silver carbene SCC1 and SCC8 demonstrated the ability of both complexes to improve the survival rates of mice in a pneumonia model utilizing the clinically isolated infectious strain of Pseudomonas aeruginosa PA M57-15.

  1. Analysis of the CFTR gene in Venezuelan cystic fibrosis patients, identification of six novel cystic fibrosis-causing genetic variants.

    Science.gov (United States)

    Sánchez, Karen; de Mendonca, Elizabeth; Matute, Xiorama; Chaustre, Ismenia; Villalón, Marlene; Takiff, Howard

    2016-01-01

    The mutations in the CFTR gene found in patients with cystic fibrosis (CF) have geographic differences, but there are scant data on their prevalence in Venezuelan patients. This study determined the frequency of common CFTR gene mutations in a group of Venezuelan patients with CF. The 27 exons of the CFTR gene from 110 Venezuelan patients in the National CF Program were amplified and sequenced. A total of 36 different mutations were identified, seven with frequencies greater than 1%: p.Phe508del (27.27%), p.Gly542* (3.18%), c.2988+1G>A (3.18%), p.Arg334Trp (1.36%), p.Arg1162* (1.36%), c.1-8G>C (1.36%), and p.[Gly628Arg;Ser1235Arg](1.36). In 40% of patients, all with a clinical diagnosis of CF, no mutations were found. This report represents the largest cohort of Venezuelan patients with CF ever examined, and includes a wider mutation panel than has been previously studied in this population. Mutations common in Southern European populations predominate, and several new mutations were discovered, but no mutations were found in 40% of the cohort.

  2. Adult non-cystic fibrosis bronchiectasis is characterised by airway luminal Th17 pathway activation.

    Directory of Open Access Journals (Sweden)

    Alice C-H Chen

    Full Text Available Non-cystic fibrosis (CF bronchiectasis is characterised by chronic airway infection and neutrophilic inflammation, which we hypothesised would be associated with Th17 pathway activation.Th17 pathway cytokines were quantified in bronchoalveolar lavage fluid (BALF, and gene expression of IL-17A, IL-1β, IL-8 and IL-23 determined from endobronchial biopsies (EBx in 41 stable bronchiectasis subjects and 20 healthy controls. Relationships between IL-17A levels and infection status, important clinical measures and subsequent Pseudomonas aeruginosa infection were determined.BALF levels of all Th17 cytokines (median (IQR pg/mL were significantly higher in bronchiectasis than control subjects, including IL-17A (1.73 (1.19, 3.23 vs. 0.27 (0.24, 0.35, 95% CI 1.05 to 2.21, p<0.0001 and IL-23 (9.48 (4.79, 15.75 vs. 0.70 (0.43, 1.79, 95% CI 4.68 to 11.21, p<0.0001. However, BALF IL-17A levels were not associated with clinical measures or airway microbiology, nor predictive of subsequent P. aeruginosa infection. Furthermore, gene expression of IL-17A in bronchiectasis EBx did not differ from control. In contrast, gene expression (relative to medians of controls in bronchiectasis EBx was significantly higher than control for IL1β (4.12 (1.24, 8.05 vs 1 (0.13, 2.95, 95% CI 0.05 to 4.07, p = 0.04 and IL-8 (3.75 (1.64, 11.27 vs 1 (0.54, 3.89, 95% CI 0.32 to 4.87, p = 0.02 and BALF IL-8 and IL-1α levels showed significant relationships with clinical measures and airway microbiology. P. aeruginosa infection was associated with increased levels of IL-8 while Haemophilus influenzae was associated with increased IL-1α.Established adult non-CF bronchiectasis is characterised by luminal Th17 pathway activation, however this pathway may be relatively less important than activation of non-antigen-specific innate neutrophilic immunity.

  3. Fifteen-year follow-up of pulmonary function in individuals heterozygous for the cystic fibrosis phenylalanine-508 deletion

    DEFF Research Database (Denmark)

    Dahl, Morten; Nordestgaard, B G; Lange, P

    2001-01-01

    In a cross-sectional study, we previously showed that cystic fibrosis phenylalanine-508 deletion (DeltaF508) heterozygosity may be overrepresented among individuals with asthma.......In a cross-sectional study, we previously showed that cystic fibrosis phenylalanine-508 deletion (DeltaF508) heterozygosity may be overrepresented among individuals with asthma....

  4. THE NATIONAL CONSENSUS PROJECT* «CYSTIC FIBROSIS: DEFINITION, DIAGNOSTIC CRITERIA, AND THERAPY». SECTION «INHALATION THERAPY» (ABRIDGED

    Directory of Open Access Journals (Sweden)

    Ye. L. Amelina

    2014-01-01

    Full Text Available The pulmonary drug administration for the treatment of a pulmonary affection in cystic fibrosis is highly effective. This consensus document summarizes data on inhalation intake of bronchodilators, mucolytics, anti-inflammatory drugs, including glucocorticoids, recommended for use in cystic fibrosis patients of all age groups in the territory of the Russian Federation

  5. Ten years' of experience in patient education of families with a child/adolescent suffering from cystic fibrosis

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke

    2007-01-01

    Aims: The patient education programme for families with children or adolescents with cystic fibrosis (the CF school) was established ten years ago to enable patients to make choices in their lives as CF patients. The CF school provides patients with knowledge about cystic fibrosis (CF), teaches...

  6. Intestinal permeability to [51Cr]EDTA in children with cystic fibrosis

    International Nuclear Information System (INIS)

    Leclercq-Foucart, J.; Forget, P.; Sodoyez-Goffaux, F.; Zappitelli, A.

    1986-01-01

    Intestinal permeability was investigated in 14 children with cystic fibrosis making use of [ 51 Cr]EDTA as probe molecule. Ten normal young adults and 11 children served as controls. After oral administration of [ 51 Cr]EDTA, 24 h urine was collected. Urinary radioactivity was calculated and results expressed as percentage of oral dose excreted in 24 h urine. Mean and SEM were as follows: 2.51 +/- 0.21, 2.35 +/- 0.24, and 13.19 +/- 1.72 for control children, normal adults, and cystic fibrosis patients, respectively. The permeability differences between cystic fibrosis patients and either control children or control adults are significant (p less than 0.001)

  7. Parenting adolescents with cystic fibrosis: an interpretive description of the adolescent point of view

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke; Schiøtz, Peter Oluf; Lomborg, Kirsten

    2011-01-01

    , we conducted a secondaryanalysis of the interview data. Results: The adolescents wanted their parents educated about the adolescent experience. They wanted their parents to learn a pedagogical parenting style, to learn to trust the adolescents, and to learn to gradually transfer responsibility......Background: Decreases in disease-related physiological and quality of life parameters are often seen in adolescents with cystic fibrosis. The aim of this study was to identify the types of parental support that adolescents with cystic fibrosis find helpful in terms of preventing these decreases...... for the adolescents’ medical treatment. Conclusion: Parenting an adolescent with cystic fibrosis is a challenge, and the adolescents felt that their parents need to learn skills to help the adolescents better manage their disease. These findings indicate that health professionals may need to educate parents about...

  8. Diagnosis and Treatment of Endocrine Co-Morbidities in Patients with Cystic Fibrosis

    Science.gov (United States)

    Siwamogsatham, Oranan; Alvarez, Jessica

    2015-01-01

    Purpose of review The aim of this review is to provide an update on various relevant endocrine aspects of care in adolescents and adults with cystic fibrosis (CF). Recent findings As life expectancy in CF has continuously improved, endocrine complications have become more apparent. The common endocrine complications include cystic fibrosis related diabetes (CFRD), cystic fibrosis related bone disease, vitamin D deficiency and poor growth and pubertal development. Thyroid and adrenal disorders have also been reported, although the prevalence appears to be less common. Summary Endocrine diseases are an increasingly recognized complication that has a significant impact on the overall health of individuals with CF. This review summarizes the updated screening and management of endocrine diseases in the CF population. PMID:25105995

  9. [Salt intake profile and blood pressure in cystic fibrosis].

    Science.gov (United States)

    Campuzano Martín, S H; Díaz Martín, J J; Perillán Méndez, C; Argüelles Luis, J; Vijande Vázquez, M; Málaga Guerrero, S

    2009-05-01

    High blood pressure (BP) is not considered a problem in patients with cystic fibrosis (CF). The loss of sodium in these patients may affect their sensitivity to the taste of salt. To study the BP in a group of patients with CF and to analyse their salt intake profile and the relationship with their BP levels. Cross-sectional analytical study with control group. Index group: 20 subjects, 4-30 years old with diagnosis of CF. 73 healthy subjects. Physical examination, BP measurement and specific tests to determine the salt ingestion profile. Systolic BP (SBP) and diastolic BP (DBP) values were lower in the CF group. SBP: 99.63+/-9.11mmHg vs. 111.94+/-10.71mmHg, P: 0.001. DBP: 57.84+/-7.40mmHg vs. 70.05+/-8.11mmHg, P: 0.001. When these values were adjusted for age, sex, weight and height of the participants, differences did not remain statistically significant. Values of the salt intake profile did not differ significantly between the two groups. While the control group showed a significant negative correlation between SBP and salt taste sensitivity (r: -0.341, P=0.003), this correlation was not confirmed in CF patients (r: -0.115 P=0.6). BP values and the salt intake profile values in CF patients are equivalent to the normal population values when their differences are adjusted to the potential confounding factors. There is no correlation between BP levels and salt taste sensitivity in patients with CF.

  10. Diffusion weighted imaging in cystic fibrosis disease: beyond morphological imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ciet, Pierluigi [Erasmus Medical Center, Department of Radiology, Rotterdam (Netherlands); Erasmus Medical Center - Sophia Children' s Hospital, Department of Paediatrics, Respiratory Medicine and Allergology, P.O. Box 2060, Rotterdam, Zuid-Holland (Netherlands); Ca' Foncello - General Hospital, Department of Radiology, Treviso (Italy); Serra, Goffredo; Catalano, Carlo [University of Rome ' ' Sapienza' ' , Department of Radiology, Rome (Italy); Andrinopoulou, Eleni Rosalina [Erasmus Medical Center, Department of Biostatistics, Rotterdam (Netherlands); Bertolo, Silvia; Morana, Giovanni [Ca' Foncello - General Hospital, Department of Radiology, Treviso (Italy); Ros, Mirco [Ca' Foncello Hospital, Department of Pediatrics, Treviso (Italy); Colagrande, Stefano [University of Florence - Azienda Ospedaliero-Universitaria Careggi, Department of Experimental and Clinical Biomedical Sciences, Radiodiagnostic Unit n. 2, Florence (Italy); Tiddens, Harm A.W.M. [Erasmus Medical Center, Department of Radiology, Rotterdam (Netherlands); Erasmus Medical Center - Sophia Children' s Hospital, Department of Paediatrics, Respiratory Medicine and Allergology, P.O. Box 2060, Rotterdam, Zuid-Holland (Netherlands)

    2016-11-15

    To explore the feasibility of diffusion-weighted imaging (DWI) to assess inflammatory lung changes in patients with Cystic Fibrosis (CF) CF patients referred for their annual check-up had spirometry, chest-CT and MRI on the same day. MRI was performed in a 1.5 T scanner with BLADE and EPI-DWI sequences (b = 0-600 s/mm{sup 2}). End-inspiratory and end-expiratory scans were acquired in multi-row scanners. DWI was scored with an established semi-quantitative scoring system. DWI score was correlated to CT sub-scores for bronchiectasis (CF-CT{sub BE}), mucus (CF-CT{sub mucus}), total score (CF-CT{sub total-score}), FEV{sub 1}, and BMI. T-test was used to assess differences between patients with and without DWI-hotspots. Thirty-three CF patients were enrolled (mean 21 years, range 6-51, 19 female). 4 % (SD 2.6, range 1.5-12.9) of total CF-CT alterations presented DWI-hotspots. DWI-hotspots coincided with mucus plugging (60 %), consolidation (30 %) and bronchiectasis (10 %). DWI{sub total-score} correlated (all p < 0.0001) positively to CF-CT{sub BE} (r = 0.757), CF-CT{sub mucus} (r = 0.759) and CF-CT{sub total-score} (r = 0.79); and negatively to FEV{sub 1} (r = 0.688). FEV{sub 1} was significantly higher (p < 0.0001) in patients without DWI-hotspots. DWI-hotspots strongly correlated with radiological and clinical parameters of lung disease severity. Future validation studies are needed to establish the exact nature of DWI-hotspots in CF patients. (orig.)

  11. Problem behaviours and parenting in preschool children with cystic fibrosis.

    Science.gov (United States)

    Ward, C; Massie, J; Glazner, J; Sheehan, J; Canterford, L; Armstrong, D; Jaffe, A; Hiscock, H

    2009-05-01

    Problems with sleep, eating and adherence to therapy may adversely affect health outcomes in children with cystic fibrosis (CF). Data on the prevalence of such problems, associated parenting styles and caregiver mental health are limited. To determine: (a) the prevalence of sleep, mealtime, therapy adherence and externalising and internalising behavioural problems in preschool children with CF; (b) the prevalence of caregiver mental health problems and poor sleep quality; and (c) associations between child behavioural problems and parenting styles. This was a cross sectional survey of caregivers of children aged 6 months to 5 years attending CF outpatient clinics at Royal Children's Hospital (Melbourne), Monash Medical Centre (Melbourne) and Sydney Children's Hospital. Main outcome measures were child externalising and internalising behaviours, sleep, eating and adherence with therapy; the predictor was parenting styles (harsh, inconsistent, overprotective). 117 of 139 families participated. Problems were common with child sleep (small 31.6%; moderate/large problem: 21.9%), eating (32.4%) and adherence with physiotherapy (50.4%). Compared to normative data, sleep and mealtime problems were more prevalent. Caregivers reported high rates of symptoms indicating depression (33.3%), anxiety (16.4%) and stress (34.2%). Harsh parenting was associated with internalising behaviours (adjusted OR 3.9, 95% CI 1.16 to 13.17, p = 0.03). Problems with sleeping, eating and physiotherapy adherence were common in preschool children with CF. Caregivers reported high rates of symptoms indicative of mental health problems. Harsh parenting was associated with internalising problems. An intervention targeting child problem behaviours and parental mental health would be appropriate for CF families.

  12. Personalized or Precision Medicine? The Example of Cystic Fibrosis

    Science.gov (United States)

    Marson, Fernando A. L.; Bertuzzo, Carmen S.; Ribeiro, José D.

    2017-01-01

    The advent of the knowledge on human genetics, by the identification of disease-associated variants, culminated in the understanding of human variability. With the genetic knowledge, the specificity of the clinical phenotype and the drug response of each individual were understood. Using the cystic fibrosis (CF) as an example, the new terms that emerged such as personalized medicine and precision medicine can be characterized. The genetic knowledge in CF is broad and the presence of a monogenic disease caused by mutations in the CFTR gene enables the phenotype–genotype association studies (including the response to drugs), considering the wide clinical and laboratory spectrum dependent on the mutual action of genotype, environment, and lifestyle. Regarding the CF disease, personalized medicine is the treatment directed at the symptoms, and this treatment is adjusted depending on the patient’s phenotype. However, more recently, the term precision medicine began to be widely used, although its correct application and understanding are still vague and poorly characterized. In precision medicine, we understand the individual as a response to the interrelation between environment, lifestyle, and genetic factors, which enabled the advent of new therapeutic models, such as conventional drugs adjustment by individual patient dosage and drug type and response, development of new drugs (read through, broker, enhancer, stabilizer, and amplifier compounds), genome editing by homologous recombination, zinc finger nucleases, TALEN (transcription activator-like effector nuclease), CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR-associated endonuclease 9), and gene therapy. Thus, we introduced the terms personalized medicine and precision medicine based on the CF. PMID:28676762

  13. Diffusion weighted imaging in cystic fibrosis disease: beyond morphological imaging

    International Nuclear Information System (INIS)

    Ciet, Pierluigi; Serra, Goffredo; Catalano, Carlo; Andrinopoulou, Eleni Rosalina; Bertolo, Silvia; Morana, Giovanni; Ros, Mirco; Colagrande, Stefano; Tiddens, Harm A.W.M.

    2016-01-01

    To explore the feasibility of diffusion-weighted imaging (DWI) to assess inflammatory lung changes in patients with Cystic Fibrosis (CF) CF patients referred for their annual check-up had spirometry, chest-CT and MRI on the same day. MRI was performed in a 1.5 T scanner with BLADE and EPI-DWI sequences (b = 0-600 s/mm 2 ). End-inspiratory and end-expiratory scans were acquired in multi-row scanners. DWI was scored with an established semi-quantitative scoring system. DWI score was correlated to CT sub-scores for bronchiectasis (CF-CT BE ), mucus (CF-CT mucus ), total score (CF-CT total-score ), FEV 1 , and BMI. T-test was used to assess differences between patients with and without DWI-hotspots. Thirty-three CF patients were enrolled (mean 21 years, range 6-51, 19 female). 4 % (SD 2.6, range 1.5-12.9) of total CF-CT alterations presented DWI-hotspots. DWI-hotspots coincided with mucus plugging (60 %), consolidation (30 %) and bronchiectasis (10 %). DWI total-score correlated (all p < 0.0001) positively to CF-CT BE (r = 0.757), CF-CT mucus (r = 0.759) and CF-CT total-score (r = 0.79); and negatively to FEV 1 (r = 0.688). FEV 1 was significantly higher (p < 0.0001) in patients without DWI-hotspots. DWI-hotspots strongly correlated with radiological and clinical parameters of lung disease severity. Future validation studies are needed to establish the exact nature of DWI-hotspots in CF patients. (orig.)

  14. Highly effective cystic fibrosis clinical research teams: critical success factors.

    Science.gov (United States)

    Retsch-Bogart, George Z; Van Dalfsen, Jill M; Marshall, Bruce C; George, Cynthia; Pilewski, Joseph M; Nelson, Eugene C; Goss, Christopher H; Ramsey, Bonnie W

    2014-08-01

    Bringing new therapies to patients with rare diseases depends in part on optimizing clinical trial conduct through efficient study start-up processes and rapid enrollment. Suboptimal execution of clinical trials in academic medical centers not only results in high cost to institutions and sponsors, but also delays the availability of new therapies. Addressing the factors that contribute to poor outcomes requires novel, systematic approaches tailored to the institution and disease under study. To use clinical trial performance metrics data analysis to select high-performing cystic fibrosis (CF) clinical research teams and then identify factors contributing to their success. Mixed-methods research, including semi-structured qualitative interviews of high-performing research teams. CF research teams at nine clinical centers from the CF Foundation Therapeutics Development Network. Survey of site characteristics, direct observation of team meetings and facilities, and semi-structured interviews with clinical research team members and institutional program managers and leaders in clinical research. Critical success factors noted at all nine high-performing centers were: 1) strong leadership, 2) established and effective communication within the research team and with the clinical care team, and 3) adequate staff. Other frequent characteristics included a mature culture of research, customer service orientation in interactions with study participants, shared efficient processes, continuous process improvement activities, and a businesslike approach to clinical research. Clinical research metrics allowed identification of high-performing clinical research teams. Site visits identified several critical factors leading to highly successful teams that may help other clinical research teams improve clinical trial performance.

  15. Brazilian guidelines for the diagnosis and treatment of cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Rodrigo Abensur Athanazio

    Full Text Available ABSTRACT Cystic fibrosis (CF is an autosomal recessive genetic disorder characterized by dysfunction of the CFTR gene. It is a multisystem disease that most often affects White individuals. In recent decades, various advances in the diagnosis and treatment of CF have drastically changed the scenario, resulting in a significant increase in survival and quality of life. In Brazil, the current neonatal screening program for CF has broad coverage, and most of the Brazilian states have referral centers for the follow-up of individuals with the disease. Previously, CF was limited to the pediatric age group. However, an increase in the number of adult CF patients has been observed, because of the greater number of individuals being diagnosed with atypical forms (with milder phenotypic expression and because of the increase in life expectancy provided by the new treatments. However, there is still great heterogeneity among the different regions of Brazil in terms of the access of CF patients to diagnostic and therapeutic methods. The objective of these guidelines was to aggregate the main scientific evidence to guide the management of these patients. A group of 18 CF specialists devised 82 relevant clinical questions, divided into five categories: characteristics of a referral center; diagnosis; treatment of respiratory disease; gastrointestinal and nutritional treatment; and other aspects. Various professionals working in the area of CF in Brazil were invited to answer the questions devised by the coordinators. We used the PubMed database to search the available literature based on keywords, in order to find the best answers to these questions.

  16. Longitudinal evaluation of bronchopulmonary disease in children with cystic fibrosis.

    Science.gov (United States)

    Farrell, Philip M; Li, Zhanhai; Kosorok, Michael R; Laxova, Anita; Green, Christopher G; Collins, Jannette; Lai, Hui-Chuan; Makholm, Linda M; Rock, Michael J; Splaingard, Mark L

    2003-09-01

    Children with cystic fibrosis (CF) develop bronchopulmonary disease at variable ages. Determining the epidemiology of chronic lung disease and quantifying its severity, however, have been difficult in infants and young children. As part of the Wisconsin CF Neonatal Screening Project, we were presented with an ideal opportunity to assess longitudinally the evolution of symptoms, signs, and quantitative measures of CF respiratory disease. After newborn screening test results led to early recognition, 64 patients diagnosed at a median age of 6.71 weeks were enrolled and studied systematically at a median age of 11.3 years to obtain clinical information, chest radiographs, and pulmonary function tests. Our observations revealed that a frequent cough by history is evident by 10.5 months of age in half the patients. Quantitative chest radiology (CXR scoring) demonstrated that potentially irreversible abnormalities are present in half the children by 2 years. The severity of Wisconsin and Brasfield CXR scores increased in association with respiratory infections. Longitudinal progression of Wisconsin CXR scores was related to age (P < 0.001), pancreatic insufficiency (P = 0.005), and respiratory secretion cultures positive for Staphylococus aureas (P = 0.039). In contrast, serial spirometry showed limited sensitivity, as did lung volume determinations; neither was satisfactory as repeated measures with acceptable quality control until after 7 years of age. Time to event analyses revealed that half the patients had % predicted FEF(25-75) and FEV(1)/FVC values greater than 80% until 10.7 and 9.9 years, respectively. We conclude that of the methods evaluated, quantitative chest radiology is currently the best procedure for frequent assessment of bronchopulmonary disease in CF, and that radiographic progression is evident in approximately 85% of patients by 5 years of age. Our results also suggest that bronchiectasis and other radiographic evidence of chronic infection are

  17. Comparison of immunoreactive serum trypsinogen and lipase in Cystic Fibrosis

    International Nuclear Information System (INIS)

    Lloyd-Still, J.D.; Weiss, S.; Wessel, H.; Fong, L.; Conway, J.J.

    1984-01-01

    The incidence of Cystic Fibrosis (CF) is 1 in 2,000. Early detection and treatment of CF may necessitate newborn screening with a reliable and cost-effective test. Serum immunoreactive trypsinogen (IRT) an enzyme produced by the pancreas, is detectable by radioimmunoassay (RIA) techniques. Recently, it has been shown that IRT is elevated in CF infants for the first few months of life and levels become subnormal as pancreatic insufficiency progresses. Other enzymes produced by the pancreas, such as lipase, are also elevated during this time. The author's earlier work confirmed previous reports of elevated IRT levels in CF infants. The development of a new RIA for lipase (nuclipase) has enabled comparison of these 2 pancreatic enzymes in C.F. Serum IRT and lipase determinations were performed on 2 groups of CF patients; infants under 1 year of age, and children between 1 and 18 years of age. Control populations of the same age groups were included. The results showed that both trypsin (161 +- 92 ng/ml, range 20 to 400) and lipase (167 +- 151 ng/ml, range 29 to 500) are elevated in CF in the majority of infants. Control infants had values of IRT ranging from 20 to 29.5 ng/ml and lipase values ranging from 23 to 34 ng/ml. IRT becomes subnormal in most CF patients by 8 years of age as pancreatic function insufficiency increases. Lipase levels and IRT levels correlate well in infancy, but IRT is a more sensitive indicator of pancreatic insufficiency in older patients with CF

  18. Improving the care of patients with cystic fibrosis (CF)

    Science.gov (United States)

    Khan, Ahsan Aftab; Nash, Edward F; Whitehouse, Joanna; Rashid, Rifat

    2017-01-01

    Background The West Midlands Adult Cystic Fibrosis (CF) Centre based at Birmingham Heartlands Hospital provides care for adults with CF in the West Midlands. People with CF are prone to pulmonary exacerbations, which often require inpatient admission for intravenous antibiotics. We observed that the admission process was efficient during working hours (9:00–17:00, Monday–Friday) when the CF team are routinely available, but out-of-working hours, there were delays in these patients being clerked and receiving their first antibiotic dose. We were concerned that this was resulting in quality and potential safety issues by causing delays in starting treatment and prolonging hospital inpatient stays. We therefore undertook a quality improvement project (QIP) aimed at addressing these issues. An initial survey showed median time to clerk of 5 hours, with 60% of patients missing their first dose of antibiotics and mean length of stay of 16 days. Methods We applied the Plan-Do-Study-Act (PDSA) cycle approach, with the first PDSA cycle involving raising awareness of the issue through education to doctors, nurses and patients. Results This led to a reduction of median time to clerk from 5 to 2 hours with 23% of patients missing their first antibiotic dose and mean length of stay reducing to 14 days. The second cycle involved introducing an admissions checklist and displaying education posters around the hospital, resulting in median time to clerk remaining at 2 hours but only 20% of patients missing their first antibiotic dose and the mean length of stay remaining at 14 days. Conclusion This QIP has improved the out-of-hours admissions process for adults with CF in our centre. We plan to review the longer term effects of the project including sustainability, effects on clinical outcomes and patient satisfaction. PMID:28959778

  19. Risk of gastrointestinal cancers in patients with cystic fibrosis: a systematic review and meta-analysis.

    Science.gov (United States)

    Yamada, Akihiro; Komaki, Yuga; Komaki, Fukiko; Micic, Dejan; Zullow, Samantha; Sakuraba, Atsushi

    2018-04-26

    The management and life expectancy of patients with cystic fibrosis have improved substantially in the past three decades, which has resulted in an increased number of these patients being diagnosed with malignancies. Our aim was to assess the risk of gastrointestinal cancers in patients with cystic fibrosis. In this systematic review and meta-analysis, we searched PubMed, MEDLINE, Google Scholar, Scopus, Embase, and Cochrane databases with no language restrictions for studies published from inception of the databases to Aug 1, 2017, assessing the risk of gastrointestinal cancers in patients with cystic fibrosis. We also searched abstracts from scientific meetings and the bibliographies of identified articles for additional references. Studies were included if they reported the standardised incidence ratio (SIR) or incidence ratio per person-years. No exclusion criteria with regard to patient characteristics (age, sex, comorbidities, cystic fibrosis mutation type), study setting (location and time period), or method of reporting cancer diagnoses were applied. The primary outcome was risk of gastrointestinal cancer and site-specific gastrointestinal cancers in patients with cystic fibrosis compared with the general population. Pooled summary estimates were calculated using a random-effects model, and subgroup analyses were done to establish whether risk of gastrointestinal cancer varied according to patient lung transplant status. The study is registered with PROSPERO, number CRD42017075396. Our search identified 95 681 records, of which six cohort studies including 99 925 patients (544 695 person-years) were eligible for the meta-analysis. The overall risk of gastrointestinal cancer was significantly higher in patients with cystic fibrosis than in the general population (pooled SIR 8·13, 95% CI 6·48-10·21; pcystic fibrosis who had a lung transplant was increased compared with that of patients who did not receive a transplant (pooled SIR 21·13, 95% CI 14

  20. The distinctly visible right upper lobe bronchus on the lateral chest: A clue to adolescent cystic fibrosis

    International Nuclear Information System (INIS)

    Reinig, J.W.; Sanchez, F.W.; Thomason, D.M.; Gobien, R.P.

    1985-01-01

    Radiographic differentiation between cystic fibrosis and asthma presenting in teenagers and young adults can be difficult. Many patients with a late presentation of cystic fibrosis display minimal changes on a chest radiograph. However, a large majority (90%) of cystic fibrosis patients with an essentially normal PA chest radiograph will have a distinctly outlined orifice of right upper lobe bronchus on a lateral chest film as opposed to a small number of asthmatics (25%) or normal patients (18%). This observation correlates well with the pathologic finding that the initial pulmonary involvement in cystic fibrosis is typically in the right upper lobe in adolescents. Teenager or young adult patients presenting with a history of repeated respiratory infections, asthma-like symptoms and a distinctly visible right upper lobe bronchus on a lateral chest film should be sweat-tested to exclude cystic fibrosis. (orig.)