Sample records for cystic fibrosis support

  1. Cystic fibrosis - resources

    MedlinePlus

    Resources - cystic fibrosis ... The following organizations are good resources for information on cystic fibrosis : Cystic Fibrosis Foundation -- www.cff.org March of Dimes -- www.marchofdimes.org/baby/cystic-fibrosis-and- ...

  2. Heart involvement in cystic fibrosis: A specific cystic fibrosis-related myocardial changes?

    PubMed

    Labombarda, Fabien; Saloux, Eric; Brouard, Jacques; Bergot, Emmanuel; Milliez, Paul

    2016-09-01

    Cystic fibrosis is a complex multi-systemic chronic disease characterized by progressive organ dysfunction with development of fibrosis, possibly affecting the heart. Over the last four decades pathological, experimental, and clinical evidence points towards the existence of a specific myocardial involvement in cystic fibrosis. Multi-modality cardiac imaging, especially recent echocardiographic techniques, evidenced diastolic and/or systolic ventricular dysfunction in cystic fibrosis leading to the concept of a cystic fibrosis-related cardiomyopathy. Hypoxemia and inflammation are among the most important factors for heart involvement in cystic fibrosis. Cystic Fibrosis Transmembrane Regulator was found to be involved in the regulation of cardiomyocyte contraction and may also account for cystic fibrosis-related myocardial dysfunction. This review, mainly focused on echocardiographic studies, seeks to synthesize the existing literature for and against the existence of heart involvement in cystic fibrosis, its mechanisms and prognostic implications. Careful investigation of the heart function may be helpful for risk stratification and therapeutic decisions in patients with cystic fibrosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Cystic fibrosis.

    PubMed

    Elborn, J Stuart

    2016-11-19

    Cystic fibrosis is a common life-limiting autosomal recessive genetic disorder, with highest prevalence in Europe, North America, and Australia. The disease is caused by mutation of a gene that encodes a chloride-conducting transmembrane channel called the cystic fibrosis transmembrane conductance regulator (CFTR), which regulates anion transport and mucociliary clearance in the airways. Functional failure of CFTR results in mucus retention and chronic infection and subsequently in local airway inflammation that is harmful to the lungs. CFTR dysfunction mainly affects epithelial cells, although there is evidence of a role in immune cells. Cystic fibrosis affects several body systems, and morbidity and mortality is mostly caused by bronchiectasis, small airways obstruction, and progressive respiratory impairment. Important comorbidities caused by epithelial cell dysfunction occur in the pancreas (malabsorption), liver (biliary cirrhosis), sweat glands (heat shock), and vas deferens (infertility). The development and delivery of drugs that improve the clearance of mucus from the lungs and treat the consequent infection, in combination with correction of pancreatic insufficiency and undernutrition by multidisciplinary teams, have resulted in remarkable improvements in quality of life and clinical outcomes in patients with cystic fibrosis, with median life expectancy now older than 40 years. Innovative and transformational therapies that target the basic defect in cystic fibrosis have recently been developed and are effective in improving lung function and reducing pulmonary exacerbations. Further small molecule and gene-based therapies are being developed to restore CFTR function; these therapies promise to be disease modifying and to improve the lives of people with cystic fibrosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Longitudinal cystic fibrosis care.

    PubMed

    Antunovic, S S; Lukac, M; Vujovic, D

    2013-01-01

    Cystic fibrosis is a complex disease entity that presents considerable lifelong challenges. Implementation of medical and surgical treatment options involves multisystem interventions to prevent and treat lung and gastrointestinal manifestations of cystic fibrosis and associated comorbidities. From birth through adulthood, cystic fibrosis care entails a longitudinal regimen aimed at achieving relief of disease symptoms and enhanced life expectancy. With increased knowledge of the molecular behavior of the cystic fibrosis transmembrane conductance regulator (CFTR) in health and disease, clinical practice has been enriched by the prospect of novel strategies, including mutation-specific drug and gene therapy targeting restoration of corrupted transepithelial ion transport. Emerging paradigms of comprehensive care increasingly enable personalized solutions to address the root cause of disease-transforming management options for individuals with cystic fibrosis.

  5. Cystic fibrosis.

    PubMed

    O'Sullivan, Brian P; Freedman, Steven D

    2009-05-30

    Cystic fibrosis is the most common lethal genetic disease in white populations. The outlook for patients with the disease has improved steadily over many years, largely as a result of earlier diagnosis, more aggressive therapy, and provision of care in specialised centres. Researchers now have a more complete understanding of the molecular-biological defect that underlies cystic fibrosis, which is leading to new approaches to treatment. One of these treatments, hypertonic saline, is already in use, whereas others are in advanced stages of development. We review clinical care for cystic fibrosis and discuss recent advances in the understanding of its pathogenesis, implementation of screening of neonates, and development of therapies aimed at treating the basic defect.

  6. A cystic fibrosis handbook for teachers.

    PubMed

    Ryan, L L; Williams, J K

    1996-01-01

    The purposes of this project were to (1) develop a handbook on cystic fibrosis for elementary school teachers and to (2) pilot this handbook with a group of teachers and school nurses. The project used a descriptive survey design in which parents, teachers, and school nurses of 14 elementary-age children with cystic fibrosis were recruited from one cystic fibrosis clinic. Interest in using the handbook with their child's teachers was elicited from parents; also, interest in using the handbook was obtained by open-ended questions in a mailed survey sent to teachers and school nurses. Levels of teacher and school nurse knowledge were measured with a true/false pretest and posttest instrument. All parents expressed a desire to use the handbook with their child's teachers. Sixty-seven percent of the teachers and 89% of the school nurses returned the survey, and all endorsed the use of the handbook in their classrooms or schools. Comparison of the pretest and posttest scores from the teachers revealed an increase in teachers' knowledge. Scores on pretest and posttest measures from school nurses were high at each testing time. Results support the use of a printed handbook to promote knowledge of cystic fibrosis in teachers and to support communication among nurses, parents, and teachers.

  7. Singing for children and adults with cystic fibrosis.

    PubMed

    Irons, Jung Yoon; Kenny, Dianna Theadora; Chang, Anne B

    2010-05-12

    Cystic fibrosis is a genetically inherited, life-threatening condition that affects major organs. The management of cystic fibrosis involves a multi-faceted daily treatment regimen that includes airway clearance physiotherapy, taking pancreatic enzymes and other medications. Previous studies identified that compliance with this intensive treatment especially among adolescents with cystic fibrosis is poor. Because of both the nature and consequences of the illness and the relentless demands of treatments, many individuals with cystic fibrosis are likely to have a poor quality of life. Anecdotal evidence suggests that singing may provide rigorous exercises for the whole respiratory system as well as a means for emotional expression, which may enhance quality of life. To evaluate the effects of a singing intervention in addition to usual therapy on the quality of life, morbidity, respiratory muscle strength and pulmonary function of children and adults with cystic fibrosis. We searched the Group's Cystic Fibrosis Trials Register, the Cochrane Central Register of Controlled Trials, major allied complementary data bases, and clinical trial registers. Hand searching for relevant conference proceedings and journals was also carried out.Date of search of Trials Register: 02 September 2009.Date of additional searches: 17 September 2009. Randomised controlled trials in which singing (as an adjunctive intervention) is compared with either a sham intervention or no singing in people with cystic fibrosis. No trials were found that met the selection criteria. No meta-analysis could be performed. As no studies that met the criteria were found, this review is unable to support or refute the benefits of singing as a therapy for people with cystic fibrosis. Future randomised controlled trials are required to evaluate singing therapy for people with cystic fibrosis.

  8. Cystic Fibrosis and Pregnancy

    MedlinePlus

    ... Global Map Premature Birth Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal ... complications > Cystic fibrosis and pregnancy Cystic fibrosis and pregnancy E-mail to a friend Please fill in ...

  9. Molecular Diagnosis of Cystic Fibrosis.

    PubMed

    Deignan, Joshua L; Grody, Wayne W

    2016-01-01

    This unit describes a recommended approach to identifying causal genetic variants in an individual suspected of having cystic fibrosis. An introduction to the genetics and clinical presentation of cystic fibrosis is initially presented, followed by a description of the two main strategies used in the molecular diagnosis of cystic fibrosis: (1) an initial targeted variant panel used to detect only the most common cystic fibrosis-causing variants in the CFTR gene, and (2) sequencing of the entire coding region of the CFTR gene to detect additional rare causal CFTR variants. Finally, the unit concludes with a discussion regarding the analytic and clinical validity of these approaches. Copyright © 2016 John Wiley & Sons, Inc.

  10. Voice Disorder in Cystic Fibrosis Patients

    PubMed Central

    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

  11. Vitamin A supplementation for cystic fibrosis.

    PubMed

    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

  12. Gastrointestinal Manifestations of Cystic Fibrosis

    PubMed Central

    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

  13. Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease.

    PubMed

    Lee, T; Southern, K W

    2007-04-18

    measured ion transport in the lower airways and demonstrated significant changes toward normal values in the participants who received gene transfer agents (P < 0.0001), weighted mean difference 6.86 (95% CI of 3.77 to 9.95). In these participants there was also evidence of increased salt transport in cells obtained by brushing the lower airway. These outcomes, whilst important, are not of direct clinical relevance. There is currently no evidence to support the use of CFTR gene transfer reagents as a treatment for lung disease in people with cystic fibrosis. Future studies need to investigate clinically important outcome measures.

  14. Abnormal Ion Permeation through Cystic Fibrosis Respiratory Epithelium

    NASA Astrophysics Data System (ADS)

    Knowles, M. R.; Stutts, M. J.; Spock, A.; Fischer, N.; Gatzy, J. T.; Boucher, R. C.

    1983-09-01

    The epithelium of nasal tissue excised from subjects with cystic fibrosis exhibited higher voltage and lower conductance than tissue from control subjects. Basal sodium ion absorption by cystic fibrosis and normal nasal epithelia equaled the short-circuit current and was amiloride-sensitive. Amiloride induced chloride ion secretion in normal but not cystic fibrosis tissue and consequently was more effective in inhibiting the short-circuit current in cystic fibrosis epithelia. Chloride ion-free solution induced a smaller hyperpolarization of cystic fibrosis tissue. The increased voltage and amiloride efficacy in cystic fibrosis reflect absorption of sodium ions across an epithelium that is relatively impermeable to chloride ions.

  15. Genetics Home Reference: cystic fibrosis

    MedlinePlus

    ... Foundation) Genetic Testing (1 link) Genetic Testing Registry: Cystic fibrosis Other Diagnosis and Management Resources (5 links) American Society for Reproductive Medicine: Male Infertility Baby's First Test GeneReview: Cystic Fibrosis and Congenital Absence of the Vas Deferens Genomics ...

  16. What's it Like to Have Cystic Fibrosis?

    MedlinePlus

    ... deal with cystic fibrosis. What Is CF? Cystic fibrosis (CF) is a disease that causes the body to make thick, sticky mucus (say: ... special protein. This protein is defective in cystic fibrosis, producing the thick, sticky mucus that causes problems for people with CF. What Causes CF? ...

  17. Vitamin A supplementation for cystic fibrosis.

    PubMed

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

    2012-08-15

    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 CF: 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: 23 May 2012. 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 vitamin A in

  18. Chloride impermeability in cystic fibrosis

    NASA Astrophysics Data System (ADS)

    Quinton, Paul M.

    1983-02-01

    Cystic fibrosis is the most common fatal genetic disease affecting Caucasians and is perhaps best characterized as an exocrinopathy involving a disturbance in fluid and electrolyte transport1. A high NaCl concentration in the sweat is characteristic of patients with this disease; the basic physiological reason for this abnormality is unknown. We have microperfused isolated sweat ducts from control subjects and cystic fibrosis patients, and report here results which suggest that abnormally low Cl- permeability in cystic fibrosis leads to poor reabsorption of NaCl in the sweat duct, and hence to a high concentration of NaCl in the sweat.

  19. Cystic Fibrosis (CF) Respiratory Screen: Sputum

    MedlinePlus

    ... for Educators Search English Español Cystic Fibrosis (CF) Respiratory Screen: Sputum KidsHealth / For Parents / Cystic Fibrosis (CF) Respiratory Screen: Sputum What's in this article? What It ...

  20. CXCR4+ granulocytes reflect fungal cystic fibrosis lung disease.

    PubMed

    Carevic, Melanie; Singh, Anurag; Rieber, Nikolaus; Eickmeier, Olaf; Griese, Matthias; Hector, Andreas; Hartl, Dominik

    2015-08-01

    Cystic fibrosis airways are frequently colonised with fungi. However, the interaction of these fungi with immune cells and the clinical relevance in cystic fibrosis lung disease are incompletely understood.We characterised granulocytes in airway fluids and peripheral blood from cystic fibrosis patients with and without fungal colonisation, non-cystic fibrosis disease controls and healthy control subjects cross-sectionally and longitudinally and correlated these findings with lung function parameters.Cystic fibrosis patients with chronic fungal colonisation by Aspergillus fumigatus were characterised by an accumulation of a distinct granulocyte subset, expressing the HIV coreceptor CXCR4. Percentages of airway CXCR4(+) granulocytes correlated with lung disease severity in patients with cystic fibrosis.These studies demonstrate that chronic fungal colonisation with A. fumigatus in cystic fibrosis patients is associated with CXCR4(+) airway granulocytes, which may serve as a potential biomarker and therapeutic target in fungal cystic fibrosis lung disease. Copyright ©ERS 2015.

  1. Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease.

    PubMed

    Lee, Tim W R; Southern, Kevin W

    2013-11-26

    who received the CFTR gene transfer agents in the Alton study, "influenza-like" symptoms were found (risk ratio 7.00 (95% confidence interval 1.10 to 44.61)). There were no other significant increases in adverse events in any of the studies.Alton measured ion transport in the lower airways and demonstrated significant changes toward normal values in the participants who received gene transfer agents (P < 0.0001), mean difference 6.86 (95% confidence interval 3.77 to 9.95). In these participants there was also evidence of increased salt transport in cells obtained by brushing the lower airway. These outcomes, whilst important, are not of direct clinical relevance. There is currently no evidence to support the use of CFTR gene transfer agents as a treatment for lung disease in people with cystic fibrosis. Future studies need to investigate clinically important outcome measures.

  2. Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease.

    PubMed

    Lee, Tim W R; Southern, Kevin W

    2012-10-17

    received the CFTR gene transfer agents in the Alton study, "influenza-like" symptoms were found (risk ratio 7.00 (95% confidence interval 1.10 to 44.61)). There were no other significant increases in adverse events in any of the studies.Alton measured ion transport in the lower airways and demonstrated significant changes toward normal values in the participants who received gene transfer agents (P < 0.0001), mean difference 6.86 (95% CI of 3.77 to 9.95). In these participants there was also evidence of increased salt transport in cells obtained by brushing the lower airway. These outcomes, whilst important, are not of direct clinical relevance. There is currently no evidence to support the use of CFTR gene transfer reagents as a treatment for lung disease in people with cystic fibrosis. Future studies need to investigate clinically important outcome measures.

  3. Molecular diagnosis of cystic fibrosis.

    PubMed

    Shrimpton, Antony E

    2002-05-01

    A review of the current molecular diagnosis of cystic fibrosis including an introduction to cystic fibrosis, the gene function, the phenotypic variation, who should be screened for which mutation, newborn and couple screening, quality assurance, phenotype-genotype correlation, methods and method limitations, options, statements, recommendations, useful Websites and treatments.

  4. Cystic fibrosis screening in assisted reproduction.

    PubMed

    Gazvani, Rafet; Lewis-Jones, Iwan

    2006-06-01

    The purpose of this review is to discuss the incidence of cystic fibrosis in the general population, in ethnically diverse populations and specifically in couples needing assisted reproduction caused by male factor subfertility. We review the current understanding of risks for reproductive couples and discuss ideal screening strategies. In ethnically diverse populations, a large difference in clinical sensitivity and birth prevalence exists between the broad racial/ethnic groups examined. Extensive data clearly demonstrate the cost-effectiveness of cystic fibrosis screening. Testing for cystic fibrosis gene mutations is reliable and, with a 26-mutation panel, nearly 90% of possible severe mutations can be detected. To halve the incidence of cystic fibrosis in the community, by offering genetic testing of the fetus if both partners are carrier positive, may also be possible. Recent guidelines suggest that all couples contemplating pregnancy should be informed of molecular screening for cystic fibrosis carrier status for purposes of genetic counselling. In ethnically diverse populations, ethnic-specific mutations should be included in the mutation panels.

  5. Cystic Fibrosis Associated with Worse Survival After Liver Transplantation.

    PubMed

    Black, Sylvester M; Woodley, Frederick W; Tumin, Dmitry; Mumtaz, Khalid; Whitson, Bryan A; Tobias, Joseph D; Hayes, Don

    2016-04-01

    Survival in cystic fibrosis patients after liver transplantation and liver-lung transplantation is not well studied. To discern survival rates after liver transplantation and liver-lung transplantation in patients with and without cystic fibrosis. The United Network for Organ Sharing database was queried from 1987 to 2013. Univariate Cox proportional hazards, multivariate Cox models, and propensity score matching were performed. Liver transplant and liver-lung transplant were performed in 212 and 53 patients with cystic fibrosis, respectively. Univariate Cox proportional hazards regression identified lower survival in cystic fibrosis after liver transplant compared to a reference non-cystic fibrosis liver transplant cohort (HR 1.248; 95 % CI 1.012, 1.541; p = 0.039). Supplementary analysis found graft survival was similar across the 3 recipient categories (log-rank test: χ(2) 2.68; p = 0.262). Multivariate Cox models identified increased mortality hazard among cystic fibrosis patients undergoing liver transplantation (HR 2.439; 95 % CI 1.709, 3.482; p < 0.001) and liver-lung transplantation (HR 2.753; 95 % CI 1.560, 4.861; p < 0.001). Propensity score matching of cystic fibrosis patients undergoing liver transplantation to non-cystic fibrosis controls identified a greater mortality hazard in the cystic fibrosis cohort using a Cox proportional hazards model stratified on matched pairs (HR 3.167; 95 % CI 1.265, 7.929, p = 0.014). Liver transplantation in cystic fibrosis is associated with poorer long-term patient survival compared to non-cystic fibrosis patients, although the difference is not due to graft survival.

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

    MedlinePlus

    Cystic Fibrosis-Related Diabetes (CFRD): Daily Management September 20, 2011 This Web cast is supported by an unrestricted educational grant from Genentech, Inc. Antoinette, Moran, MD Professor, Pediatric Endocrinology ...

  7. Intestinal bile acid malabsorption in cystic fibrosis.

    PubMed

    O'Brien, S; Mulcahy, H; Fenlon, H; O'Broin, A; Casey, M; Burke, A; FitzGerald, M X; Hegarty, J E

    1993-08-01

    This study aimed at examining the mechanisms participating in excessive faecal bile acid loss in cystic fibrosis. The study was designed to define the relation between faecal fat and faecal bile acid loss in patients with and without cystic fibrosis related liver disease; to assess terminal ileal bile acid absorption by a seven day whole body retention of selenium labelled homotaurocholic acid (SeHCAT); and to determine if small intestinal bacterial overgrowth contributes to faecal bile acid loss. The study population comprised 40 patients (27 men; median age 18 years) with cystic fibrosis (n = 8) and without (n = 32) liver disease and eight control subjects. Faecal bile acid excretion was significantly higher in cystic fibrosis patients without liver disease compared with control subjects (mean (SEM) 21.5 (2.4) and 7.3 (1.2) micromoles/kg/24 hours respectively; p < 0.01) and patients with liver disease (7.9 (1.3) micromoles/kg/24 hours; p < 0.01). No correlation was found between faecal fat (g fat/24 hours) and faecal bile acid (micromoles 24 hours) excretion. Eight (33%) of cystic fibrosis patients had seven day SeHCAT retention < 10% (normal retention > 20%). SeHCAT retention in cystic fibrosis patients with liver disease was comparable with control subjects (30.0 (SEM) 8.3% v 36.8 (5.9)%; p = NS) while SeHCAT retention in cystic fibrosis patients who did not have liver disease was significantly reduced (19.9 (3.8); p < 0.05). Although evidence of small bowel bacterial overgrowth was present in 40% of patients no relation was found between breath hydrogen excretion, faecal fat, and faecal bile acid loss. The results are consistent with the presence of an abnormality in terminal ideal function in patients with cystic fibrosis who do not have liver disease and that a defect in the ileal absorption of bile acids may be a contributory factor to excessive faecal bile acid loss. Faecal bile acid loss in cystic fibrosis is unrelated to the presence of intraluminal fat

  8. Intestinal bile acid malabsorption in cystic fibrosis.

    PubMed Central

    O'Brien, S; Mulcahy, H; Fenlon, H; O'Broin, A; Casey, M; Burke, A; FitzGerald, M X; Hegarty, J E

    1993-01-01

    This study aimed at examining the mechanisms participating in excessive faecal bile acid loss in cystic fibrosis. The study was designed to define the relation between faecal fat and faecal bile acid loss in patients with and without cystic fibrosis related liver disease; to assess terminal ileal bile acid absorption by a seven day whole body retention of selenium labelled homotaurocholic acid (SeHCAT); and to determine if small intestinal bacterial overgrowth contributes to faecal bile acid loss. The study population comprised 40 patients (27 men; median age 18 years) with cystic fibrosis (n = 8) and without (n = 32) liver disease and eight control subjects. Faecal bile acid excretion was significantly higher in cystic fibrosis patients without liver disease compared with control subjects (mean (SEM) 21.5 (2.4) and 7.3 (1.2) micromoles/kg/24 hours respectively; p < 0.01) and patients with liver disease (7.9 (1.3) micromoles/kg/24 hours; p < 0.01). No correlation was found between faecal fat (g fat/24 hours) and faecal bile acid (micromoles 24 hours) excretion. Eight (33%) of cystic fibrosis patients had seven day SeHCAT retention < 10% (normal retention > 20%). SeHCAT retention in cystic fibrosis patients with liver disease was comparable with control subjects (30.0 (SEM) 8.3% v 36.8 (5.9)%; p = NS) while SeHCAT retention in cystic fibrosis patients who did not have liver disease was significantly reduced (19.9 (3.8); p < 0.05). Although evidence of small bowel bacterial overgrowth was present in 40% of patients no relation was found between breath hydrogen excretion, faecal fat, and faecal bile acid loss. The results are consistent with the presence of an abnormality in terminal ideal function in patients with cystic fibrosis who do not have liver disease and that a defect in the ileal absorption of bile acids may be a contributory factor to excessive faecal bile acid loss. Faecal bile acid loss in cystic fibrosis is unrelated to the presence of intraluminal fat

  9. Diabetes in cystic fibrosis.

    PubMed

    Bridges, Nicola

    2013-05-01

    Cystic fibrosis related diabetes (CFRD) is a common complication of cystic fibrosis, caused by a fall in insulin secretion with age in individuals with pancreatic insufficiency. CFRD is associated with worse clinical status and increased mortality. Treatment of CFRD with insulin results in sustained improvements in lung function and nutrition. While clinical experience with insulin treatment in CF has increased, the selection of who to treat and glycaemic targets remain unclear. Copyright © 2013. Published by Elsevier Ltd.

  10. Pregnancy and cystic fibrosis: Approach to contemporary management

    PubMed Central

    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

  11. Recent progress in translational cystic fibrosis research using precision medicine strategies.

    PubMed

    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.

  12. Diagnosing cystic fibrosis-related diabetes: current methods and challenges.

    PubMed

    Prentice, Bernadette; Hameed, Shihab; Verge, Charles F; Ooi, Chee Y; Jaffe, Adam; Widger, John

    2016-07-01

    Cystic fibrosis-related diabetes (CFRD) is the end-point of a spectrum of glucose abnormalities in cystic fibrosis that begins with early insulin deficiency and ultimately results in accelerated nutritional decline and loss of lung function. Current diagnostic and management regimens are unable to entirely reverse this clinical decline. This review summarises the current understanding of the pathophysiology of CFRD, the issues associated with using oral glucose tolerance tests in CF and the challenges faced in making the diagnosis of CFRD. Medline database searches were conducted using search terms "Cystic Fibrosis Related Diabetes", "Cystic Fibrosis" AND "glucose", "Cystic Fibrosis" AND "insulin", "Cystic Fibrosis" AND "Diabetes". Additionally, reference lists were studied. Expert commentary: Increasing evidence points to early glucose abnormalities being clinically relevant in cystic fibrosis and as such novel diagnostic methods such as continuous glucose monitoring or 30 minute sampled oral glucose tolerance test (OGTT) may play a key role in the future in the screening and diagnosis of early glucose abnormalities in CF.

  13. Chloride and potassium channels in cystic fibrosis airway epithelia

    NASA Astrophysics Data System (ADS)

    Welsh, Michael J.; Liedtke, Carole M.

    1986-07-01

    Cystic fibrosis, the most common lethal genetic disease in Caucasians, is characterized by a decreased permeability in sweat gland duct and airway epithelia. In sweat duct epithelium, a decreased Cl- permeability accounts for the abnormally increased salt content of sweat1. In airway epithelia a decreased Cl- permeability, and possibly increased sodium absorption, may account for the abnormal respiratory tract fluid2,3. The Cl- impermeability has been localized to the apical membrane of cystic fibrosis airway epithelial cells4. The finding that hormonally regulated Cl- channels make the apical membrane Cl- permeable in normal airway epithelial cells5 suggested abnormal Cl- channel function in cystic fibrosis. Here we report that excised, cell-free patches of membrane from cystic fibrosis epithelial cells contain Cl- channels that have the same conductive properties as Cl- channels from normal cells. However, Cl- channels from cystic fibrosis cells did not open when they were attached to the cell. These findings suggest defective regulation of Cl- channels in cystic fibrosis epithelia; to begin to address this issue, we performed two studies. First, we found that isoprenaline, which stimulates Cl- secretion, increases cellular levels of cyclic AMP in a similar manner in cystic fibrosis and non-cystic fibrosis epithelial cells. Second, we show that adrenergic agonists open calcium-activated potassium channels, indirectly suggesting that calcium-dependent stimulus-response coupling is intact in cystic fibrosis. These data suggest defective regulation of Cl- channels at a site distal to cAMP accumulation.

  14. Enteral tube feeding for cystic fibrosis.

    PubMed

    Conway, S P; Morton, A; Wolfe, S

    2008-04-16

    Enteral tube feeding is routinely used in many cystic fibrosis centres when weight for height percentage is less than 85%, when there has been weight loss for longer than a two-month period or when there has been no weight gain for two to three months (under five years old) or for six months (over five years old). To examine the evidence that in people with cystic fibrosis supplemental enteral tube feeding improves nutritional status, respiratory function, and quality of life without significant adverse effects. 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. We also contacted the companies that market enteral feeds and reviewed their databases. Date of the most recent search of the Group's Cystic Fibrosis Trials Register: November 2007. All randomised controlled trials comparing supplemental enteral tube feeding for one month or longer with no specific intervention in people with cystic fibrosis. Thirteen trials were identified by the search; however, none were eligible for inclusion in this review. There are no trials included in this review. Supplemental enteral tube feeding is widely used throughout the world to improve nutritional status in people with cystic fibrosis. The methods mostly used, nasogastric or gastrostomy feeding, are invasive, expensive, and may have a negative effect on self-esteem and body image. Reported use of enteral tube feeding suggests that it results in nutritional and respiratory improvement and it is disappointing that their efficacy has not been fully assessed by randomised controlled trials. With the more frequent recommendations to use enteral tube feeding as an early rather than a late intervention, this systematic review identifies the need for a multicentre, randomised controlled trial assessing both efficacy and possible

  15. New animal models of cystic fibrosis: what are they teaching us?

    PubMed Central

    Keiser, Nicholas W.; Engelhardt, John F.

    2013-01-01

    Purpose of review Cystic fibrosis is the first human genetic disease to benefit from the directed engineering of three different species of animal models (mice, pigs, and ferrets). Recent studies on the cystic fibrosis pig and ferret models are providing new information about the pathophysiology of cystic fibrosis in various organ systems. Additionally, new conditional cystic fibrosis transmembrane conductance regulator (CFTR) knockout mice are teaching unexpected lessons about CFTR function in surprising cellular locations. Comparisons between these animal models and the human condition are key to dissecting the complexities of disease pathophysiology in cystic fibrosis. Recent findings Cystic fibrosis pigs and ferrets have provided new models to study the spontaneous development of disease in the lung and pancreas, two organs that are largely spared overt spontaneous disease in cystic fibrosis mice. New cystic fibrosis mouse models are now interrogating CFTR functions involved in growth and inflammation at an organ-based level using conditional knockout technology. Together, these models are providing new insights on the human condition. Summary Basic and clinical cystic fibrosis research will benefit greatly from the comparative pathophysiology of cystic fibrosis mice, pigs, and ferrets. Both similarities and differences between these three cystic fibrosis models will inform pathophysiologically important mechanisms of CFTR function in humans and aid in the development of both organ-specific and general therapies for cystic fibrosis. PMID:21857224

  16. Cystic fibrosis-related diabetes mellitus: etiology, evaluation, and management.

    PubMed

    Fischman, Daniel; Nookala, Vinod K

    2008-12-01

    To review the pathophysiology, diagnosis, and management of cystic fibrosis-related diabetes mellitus (CFRD). We performed a MEDLINE search of the literature, using the search terms "cystic fibrosis-related diabetes, "CFRD," and "cystic fibrosis and diabetes," to identify pertinent articles available in English. In patients with cystic fibrosis (CF), CFRD is a major cause for an accelerated decline in health. It is the result of multiple pathophysiologic mechanisms, including destruction of pancreatic islet cells, impaired hepatic response to the antigluconeogenic effects of insulin, and impaired insulin sensitivity. Nutritional management and adequate caloric intake are paramount to successful management of CF. Although insulin remains the standard of care for treating CFRD in conjunction with fasting hyperglycemia, a small but growing body of literature supports the use of oral therapies. In this article, we discuss the benefits of and possible adverse reactions to the various classes of oral and injectable agents used in the treatment of diabetes mellitus, with special attention to the population of patients with CF. Orally administered agents can have a role in the treatment of CFRD. Further study is needed to determine the optimal combination of therapeutic modalities for CFRD.

  17. 'I have cystic fibrosis': an analysis of web-based disclosures of a chronic illness.

    PubMed

    Ravert, Russell D; Crowell, Toni L

    2008-11-01

    This study examined instances where individuals with cystic fibrosis disclosed their illness on the World Wide Web, better understand their experiences and needs across stages of the lifespan. Disclosing one's chronic illness is typically done purposefully, so examining those disclosures allows a naturalistic window into individuals' experiences and needs. This study is unique to Internet-based studies of chronic illness in that data are not limited to interactions at health-related websites, but include disclosure instances gathered across a variety of Internet contexts. Qualitative content analysis with a summative component was used. A web-based search engine was used to identify all web pages containing the phrases 'I have cystic fibrosis' and 'I have cf' (n = 277). Constant comparative analysis methods were used to identify thematic categories of context. Quantitative methods were used to examine age-related differences in the distribution of those disclosure statements. Findings were interpreted within a framework of Erikson's lifespan psychosocial theory. Adolescents (13-18 years) most frequently expressed psychosocial concerns and enlisted social support. Emerging adults (19-25 years) tended to present cystic fibrosis as just one of many self-characteristics. Adults (>25 years) tended to reach out to support others with cystic fibrosis. The study identified age-related differences in the types of illness disclosures found among individuals with cystic fibrosis. It also demonstrated that web-based research into chronic illness need not be limited to analysis of illness-specific online communities. Findings suggest that psychosocial interventions for individuals with cystic fibrosis across the lifespan might focus on (a) facilitating social support and incorporating illness into one's emerging identity among adolescents, (b) supporting emerging adults in presenting and incorporating themselves into larger social networks and (c) partnering with

  18. Acute Scedosporium apiospermum Endobronchial Infection in Cystic Fibrosis.

    PubMed

    Padoan, Rita; Poli, Piercarlo; Colombrita, Domenico; Borghi, Elisa; Timpano, Silviana; Berlucchi, Marco

    2016-06-01

    Fungi are known pathogens in cystic fibrosis patients. A boy with cystic fibrosis boy presented with acute respiratory distress. Bronchoscopy showed airways obstruction by mucus plugs and bronchial casts. Scedosporium apiospermum was identified as the only pathogen. Bronchoalveolar lavage successfully resolved the acute obstruction. Plastic bronchitis is a new clinical picture of acute Scedosporium endobronchial colonization in cystic fibrosis patients.

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

    PubMed

    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.

  20. Management of the Upper Airway in Cystic Fibrosis

    PubMed Central

    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

  1. [Genetic counseling in cystic fibrosis].

    PubMed

    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.

  2. [News in cystic fibrosis].

    PubMed

    Delaisi, B

    2013-08-01

    The improvement over the last two decades in the treatment of cystic fibrosis led to an increase in life expectancy approaching 40 years at birth. Logically, the population of adult patients has been increasing and is currently 50% of patients followed in France. These therapeutic advances have justified the establishment in 2003 of a generalized neonatal screening for cystic fibrosis. The latest data of this screening show an incidence of CF of 1/5359 live births, far below the incidence of 1/2500 which was widely accepted twenty years ago. The performance of this screening is currently based on the dosage of trypsin immuno reactive, followed in case of exceeding the threshold of a search of the 30 most common mutations, can detect around 96% of 150 to 200 CF cases every year. Therefore, the possibility of a false negative of the screening cannot be excluded and evocative symptoms of cystic fibrosis, even for children born after 2003, will lead to prescribe a sweat test. While treatments available so far goal consequences of cystic fibrosis, a new therapeutic class to correct the functional defect of the mutated protein, called CFTR modulators, is emerging. Ivacaftor, leader of this new class, belonging to the category of "CFTR potentiator" got its access on the market in September 2012 for patients carrying the G551D mutation. New other molecules, named "CFTR correctors" which can have synergistic effect with ivacaftor and concern patients carrying the most common mutation--DF 508--are under development. Copyright © 2013. Published by Elsevier Masson SAS.

  3. Prevalence of Mycobacterium lentiflavum in cystic fibrosis patients, France.

    PubMed

    Phelippeau, Michael; Dubus, Jean-Christophe; Reynaud-Gaubert, Martine; Gomez, Carine; Stremler le Bel, Nathalie; Bedotto, Marielle; Prudent, Elsa; Drancourt, Michel

    2015-10-26

    Mycobacterium lentiflavum is rarely isolated in respiratory tract samples from cystic fibrosis patients. We herein describe an unusually high prevalence of M. lentiflavum in such patients. M. lentiflavum, isolated from the respiratory tract of cystic fibrosis patients, was identified using both rpoB partial sequencing and detected directly in the sputum by using real-time PCR targeting the smpB gene. M. lentiflavum emerged as the third most prevalent nontuberculous mycobacterial species isolated in cystic fibrosis patients in Marseille, France. Six such patients were all male, and two of them may have fulfilled the American Thoracic Society clinical and microbiological criteria for M. lentiflavum potential lung infection. M. lentiflavum was the third most common mycobacteria isolated in cystic fibrosis patients, particularly in six male patients. M. lentiflavum outbreaks are emerging particularly in cystic fibrosis patients.

  4. Isolation, motivation and balance: living with type 1 or cystic fibrosis-related diabetes.

    PubMed

    Tierney, Stephanie; Deaton, Christi; Webb, Kevin; Jones, Andrew; Dodd, Mary; McKenna, Diane; Rowe, Rachel

    2008-04-01

    To explore patients' responses to developing and managing cystic fibrosis-related diabetes and to contrast their views with those of individuals with type 1 diabetes mellitus. The incidence of diabetes among people with cystic fibrosis has increased with improvement in life expectancy. However, little is known about how patients respond to and manage cystic fibrosis-related diabetes, and how this compares with people living with type 1 diabetes mellitus. Qualitative research was undertaken in order to fully explore meanings and views. Semi-structured telephone or face-to-face interviews were conducted with patients who had cystic fibrosis-related diabetes or type 1 diabetes mellitus, during which, they discussed diagnosis and management of diabetes. Framework analysis was employed to identify themes and to consider similarities and differences between the two groups. Eleven cystic fibrosis-related diabetes and 12 type 1 diabetes mellitus patients were interviewed in 2006. Patients with cystic fibrosis-related diabetes described their diabetes diagnosis as a progression of their primary illness, management of which was important owing to the benefits it brought to their cystic fibrosis. Those with type 1 diabetes mellitus were more likely to report feeling psychologically low because of diabetes and to list long-term complications as a key factor motivating self-management. Both groups struggled to balance the demands of diabetes with other life and health obligations, and experienced isolation because of diabetes. Conclusions. Variation in perceptions recalled during interviews stemmed from diabetes being part of an existing life-threatening chronic illness in people with cystic fibrosis-related diabetes. Similarities and differences in attitudes and management practices were found, with less urgency regarding glucose monitoring and fewer information resources available for those with cystic fibrosis-related diabetes. Both groups need support for optimal diabetes

  5. About Cystic Fibrosis

    MedlinePlus

    ... Testing for Cystic Fibrosis CFTR-Related Metabolic Syndrome (CRMS) How Babies Are Screened in IRT-Only vs. ... Guidelines Infant Care Clinical Care Guidelines Management of CRMS in First 2 Years and Beyond Clinical Care ...

  6. Diagnosis and treatment of endocrine comorbidities in patients with cystic fibrosis.

    PubMed

    Siwamogsatham, Oranan; Alvarez, Jessica A; Tangpricha, Vin

    2014-10-01

    The aim of this review is to provide an update on various relevant endocrine aspects of care in adolescents and adults with cystic fibrosis. As life expectancy in cystic fibrosis has continuously improved, endocrine complications have become more apparent. The common endocrine complications include cystic fibrosis related diabetes, 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. Endocrine diseases are an increasingly recognized complication that has a significant impact on the overall health of individuals with cystic fibrosis. This review summarizes the updated screening and management of endocrine diseases in the cystic fibrosis population.

  7. Liver Disease in Cystic Fibrosis: an Update

    PubMed Central

    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

  8. Air trapping and airflow obstruction in newborn cystic fibrosis piglets.

    PubMed

    Adam, Ryan J; Michalski, Andrew S; Bauer, Christian; Abou Alaiwa, Mahmoud H; Gross, Thomas J; Awadalla, Maged S; Bouzek, Drake C; Gansemer, Nicholas D; Taft, Peter J; Hoegger, Mark J; Diwakar, Amit; Ochs, Matthias; Reinhardt, Joseph M; Hoffman, Eric A; Beichel, Reinhard R; Meyerholz, David K; Stoltz, David A

    2013-12-15

    Air trapping and airflow obstruction are being increasingly identified in infants with cystic fibrosis. These findings are commonly attributed to airway infection, inflammation, and mucus buildup. To learn if air trapping and airflow obstruction are present before the onset of airway infection and inflammation in cystic fibrosis. On the day they are born, piglets with cystic fibrosis lack airway infection and inflammation. Therefore, we used newborn wild-type piglets and piglets with cystic fibrosis to assess air trapping, airway size, and lung volume with inspiratory and expiratory X-ray computed tomography scans. Micro-computed tomography scanning was used to assess more distal airway sizes. Airway resistance was determined with a mechanical ventilator. Mean linear intercept and alveolar surface area were determined using stereologic methods. On the day they were born, piglets with cystic fibrosis exhibited air trapping more frequently than wild-type piglets (75% vs. 12.5%, respectively). Moreover, newborn piglets with cystic fibrosis had increased airway resistance that was accompanied by luminal size reduction in the trachea, mainstem bronchi, and proximal airways. In contrast, mean linear intercept length, alveolar surface area, and lung volume were similar between both genotypes. The presence of air trapping, airflow obstruction, and airway size reduction in newborn piglets with cystic fibrosis before the onset of airway infection, inflammation, and mucus accumulation indicates that cystic fibrosis impacts airway development. Our findings suggest that early airflow obstruction and air trapping in infants with cystic fibrosis might, in part, be caused by congenital airway abnormalities.

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

    PubMed

    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

  10. L206W mutation of the cystic fibrosis gene, relatively frequent in French Canadians, is associated with atypical presentations of cystic fibrosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rozen, R.; Ferreira-Rajabi, L.; Robb, L.

    Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Over 400 mutations have been reported at this locus. Although severe forms of cystic fibrosis are usually associated with pancreatic insufficiency, pulmonary dysfunction, and elevated sweat chloride, there is a wide range of phenotypes, including congenital absence of the vas deferens, observed with some of the milder mutations. The L206W mutation, which was first identified in patients from South France, is relatively frequent in French Canadians from Quebec. In this report, we document the atypical form of cystic fibrosis associated with this mutation in amore » cohort of 7 French Canadian probands. 20 refs.« less

  11. Death after cessation of treatment by cystic fibrosis patients: An international survey of clinicians.

    PubMed

    Pisaturo, Marisa; Deppen, Alain; Rochat, Isabelle; Robinson, Walter M; Hafen, Gaudenz M

    2017-01-01

    Little is known about cystic fibrosis patients, who are not considered to be terminally ill, and who die after voluntary cessation of treatment. This study was undertaken to provide an international snapshot of this issue. An online survey was distributed across three continents. Distribution to the medical directors of the cystic fibrosis centres affiliated with the US Cystic Fibrosis Foundation, Cystic Fibrosis Australia (inclusion of New Zealand) and to every clinician member of the European Cystic Fibrosis Society. More than 200 cystic fibrosis patients not considered to be terminally ill and, who voluntarily ceased treatment, were reported by the clinicians surveyed. Detailed data were reported in 102 patients (4 children, 25 adolescents and 73 adults). Only one child, six adolescents and one adult were judged by clinicians not to be competent to make the decision to stop treatment. Time-consuming and low immediate-impact therapies, such as respiratory physiotherapy, were most frequently discontinued. Resignation was the main reported reason for discontinuing treatment, followed by reactive depression and lack of familial support. A total of 69% of the patients received palliative care and 72% died in the 6 months following cessation of treatment. Death of cystic fibrosis patients, not considered to be terminally ill, is reported in Europe, the United States and Australia due to voluntary cessation of treatment.

  12. A universal array-based multiplexed test for cystic fibrosis carrier screening.

    PubMed

    Amos, Jean A; Bridge-Cook, Philippa; Ponek, Victor; Jarvis, Michael R

    2006-01-01

    Cystic fibrosis is a multisystem autosomal recessive disorder with high carrier frequencies in caucasians and significant, but lower, carrier frequencies in other ethnicities. Based on technology that allows high detection of mutations in caucasians and significant detection in other ethnic groups, the American College of Medical Genetics (ACMG) and American College of Obstetricians and Gynecologists (ACOG) have recommended pan-ethnic cystic fibrosis carrier screening for all reproductive couples. This paper discusses carrier screening using the Tag-It multiplex mutation platform and the Cystic Fibrosis Mutation Detection Kit. The Tag-It cystic fibrosis assay is a multiplexed genotyping assay that detects a panel of 40 cystic fibrosis transmembrane conductance regulator mutations including the 23 mutations recommended by the ACMG and ACOG for population screening. A total of 16 additional mutations detected by the Tag-It cystic fibrosis assay may also be common. The assay method is described in detail, and its performance in a genetics reference laboratory performing high-volume cystic fibrosis carrier screening is assessed.

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

    ERIC Educational Resources Information Center

    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;…

  14. Rehabilitation with Cystic Fibrosis: From Utopia to Reality.

    ERIC Educational Resources Information Center

    Goldberg, Richard T.; And Others

    1980-01-01

    The paper dispels some of the myths regarding cystic fibrosis (a genetic metabolism disorder), provides information on the latest developments in rehabilitation, summarizes research in the field, and projects future needs of the patient with cystic fibrosis. (SBH)

  15. Interactions Between DNA and Actin in Model Cystic Fibrosis Sputum

    NASA Astrophysics Data System (ADS)

    Kyung, Hee; Sanders, Lori; Angelini, Thomas; Butler, John; Wong, Gerard

    2003-03-01

    Cystic fibrosis sputum is a complex fluid which has a high concentration of DNA and F-actin, two anionic biological polyelectrolytes. In this work, we study the interactions between DNA and actin in an aqueous environment over a wide range of polyelectrolyte lengths and salt levels, using synchrotron Small Angle X-ray Scattering(SAXS) and confocal microscopy. Perliminary results indicate the existence of a compressed phase of nematic F-actin in the presence of DNA. This work was supported by NSF DMR-0071761, the Beckman Young Investigator Program, and the Cystic Fibrosis Foundation.

  16. Dental treatment for people with cystic fibrosis.

    PubMed

    Harrington, N; Barry, P J; Barry, S M

    2016-06-01

    To describe the nature and consequences of the multi-system genetic condition cystic fibrosis with a view to ensuring optimal dental treatment planning for these patients. A literature search was conducted to identify the key medical and dental manifestations of cystic fibrosis. These findings are discussed and utilised to create recommendations for treatment planning in patients with cystic fibrosis for the practising dental practitioner. Cystic fibrosis is a complex, lethal, multisystem autosomal recessive disorder resulting from mutations on chromosome 7 which result in dysfunction of an ion channel that sits on epithelial surfaces. Respiratory disease remains the leading cause of mortality. Survival has greatly increased in recent decades secondary to improved treatment and specialist care. Specific dental manifestations of the disease may result from the condition itself or complications of treatment. Modification of patient management may be necessary to provide optimum patient care. The pathophysiology and clinical manifestations are relevant to practicing dental practitioners and inform recommendations to be utilised to ensure optimal treatment planning for these patients.

  17. How the airway smooth muscle in cystic fibrosis reacts in proinflammatory conditions: implications for airway hyper-responsiveness and asthma in cystic fibrosis.

    PubMed

    McCuaig, Sarah; Martin, James G

    2013-04-01

    Among patients with cystic fibrosis there is a high prevalence (40-70%) of asthma signs and symptoms such as cough and wheezing and airway hyper-responsiveness to inhaled histamine or methacholine. Whether these abnormal airway responses are due to a primary deficiency in the cystic fibrosis transmembrane conductance regulator (CFTR) or are secondary to the inflammatory environment in the cystic fibrosis lungs is not clear. A role for the CFTR in smooth muscle function is emerging, and alterations in contractile signalling have been reported in CFTR-deficient airway smooth muscle. Persistent bacterial infection, especially with Pseudomonas aeruginosa, stimulates interleukin-8 release from the airway epithelium, resulting in neutrophilic inflammation. Increased neutrophilia and skewing of CFTR-deficient T-helper cells to type 2 helper T cells creates an inflammatory environment characterised by high concentrations of tumour necrosis factor α, interleukin-8, and interleukin-13, which might all contribute to increased contractility of airway smooth muscle in cystic fibrosis. An emerging role of interleukin-17, which is raised in patients with cystic fibrosis, in airway smooth muscle proliferation and hyper-responsiveness is apparent. Increased understanding of the molecular mechanisms responsible for the altered smooth muscle physiology in patients with cystic fibrosis might provide insight into airway dysfunction in this disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Physical exercise training for cystic fibrosis.

    PubMed

    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. Inadequate erythroid response to hypoxia in cystic fibrosis.

    PubMed

    Vichinsky, E P; Pennathur-Das, R; Nickerson, B; Minor, M; Kleman, K; Higashino, S; Lubin, B

    1984-07-01

    An increase in hemoglobin concentration characterizes the normal compensatory response to chronic tissue hypoxia. We observed no such increase in 42 chronically hypoxic patients with cystic fibrosis, in whom the mean concentration was 12.6 gm/dl; one third of the patients were anemic. Compared with patients with cyanotic heart disease, patients with cystic fibrosis did not have a compensatory increase in P50 or 2,3-diphosphoglycerate. Despite anemia, erythropoietin levels in patients with cystic fibrosis were not significantly different from normal control values. The growth of colony-forming units-erythroid in patients with cystic fibrosis was similar to that in control subjects, and there was no inhibition of growth with the addition of autologous serum. Erythropoietin sensitivity, determined by measuring the CFUe dose response curve, was normal in both patients and controls. Results of iron studies were consistent with iron deficiency in the majority of patients. Impaired absorption of iron was observed in six of 13 iron-deficient patients with cystic fibrosis. An inverse correlation between erythrocyte sedimentation rate and peak serum iron was obtained during the iron absorption study. Eight patients who underwent a therapeutic trial of iron demonstrated a 1.8 gm/dl rise in hemoglobin concentration. Two patients with previously documented iron malabsorption responded to parenteral iron therapy after failure to respond to oral supplementation. These studies demonstrate that patients with cystic fibrosis not only have an impaired erythroid response to hypoxia, but are frequently anemic. Their inadequate erythroid response to hypoxia results in part from disturbances in erythropoietin regulation and iron availability.

  20. Serum lipoprotein concentrations in cystic fibrosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vaughan, W.J.; Lindgren, F.T.; Whalen, J.B.

    1978-02-17

    Two major classes of lipoproteins, low density and high density, are decreased in the serum of patients with cystic fibrosis; major apoproteins are also decreased. Since essential fatty acids and certain fat-soluble vitamins depend on lipoproteins for transport in the serum, knowledge of lipoprotein levels in cystic fibrosis patients could prove valuable in understanding (i) the basis for the abnormally low serum levels of these fatty acids and vitamins and (ii) the effects of therapies involving these molecules.

  1. Normal sweat chloride test does not rule out cystic fibrosis.

    PubMed

    Başaran, Abdurrahman Erdem; Karataş-Torun, Nimet; Maslak, İbrahim Cemal; Bingöl, Ayşen; Alper, Özgül M

    2017-01-01

    Başaran AE, Karataş-Torun N, Maslak İC, Bingöl A, Alper ÖM. Normal sweat chloride test does not rule out cystic fibrosis. Turk J Pediatr 2017; 59: 68-70. A 5-month-old patient presented with complaints of fever and cough. He was hospitalized with the diagnosis of bronchopneumonia and pseudo-Bartter's syndrome. Patient was further investigated for diagnosis of cystic fibrosis. The chloride (Cl) level in sweat was determined within the normal range (25.1 mmol/L, 20.3 mmol/L). CFTR (Cystic Fibrosis Transmembrane Regulator gene; NM_000492.2) genotyping results were positive for p.E92K; p.F1052V mutations. The patient was diagnosed with cystic fibrosis. In our patient, with features of CF and normal sweat test, mutation analysis was helpful for the diagnosis of cystic fibrosis.

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

    PubMed

    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.

  3. Festival food coma in cystic fibrosis.

    PubMed

    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.

  4. Therapies for Cystic Fibrosis

    MedlinePlus

    ... Testing for Cystic Fibrosis CFTR-Related Metabolic Syndrome (CRMS) How Babies Are Screened in IRT-Only vs. ... Guidelines Infant Care Clinical Care Guidelines Management of CRMS in First 2 Years and Beyond Clinical Care ...

  5. Cystic fibrosis respiratory tract salt concentration: An Exploratory Cohort Study.

    PubMed

    Grandjean Lapierre, Simon; Phelippeau, Michael; Hakimi, Cyrine; Didier, Quentin; Reynaud-Gaubert, Martine; Dubus, Jean-Christophe; Drancourt, Michel

    2017-11-01

    In cystic fibrosis patients, electrolytic and osmolality imbalance secondary to cystic fibrosis transmembrane conductance regulator mutations may impact on mucoid secretion accumulation and secondary colonization by opportunistic pathogens such as nontuberculous mycobacteria.We performed a noninvasive exploratory prospective controlled clinical study comparing sputum salinity and acid-base characteristics of cystic fibrosis and noncystic fibrosis control patients. A total of 57 patients and 62 controls were included.Sputum salt concentrations were 10.5 g/L (95% CI: 7.7-13.3) in patients and 7.4 g/L (95% CI: 5.9-8.9) in aged-matched controls, a difference that was found to be statistically significant (P < .05). No difference in pH was observed between patients and controls.These differences in respiratory secretions salt concentrations could influence host-pathogen interactions in the context of cystic fibrosis respiratory infections. We propose to include respiratory secretion salt measurement as a routine analysis on cystic fibrosis patients' sputum submitted for bacterial culture. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  6. Intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Verhaeghe, Catherine; Tabruyn, Sebastien P.; Oury, Cecile

    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. Conditionedmore » 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.« less

  7. Genetic counselling issues in cystic fibrosis.

    PubMed

    Culling, Bronwyn; Ogle, Robert

    2010-06-01

    Cystic fibrosis is a chronic condition for which genetic testing offers much for the individuals affected in terms of an early diagnosis and offers timely additional information for families with regard to family planning and prenatal testing. Genetic counselling encompasses a range of clinical issues for families and forms a complementary resource for clinicians caring for people with cystic fibrosis. This review will discuss the range of genetic information readily available to patients and families through genetic counselling. Copyright 2010 Elsevier Ltd. All rights reserved.

  8. Actin - Lysozyme Interactions in Model Cystic Fibrosis Sputum

    NASA Astrophysics Data System (ADS)

    Sanders, Lori; Slimmer, Scott; Angelini, Thomas; Wong, Gerard C. L.

    2003-03-01

    Cystic fibrosis sputum is a complex fluid consisting of mucin (a glycoprotein), lysozyme (a cationic polypeptide), water, salt, as well as a high concentration of a number of anionic biological polyelectrolytes such as DNA and F-actin. The interactions governing these components are poorly understood, but may have important clinical consequences. For example, the formation of these biological polyelectrolytes into ordered gel phases may contribute significantly to the observed high viscosity of CF sputum. In this work, a number of model systems containing actin, lysozyme, and KCl were created to simulate CF sputum in vitro. These model systems were studied using small angle x-ray scattering and confocal fluorescence microscopy. Preliminary results will be presented. This work was supported by NSF DMR-0071761, the Beckman Young Investigator Program, and the Cystic Fibrosis Foundation.

  9. Cystic fibrosis carrier screening in a North American population.

    PubMed

    Zvereff, Val V; Faruki, Hawazin; Edwards, Marcia; Friedman, Kenneth J

    2014-07-01

    The aim of this study was to compare the mutation frequency distribution for a 32-mutation panel and a 69-mutation panel used for cystic fibrosis carrier screening. Further aims of the study were to examine the race-specific detection rates provided by both panels and to assess the performance of extended panels in large-scale, population-based cystic fibrosis carrier screening. Although genetic screening for the most common CFTR mutations allows detection of nearly 90% of cystic fibrosis carriers, the large number of other mutations, and their distribution within different ethnic groups, limits the utility of general population screening. Patients referred for cystic fibrosis screening from January 2005 through December 2010 were tested using either a 32-mutation panel (n = 1,601,308 individuals) or a 69-mutation panel (n = 109,830). The carrier frequencies observed for the 69-mutation panel study population (1/36) and Caucasian (1/27) and African-American individuals (1/79) agree well with published cystic fibrosis carrier frequencies; however, a higher carrier frequency was observed for Hispanic-American individuals (1/48) using the 69-mutation panel as compared with the 32-mutation panel (1/69). The 69-mutation panel detected ~20% more mutations than the 32-mutation panel for both African-American and Hispanic-American individuals. Expanded panels using race-specific variants can improve cystic fibrosis carrier detection rates within specific populations. However, it is important that the pathogenicity and the relative frequency of these variants are confirmed.

  10. Vitamin D supplementation for cystic fibrosis.

    PubMed

    Ferguson, Janet H; Chang, Anne B

    2014-05-14

    Cystic fibrosis (CF) is a genetic disorder with multiorgan effects. In a subgroup with pancreatic insufficiency malabsorption of the fat soluble vitamins (A, D, E, K) may occur. Vitamin D is involved in calcium homeostasis and bone mineralisation and may have extraskeletal effects. This review examines the evidence for vitamin D supplementation in cystic fibrosis. To assess the effects of vitamin D supplementation on the frequency of vitamin D deficiency, respiratory outcomes and vitamin D toxicity in the cystic fibrosis population. 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.Date of the most recent search: 08 July 2013. Randomised and quasi-randomised controlled studies of vitamin D supplementation compared to placebo in the cystic fibrosis population regardless of exocrine pancreatic function. Both authors independently assessed the risk of bias of each included study and extracted outcome data (from published study information) for assessment of bone mineralization, growth and nutritional status, frequency of vitamin D deficiency, respiratory status, quality of life and adverse events. Six studies (239 participants) are included, although only three studies provided data from 69 adults and children with cystic fibrosis for analysis. One study compared a single high dose of vitamin D (250,000 IU) to placebo at the time of hospital admission with a respiratory exacerbation in 30 pancreatic insufficient adults with cystic fibrosis. The second study compared supplemental 800 international units (IU) vitamin D and placebo for 12 months in 30 osteopenic pancreatic insufficient adults; both groups continued 900 IU vitamin D daily. The third study compared supplemental 1 g calcium alone, 1600 IU vitamin D alone, 1600 IU vitamin D and 1 g calcium and placebo in a double

  11. Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells

    NASA Astrophysics Data System (ADS)

    Rich, Devra P.; Anderson, Matthew P.; Gregory, Richard J.; Cheng, Seng H.; Paul, Sucharita; Jefferson, Douglas M.; McCann, John D.; Klinger, Katherine W.; Smith, Alan E.; Welsh, Michael J.

    1990-09-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) was expressed in cultured cystic fibrosis airway epithelial cells and Cl- channel activation assessed in single cells using a fluorescence microscopic assay and the patch-clamp technique. Expression of CFTR, but not of a mutant form of CFTR (ΔF508), corrected the Cl- channel defect. Correction of the phenotypic defect demonstrates a causal relationship between mutations in the CFTR gene and defective Cl- transport which is the hallmark of the disease.

  12. Nutrient Status of Adults with Cystic Fibrosis

    PubMed Central

    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. Episodic seasonal Pseudo-Bartter syndrome in cystic fibrosis.

    PubMed

    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.

  14. Effect of taurine supplementation on fat and energy absorption in cystic fibrosis.

    PubMed

    De Curtis, M; Santamaria, F; Ercolini, P; Vittoria, L; De Ritis, G; Garofalo, V; Ciccimarra, F

    1992-09-01

    In 10 children with cystic fibrosis and persisting steatorrhoea, supplementation with taurine (30-40 mg/kg/day) was given for two months as an adjunct to the usual pancreatic enzyme treatment. A three day fat and energy balance was performed in patients with cystic fibrosis, before and after the supplementation, and in seven healthy controls who did not receive taurine. Faecal fat was measured by a gravimetric method and stool energy was determined using a bomb calorimeter. Patients with cystic fibrosis, before and after taurine, and healthy controls received the same fat and energy intake (calculated by a dietitian). In patients with cystic fibrosis taurine did not produce any improvement of steatorrhoea (mean (SD) faecal fat 8.7 (3.3) v 11.2 (7.0) g/day, respectively before and after the supplementation), of faecal energy loss (0.978 (0.468) v 1.133 (0.539) MJ/day), of faecal fat expressed as percent of fat intake (13.4 (5.6) v 15.1 (9.8)%), and of faecal energy expressed as percent of energy intake (9.9 (3.6) v 11.2 (5.7)%). Healthy controls had significant lower fat (3.5 (2.3) g/day) and energy 0.576 (0.355) MJ/day faecal losses. In conclusion, taurine failed to decrease significantly fat and energy losses. Our study does not support the use of taurine supplementation in the nutritional management of cystic fibrosis.

  15. Effect of taurine supplementation on fat and energy absorption in cystic fibrosis.

    PubMed Central

    De Curtis, M; Santamaria, F; Ercolini, P; Vittoria, L; De Ritis, G; Garofalo, V; Ciccimarra, F

    1992-01-01

    In 10 children with cystic fibrosis and persisting steatorrhoea, supplementation with taurine (30-40 mg/kg/day) was given for two months as an adjunct to the usual pancreatic enzyme treatment. A three day fat and energy balance was performed in patients with cystic fibrosis, before and after the supplementation, and in seven healthy controls who did not receive taurine. Faecal fat was measured by a gravimetric method and stool energy was determined using a bomb calorimeter. Patients with cystic fibrosis, before and after taurine, and healthy controls received the same fat and energy intake (calculated by a dietitian). In patients with cystic fibrosis taurine did not produce any improvement of steatorrhoea (mean (SD) faecal fat 8.7 (3.3) v 11.2 (7.0) g/day, respectively before and after the supplementation), of faecal energy loss (0.978 (0.468) v 1.133 (0.539) MJ/day), of faecal fat expressed as percent of fat intake (13.4 (5.6) v 15.1 (9.8)%), and of faecal energy expressed as percent of energy intake (9.9 (3.6) v 11.2 (5.7)%). Healthy controls had significant lower fat (3.5 (2.3) g/day) and energy 0.576 (0.355) MJ/day faecal losses. In conclusion, taurine failed to decrease significantly fat and energy losses. Our study does not support the use of taurine supplementation in the nutritional management of cystic fibrosis. PMID:1417050

  16. Report of the European Respiratory Society/European Cystic Fibrosis Society task force on the care of adults with cystic fibrosis.

    PubMed

    Elborn, J Stuart; Bell, Scott C; Madge, Susan L; Burgel, Pierre-Regis; Castellani, Carlo; Conway, Steven; De Rijcke, Karleen; Dembski, Birgit; Drevinek, Pavel; Heijerman, Harry G M; Innes, J Alistair; Lindblad, Anders; Marshall, Bruce; Olesen, Hanne V; Reimann, Andreas L; Solé, Ampara; Viviani, Laura; Wagner, Thomas O F; Welte, Tobias; Blasi, Francesco

    2016-02-01

    The improved survival in people with cystic fibrosis has led to an increasing number of patients reaching adulthood. This trend is likely to be maintained over the next decades, suggesting a need to increase the number of centres with expertise in the management of adult patients with cystic fibrosis. These centres should be capable of delivering multidisciplinary care addressing the complexity of the disease, in addition to addressing the psychological burden on patients and their families. Further issues that require attention are organ transplantation and end of life management.Lung disease in adults with cystic fibrosis drives most of the clinical care requirements, and major life-threatening complications, such as respiratory infection, respiratory failure, pneumothorax and haemoptysis, and the management of lung transplantation require expertise from trained respiratory physicians. The taskforce therefore strongly reccommends that medical leadership in multidisciplinary adult teams should be attributed to a respiratory physician adequately trained in cystic fibrosis management.The task force suggests the implementation of a core curriculum for trainees in adult respiratory medicine and the selection and accreditation of training centres that deliver postgraduate training to the standards of the HERMES programme. Copyright ©ERS 2016.

  17. [Historical compilation of cystic fibrosis].

    PubMed

    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.

  18. Renal diseases in adults with cystic fibrosis: a 40 year single centre experience.

    PubMed

    Wilcock, M J; Ruddick, A; Gyi, K M; Hodson, M E

    2015-10-01

    There is a sizable literature describing renal disease in patients with cystic fibrosis. Previous studies have focused on single disease processes alone, most commonly renal stone disease or acute kidney injury. In this study we report for the first time on the prevalence of all forms of renal disease in a cystic fibrosis population. A retrospective review of adult patients with cystic fibrosis attending the Adult Cystic Fibrosis Department at the Royal Brompton Hospital was carried out by searching the department's database to identify patients with renal problems and subsequently retrieving clinical information from medical notes. The prevalence of all renal diseases in our population was 5.1 %. The most commonly identified problem was renal stones. At 2.0 % the prevalence of renal stones in adult patients with cystic fibrosis was comparable to the general population. A range of other renal diseases were identified, the next most common being drug-induced acute kidney injury. A range of cystic fibrosis independent and attributable diseases has been identified but no cystic fibrosis specific disease. In contrast to other cystic fibrosis centres no increased prevalence of renal stones was found.

  19. Caring for Children with Cystic Fibrosis: A Collaborative Clinical and School Approach

    ERIC Educational Resources Information Center

    Strawhacker, MaryAnn Tapper; Wellendorf, Joyce

    2004-01-01

    Earlier diagnosis and more effective treatments have improved both morbidity and mortality associated with cystic fibrosis, making regular school attendance a reality. School nurses have a unique opportunity to assist students with cystic fibrosis successfully manage their disease. Medical treatment for cystic fibrosis can be complex, leaving…

  20. Hormonal abnormalities of the pancreas and gut in cystic fibrosis.

    PubMed

    Adrian, T E; McKiernan, J; Johnstone, D I; Hiller, E J; Vyas, H; Sarson, D L; Bloom, S R

    1980-09-01

    We have investigated the effect of cystic fibrosis on alimentary hormones in 10 children by measuring the pancreatic and gut hormone rsponse to a milk drink. Plasma insulin and gastric inhibitory peptide were both significantly reduced (P < 0.05 and P < 0.005, respectively, at 15 min) in the patients with cystic fibrosis, compared with controls, even though the early glucose rise was greater in the former group (P < 0.05 at 15 min). Fasting levels of pancreatic polypeptide were significantly lower in the fibrocystic children (P < 0.01), and the normal response to milk was completely abolished in these patients (P < 0.001). Fasting plasma enteroglucagon concentrations were grossly abolished in the cystic fibrosis patients (P < 0.001) and these remained elevated throughout the test. No significant differences were seen in basal or postmilk responses of plasma glucagon, gastrin, secretin, vasoactive intestinal peptide, or motilin in cystic fibrosis. It would thus appear that the pancreatic polypeptide cell is more susceptible to the effects of the disease process than the beta or alpha cell in cystic fibrosis. Some aspects of the abnormalities in the gastrointestinal endocrine system were similar to those seen in celiac disease and tropical sprue and may, therefore, effect a similar hormonal response in these patients with cystic fibrosis to those with mucosal damage.

  1. Diagnostic problems in cystic fibrosis - specific characteristics of a group of infants and young children diagnosed positive through neonatal screening, in whom cystic fibrosis had not been diagnosed.

    PubMed

    Woś, Halina; Sankiewicz-Szkółka, Magda; Więcek, Sabina; Kordys-Darmolińska, Bożena; Grzybowska-Chlebowczyk, Urszula; Kniażewska, Maria

    2015-01-01

    Neonatal cystic fibrosis screening contributes to an early diagnosis of cystic fibrosis and to implementing appropriate therapeutic management. Long-standing screening tests have made it possible to identify a group of newborns in whom the diagnosis was ambiguous and required further specialised tests. The aim is to present cases of patients with a positive result of newborn screening for cystic fibrosis who were found to be carriers of the mutation in both alleles, however the lack of clinical symptoms and correct sweat testing values did not lead doctors to diagnosing cystic fibrosis and by the same token implementing the treatment. The analysis encompassed a group of 22 infants and children 3 months to 3 years of age, in whom, in spite of a positive result of newborn screening for cystic fibrosis and the presence of 2 mutations in the CFTR gene, the diagnosis of cystic fibrosis was not made, and appropriate treatment was not administered because of diagnostic doubts (due to correct concentration of chlorides in sweat, correct IRT level and lack of clinical signs of cystic fibrosis). The control group consisted of 55 children treated in our centre, in whom neonatal screening for cystic fibrosis was positive and the diagnosis was confirmed by genetic testing, sweat chloride testing and IRT concentration. There were no differences in birth body weight between the groups. The differences in chlorideion levels in sweat secretion tests and mean IRT values were statistically significant and were: 97.5 for the control group and 26.4 for the test group. At the present time there are no clinical symptoms to give a diagnosis of cystic fibrosis and start treatment in the test group. Newborn screening contributes not only to an early diagnosis of cystic fibrosis but also to CFTR-related metabolic syndromes (CRMS), which is a phenomenon requiring further observation. This fact constitutes a definite psychological problem for the parents of these patients. .

  2. Early detection of cystic fibrosis lung disease: multiple‐breath washout versus raised volume tests

    PubMed Central

    Lum, Sooky; Gustafsson, Per; Ljungberg, Henrik; Hülskamp, Georg; Bush, Andrew; Carr, Siobhán B; Castle, Rosemary; Hoo, Ah‐fong; Price, John; Ranganathan, Sarath; Stroobant, John; Wade, Angie; Wallis, Colin; Wyatt, Hilary; Stocks, Janet

    2007-01-01

    Background Lung clearance index (LCI), a measure of ventilation inhomogeneity derived from the multiple‐breath inert gas washout (MBW) technique, has been shown to detect abnormal lung function more readily than spirometry in preschool children with cystic fibrosis, but whether this holds true during infancy is unknown. Objectives To compare the extent to which parameters derived from the MBW and the raised lung volume rapid thoraco–abdominal compression (RVRTC) techniques identify diminished airway function in infants with cystic fibrosis when compared with healthy controls. Methods Measurements were performed during quiet sleep, with the tidal breathing MBW technique being performed before the forced expiratory manoeuvres. Results Measurements were obtained in 39 infants with cystic fibrosis (mean (SD) age 41.4 (22.0) weeks) and 21 controls (37.0 (15.1) weeks). Infants with cystic fibrosis had a significantly higher respiratory rate (38 (10) vs 32 (5) bpm) and LCI (8.4 (1.5) vs 7.2 (0.3)), and significantly lower values for all forced expiratory flow‐volume parameters compared with controls. Girls with cystic fibrosis had significantly lower forced expiratory volume (FEV0.5 and FEF25–75 ) than boys (mean (95% CI girls–boys): –1.2 (–2.1 to −0.3) for FEV0.5 Z score; FEF25–75: –1.2 (–2.2 to −0.15)). When using both the MBW and RVRTC techniques, abnormalities were detected in 72% of the infants with cystic fibrosis, with abnormalities detected in 41% using both techniques and a further 15% by each of the two tests performed. Conclusions These findings support the view that inflammatory and/or structural changes in the airways of children with cystic fibrosis start early in life, and have important implications regarding early detection and interventions. Monitoring of early lung disease and functional status in infants and young children with cystic fibrosis may be enhanced by using both MBW and the RVRTC. PMID:17121870

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

    PubMed Central

    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

  4. What is Cystic Fibrosis?

    MedlinePlus

    ... pass the faulty CFTR gene to their children. Example of an Inheritance Pattern for Cystic Fibrosis The image shows how CFTR genes are inherited. A person inherits two copies of the CFTR gene—one from each parent. If each parent has a ...

  5. Predictive 5-Year Survivorship Model of Cystic Fibrosis

    PubMed Central

    Liou, Theodore G.; Adler, Frederick R.; FitzSimmons, Stacey C.; Cahill, Barbara C.; Hibbs, Jonathan R.; Marshall, Bruce C.

    2007-01-01

    The objective of this study was to create a 5-year survivorship model to identify key clinical features of cystic fibrosis. Such a model could help researchers and clinicians to evaluate therapies, improve the design of prospective studies, monitor practice patterns, counsel individual patients, and determine the best candidates for lung transplantation. The authors used information from the Cystic Fibrosis Foundation Patient Registry (CFFPR), which has collected longitudinal data on approximately 90% of cystic fibrosis patients diagnosed in the United States since 1986. They developed multivariate logistic regression models by using data on 5,820 patients randomly selected from 11,630 in the CFFPR in 1993. Models were tested for goodness of fit and were validated for the remaining 5,810 patients for 1993. The validated 5-year survivorship model included age, forced expiratory volume in 1 second as a percentage of predicted normal, gender, weight-for-age z score, pancreatic sufficiency, diabetes mellitus, Staphylococcus aureus infection, Burkerholderia cepacia infection, and annual number of acute pulmonary exacerbations. The model provides insights into the complex nature of cystic fibrosis and supplies a rigorous tool for clinical practice and research. PMID:11207152

  6. New and emerging targeted therapies for cystic fibrosis

    PubMed Central

    Rowe, Steven M

    2016-01-01

    Cystic fibrosis (CF) is a monogenic autosomal recessive disorder that affects about 70 000 people worldwide. The clinical manifestations of the disease are caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The discovery of the CFTR gene in 1989 has led to a sophisticated understanding of how thousands of mutations in the CFTR gene affect the structure and function of the CFTR protein. Much progress has been made over the past decade with the development of orally bioavailable small molecule drugs that target defective CFTR proteins caused by specific mutations. Furthermore, there is considerable optimism about the prospect of gene replacement or editing therapies to correct all mutations in cystic fibrosis. The recent approvals of ivacaftor and lumacaftor represent the genesis of a new era of precision medicine in the treatment of this condition. These drugs are having a positive impact on the lives of people with cystic fibrosis and are potentially disease modifying. This review provides an update on advances in our understanding of the structure and function of the CFTR, with a focus on state of the art targeted drugs that are in development. PMID:27030675

  7. Insulin and oral agents for managing cystic fibrosis-related diabetes.

    PubMed

    Onady, Gary M; Stolfi, Adrienne

    2016-04-18

    controlling hyperglycemia or clinical outcomes associated with cystic fibrosis-related diabetes. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes with this impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority.There is no demonstrated advantage yet established for using oral hypoglycemic agents over insulin, and further trials need to be evaluated to establish whether there is clear benefit for using hypoglycemic agents. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should be further investigated to see if there may be a clinical advantage to adding these medications to insulin as adjuvant therapy.

  8. Pharmacogenetics of cystic fibrosis treatment.

    PubMed

    Carter, Suzanne C; McKone, Edward F

    2016-08-01

    Cystic fibrosis (CF) is genetic autosomal recessive disease caused by reduced or absent function of CFTR protein. Treatments for patients with CF have primarily focused on the downstream end-organ consequences of defective CFTR. Since the discovery of the CFTR gene that causes CF in 1989 there have been tremendous advances in our understanding of the genetics and pathophysiology of CF. This has recently led to the development of new CFTR mutation-specific targeted therapies for select patients with CF. This review will discuss the characteristics of the CFTR gene, the CFTR mutations that cause CF and the new mutation specific pharmacological treatments including gene therapy that are contributing to the dawning of a new era in cystic fibrosis care.

  9. Early bronchiectasis in cystic fibrosis detected by surveillance CT.

    PubMed

    Pillarisetti, Naveen; Linnane, Barry; Ranganathan, Sarath

    2010-08-01

    There is emerging evidence that cystic fibrosis lung disease begins early in infancy. Newborn screening allows early detection and surveillance of pulmonary disease and the possibility of early intervention in this life-shortening condition. We report two children with cystic fibrosis who underwent a comprehensive assessment from diagnosis that included measurement of lung function, limited-slice high-resolution CT and BAL performed annually. Early aggressive surveillance enabled significant lung disease and bronchiectasis to be detected during the first few years of life and led to a change in management, highlighting a clinical role for CT scanning during the preschool years in children with cystic fibrosis.

  10. Respiratory infections in patients with cystic fibrosis undergoing lung transplantation.

    PubMed

    Lobo, Leonard J; Noone, Peadar G

    2014-01-01

    Cystic fibrosis is an inherited disease characterised by chronic respiratory infections associated with bronchiectasis. Lung transplantation has helped to extend the lives of patients with cystic fibrosis who have advanced lung disease. However, persistent, recurrent, and newly acquired infections can be problematic. Classic cystic fibrosis-associated organisms, such as Staphylococcus aureus and Pseudomonas aeruginosa, are generally manageable post-transplantation, and are associated with favourable outcomes. Burkholderia cenocepacia poses particular challenges, although other Burkholderia species are less problematic. Despite concerns about non-tuberculous mycobacteria, especially Mycobacterium abscessus, post-transplantation survival has not been definitively shown to be less than average in patients with these infections. Fungal species can be prevalent before and after transplantation and are associated with high morbidity, so should be treated aggressively. Appropriate viral screening and antiviral prophylaxis are necessary to prevent infection with and reactivation of Epstein-Barr virus and cytomegalovirus and their associated complications. Awareness of drug pharmacokinetics and interactions in cystic fibrosis is crucial to prevent toxic effects and subtherapeutic or supratherapeutic drug dosing. With the large range of potential infectious organisms in patients with cystic fibrosis, infection control in hospital and outpatient settings is important. Despite its complexity, lung transplantation in the cystic fibrosis population is safe, with good outcomes if the clinician is aware of all the potential pathogens and remains vigilant by means of surveillance and proactive treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    PubMed

    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.

  12. Polyelectrolyte Structure and Interactions in Model Cystic Fibrosis Sputum

    NASA Astrophysics Data System (ADS)

    Slimmer, Scott; Angelini, Thomas; Liang, Hongjun; Butler, John; Wong, Gerard C. L.

    2002-03-01

    Cystic fibrosis sputum is a complex fluid consisting of a number of components, including mucin (a glycoprotein), lysozyme (a cationic polypeptide), water, salt, as well as a high concentration of a number of anionic biological polyelectrolytes such as DNA and F-actin. The interactions governing these components are poorly understood, but may have important clinical consequences. For example, the formation of these biological polyelectrolytes into ordered gel phases may contribute significantly to the observed high viscosity of CF sputum. In this work, a number of model systems were created to simulate CF sputum in vitro, in order to elucidate the contributions of the different components. Preliminary results will be presented. This work was supported by NSF DMR-0071761, DOE DEFG02-91ER45439, the Beckman Young Investigator Program, and the Cystic Fibrosis Foundation.

  13. Bone Mineral Density of Indian Children and Adolescents with Cystic Fibrosis.

    PubMed

    Gupta, Sumita; Mukherjee, Aparna; Khadgawat, Rajesh; Kabra, Madhulika; Lodha, Rakesh; Kabra, Sushil K

    2017-07-15

    To document bone mineral density of children and adolescents with cystic fibrosis. Cross-sectional study. Tertiary-care center of Northern India, July 2012 to August 2015. 52 children aged 6-18 years with cystic fibrosis and 62 healthy controls of similar age and sex. Both patients and controls were stratified into two groups, as pre-pubertal and peri-/post-pubertal, and compared for whole body bone mineral density, measured using dual energy X-ray absorptiometry. Serum levels of calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D and parathyroid hormone were measured in children with cystic fibrosis. Compared with controls, the mean (SD) bone mineral density of children with cystic fibrosis was significantly lower in both the pre-pubertal (0.7 (0.1) g/cm2 vs 0.9 (0.1) g/cm2; P<0.001)) and peri-/post-pubertal groups (0.9 (0.1) g/cm2 vs 1.1 (0.1) g/cm2; P<0.001). Also, the mean (SD) bone mineral apparent density of pre-pubertal and peri-/post-pubertal cystic fibrosis patients was lower than the controls (P <0.001 and P= 0.01, respectively). Thirty-seven (71.2%) cystic fibrosis patients had serum 25-hydroxyvitamin D level below 15 ng/mL. Bone mineral density of children with cystic fibrosis was significantly lower than controls; majority of them were vitamin-D deficient. Intervening at an early stage of the disease and providing optimal therapy involving simultaneous management of the several factors affecting bone mineral accretion may be beneficial in improving bone health of these patients.

  14. Cystic fibrosis: a mucosal immunodeficiency syndrome

    PubMed Central

    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

  15. [Nutritional status of adults with cystic fibrosis - current methods of assessment].

    PubMed

    Szabla, Anna; Skorupa, Wojciech; Milewska, Magdalena; Weker, Halina

    2015-11-01

    Cystic fibrosis (CF) is one of the most frequent monogenic disease in the Caucasian population, inherited in an autosomal recessive pattern. This is a multiple organ disease and its main manifestations include pulmonary and gastrointestinal dysfunction. The exocrine pancreatic deficiency results in impaired digestion and absorption what may lead to malnutrition and vitamins and minerals deficiencies. The life expectancy of cystic fibrosis patients has been increasing over the past years, so there is a need to verify usefulness of existing or create new methods of nutritional status assessment. The aim of this paper was presentation current data on the methods of assessment and monitoring of nutritional status. Particular attention has been paid to appropriate nutritional support in prevention and treatment of malnutrition patients with cystic fibrosis. On the basis of recent literature we can conclude that the advanced nutritional status assessment is recommended in patient with CF by using anthropometrical methods, body composition analysis and biochemical data. Good nutritional status is connected with pulmonary functions, quality and life length. © 2015 MEDPRESS.

  16. Characteristics of Resting Metabolic Rate in Critically Ill, Mechanically Ventilated Adults With Cystic Fibrosis.

    PubMed

    Frankenfield, David C; Ashcraft, Christine M; Drasher, Tammy L; Reid, Elizabeth K; Vender, Robert L

    2017-05-01

    Critically ill patients with cystic fibrosis may be especially sensitive to the negative consequences of overfeeding and underfeeding, yet there is almost no information available about the energy needs of these patients. The purpose of this study was to characterize the metabolic rate of critically ill adult patients with cystic fibrosis requiring mechanical ventilation. This was an observational study in which the resting metabolic rate, oxygen consumption, and carbon dioxide production of adult patients with cystic fibrosis requiring critical care, sedation, and mechanical ventilation were measured with indirect calorimetry. This group was compared with a cohort of adult critical care patients without cystic fibrosis. Twelve patients with cystic fibrosis were identified and measured. These were compared with a control group of 25 critically ill patients. Both groups were underweight (body mass index, 17.4 ± 4.0 kg/m 2 in cystic fibrosis and 18.4 ± 2.3 kg/m 2 in control). Adjusting for differences in age, sex, height, and weight, there was no difference in resting metabolic rate between the cystic fibrosis and control groups (1702 ± 193 vs 1642 ± 194 kcal/d, P = .388). Measured resting metabolic rate matched predicted values 58% of the time in cystic fibrosis and 60% of the time in control. The resting metabolic rate of sedated adult patients with cystic fibrosis being assisted with mechanical ventilation is not different from that of adult critical care patients without cystic fibrosis. In both these underweight groups, accurate prediction of resting metabolic rate is difficult to obtain.

  17. The experience of men and women with cystic fibrosis who have become a parent: A qualitative study.

    PubMed

    Jessup, Melanie; Li, Anne; Fulbrook, Paul; Bell, Scott C

    2018-04-01

    To explore the experiences of men and women with cystic fibrosis in becoming parents. As lifespan for people with cystic fibrosis increases, and reproductive technology advances, having a child of their own becomes a possibility. This study used a phenomenological framework. Seven Australian adults with cystic fibrosis were invited to describe their experiences of becoming parents in the context of a semi-structured interview. Analysis of the data involved highlighting recurrent phrases and isolating emergent themes. Two overarching themes characterised the participants' experience: Counting the cost, as they recalled Concentric communication and Pathways to pregnancy; and Living the dream, as they cast a retrospective view over this, their major achievement, in the light of their Reaction: a dream comes true, Coping: a question of balance, Conjecture: the future redefined and Confidence: recalibrating. While advances in cystic fibrosis care and reproductive technology have increased the possibility of individuals with cystic fibrosis becoming parents, the passage to becoming a parent is a complex process. These findings can inform health professionals to support the adaptive work necessary for families that include members with cystic fibrosis. A contemporary understanding of this phenomenon is necessary for facilitating clinically relevant communication. © 2017 John Wiley & Sons Ltd.

  18. Respiratory muscle training for cystic fibrosis.

    PubMed

    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

  19. Vitamin A absorption in cystic fibrosis: risk of hypervitaminosis A.

    PubMed Central

    James, D R; Owen, G; Campbell, I A; Goodchild, M C

    1992-01-01

    Vitamin A status was examined in nine adult cystic fibrosis patients and six adult control subjects, together with an assessment of their ability to absorb 10,000 IU of retinyl palmitate from a test meal, taken with appropriate pancreatic enzyme supplements. Median baseline values for plasma retinol and carotene, as well as median serum retinol binding protein concentrations, were significantly lower in cystic fibrosis patients than in control subjects. One cystic fibrosis patient had a raised fasting plasma retinyl ester concentration suggestive of chronic hypervitaminosis A, but no symptoms of toxicity. Measures of vitamin A absorption were also significantly lower in cystic fibrosis patients, although there was considerable overlap with control values. No correlation was observed between measures of baseline status and vitamin A absorption. Measurement of plasma retinyl esters may be an appropriate investigation in those patients considered to be at risk of chronic hypervitaminosis A. PMID:1612491

  20. 21 CFR 866.5910 - Quality control material for cystic fibrosis nucleic acid assays.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Quality control material for cystic fibrosis... Test Systems § 866.5910 Quality control material for cystic fibrosis nucleic acid assays. (a) Identification. Quality control material for cystic fibrosis nucleic acid assays. A quality control material for...

  1. 21 CFR 866.5910 - Quality control material for cystic fibrosis nucleic acid assays.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Quality control material for cystic fibrosis... Test Systems § 866.5910 Quality control material for cystic fibrosis nucleic acid assays. (a) Identification. Quality control material for cystic fibrosis nucleic acid assays. A quality control material for...

  2. 21 CFR 866.5910 - Quality control material for cystic fibrosis nucleic acid assays.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Quality control material for cystic fibrosis... Test Systems § 866.5910 Quality control material for cystic fibrosis nucleic acid assays. (a) Identification. Quality control material for cystic fibrosis nucleic acid assays. A quality control material for...

  3. 21 CFR 866.5910 - Quality control material for cystic fibrosis nucleic acid assays.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Quality control material for cystic fibrosis... Test Systems § 866.5910 Quality control material for cystic fibrosis nucleic acid assays. (a) Identification. Quality control material for cystic fibrosis nucleic acid assays. A quality control material for...

  4. Appetite stimulants for people with cystic fibrosis.

    PubMed

    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 < 0.001) (n = 40) with no evidence of a difference in effect between two different appetite stimulants. One of these trials also reported a significant weight increase with megesterol acetate compared to placebo at six months (n = 17). The three trials reported no significant differences in forced expiratory volume at one second (per cent predicted

  5. Cost-Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.

    PubMed

    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

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

    PubMed Central

    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. PMID:26666259

  7. Oral calorie supplements for cystic fibrosis.

    PubMed

    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

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

    PubMed

    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.

  9. Mycobacterium chimaera pulmonary infection complicating cystic fibrosis: a case report.

    PubMed

    Cohen-Bacrie, Stéphan; David, Marion; Stremler, Nathalie; Dubus, Jean-Christophe; Rolain, Jean-Marc; Drancourt, Michel

    2011-09-22

    Mycobacterium chimaera is a recently described species within the Mycobacterium avium complex. Its pathogenicity in respiratory tract infection remains disputed. It has never been isolated during cystic fibrosis respiratory tract infection. An 11-year-old boy of Asian ethnicity who was born on Réunion Island presented to our hospital with cystic fibrosis after a decline in his respiratory function over the course of seven years. We found that the decline in his respiratory function was correlated with the persistent presence of a Mycobacterium avium complex organism further identified as M. chimaera. Using sequencing-based methods of identification, we observed that M. chimaera organisms contributed equally to respiratory tract infections in patients with cystic fibrosis when compared with M. avium subsp. hominissuis isolates. We believe that M. chimaera should be regarded as an emerging opportunistic respiratory pathogen in patients with cystic fibrosis, including young children, and that its detection warrants long-lasting appropriate anti-mycobacterial treatment to eradicate it.

  10. Variation in Cilia Protein Genes and Progression of Lung Disease in Cystic Fibrosis.

    PubMed

    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.

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

    PubMed

    Biazotti, Maria Cristina Santoro; Pinto Junior, Walter; Albuquerque, Maria Cecília Romano Maciel de; 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.

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

    PubMed

    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.

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

    PubMed Central

    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

  14. Pediatric heart-lung transplantation for cystic fibrosis.

    PubMed

    Maynard, L C

    1994-01-01

    To describe the preoperative and postoperative experience of children who have undergone heart-lung transplantation for cystic fibrosis. Retrospective descriptive study. Paediatric Surgical Unit, Harefield Hospital, Middlesex, Great Britain. Twelve children less than 15 years of age (mean age 11 years 10 months; range 7 to 14 years), six boys and six girls, who received heart-lung transplants between September 1987 and March 1991. All 12 children were alive and well 1 year after surgery, although one girl had undergone retransplantation in the eighth postoperative month. Actuarial survival rate was 66% at 2 years. Early results suggest that heart-lung transplantation is a successful therapeutic option for children with cystic fibrosis. Cystic fibrosis-related postoperative complications were malabsorption of immunosuppressive drugs, meconium ileus equivalent, and persisting infection in the upper respiratory tract. These and general complications of acute rejection and infection did not prevent 66% of the group from returning to their normal schooling within the first postoperative year. Obliterative bronchiolitis remains the most serious late complication after lung transplantation, and further research is needed into treatment and prevention.

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

    PubMed

    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 <18 years) and 16 age-matched children without cystic fibrosis. Duration of acid neutralization during 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.

  16. Serum galactomannan in cystic fibrosis patients colonized with Aspergillus species.

    PubMed

    Warren, Thomas A; Yau, Yvonne; Ratjen, Felix; Tullis, Elizabeth; Waters, Valerie

    2012-08-01

    Cystic fibrosis patients are often colonized by Aspergillus species. Sera from 138 pediatric and adult cystic fibrosis patients were tested for the presence of galactomannan. All serum samples were negative for galactomannan and there was no difference among patients who were chronically, intermittently, and never colonized with Aspergillus.

  17. Recent advances in understanding and managing cystic fibrosis transmembrane conductance regulator dysfunction

    PubMed Central

    Alton, Eric W.F.W.

    2015-01-01

    Cystic fibrosis is the most common autosomal recessive genetic disease in Caucasians and has been extensively studied for many decades. The cystic fibrosis transmembrane conductance regulator gene was identified in 1989. It encodes a complex protein which has numerous cellular functions. Our understanding of cystic fibrosis pathophysiology and genetics is constantly expanding and being refined, leading to improved management of the disease and increased life expectancy in affected individuals. PMID:26097737

  18. Young patients with cystic fibrosis demonstrate subtle alterations of the cardiovascular system.

    PubMed

    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 <0.01). Systolic strain rate of basal segment of the left ventricle, the mid segment of the right ventricle and the apical septum were significantly lower in the 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

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

    PubMed

    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

  20. TESTS TO ASSESS SENSITIZATION TO ASPERGILLUS FUMIGATUS IN CYSTIC FIBROSIS

    PubMed Central

    Aguiar, Simone Santana; Damaceno, Neiva; Forte, Wilma Carvalho Neves

    2017-01-01

    ABSTRACT Objective: To evaluate the results of the tests used to identify the IgE mediated sensitization to Aspergillus fumigatus in patients with cystic fibrosis. Methods: This is a cross-sectional descriptive study with a convenience sample of 86 patients diagnosed with cystic fibrosis in the Reference Service in Cystic Fibrosis at a tertiary teaching hospital. The following tests were performed to assess the sensitization to A. fumigatus in patients with cystic fibrosis: Total serum IgE, eosinophil count, fungus detection through oropharyngeal swab or sputum culture, serum-specific IgE, and immediate-type hypersensitivity (IgE) skin tests. We compared the results of the different tests performed. Results: In 33 (38.4%) patients with cystic fibrosis, with ages ranging from 1 to 33 years (median of 8 years), the IgE-mediated A. fumigatus sensitization test results were: in 16 patients, there was an increase in serum-specific IgE (>0.35 kU/L); in 23, skin tests were positive; and six had sensitization in both tests. We observed two patients with eosinophilia (>1,000 eosinophils/mm3) and seven with increasing total serum IgE (>1,000 IU/mL), all of whom obtained negative results in skin tests and had no IgE increase specific to A. fumigatus. A. fumigatus was not detected in oropharyngeal swabs and/or sputum culture of any patients. Conclusions: We conclude that, among the tests used to assess sensitization to A. fumigatus in cystic fibrosis patients, both serum-specific IgE and immediate-type hypersensitivity (IgE) skin tests are required. Serum eosinophilia and respiratory secretion culture were not essential in this study. PMID:28977288

  1. Cystic fibrosis liver disease - from diagnosis to risk factors.

    PubMed

    Ciucă, Ioana Mihaiela; Pop, Liviu; Tămaş, Liviu; Tăban, Sorina

    2014-01-01

    Cystic fibrosis (CF) is the most frequent monogenic genetic disease, autosomal recessive transmitted, characterized by an impressive clinical polymorphism and appreciative fatal prospective. Liver disease is the second non-pulmonary cause of death in cystic fibrosis, which, with increasing life expectancy, became an important management problem. Predisposing factors like male gender, pancreatic insufficiency, meconium ileus and severe mutation are incriminated to influence the occurrence of cystic fibrosis associated liver disease (CFLD). Our study included 174 patients with CF, monitored in the National Cystic Fibrosis Centre, Timisoara, Romania. They were routinely followed-up by clinical assessment, liver biochemical tests, ultrasound examinations and other methods like transient elastography, biopsy, in selected cases. Sixty-six patients, with median age at diagnosis 4.33 years, diagnosed with CFLD, without significant gender gap. CFLD was frequent in patients aged over eight years, with meconium ileus history, carriers of severe mutations (p=0.002). Pancreatic insufficiency, although present in 75% of patients with CFLD was not confirmed as risk factor, not male gender, in our study. CF children older than eight years, carriers of a severe genotype, with a positive history of meconium ileus, were more likely predisposed to CFLD.

  2. Heterogeneity of the cystic fibrosis phenotype in a large kindred family in Qatar with cystic fibrosis mutation (I1234V).

    PubMed

    Abdul Wahab, A; Al Thani, G; Dawod, S T; Kambouris, M; Al Hamed, M

    2001-04-01

    Twenty-nine subjects (17 families) with cystic fibrosis belonging to the same Bedouin tribe were screened for cystic fibrosis transmembrane regulator gene mutations (CFTR). Homozygous I1234V mutation in exon 19 was identified in all families with a relatively high rate of consanguinity (96.6 per cent). The homozygous I1234V mutation tended to present with a variable degree of pulmonary disease, pancreatic insufficiency and electrolyte imbalance. Homozygous I1234V was found to be a common mutation in the studied Bedouin tribe in Qatar.

  3. How can the cystic fibrosis respiratory microbiome influence our clinical decision-making?

    PubMed

    Rogers, Geraint B; Bruce, Kenneth D; Hoffman, Lucas R

    2017-11-01

    Almost 15 years have now passed since bacterial community profiling techniques were first used to analyse respiratory samples from people with cystic fibrosis. Since then, many different analytical approaches have been used to try to better understand the contribution of the cystic fibrosis lung microbiota to disease, with varying degrees of success. We examine the extent to which cystic fibrosis respiratory microbiome research has been successful in informing clinical decision-making, and highlight areas that we believe have the potential to yield important insight. Recent research on the cystic fibrosis lung microbiome can be broadly divided into efforts to better characterize microbiota composition, particularly relative to key clinical events, and attempts to understand the cystic fibrosis lung microbiology as an interactive microbial system. The latter, in particular, has led to the development of a number of models in which microbiome-mediated processes precipitate clinical events. Growing technological sophistication is enabling increasingly detailed microbiological data to be generated from cystic fibrosis respiratory samples. However, translating these data into clinically useful measures that accurately predict outcomes and guide treatments remains a formidable challenge. The development of systems biology approaches that enable the integration of complex microbiome and host-derived data provide an exciting opportunity to address this goal.

  4. New and emerging targeted therapies for cystic fibrosis.

    PubMed

    Quon, Bradley S; Rowe, Steven M

    2016-03-30

    Cystic fibrosis (CF) is a monogenic autosomal recessive disorder that affects about 70,000 people worldwide. The clinical manifestations of the disease are caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The discovery of the CFTR gene in 1989 has led to a sophisticated understanding of how thousands of mutations in the CFTR gene affect the structure and function of the CFTR protein. Much progress has been made over the past decade with the development of orally bioavailable small molecule drugs that target defective CFTR proteins caused by specific mutations. Furthermore, there is considerable optimism about the prospect of gene replacement or editing therapies to correct all mutations in cystic fibrosis. The recent approvals of ivacaftor and lumacaftor represent the genesis of a new era of precision medicine in the treatment of this condition. These drugs are having a positive impact on the lives of people with cystic fibrosis and are potentially disease modifying. This review provides an update on advances in our understanding of the structure and function of the CFTR, with a focus on state of the art targeted drugs that are in development. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Antimicrobial resistance in the respiratory microbiota of people with cystic fibrosis.

    PubMed

    Sherrard, Laura J; Tunney, Michael M; Elborn, J Stuart

    2014-08-23

    Cystic fibrosis is characterised by chronic polymicrobial infection and inflammation in the airways of patients. Antibiotic treatment regimens, targeting recognised pathogens, have substantially contributed to increased life expectancy of patients with this disease. Although the emergence of antimicrobial resistance and selection of highly antibiotic-resistant bacterial strains is of major concern, the clinical relevance in cystic fibrosis is yet to be defined. Resistance has been identified in recognised cystic fibrosis pathogens and in other bacteria (eg, Prevotella and Streptococcus spp) detected in the airway microbiota, but their role in the pathophysiology of infection and inflammation in chronic lung disease is unclear. Increased antibiotic resistance in cystic fibrosis might be attributed to a range of complex factors including horizontal gene transfer, hypoxia, and biofilm formation. Strategies to manage antimicrobial resistance consist of new antibiotics or localised delivery of antimicrobial agents, iron sequestration, inhibition of quorum-sensing, and resistome analysis. Determination of the contributions of every bacterial species to lung health or disease in cystic fibrosis might also have an important role in the management of antibiotic resistance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Hyponatremia-associated rhabdomyolysis following exercise in an adolescent with cystic fibrosis.

    PubMed

    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.

  7. Blunted perception of neural respiratory drive and breathlessness in patients with cystic fibrosis

    PubMed Central

    Jolley, Caroline J.; Elston, Caroline; Moxham, John; Rafferty, Gerrard F.

    2016-01-01

    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 fibrosis

  8. Blunted perception of neural respiratory drive and breathlessness in patients with cystic fibrosis.

    PubMed

    Reilly, Charles C; Jolley, Caroline J; Elston, Caroline; Moxham, John; Rafferty, Gerrard F

    2016-01-01

    The electromyogram recorded from the diaphragm (EMG di ) and parasternal intercostal muscle using surface electrodes (sEMG para ) 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 (FEV 1 ) 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. EMG di and sEMG para 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. EMG di % max and sEMG para % max and associated Borg breathlessness scores differed significantly between healthy subjects and cystic fibrosis patients at rest and during exercise. The relationship between EMG di % max and sEMG para % max and Borg score was shifted to the right in the cystic fibrosis patients, such that at comparable levels of EMG di % max and sEMG para % 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 EMG di % max (20.2±12% versus 32.15±15%, p=0.02) and sEMG para % max (18.9±8% versus 29.2±15%, p=0.04) were lower in the healthy individuals compared to the cystic

  9. Biomarkers for Cystic Fibrosis Drug Development

    PubMed Central

    Muhlebach, Marianne S.; Clancy, JP; Heltshe, Sonya L.; Ziady, Assem; Kelley, Tom; Accurso, Frank; Pilewski, Joseph; Mayer-Hamblett, Nicole; Joseloff, Elizabeth; Sagel, Scott D.

    2016-01-01

    Purpose To provide a review of the status of biomarkers in cystic fibrosis drug development, including regulatory definitions and considerations, a summary of biomarkers in current use with supportive data, current gaps, and future needs. Methods Biomarkers are considered across several areas of CF drug development, including cystic fibrosis transmembrane conductance regulator modulation, infection, and inflammation. Results Sweat chloride, nasal potential difference, and intestinal current measurements have been standardized and examined in the context of multicenter trials to quantify CFTR function. Detection and quantification of pathogenic bacteria in CF respiratory cultures (e.g.: Pseudomonas aeruginosa) is commonly used in early phase antimicrobial clinical trials, and to monitor safety of therapeutic interventions. Sputum (e.g.: neutrophil elastase, myeloperoxidase, calprotectin) and blood biomarkers (e.g.: C reactive protein, calprotectin, serum amyloid A) have had variable success in detecting response to inflammatory treatments. Conclusions Biomarkers are used throughout the drug development process in CF, and many have been used in early phase clinical trials to provide proof of concept, detect drug bioactivity, and inform dosing for later-phase studies. Advances in the precision of current biomarkers, and the identification of new biomarkers with ‘omics-based technologies, are needed to accelerate CF drug development. PMID:28215711

  10. Antenatal testing for cystic fibrosis in Cuba, 1988-2011.

    PubMed

    Collazo, Teresa; López, Ixchel; Clark, Yulia; Piloto, Yaixa; González, Laura; Gómez, Manuel; García, Marileivis; Reyes, Lidice; Rodríguez, Fidel

    2014-01-01

    INTRODUCTION Cystic fibrosis is a multisystem autosomal recessive disease with wide variability in clinical severity. It is incurable and characterized by elevated and premature mortality, as well as poor quality of life. Its frequency, lethality and devastating impact on both the physical and psychological wellbeing of patients and their families, make it a serious health problem. Its frequency in Cuba is 1 in 9862 live births, where marked molecular heterogeneity of the CFTR gene makes molecular diagnosis difficult. Six mutations have been identified that together enable molecular characterization of only 55.5% of cystic fibrosis chromosomes. This paper presents national results of antenatal diagnostic testing, using direct and indirect methods, for detection of cystic fibrosis. OBJECTIVE Characterize the Cuban public health system's experience with antenatal molecular testing for cystic fibrosis from 1988 through 2011. METHODS A retrospective descriptive study was conducted with results of antenatal diagnostic testing of amniotic fluid, performed nationwide from 1988 through 2011, for 108 fetuses of couples with some risk of having children affected by cystic fibrosis, who requested testing. Polymerase chain reaction detected mutations p.F508del, p.G542X, p.R1162X, p.R334W, p.R553X and c.3120+1G>A, and markers XV2C and KM19. Data were analyzed using absolute frequencies and percentages, and presented in tables. RESULTS For 93 cases (86.1%), testing for cystic fibrosis was done using direct analysis of mutations p.F508del, p.G542X, p.R1162X, p.R334W, p.R553X and c.3120+1G>A; five cases (4.6%) were tested indirectly using markers XV2C/Taq I and KM19/Pst I; and 10 (9.3%) were tested using a combination of the two methods. A total of 72 diagnoses (66.7% of studies done) were concluded, of which there were 20 healthy fetuses, 16 affected, 27 carrier, and 9 who were either healthy or carriers of an unknown mutation. CONCLUSIONS Direct or indirect molecular study was

  11. Pulmonary function outcomes for assessing cystic fibrosis care.

    PubMed

    Wagener, Jeffrey S; Elkin, Eric P; Pasta, David J; Schechter, Michael S; Konstan, Michael W; Morgan, Wayne J

    2015-05-01

    Assessing cystic fibrosis (CF) patient quality of care requires the choice of an appropriate outcome measure. We looked systematically and in detail at pulmonary function outcomes that potentially reflect clinical practice patterns. Epidemiologic Study of Cystic Fibrosis data were used to evaluate six potential outcome variables (2002 best FVC, FEV(1), and FEF(25-75) and rate of decline for each from 2000 to 2002). We ranked CF care sites by outcome measure and then assessed any association with practice patterns and follow-up pulmonary function. Sites ranked in the top quartile had more frequent monitoring, treatment of exacerbations, and use of chronic therapies and oral corticosteroids. The follow-up rate of pulmonary function decline was not predicted by site ranking. Different pulmonary function outcomes associate slightly differently with practice patterns, although annual FEV(1) is at least as good as any other measure. Current site ranking only moderately predicts future ranking. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  12. Update on fat-soluble vitamins in cystic fibrosis.

    PubMed

    Maqbool, Asim; Stallings, Virginia A

    2008-11-01

    We review and critique recent scientific advances in the understanding of fat-soluble vitamins and the care of people with cystic fibrosis. A shift in the conceptual approach to fat-soluble vitamin status has occurred. Vitamin status in cystic fibrosis had previously been discussed in terms of sufficiency versus insufficiency as compared with healthy populations. The discussion of vitamin status has now shifted to that of suboptimal versus optimal with respect to health outcomes. This is best illustrated by advances in the study of vitamin D. Newer metabolic and immunological roles and biomarkers have been identified. With supplementation of water-miscible formulations of preformed vitamin A, increased serum retinol has been observed, and may increase the risk for toxicity. A paradigm shift has occurred in defining fat-soluble vitamin status by utilizing different biomarkers and associations with health outcomes. Identification of additional biomarkers, redefining definitions of adequacy, optimal surveillance for toxicity as well as adequacy is needed for care of patients with cystic fibrosis.

  13. Prenatal diagnosis of cystic fibrosis: 10-years experience.

    PubMed

    Hadj Fredj, S; Ouali, F; Siala, H; Bibi, A; Othmani, R; Dakhlaoui, B; Zouari, F; Messaoud, T

    2015-06-01

    We present in this study our 10years experience in prenatal diagnosis of cystic fibrosis performed in the Tunisian population. Based on family history, 40 Tunisian couples were selected for prenatal diagnosis. Fetal DNA was isolated from amniotic fluid collected by transabdominal amniocentesis or from chronic villi by transcervical chorionic villus sampling. The genetic analysis for cystic fibrosis mutations was performed by denaturant gradient gel electrophoresis and denaturing high-pressure liquid phase chromatography. We performed microsatellites analysis by capillary electrophoresis in order to verify the absence of maternal cell contamination. Thirteen fetuses were affected, 21 were heterozygous carriers and 15 were healthy with two normal alleles of CFTR gene. Ten couples opted for therapeutic abortion. The microsatellites genotyping showed the absence of contamination of the fetal DNA by maternal DNA in 93.75%. Our diagnostic strategy provides rapid and reliable prenatal diagnosis at risk families of cystic fibrosis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. Sweat Chlorides in Salt-Deprived Cystic Fibrosis Heterozygotes

    PubMed Central

    Myers, Michael F.

    1965-01-01

    Sweat chlorides of 10 sets of parents of children with cystic fibrosis and 11 controls were studied in an attempt to develop a test for the diagnosis of cystic fibrosis heterozygotes by subjecting both the parents and controls to a low sodium diet and comparing sweat chloride values as the diet progressed. It was hoped that the sweat chloride levels of the parents, the heterozygotes, would remain stationary throughout the diet, since their children, the homozygotes, reveal this finding under similar conditions of salt deprivation. The sweat chloride levels of the controls, because of effects of aldosterone, were expected to decrease steadily from the commencement of the diet to its termination. A decrease in sweat chloride values of similar magnitude was found in both parents and controls as the diet continued. It is concluded that the study of sweat electrolyte levels in salt-deprived subjects is of no value in the diagnosis of cystic fibrosis heterozygotes. PMID:14289142

  15. Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

    PubMed

    Elphick, Heather E; Southern, Kevin W

    2014-11-28

    Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, their many side effects are well-documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis:1. improve clinical status compared to placebo or standard therapy (no placebo);2. do not have unacceptable adverse effects.If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.In addition, pharmaceutical companies were approached.Date of the most recent search of the Group's Trials Register: 17 March 2014. Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis. Four trials were identified by the searches; none of which was judged eligible for inclusion in the review. No completed randomised controlled trials

  16. A service evaluation of an integrated model of palliative care of cystic fibrosis.

    PubMed

    Bourke, Stephen J; Booth, Zoe; Doe, Simon; Anderson, Alan; Rice, Sarah; Gascoigne, Alistair; Quibell, Rachel

    2016-07-01

    Patients with advanced cystic fibrosis have severe symptoms with a complex trajectory of exacerbations and recovery. They are often awaiting lung transplantation, and many die without receiving specialist palliative care. We introduced an integrated model whereby palliative specialists joined the cystic fibrosis team to provide palliative care in parallel with standard care. A service evaluation of this model of care was undertaken in a prospective case series documenting symptoms and outcomes, the views of the cystic fibrosis team and the experience of the palliative specialists. Over 3 years, 28 (10%) of 282 patients attending the cystic fibrosis centre had specialist palliative care. They had advanced lung disease (mean forced expiratory volume in 1 s (FEV1) = 0.86 L (25% predicted)), and 17 died: 6 were on a transplant waiting list at death; 10 were unsuitable and 1 died post transplantation. All who died over these 3 years had specialist palliative care. Four patients had successful transplants. Assessment showed a high prevalence of breathlessness, cough, pain, vomiting and fatigue, with a significant impact on daily life. The cystic fibrosis team rated this model of care highly, felt that palliative care should be members of the team, and thought that patients had found it helpful. The palliative specialists gained knowledge of cystic fibrosis, found it beneficial to meet patients earlier in the disease, and identified unmet needs in managing bereavement and the effects of deaths on other patients with cystic fibrosis. This model has been successful in overcoming the difficulties in access to specialist palliative care for patients with cystic fibrosis. © The Author(s) 2016.

  17. Cystic fibrosis identified by neonatal screening: incidence, genotype, and early natural history.

    PubMed

    Green, M R; Weaver, L T; Heeley, A F; Nicholson, K; Kuzemko, J A; Barton, D E; McMahon, R; Payne, S J; Austin, S; Yates, J R

    1993-04-01

    The incidence of cystic fibrosis over the last 10 years in East Anglia (a region of the United Kingdom with a population of 2.1 million) has halved. This has happened during the establishment of a neonatal screening programme, which has enabled early diagnosis, genetic counselling, and lately the option of prenatal diagnosis in subsequent pregnancies. One hundred and seven children were born with cystic fibrosis between 1981 and 1990, eight of whom were siblings. The Guthrie blood spots of 82 infants detected by neonatal immunoreactive trypsin screening between 1981 and 1990 were examined for the presence of the most common cystic fibrosis gene mutation (delta F508). It was present in 135 (82%) of the 164 cystic fibrosis genes analysed with 54 (66%) cases being homozygous and 27 (33%) heterozygous. Sixty nine per cent of infants were symptomatic at the time of diagnosis regardless of genotype. No association was found between the early clinical or biochemical features of the disease and homozygosity or heterozygosity for this mutation. Screening for cystic fibrosis using the blood immunoreactive trypsin assay alone remains an effective method of identifying infants with the disease soon after birth, thereby allowing early therapeutic intervention. Genetic counselling and prenatal diagnosis have contributed to a reduction in the number of children born with cystic fibrosis, but may not entirely explain the decreasing incidence of the disease.

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

    PubMed

    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.

  19. Cost Effectiveness of Screening Individuals With Cystic Fibrosis for Colorectal Cancer.

    PubMed

    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

  20. The evaluation of selected insomnia predictors in adolescents and young adults with cystic fibrosis.

    PubMed

    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.

  1. Diagnosis of Adult Patients with Cystic Fibrosis.

    PubMed

    Nick, Jerry A; Nichols, David P

    2016-03-01

    The diagnosis of cystic fibrosis (CF) is being made with increasing frequency in adults. Patients with CF diagnosed in adulthood typically present with respiratory complaints, and often have recurrent or chronic airway infection. At the time of initial presentation individuals may appear to have clinical manifestation limited to a single organ, but with subclinical involvement of the respiratory tract. Adult-diagnosed patients have a good response to CF center care, and newly available cystic fibrosis transmembrane receptor-modulating therapies are promising for the treatment of residual function mutation, thus increasing the importance of the diagnosis in adults with unexplained bronchiectasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Influence of macrolides, nutritional support and respiratory therapies in diabetes and normal glucose tolerance in cystic fibrosis. A retrospective analysis of a cohort of adult and younger patients.

    PubMed

    Megías, Marta Cano; Albarrán, Olga González; Vasco, Pablo Guisado; Ferreiro, Adelaida Lamas; Carro, Luis Maiz

    2015-01-01

    The development of cystic fibrosis related diabetes is associated with increased morbidity and mortality, worse nutritional status and lung function decline. It is known that patients with cystic fibrosis have a chronic inflammation status and that β pancreatic cells are very sensitive to oxidative stress. So these inflammatory mediators could contribute to the onset of progressive pancreatic fibrosis and, hence, to impair glucose metabolism. So, it could be hypothesized that the treatment with macrolides would protect and preserve β-cell function by decreasing pro-inflammatory cytokines and free oxidative radicals. We retrospectively analyzed a cohort of 64 patients affected of cystic fibrosis, older than 14 years, by using the first pathological 2-h oral glucose tolerance test; peripheral insulin resistance was calculated using the homeostasis model assessment for insulin resistance (HOMA - IR) and pancreatic β-cell function was estimated according to Wareham. The influence of macrolides, microbiological colonization, nutritional support and related clinical parameters were analyzed. Comparing CFRD without FPG and NGT, and after adjustment for microbial colonization, the significance of the use of macrolides was lost (p=0.1), as a risk or protective factor for any of the studied groups. Non-significative associations were found in the use of macrolides, inhaled corticosteroids and nutritional support therapies within the different disorders of carbohydrate metabolism. The anti-inflammatory and immunomodulating effect of macrolides did not seem to affect the β cell function or insulin resistance in patients with cystic fibrosis. The use of inhaled corticosteroids or nutritional supplements have not any influence in the carbohydrate metabolism. Further prospective studies are needed to analyze a potential protective role of macrolides in the development of carbohydrate metabolism alterations in cystic fibrosis. Copyright © 2014 Diabetes India. Published by

  3. Recombinant Human DNase I Reduces the Viscosity of Cystic Fibrosis Sputum

    NASA Astrophysics Data System (ADS)

    Shak, Steven; Capon, Daniel J.; Hellmiss, Renate; Marsters, Scot A.; Baker, Carrie 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.

  4. Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum.

    PubMed

    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.

  5. Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis.

    PubMed

    Robinson, Karen A; Odelola, Olaide A; Saldanha, Ian J; McKoy, Naomi A

    2013-06-05

    Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis. To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 11 October 2012. Randomised and quasi-randomised studies. The authors independently extracted data and assessed risk of bias. One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. At six months follow-up, one participant in each group was hospitalised due to respiratory syncytial virus; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while five and four children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab

  6. Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

    PubMed

    Elphick, Heather E; Southern, Kevin W

    2012-06-13

    Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, their many side effects are well-documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); 2. do not have unacceptable adverse effects.If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.In addition, pharmaceutical companies were approached.Date of the most recent search of the Group's Trials Register: 09 February 2012. Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis. Two trials were identified by the searches; neither was judged eligible for inclusion in the review. No completed randomised controlled trials were

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

    PubMed

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

    2014-12-15

    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. 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.Date of the most recent search of the Group's trials register: 29 May 2014. 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. Ten trials have been identified, of which three trials involving 118 participants were included; 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 participants from two trials. Improvement in biliary excretion was reported in only one trial and no significant change after treatment was shown. There were no data available for analysis for long-term outcomes such as death or need for liver transplantation. There are few

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

    PubMed Central

    Kalnins, Daina; Wilschanski, Michael

    2012-01-01

    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. PMID:22787388

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

    PubMed

    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/

  10. The structure of tracheobronchial mucins from cystic fibrosis and control patients.

    PubMed

    Gupta, R; Jentoft, N

    1992-02-15

    Tracheobronchial mucin samples from control and cystic fibrosis patients were purified by gel filtration chromatography on Sephacryl S-1000 and by density gradient centrifugation. Normal secretions contained high molecular weight (approximately 10(7] mucins, whereas the cystic fibrosis secretions contained relatively small amounts of high molecular weight mucin together with larger quantities of lower molecular weight mucin fragments. These probably represent products of protease digestion. Reducing the disulfide bonds in either the control or cystic fibrosis high molecular weight mucin fractions released subunits of approximately 2000 kDa. Treating these subunits with trypsin released glycopeptides of 300 kDa. Trypsin treatment of unreduced mucin also released fragments of 2000 kDa that could be converted into 300-kDa glycopeptides upon disulfide bond reduction. Thus, protease-susceptible linkages within these mucins must be cross-linked by disulfide bonds so that the full effects of proteolytic degradation of mucins remain cryptic until disulfide bonds are reduced. Since various combinations of protease treatment and disulfide bond reduction release either 2000- or 300-kDa fragments, these fragments must represent important elements of mucin structure. The high molecular weight fractions of cystic fibrosis mucins appear to be indistinguishable from control mucins. Their amino acid compositions are the same, and various combinations of disulfide bond reduction and protease treatment release products of identical size and amino acid composition. Sulfate and carbohydrate compositions did vary considerably from sample to sample, but the limited number of samples tested did not demonstrate a cystic fibrosis-specific pattern. Thus, tracheobronchial mucins from cystic fibrosis and control patients are very similar, and both share the same generalized structure previously determined for salivary, cervical, and intestinal mucins.

  11. [Measurement of nasal transepithelial potential difference: a diagnostic test for cystic fibrosis].

    PubMed

    Charfi, M R; Matran, R; Regnard, J; Lockhart, A

    1996-01-01

    Measurement of nasal transepithelial potential difference allows the exploration of transepithelial ionic transports in vivo. Cystic fibrosis is an interesting indication of this test. Indeed, this disease is characterized by a chloride and water secretion deficit across respiratory epithelium. We have measured nasal potential in 8 healthy volunteers. Measurements were repeated 3 times a day, during 3 days for each subject. The reproducibility of the data was analysed with factorial variance model. The mean nasal potential in the healthy volunteers group and in 10 patients with cystic fibrosis was compared. In the cystic fibrosis group, the nasal potential was measured 3 times with a 2 mn-interval between the measurements. No significant variation of the nasal potential values was found from day to day or in the same day from one measurement to another. Mean value was -19 +/- 3.5 mv in normal subjects and -42.6 +/- 5.1 mv in cystic fibrosis patients. We conclude that nasal potential measurement is an easy and reproducible test that might be a complementary tool routinely used along with the classical tests in the diagnosis of cystic fibrosis.

  12. Antifungal therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

    PubMed

    Elphick, Heather E; Southern, Kevin W

    2016-11-08

    Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, their many side effects are well-documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review. The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis:1. improve clinical status compared to placebo or standard therapy (no placebo);2. do not have unacceptable adverse effects.If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.In addition, pharmaceutical companies were approached.Date of the most recent search of the Group's Trials Register: 29 September 2016. Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis. Four trials were identified by the searches; none of which was judged eligible for inclusion in

  13. The Swiss Cystic Fibrosis Infant Lung Development (SCILD) cohort.

    PubMed

    Korten, Insa; Kieninger, Elisabeth; Yammine, Sophie; Regamey, Nicolas; Nyilas, Sylvia; Ramsey, Kathryn; Casaulta, Carmen; Latzin, Philipp; For The Scild Study Group

    2018-04-26

    The Swiss Cystic Fibrosis Infant Lung Development (SCILD) cohort is a prospective birth cohort study investigating the initiating events of cystic fibrosis lung disease during infancy, and their influence on the trajectory of disease progression throughout early childhood. Infants with cystic fibrosis are recruited throughout Switzerland after diagnosis by new-born screening. It is the first European population-based prospective cohort study of infants with cystic fibrosis taking advantage of a nationwide new-born screening programme. The study was established in 2011 and recruitment is ongoing. The cohort study is currently divided into three study phases (phase 1: diagnosis to age 1 year; phase 2: age 1 to 3 years; and phase 3: age 3 to 6 years). Study participants have weekly telephone interviews, weekly anterior nasal swab collection and two study visits in the first year of life. They also complete follow-up study visits at 3 and 6 years of age. Data for this study are derived from questionnaires, lung function measurements, telephone interviews, nasal swab material and magnetic resonance imaging. To date, 70 infants have been recruited into the study and 56 have completed phase 1, including a baseline study visit at 6 weeks of age, weekly surveillance and a study visit at one year of age. More than 2500 data points on respiratory health and almost 2000 nasal samples have been collected. Phases 2 and 3 will commence in 2018. The dataset of the SCILD cohort combines lung function data, the collection of environmental and sociodemographic factors, documentation of respiratory symptoms, and microbiological analyses. The design not only allows tracking of the cystic fibrosis lung disease independent of clinical status, but also surveillance of early disease prior to severe clinical symptoms. This cohort profile provides details on the study design and summarizes the first published results of the SCILD cohort.

  14. ∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis.

    PubMed

    Pankow, Sandra; Bamberger, Casimir; Calzolari, Diego; Martínez-Bartolomé, Salvador; Lavallée-Adam, Mathieu; Balch, William E; Yates, John R

    2015-12-24

    Deletion of phenylalanine 508 of the cystic fibrosis transmembrane conductance regulator (∆F508 CFTR) is the major cause of cystic fibrosis, one of the most common inherited childhood diseases. The mutated CFTR anion channel is not fully glycosylated and shows minimal activity in bronchial epithelial cells of patients with cystic fibrosis. Low temperature or inhibition of histone deacetylases can partly rescue ∆F508 CFTR cellular processing defects and function. A favourable change of ∆F508 CFTR protein-protein interactions was proposed as a mechanism of rescue; however, CFTR interactome dynamics during temperature shift and inhibition of histone deacetylases are unknown. Here we report the first comprehensive analysis of the CFTR and ∆F508 CFTR interactome and its dynamics during temperature shift and inhibition of histone deacetylases. By using a novel deep proteomic analysis method, we identify 638 individual high-confidence CFTR interactors and discover a ∆F508 deletion-specific interactome, which is extensively remodelled upon rescue. Detailed analysis of the interactome remodelling identifies key novel interactors, whose loss promote ∆F508 CFTR channel function in primary cystic fibrosis epithelia or which are critical for CFTR biogenesis. Our results demonstrate that global remodelling of ∆F508 CFTR interactions is crucial for rescue, and provide comprehensive insight into the molecular disease mechanisms of cystic fibrosis caused by deletion of F508.

  15. Loss of Cystic Fibrosis Transmembrane Regulator Impairs Intestinal Oxalate Secretion.

    PubMed

    Knauf, Felix; Thomson, Robert B; Heneghan, John F; Jiang, Zhirong; Adebamiro, Adedotun; Thomson, Claire L; Barone, Christina; Asplin, John R; Egan, Marie E; Alper, Seth L; Aronson, Peter S

    2017-01-01

    Patients with cystic fibrosis have an increased incidence of hyperoxaluria and calcium oxalate nephrolithiasis. Net intestinal absorption of dietary oxalate results from passive paracellular oxalate absorption as modified by oxalate back secretion mediated by the SLC26A6 oxalate transporter. We used mice deficient in the cystic fibrosis transmembrane conductance regulator gene (Cftr) to test the hypothesis that SLC26A6-mediated oxalate secretion is defective in cystic fibrosis. We mounted isolated intestinal tissue from C57BL/6 (wild-type) and Cftr -/- mice in Ussing chambers and measured transcellular secretion of [ 14 C]oxalate. Intestinal tissue isolated from Cftr -/- mice exhibited significantly less transcellular oxalate secretion than intestinal tissue of wild-type mice. However, glucose absorption, another representative intestinal transport process, did not differ in Cftr -/- tissue. Compared with wild-type mice, Cftr -/- mice showed reduced expression of SLC26A6 in duodenum by immunofluorescence and Western blot analysis. Furthermore, coexpression of CFTR stimulated SLC26A6-mediated Cl - -oxalate exchange in Xenopus oocytes. In association with the profound defect in intestinal oxalate secretion, Cftr -/- mice had serum and urine oxalate levels 2.5-fold greater than those of wild-type mice. We conclude that defective intestinal oxalate secretion mediated by SLC26A6 may contribute to the hyperoxaluria observed in this mouse model of cystic fibrosis. Future studies are needed to address whether similar mechanisms contribute to the increased risk for calcium oxalate stone formation observed in patients with cystic fibrosis. Copyright © 2016 by the American Society of Nephrology.

  16. Doxycycline improves clinical outcomes during cystic fibrosis exacerbations.

    PubMed

    Xu, Xin; Abdalla, Tarek; Bratcher, Preston E; Jackson, Patricia L; Sabbatini, Gina; Wells, J Michael; Lou, Xiang-Yang; Quinn, Rebecca; Blalock, J Edwin; Clancy, J P; Gaggar, Amit

    2017-04-01

    Matrix metalloprotease-9 (MMP-9) plays a role in progression of cystic fibrosis, and doxycycline can reduce MMP-9 in vitro Here, we explore the effect of doxycycline during cystic fibrosis exacerbation treatment on MMP-9 related readouts and clinical end-points.This randomised, double-blind, placebo-controlled study enrolled hospitalised patients with cystic fibrosis undergoing exacerbation. In total, 20 participants were given doxycycline and 19 participants were given placebo over an 8-day period during hospitalisation. Biospecimens were collected at the beginning and the end of the study period. Primary end-points were total MMP-9 levels in the sputum and safety/tolerability. Secondary end-points included change in lung function, time to next exacerbation, and markers of MMP-9-related protease activity (active MMP-9 and TIMP-1). Nonparametric testing was used for within-group and between-group analyses.Doxycycline was well tolerated, with no treatment discontinuations or serious adverse events. Doxycycline reduced total sputum MMP-9 levels by 63.2% (p<0.05), and was also associated with a 56.5% reduction in active MMP-9 levels (p<0.05), a 1.6-fold increase in sputum TIMP-1 (p<0.05), improvement in forced expiratory volume in 1 s (p<0.05), and an increase in time to next exacerbation (p<0.01).Adjunctive use of doxycycline improved dysregulated MMP-9 levels in sputum, along with biomarkers consistent with a reduced proteolytic pulmonary environment. Improvement in clinical outcome measures suggests an important therapeutic benefit of doxycycline for individuals with cystic fibrosis. Copyright ©ERS 2017.

  17. Macrolide antibiotics for cystic fibrosis.

    PubMed

    Southern, Kevin W; Barker, Pierre M; Solis-Moya, Arturo; Patel, Latifa

    2012-11-14

    Macrolide antibiotics may have a modifying role in diseases which involve airway infection and inflammation, like cystic fibrosis. To test the hypotheses that, in people with cystic fibrosis, macrolide antibiotics: 1. improve clinical status compared to placebo or another antibiotic; 2. do not have unacceptable adverse effects. If benefit was demonstrated, we aimed to assess the optimal type, dose and duration of macrolide therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.We contacted investigators known to work in the field, previous authors and pharmaceutical companies manufacturing macrolide antibiotics for unpublished or follow-up data (May 2010).Latest search of the Group's Cystic Fibrosis Trials Register: 29 February 2012. Randomised controlled trials of macrolide antibiotics compared to: placebo; another class of antibiotic; another macrolide antibiotic; or the same macrolide antibiotic at a different dose. Two authors independently extracted data and assessed risk of bias. Seven groups were contacted and provided additional data which were incorporated into the review. Ten of 31 studies identified were included (959 patients). Five studies with a low risk of bias examined azithromycin versus placebo and demonstrated consistent improvement in forced expiratory volume in one second over six months (mean difference at six months 3.97% (95% confidence interval 1.74% to 6.19%; n = 549, from four studies)). Patients treated with azithromycin were approximately twice as likely to be free of pulmonary exacerbation at six months, odds ratio 1.96 (95% confidence interval 1.15 to 3.33). With respect to secondary outcomes, there was a significant reduction in need for oral antibiotics and greater weight gain in those taking azithromycin. Adverse events were uncommon

  18. Na and K Dependence of the Na/K Pump in Cystic Fibrosis Fibroblasts

    NASA Astrophysics Data System (ADS)

    Reznik, Vivian M.; Schneider, Jerry A.; Mendoza, Stanley A.

    1981-11-01

    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 fibrosis, the Na/K pump had a significantly lower affinity for K (Km = 1.6 mM) when compared to normals (Km = 0.9 mM). This difference was demonstrated by using two independent experimental designs.

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

    PubMed

    Derichs, Nico

    2013-03-01

    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.

  20. 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.

    ERIC Educational Resources Information Center

    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…

  1. Supporting cystic fibrosis disease management during adolescence: the role of family and friends.

    PubMed

    Barker, D H; Driscoll, K A; Modi, A C; Light, M J; Quittner, A L

    2012-07-01

    Successful management of a complex disease, such as cystic fibrosis (CF), requires support from family and friends; however, few studies have examined social support in adolescents with CF. Twenty-four adolescents were interviewed about the support they receive from family and friends. Interviews were transcribed, coded and analysed to determine the types, frequency and perceived supportiveness of specific behaviours. Both family and friends provided treatment-related support to adolescents with CF. Family provided more tangible support and friends provided more relational support. Adolescents also reported that the manner, timing and context of support behaviours influenced their perceptions of the behaviours' supportiveness. A subset of adolescents (17%) chose not to disclose their diagnosis to their friends. The provision of support appears to be distinct from adolescent's perception of support and there may be some behaviours, such as treatment reminders, that are important to disease management but viewed as less supportive by adolescents. Facilitating increased social support holds the promise of improving disease management during adolescents, but more work is need to understand which aspects of support are related to management outcomes. © 2011 Blackwell Publishing Ltd.

  2. Supporting cystic fibrosis disease management during adolescence: the role of family and friends

    PubMed Central

    Barker, D. H.; Driscoll, K. A.; Modi, A. C.; Light, M. J.; Quittner, A. L.

    2012-01-01

    Background Successful management of a complex disease, such as cystic fibrosis (CF), requires support from family and friends; however, few studies have examined social support in adolescents with CF. Methods Twenty-four adolescents were interviewed about the support they receive from family and friends. Interviews were transcribed, coded and analysed to determine the types, frequency and perceived supportiveness of specific behaviours. Results Both family and friends provided treatment-related support to adolescents with CF. Family provided more tangible support and friends provided more relational support. Adolescents also reported that the manner, timing and context of support behaviours influenced their perceptions of the behaviours’ supportiveness. A subset of adolescents (17%) chose not to disclose their diagnosis to their friends. Conclusions The provision of support appears to be distinct from adolescent’s perception of support and there may be some behaviours, such as treatment reminders, that are important to disease management but viewed as less supportive by adolescents. Facilitating increased social support holds the promise of improving disease management during adolescents, but more work is need to understand which aspects of support are related to management outcomes. PMID:21771002

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

    PubMed

    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.

  4. Variants in mannose‐binding lectin and tumour necrosis factor α affect survival in cystic fibrosis

    PubMed Central

    Buranawuti, Kitti; Boyle, Michael P; Cheng, Suzanne; Steiner, Lori L; McDougal, Kathryn; Fallin, M Daniele; Merlo, Christian; Zeitlin, Pamela L; Rosenstein, Beryl J; Mogayzel, Peter J; Wang, Xinjing; Cutting, Garry R

    2007-01-01

    Background Patients with cystic fibrosis with the same mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene differ widely in survival suggesting other factors have a substantial role in mortality. Objective To determine if the genotype distribution of variants in three putative cystic fibrosis modifier genes (tumour necrosis factor α (TNFα), transforming growth factor β1 (TGFβ1) or mannose‐binding lectin (MBL2)) differed among patients with cystic fibrosis grouped according to age and survival status. Methods Genotypes of four variants (TNFα‐238, TNFα‐308, TGFβ1‐509 and MBL2 O) were determined in three groups of Caucasians from a single medical centre: 101 children with cystic fibrosis (aged <17 years; mean age 9.4 years), 115 adults with cystic fibrosis (aged ⩾17 years; mean age 30.8 years) and 38 non‐surviving adults with cystic fibrosis (21 deceased and 17 lung transplant after 17 years of age). Genotypes of 127 healthy Caucasians in the same geographical region were used as controls. Kaplan–Meier and Cox hazard regression were used to evaluate the genotype effect on cumulative survival. Results Genotype frequencies among adults and children with cystic fibrosis differed for TNFα‐238 (G/G vs G/A; p = 0.022) and MBL2 (A/A vs O/O; p = 0.016). When adults with cystic fibrosis were compared to non‐surviving adults with cystic fibrosis, genotype frequencies of both genes differed (TNFα‐238G/G vs G/A; p =  0.0015 and MBL2: A/A vs O/O; p = 0.009). The hazard ratio for TNFα‐238G/G vs G/A was 0.25 (95% CI 0.06 to 1.0, p = 0.04) and for MBL2 O/O vs A/A or A/O was 2.5 (95% CI 1.3 to 4.9, p = 0.007). Conclusions TNFα‐238 G/A and MBL2 O/O genotypes appear to be genetic modifiers of survival of cystic fibrosis. PMID:17158822

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

    PubMed

    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.

  6. Host response to Staphylococcus aureus cytotoxins in children with cystic fibrosis.

    PubMed

    Chadha, Ashley D; Thomsen, Isaac P; Jimenez-Truque, Natalia; Soper, Nicole R; Jones, Lauren S; Sokolow, Andrew G; Torres, Victor J; Creech, C Buddy

    2016-09-01

    Staphylococcus aureus is one of the earliest bacterial pathogens to colonize the lungs of children with cystic fibrosis and is an important contributor to pulmonary exacerbations. The adaptive host response to S. aureus in cystic fibrosis remains inadequately defined and has important implications for pathogenesis and potential interventions. The objectives of this study were to determine the functional antibody response to select staphylococcal exotoxins (LukAB, alpha-hemolysin, and PVL) in children with cystic fibrosis and to evaluate the relationship of this response with pulmonary exacerbations. Fifty children with cystic fibrosis were enrolled and followed prospectively for 12months. Clinical characteristics and serologic profiles were assessed at routine visits and during pulmonary exacerbations, and functional antibody assessments were performed to measure neutralization of LukAB-mediated cytotoxicity. For each antigen, geometric mean titers were significantly higher if S. aureus was detected at the time of exacerbation. For LukAB, geometric mean titers were significantly higher at exacerbation follow-up compared to titers during the exacerbation, consistent with expression during human disease, and the humoral response capably neutralized LukAB-mediated cytotoxicity. Moreover, the presence of a positive S. aureus culture during a pulmonary exacerbation was associated with 31-fold higher odds of having a LukA titer ≥1:160, suggesting potential diagnostic capability of this assay. The leukotoxin LukAB is expressed by S. aureus and recognized by the human adaptive immune response in the setting of pulmonary infection in cystic fibrosis. Anti-LukAB antibodies were not only predictive of positive staphylococcal culture during exacerbation, but also functional in the neutralization of this toxin. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  7. Impact of cystic fibrosis disease on archaea and bacteria composition of gut microbiota.

    PubMed

    Miragoli, Francesco; Federici, Sara; Ferrari, Susanna; Minuti, Andrea; Rebecchi, Annalisa; Bruzzese, Eugenia; Buccigrossi, Vittoria; Guarino, Alfredo; Callegari, Maria Luisa

    2017-02-01

    Cystic fibrosis is often associated with intestinal inflammation due to several factors, including altered gut microbiota composition. In this study, we analyzed the fecal microbiota among patients with cystic fibrosis of 10-22 years of age, and compared the findings with age-matched healthy subjects. The participating patients included 14 homozygotes and 14 heterozygotes with the delF508 mutation, and 2 heterozygotes presenting non-delF508 mutations. We used PCR-DGGE and qPCR to analyze the presence of bacteria, archaea and sulfate-reducing bacteria. Overall, our findings confirmed disruption of the cystic fibrosis gut microbiota. Principal component analysis of the qPCR data revealed no differences between homozygotes and heterozygotes, while both groups were distinct from healthy subjects who showed higher biodiversity. Archaea were under the detection limit in all homozygotes subjects, whereas methanogens were detected in 62% of both cystic fibrosis heterozygotes and healthy subjects. Our qPCR results revealed a low frequency of sulfate-reducing bacteria in the homozygote (13%) and heterozygote (13%) patients with cystic fibrosis compared with healthy subjects (87.5%). This is a pioneer study showing that patients with cystic fibrosis exhibit significant reduction of H 2 -consuming microorganisms, which could increase hydrogen accumulation in the colon and the expulsion of this gas through non-microbial routes. © FEMS 2016.

  8. Cystic fibrosis swine fail to secrete airway surface liquid in response to inhalation of pathogens.

    PubMed

    Luan, Xiaojie; Belev, George; Tam, Julian S; Jagadeeshan, Santosh; Hassan, Noman; Gioino, Paula; Grishchenko, Nikolay; Huang, Yanyun; Carmalt, James L; Duke, Tanya; Jones, Teela; Monson, Bev; Burmester, Monique; Simovich, Tomer; Yilmaz, Orhan; Campanucci, Veronica A; Machen, Terry E; Chapman, L Dean; Ianowski, Juan P

    2017-10-05

    Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) channel, which can result in chronic lung disease. The sequence of events leading to lung disease is not fully understood but recent data show that the critical pathogenic event is the loss of the ability to clear bacteria due to abnormal airway surface liquid secretion (ASL). However, whether the inhalation of bacteria triggers ASL secretion and whether this is abnormal in cystic fibrosis has never been tested. Here we show, using a novel synchrotron-based in vivo imaging technique, that wild-type pigs display both a basal and a Toll-like receptor-mediated ASL secretory response to the inhalation of cystic fibrosis relevant bacteria. Both mechanisms fail in CFTR -/- swine, suggesting that cystic fibrosis airways do not respond to inhaled pathogens, thus favoring infection and inflammation that may eventually lead to tissue remodeling and respiratory disease.Cystic fibrosis is caused by mutations in the CFTR chloride channel, leading to reduced airway surface liquid secretion. Here the authors show that exposure to bacteria triggers secretion in wild-type but not in pig models of cystic fibrosis, suggesting an impaired response to pathogens contributes to infection.

  9. An evaluation of different steam disinfection protocols for cystic fibrosis nebulizers.

    PubMed

    Hohenwarter, K; Prammer, W; Aichinger, W; Reychler, G

    2016-01-01

    Contamination is a key element in cystic fibrosis. For this reason, nebulizer hygiene is an important, but complex and time-consuming task for cystic fibrosis patients. The aim of this study was to compare different steam disinfection and drying protocols. One hundred nebulizer parts were inoculated with cystic fibrosis-related bacteria in high concentrations (Burkholderia multivorans 3.9 × 10(10)/ml, Staphylococcus aureus 8.9 × 10(8/)ml and Pseudomonas aeruginosa 2.1 × 10(9)/ml). Tubes with Mycobacterium abscessus complex were additionally tested. Six steam disinfectors were compared. Different methods of drying were examined. All tested bacteria were efficiently killed by the different steam disinfectors tested. The risk of contamination depended on the method of drying. Steam disinfection is a safe disinfection method. It is better to leave the nebulizers wet after steam disinfection than to manipulate them by active drying, which seems to be a source of recontamination. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  10. Atomic Structure of the Cystic Fibrosis Transmembrane Conductance Regulator.

    PubMed

    Zhang, Zhe; Chen, Jue

    2016-12-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel evolved from the ATP-binding cassette (ABC) transporter family. In this study, we determined the structure of zebrafish CFTR in the absence of ATP by electron cryo-microscopy to 3.7 Å resolution. Human and zebrafish CFTR share 55% sequence identity, and 42 of the 46 cystic-fibrosis-causing missense mutational sites are identical. In CFTR, we observe a large anion conduction pathway lined by numerous positively charged residues. A single gate near the extracellular surface closes the channel. The regulatory domain, dephosphorylated, is located in the intracellular opening between the two nucleotide-binding domains (NBDs), preventing NBD dimerization and channel opening. The structure also reveals why many cystic-fibrosis-causing mutations would lead to defects either in folding, ion conduction, or gating and suggests new avenues for therapeutic intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Early respiratory infection is associated with reduced spirometry in children with cystic fibrosis.

    PubMed

    Ramsey, Kathryn A; Ranganathan, Sarath; Park, Judy; Skoric, Billy; Adams, Anne-Marie; Simpson, Shannon J; Robins-Browne, Roy M; Franklin, Peter J; de Klerk, Nick H; Sly, Peter D; Stick, Steve M; Hall, Graham L

    2014-11-15

    Pulmonary inflammation, infection, and structural lung disease occur early in life in children with cystic fibrosis. We hypothesized that the presence of these markers of cystic fibrosis lung disease in the first 2 years of life would be associated with reduced lung function in childhood. Lung function (forced expiratory volume in the first three-quarters of a second [FEV0.75], FVC) was assessed in individuals with cystic fibrosis diagnosed after newborn screening and healthy subjects during infancy (0-2 yr) and again at early school age (4-8 yr). Individuals with cystic fibrosis underwent annual bronchoalveolar lavage fluid examination, and chest computed tomography. We examined which clinical outcomes (pulmonary inflammation, infection, structural lung disease, respiratory hospitalizations, antibiotic prophylaxis) measured in the first 2 years of life were associated with reduced lung function in infants and young children with cystic fibrosis, using a mixed effects model. Children with cystic fibrosis (n = 56) had 8.3% (95% confidence interval [CI], -15.9 to -6.6; P = 0.04) lower FEV0.75 compared with healthy subjects (n = 18). Detection of proinflammatory bacterial pathogens (Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Aspergillus species, Streptococcus pneumoniae) in bronchoalveolar lavage fluid was associated with clinically significant reductions in FEV0.75 (ranging between 11.3 and 15.6%). The onset of lung disease in infancy, specifically the occurrence of lower respiratory tract infection, is associated with low lung function in young children with cystic fibrosis. Deficits in lung function measured in infancy persist into childhood, emphasizing the need for targeted therapeutic interventions in infancy to maximize functional outcomes later in life.

  12. Omega-3 fatty acids for cystic fibrosis.

    PubMed

    Oliver, Colleen; Watson, Helen

    2016-01-05

    Studies suggest that a diet rich in omega-3 essential fatty acids may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis. This is an updated version of a previously published review. To determine whether there is evidence that omega-3 polyunsaturated fatty acid supplementation reduces morbidity and mortality and to identify any adverse events associated with supplementation. 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. Authors and persons interested in the subject of the review were contacted.Date of last search: 13 August 2013. Randomised controlled trials in people with cystic fibrosis comparing omega-3 fatty acid supplements with placebo. Two authors independently selected studies for inclusion, extracted data and assessed the risk of bias of the studies. The searches identified 15 studies; four studies with 91 participants (children and adults) were included; duration of studies ranged from six weeks to six months. Two studies were judged to be at low risk of bias based on adequate randomisation but this was unclear in the other two studies. Three of the studies adequately blinded patients, however, the risk of bias was unclear in all studies with regards to allocation concealment and selective reporting.Two studies compared omega-3 fatty acids to olive oil for six weeks. One study compared a liquid dietary supplement containing omega-3 fatty acids to one without for six months. One study compared omega-3 fatty acids and omega-6 fatty acids to a control (capsules with customised fatty acid blends) for three months. Only one short-term study (19 participants) comparing omega-3 to placebo reported a significant improvement in lung function and Shwachman score and a reduction in sputum volume in the omega-3 group. Another

  13. Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis.

    PubMed

    Robinson, Karen A; Odelola, Olaide A; Saldanha, Ian J

    2016-07-20

    Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis. This is an update of a previously published review. To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 05 May 2016. Randomised and quasi-randomised studies. The authors independently extracted data and assessed risk of bias. One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. We judged there to be a low risk of bias with respect to the concealment of the randomization schedule (although it was not clear how this was generated) and to blinding of participants and study personnel. There is also a low risk of bias with regards to incomplete outcome data. However, we judged there to be a high risk of bias from selective reporting (summary statements presented but no data

  14. Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis.

    PubMed

    Robinson, Karen A; Odelola, Olaide A; Saldanha, Ian J

    2014-05-22

    Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis. To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 17 March 2014. Randomised and quasi-randomised studies. The authors independently extracted data and assessed risk of bias. One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. We judged there to be a low risk of bias with respect to the concealment of the randomization schedule (although it was not clear how this was generated) and to blinding of participants and study personnel. There is also a low risk of bias with regards to incomplete outcome data. However, we judged there to be a high risk of bias from selective reporting (summary statements presented but no data) and the fact that this industry-supported study has

  15. Altered steady state pharmacokinetics of levofloxacin in adult cystic fibrosis patients receiving calcium carbonate.

    PubMed

    Pai, Manjunath P; Allen, Sarah E; Amsden, Guy W

    2006-08-01

    Levofloxacin is used in adult patients with cystic fibrosis but its pharmacokinetics is not well characterized in this population. Patients with cystic fibrosis use calcium routinely to prevent osteoporosis. A slower intestinal transit time is common in cystic fibrosis implying that the standard 2-h spacing of minerals and levofloxacin to prevent a chelation interaction may be insufficient. The objectives of this study were to characterize the steady state pharmacokinetics of oral levofloxacin 750 mg with and without 2-h spaced calcium carbonate in patients with cystic fibrosis compared to matched healthy volunteers. In an open-label, randomized, cross-over study of five patients with cystic fibrosis and five age, sex, race, and serum creatinine matched healthy volunteers received 750 mg of oral levofloxacin alone daily for 5 days and the same dose of levofloxacin with 2-h spaced calcium carbonate supplementation 500 mg po thrice daily with meals in random sequence. Blood was collected for plasma assay of levofloxacin pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, and 24h after the fifth levofloxacin dose. There was no significant interaction in healthy volunteers, however, when cystic fibrosis patients were given levofloxacin with 2-h spaced calcium, the maximum plasma concentration (Cmax) decreased by 19% and time to Cmax increased by 37% (p<0.05). This difference in peak concentrations resulted in a lack of bioequivalence (Cmax geometric mean ratio 81.6%, 90% confidence intervals: 71.8%, 91.4%) even when levofloxacin and calcium supplements were spaced by the standard 2h administration instruction in patients with cystic fibrosis. These results indicate that multivalent cations such as calcium should be maximally separated from oral levofloxacin administration in adult patients with cystic fibrosis to prevent this drug interaction, thereby better optimizing antibiotic efficacy and decreasing the potential for resistance development.

  16. An exploration of how young people and parents use online support in the context of living with cystic fibrosis.

    PubMed

    Kirk, Susan; Milnes, Linda

    2016-04-01

    There is increasing recognition of the Internet's potential role in providing information and support for people living with long-term conditions. However, how young people and parents use online forms of self-care support in the context of living with childhood chronic illness has been under-researched. To explore how online peer support is used by young people and parents to support self-care in relation to cystic fibrosis (CF). Online forum for young people and parents based on a CF charity website. A total of 279 individuals participated in the forum during the study. An online ethnographical approach, involving observing, downloading and analysing discussion group postings. All postings made over a random 4-month period were included (151 discussion threads). The online setting enabled a physically disconnected group to connect and create a safe space to collectively share experiences and receive support to manage and live with cystic fibrosis. Participants exchanged experientially derived advice and views on how to manage treatments, emotions, relationships, identity and support from services. While parents sought information and support on managing specific therapies/services and ways of maintaining their child's health, the information and support young people desired appeared to be more directed at how to 'fit' CF into their everyday lives. Online support groups appear to supplement professional support in relation to self-management. They enable young people and parents to share experiences, feelings and strategies for living with long-term conditions with peers and develop the expertise to empower them in interactions with health-care professionals. © 2015 John Wiley & Sons Ltd.

  17. Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis.

    PubMed

    Robinson, Karen A; Odelola, Olaide A; Saldanha, Ian J; McKoy, Naomi A

    2012-02-15

    Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis. To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 25 October 2011. Randomised and quasi-randomised studies. The authors independently extracted data and assessed risk of bias. One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. At six months follow-up, one participant in each group was hospitalised due to respiratory syncytial virus; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while 5 and 4 children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab discontinued

  18. Lung transplantation for cystic fibrosis.

    PubMed

    Coloni, G F; Venuta, F; Ciccone, A M; Rendina, E A; De Giacomo, T; Filice, M J; Diso, D; Anile, M; Andreetti, C; Aratari, M T; Mercadante, E; Moretti, M; Ibrahim, M

    2004-04-01

    Lung transplantation is a robust therapeutic option to treat patients with cystic fibrosis. Since 1996, 109 patients with cystic fibrosis were accepted onto our waiting list with 58 bilateral sequential lung transplants performed in 56 patients and two patients retransplanted for obliterative bronchiolitis syndrome. Preoperative mean FEV(1) was 0.64 L/s, mean PaO(2) with supplemental oxygen was 56 mm Hg, and the mean 6-minute walking test was 320 m. Transplantation was performed through a "clam shell incision" in the first 29 patients and via bilateral anterolateral thoracotomies without sternal division in the remaining patients. Cardiopulmonary bypass was required in 14 patients. In 21 patients the donor lungs had to be trimmed by wedge resections with mechanical staplers and bovine pericardium buttressing to fit the recipient chest size. Eleven patients were extubated in the operating room immediately after the procedure. Hospital mortality of 13.8% was related to infection (n = 5), primary graft failure (n = 2), and myocardial infarction (n = 1). Acute rejection episodes occurred 1.6 times per patient/year; lower respiratory tract infections occurred 1.4 times per patient in the first year after transplantation. The mean FEV(1) increased to 82% at 1 year after operation. The 5-year survival rate was 61%. A cyclosporine-based immunosuppressive regimen was initially employed in all patients; 24 were subsequently switched to tacrolimus because of central nervous system toxicity, cyclosporine-related myopathy, or renal failure, obliterative bronchiolitis syndrome, gingival hyperplasia, or hypertrichosis. Ten patients were subsequently switched to sirolimus. Freedom from bronchiolitis obliterans at 5 years was 60%. Our results confirm that bilateral sequential lung transplantation is a robust therapeutic option for patients with cystic fibrosis.

  19. Vitamin K supplementation for cystic fibrosis.

    PubMed

    Jagannath, Vanitha A; Fedorowicz, Zbys; Thaker, Vidhu; Chang, Anne B

    2015-01-18

    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. 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: 08 October 2014. 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 levels to the normal range after one month of

  20. Vitamin K supplementation for cystic fibrosis.

    PubMed

    Jagannath, Vanitha A; Fedorowicz, Zbys; Thaker, Vidhu; Chang, Anne B

    2011-01-19

    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. 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: 15 April 2010. 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) were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial; and the other had a cross-over design, 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 levels to the normal range after one month of daily supplementation with 1 mg of vitamin K. Evidence from randomised controlled trials on the benefits of routine

  1. Vitamin K supplementation for cystic fibrosis.

    PubMed

    Jagannath, Vanitha A; Fedorowicz, Zbys; Thaker, Vidhu; Chang, Anne B

    2013-04-30

    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. 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: 11 October 2012. 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) were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial; and the other had a cross-over design, 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 levels to the normal range after one month of daily supplementation with 1 mg of vitamin K. Evidence from randomised controlled trials on the benefits of routine

  2. Aspergillus infections in cystic fibrosis.

    PubMed

    King, Jill; Brunel, Shan F; Warris, Adilia

    2016-07-05

    Patients with cystic fibrosis (CF) suffer from chronic lung infection and airway inflammation. Respiratory failure secondary to chronic or recurrent infection remains the commonest cause of death and accounts for over 90% of mortality. Bacteria as Staphylococcus aureus, Pseudomonas aeruginosa and Burkholderia cepacia complex have been regarded the main CF pathogens and their role in progressive lung decline has been studied extensively. Little attention has been paid to the role of Aspergillus spp. and other filamentous fungi in the pathogenesis of non-ABPA (allergic bronchopulmonary aspergillosis) respiratory disease in CF, despite their frequent recovery in respiratory samples. It has become more apparent however, that Aspergillus spp. may play an important role in chronic lung disease in CF. Research delineating the underlying mechanisms of Aspergillus persistence and infection in the CF lung and its link to lung deterioration is lacking. This review summarizes the Aspergillus disease phenotypes observed in CF, discusses the role of CFTR (cystic fibrosis transmembrane conductance regulator)-protein in innate immune responses and new treatment modalities. Copyright © 2016. Published by Elsevier Ltd.

  3. Analysis of cystic fibrosis gene mutations in children with cystic fibrosis and in 964 infertile couples within the region of Basilicata, Italy: a research study.

    PubMed

    Dell'Edera, Domenico; Benedetto, Michele; Gadaleta, Gemma; Carone, Domenico; Salvatore, Donatello; Angione, Antonella; Gallo, Massimiliano; Milo, Michele; Pisaturo, Maria Laura; Di Pierro, Giuseppe; Mazzone, Eleonora; Epifania, Annunziata Anna

    2014-10-10

    Cystic fibrosis is the most common autosomal recessive genetic disease in the Caucasian population. Extending knowledge about the molecular pathology on the one hand allows better delineation of the mutations in the CFTR gene and the other to dramatically increase the predictive power of molecular testing. This study reports the results of a molecular screening of cystic fibrosis using DNA samples of patients enrolled from January 2009 to December 2013. Patients were referred to our laboratory for cystic fibrosis screening for infertile couples. In addition, we identified the gene mutations present in 76 patients affected by cystic fibrosis in the pediatric population of Basilicata. In the 964 infertile couples examined, 132 subjects (69 women and 63 men) resulted heterozygous for one of the CFTR mutations, with a recurrence of carriers of 6.85%. The recurrence of carriers in infertile couples is significantly higher from the hypothetical value of the general population (4%). This study shows that in the Basilicata region of Italy the CFTR phenotype is caused by a small number of mutations. Our aim is to develop a kit able to detect not less than 96% of CTFR gene mutations so that the relative risk for screened couples is superimposable with respect to the general population.

  4. The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis.

    PubMed

    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/.

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

    PubMed

    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.

  6. Failure of the Cystic Fibrosis Transmembrane Conductance Regulator to Conduct ATP

    NASA Astrophysics Data System (ADS)

    Reddy, M. M.; Quinton, P. M.; Haws, C.; Wine, J. J.; Grygorczyk, R.; Tabcharani, J. A.; Hanrahan, J. W.; Gunderson, K. L.; Kopito, R. R.

    1996-03-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) is chloride ion channel regulated by protein kinase A and adenosine triphosphate (ATP). Loss of CFTR-mediated chloride ion conductance from the apical plasma membrane of epithelial cells is a primary physiological lesion in cystic fibrosis. CFTR has also been suggested to function as an ATP channel, although the size of the ATP anion is much larger than the estimated size of the CFTR pore. ATP was not conducted through CFTR in intact organs, polarized human lung cell lines, stably transfected mammalian cell lines, or planar lipid bilayers reconstituted with CFTR protein. These findings suggest that ATP permeation through the CFTR is unlikely to contribute to the normal function of CFTR or to the pathogenesis of cystic fibrosis.

  7. Highlights from the 2017 North American Cystic Fibrosis Conference.

    PubMed

    Martiniano, Stacey L; Toprak, Demet; Ong, Thida; Zemanick, Edith T; Daines, Cori L; Muhlebach, Marianne S; Esther, Charles R; Dellon, Elisabeth P

    2018-04-16

    The 31st annual North American Cystic Fibrosis Conference (NACFC) was held in Indianapolis, IN on November 2-4, 2017. Abstracts of presentations from the conference were published in a supplement to Pediatric Pulmonology [2017; Pediatr Pulmonol Suppl. 52: S1-S776]. The current review summarizes several major topic areas addressed at the conference: the pathophysiology and basic science of cystic fibrosis (CF) lung disease, clinical trials, clinical management issues, and quality improvement (QI). In this review, we describe emerging concepts in several areas of CF research and care. © 2018 Wiley Periodicals, Inc.

  8. Poetry, Music, Writing and Painting; Developing the artistic talents of Adults with Cystic Fibrosis.

    PubMed

    Webb, Anthony Kevin; Fitzjohn, Joan

    2016-01-01

    Art is an expressive outlet for the physical limitations and emotional frustrations of living with a life limiting condition such cystic fibrosis. In the Manchester Adult Cystic Fibrosis Centre we have facilitated the sharing of the inherent artistic talent of our patients with the support of painters, musicians, potters, creative writers, photographers and textile specialists and our own ward staff in our dedicated 22 bed CF inpatient unit. The programme has provided some splendid works that enliven our ward and, more importantly, continue to inspire our patients as they attempt to overcome the socially limiting consequences of hospital admission. Copyright © 2015. Published by Elsevier Ltd.

  9. Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease.

    PubMed

    Lee, Tim W R; Southern, Kevin W; Perry, Luke A; Penny-Dimri, Jahan C; Aslam, Aisha A

    2016-06-17

    Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic lung infection resulting in inflammation and progressive lung damage that results in a reduced life expectancy. To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes, and to assess any adverse effects. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.Date of most recent search: 05 May 2016.An additional search of the National Institutes for Health (NIH) Genetic Modification Clinical Research Information System (GeMCRIS) was also performed for the years 1992 to 2015.Date of most recent search: 20 April 2016. Randomised controlled studies comparing topical CFTR gene delivery to the lung, using either viral or non-viral delivery systems, with placebo or an alternative delivery system in people with confirmed cystic fibrosis. The authors independently extracted data and assessed study quality. Authors of included studies were contacted and asked for any available additional data. Meta-analysis was limited due to differing study designs. Four randomised controlled studies met the inclusion criteria for this review, involving a total of 302 participants lasting from 29 days to 13 months; 14 studies were excluded. The included studies differed in terms of CFTR gene replacement agent and study design, which limited the meta-analysis. One study only enrolled adult males, the remaining studies included both males and females aged 12 years and over.Risk of bias in the studies was moderate. Random sequence generation and allocation concealment was only described in the more recent study; the remaining three studies were

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

    PubMed

    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.

  11. Epidemiology of Cystic Fibrosis.

    PubMed

    Spoonhower, Kimberly A; Davis, Pamela B

    2016-03-01

    Improved quality of care and rapidly emerging therapeutic strategies to restore chloride transport profoundly impact the epidemiology and pathobiology of cystic fibrosis (CF) in the twenty-first century. CF now serves as a model for chronic illness management, continuous quality improvement via registry data, and a seamless link between basic science research, translational studies, clinical trials, and outcomes research to enable rapid expansion of treatment options. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Risk factors for bronchiectasis in children with cystic fibrosis.

    PubMed

    Sly, Peter D; Gangell, Catherine L; Chen, Linping; Ware, Robert S; Ranganathan, Sarath; Mott, Lauren S; Murray, Conor P; Stick, Stephen M

    2013-05-23

    Bronchiectasis develops early in the course of cystic fibrosis, being detectable in infants as young as 10 weeks of age, and is persistent and progressive. We sought to determine risk factors for the onset of bronchiectasis, using data collected by the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) intensive surveillance program. We examined data from 127 consecutive infants who received a diagnosis of cystic fibrosis after newborn screening. Chest computed tomography (CT) and bronchoalveolar lavage (BAL) were performed, while the children were in stable clinical condition, at 3 months and 1, 2, and 3 years of age. Longitudinal data were used to determine risk factors associated with the detection of bronchiectasis from 3 months to 3 years of age. The point prevalence of bronchiectasis at each visit increased from 29.3% at 3 months of age to 61.5% at 3 years of age. In multivariate analyses, risk factors for bronchiectasis were presentation with meconium ileus (odds ratio, 3.17; 95% confidence interval [CI], 1.51 to 6.66; P=0.002), respiratory symptoms at the time of CT and BAL (odds ratio, 2.27; 95% CI, 1.24 to 4.14; P=0.008), free neutrophil elastase activity in BAL fluid (odds ratio, 3.02; 95% CI, 1.70 to 5.35; P<0.001), and gas trapping on expiratory CT (odds ratio, 2.05; 95% CI, 1.17 to 3.59; P=0.01). Free neutrophil elastase activity in BAL fluid at 3 months of age was associated with persistent bronchiectasis (present on two or more sequential scans), with the odds seven times as high at 12 months of age and four times as high at 3 years of age. Neutrophil elastase activity in BAL fluid in early life was associated with early bronchiectasis in children with cystic fibrosis. (Funded by the National Health and Medical Research Council of Australia and Cystic Fibrosis Foundation Therapeutics.)

  13. Incidental late diagnosis of cystic fibrosis following AH1N1 influenza virus pneumonia: a case report.

    PubMed

    Iadevaia, Carlo; Iacotucci, Paola; Carnovale, Vincenzo; Calabrese, Cecilia; Rea, Gaetano; Ferrara, Nicola; Perrotta, Fabio; Mazzarella, Gennaro; Bianco, Andrea

    2017-10-01

    Cystic fibrosis is an autosomal recessive disorder characterized by chronic progressive multisystem involvement. AH1N1 virus infections caused classic influenza symptoms in the majority of cystic fibrosis patients while others experienced severe outcomes. We report a case of late incidental cystic fibrosis diagnosis in a young Caucasian man suffering from respiratory failure following infection due to AH1N1 influenza virus. The patient was admitted to our department with fever, cough, and dyspnea at rest unresponsive to antibiotics CONCLUSIONS: Late diagnosis of cystic fibrosis in uncommon. This report highlights the importance of early cystic fibrosis diagnosis to minimize risk of occurrence of potential life-threatening complications.

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

    PubMed

    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.

  15. Magnetomotive optical coherence elastography for relating lung structure and function in cystic fibrosis

    NASA Astrophysics Data System (ADS)

    Chhetri, Raghav K.; Carpenter, Jerome; Superfine, Richard; Randell, Scott H.; Oldenburg, Amy L.

    2010-02-01

    Cystic fibrosis (CF) is a genetic defect in the cystic fibrosis transmembrane conductance regulator protein and is the most common life-limiting genetic condition affecting the Caucasian population. It is an autosomal recessive, monogenic inherited disorder characterized by failure of airway host defense against bacterial infection, which results in bronchiectasis, the breakdown of airway wall extracellular matrix (ECM). In this study, we show that the in vitro models consisting of human tracheo-bronchial-epithelial (hBE) cells grown on porous supports with embedded magnetic nanoparticles (MNPs) at an air-liquid interface are suitable for long term, non-invasive assessment of ECM remodeling using magnetomotive optical coherence elastography (MMOCE). The morphology of ex vivo CF and normal lung tissues using OCT and correlative study with histology is also examined. We also demonstrate a quantitative measure of normal and CF airway elasticity using MMOCE. The improved understanding of pathologic changes in CF lung structure and function and the novel method of longitudinal in vitro ECM assessment demonstrated in this study may lead to new in vivo imaging and elastography methods to monitor disease progression and treatment in cystic fibrosis.

  16. The cystic fibrosis gene: Medical and social implications for heterozygote detection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wilfond, B.S.; Fost, N.

    1990-05-23

    The primary goal of mass screening programs for cystic fibrosis carriers should be to allow people to make more informed reproductive decisions. However, previous experience with genetic screening programs, including those for phenylketonuria and sickle cell disease, have revealed complex problems including error, confusion, and stigmatization. These problems could be greater with cystic fibrosis, since more than 8 million Americans may be carriers and entrepreneurial interests can be expected to promote screening in what could become a billion-dollar industry. The present frequency of the detectable mutation ({Delta}F{sub 508}), 75%, will complicate the counseling process. The sensitivity of the test tomore » detect at-risk couples would be 56%. The cost of screening could be as much as $2.2 million for each cystic fibrosis birth avoided. Regardless of improvements in the detection rate, implementation of population screening should be delayed until pilot studies that demonstrate its safety and effectiveness are completed. While studies are in progress, preconception testing should be offered to adult relatives of cystic fibrosis patients as part of a comprehensive program following institutional review board approval for compassionate use.« less

  17. Immunosuppressive drug therapy for preventing rejection following lung transplantation in cystic fibrosis.

    PubMed

    Saldanha, Ian J; Akinyede, Oluwaseun; Robinson, Karen A

    2018-06-18

    For people with cystic fibrosis and advanced pulmonary damage, lung transplantation is an available and viable option. However, graft rejection is an important potential consequence after lung transplantation. Immunosuppressive therapy is needed to prevent episodes of graft rejection and thus subsequently reduce morbidity and mortality in this population. There are a number of classes of immunosuppressive drugs which act on different components of the immune system. There is considerable variability in the use of immunosuppressive agents after lung transplantation in cystic fibrosis. While much of the research in immunosuppressive drug therapy has focused on the general population of lung transplant recipients, little is known about the comparative effectiveness and safety of these agents in people with cystic fibrosis. This is an update of a previously published review. To assess the effects of individual drugs or combinations of drugs compared to placebo or other individual drugs or combinations of drugs in preventing rejection following lung transplantation in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the potentially eligible study. We also searched the www.clinicaltrials.gov registry and the World Health Organisation (WHO) International Clinical Trials Registry Platform (ICTRP) to obtain information on unpublished and ongoing studies.Date of latest search: 29 May 2018. Randomised and quasi-randomised studies. We independently assessed the studies identified from our searches for inclusion in the review. Should eligible studies be identified and included in future updates of the review, we will independently extract data and assess the risk of bias. We will use GRADE to summarize our results through a summary of findings table for each comparison we present in the review. While five studies addressed the interventions of interest, we did not include them in the

  18. Cystic fibrosis year in review 2016.

    PubMed

    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.

  19. Surgeon's viewpoint on lung transplantation in cystic fibrosis patients - preliminary report.

    PubMed

    Kubisa, Bartosz; Piotrowska, Maria; Milczewska, Justyna; Bielewicz, Michał; Pieróg, Jarosław; Kozak, Anna; Czarnecka, Michalina; Wójcik, Norbert; Wasilewski, Piotr; Feledyk, Grzegorz; Kubisa, Anna; Brykczyński, Mirosław; Sielicki, Piotr; Grodzki, Tomasz

    2015-01-01

    The surgeon's viewpoint on a patient with cystic fibrosis differs from that of a pediatrician or internist. The problems a cystic fibrosis specialist encounters are different from those faced by the surgeon who takes over the patient in a very advanced, often terminal stage of the disease. Hence, the main problem for the surgeon is the decision concerning the surgery (lung transplantation, pneumonectomy, lobectomy). It is, therefore, important to lay down fundamental and appropriate rules concerning the indications and contraindications for lung transplantation, especially in patients with cystic fibrosis. The aim of this study was to analyze the methods of qualifying and preparing patients for surgery, as well as carrying out the procedure of transplantation and postoperative short and long-term care. The investigation was carried out on 16 patients with cystic fibrosis. Three were operated on and 10 were on the waiting list for transplantation. Two patients on the waiting list died, one patient was disqualified from transplantation. During qualification for lung transplantation, strict indications, contraindications and other factors (such as blood type, patient's height, coexisting complications) were taken under consideration. All the 3 patients after lung transplantation are alive and under our constant surveillance. Ten patients await transplantation, though four of them are suspended due to hepatitis C infection. Two patients on the waiting list died: one from respiratory insufficiency and the other in the course of bridge to-transplant veno-venous extracorporeal membrane oxygenation due to hepatic failure. One patient has been disqualified because of cachexia. Since lung transplantation is the final treatment of the end-stage pulmonary insufficiency in cystic fibrosis patients, the number of such procedures in cystic fibrosis is still too low in Poland. The fast development of these procedures is highly needed. It is necessary to develop better cooperation

  20. Multiple-Breath Washout Outcomes Are Sensitive to Inflammation and Infection in Children with Cystic Fibrosis.

    PubMed

    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.

  1. Evolution of cystic fibrosis lung function in the early years.

    PubMed

    Bush, Andrew; Sly, Peter D

    2015-11-01

    Most treatment of newborn screening-diagnosed cystic fibrosis is not evidence-based; there are very few randomized controlled trials (RCTs). Furthermore, the advent of novel molecular therapies, which could be started at diagnosis, mandates performing RCTs in very young children. However, unless the natural history of early cystic fibrosis lung disease is known, RCTs are impossible. Here, we review the results of two large prospective cohorts of these infants - London Cystic Fibrosis Collaboration (LCFC) (London, UK) and Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST-CF) (Australia). Nutritional status remained excellent in both the cohorts. Both cohorts reported abnormal lung function aged at 3 months. AREST-CF, which previously reported rapidly declining preschool lung function, now report good conventional school-age spirometry. LCFC reported improvement between 3 months and 1 year, and stability in the second year. AREST-CF also reported a high prevalence of high resolution computed tomographic abnormalities related to free neutrophil elastase in bronchoalveolar lavage; LCFC reported high resolution computed tomographic changes at 1 year, which were too mild to be scored reproducibly. At least in the first 2 years of life, lung function is not a good end-point for RCTs; routine bronchoalveolar lavage and HRCT cannot be justified. Newborn screening has greatly improved outcomes, but we need better point-of-care biomarkers.

  2. Digestive system dysfunction in cystic fibrosis: challenges for nutrition therapy.

    PubMed

    Li, Li; Somerset, Shawn

    2014-10-01

    Cystic fibrosis can affect food digestion and nutrient absorption. The underlying mutation of the cystic fibrosis trans-membrane regulator gene depletes functional cystic fibrosis trans-membrane regulator on the surface of epithelial cells lining the digestive tract and associated organs, where Cl(-) secretion and subsequently secretion of water and other ions are impaired. This alters pH and dehydrates secretions that precipitate and obstruct the lumen, causing inflammation and the eventual degradation of the pancreas, liver, gallbladder and intestine. Associated conditions include exocrine pancreatic insufficiency, impaired bicarbonate and bile acid secretion and aberrant mucus formation, commonly leading to maldigestion and malabsorption, particularly of fat and fat-soluble vitamins. Pancreatic enzyme replacement therapy is used to address this insufficiency. The susceptibility of pancreatic lipase to acidic and enzymatic inactivation and decreased bile availability often impedes its efficacy. Brush border digestive enzyme activity and intestinal uptake of certain disaccharides and amino acids await clarification. Other complications that may contribute to maldigestion/malabsorption include small intestine bacterial overgrowth, enteric circular muscle dysfunction, abnormal intestinal mucus, and intestinal inflammation. However, there is some evidence that gastric digestive enzymes, colonic microflora, correction of fatty acid abnormalities using dietary n-3 polyunsaturated fatty acid supplementation and emerging intestinal biomarkers can complement nutrition management in cystic fibrosis. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  3. Cost of care of patients with cystic fibrosis in The Netherlands in 1990-1.

    PubMed Central

    Wildhagen, M. F.; Verheij, J. B.; Verzijl, J. G.; Hilderink, H. B.; Kooij, L.; Tijmstra, T.; ten Kate, L. P.; Gerritsen, J.; Bakker, W.; Habbema, J. D.; Habbema, F.

    1996-01-01

    BACKGROUND: Research on the cost of care of patients with cystic fibrosis is scarce. The aim of this study was to estimate the costs using age-specific medical consumption from real patient data. METHODS: The age-specific medical consumption of patients with cystic fibrosis in The Netherlands in 1991 was estimated from a survey of medical records and a patient questionnaire. A distinction was made between costs of hospital care, hospital and non-hospital medication, and home care. Costs per year were obtained by multiplying the yearly amount of care and the costs per unit. RESULTS: On average the annual cost of a patient with cystic fibrosis in 1991 was 10,908 pounds (hospital care 42%, medication 37%, home care 20%). The cost of care of cystic fibrosis in The Netherlands, with approximately 1000 patients, is estimated at 10.9 million pounds per year, which is 0.07% of the total health care budget. The cost of care of a patient up to the age of 35 is estimated at 614,587 pounds. When year-to-year survival is taken into account and future costs are discounted to the year of birth with a yearly discount rate of 5%, the cost of care of a patient with cystic fibrosis is estimated at 164,365 pounds for 1991. This estimate will be used in a prospective evaluation of screening for cystic fibrosis carriers. CONCLUSIONS: The cost of care of patients with cystic fibrosis estimated by age-specific medical consumption of real patients is higher than that estimated by non-age-specific medical consumption and/or expert opinions. PMID:8779135

  4. 21 CFR 866.5910 - Quality control material for cystic fibrosis nucleic acid assays.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5910 Quality control material for cystic fibrosis nucleic acid assays. (a... cystic fibrosis nucleic acid assays is a device intended to help monitor reliability of a test system by...

  5. Intestinal permeability to (/sup 51/Cr)EDTA in children with cystic fibrosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Leclercq-Foucart, J.; Forget, P.; Sodoyez-Goffaux, F.

    1986-05-01

    Intestinal permeability was investigated in 14 children with cystic fibrosis making use of (/sup 51/Cr)EDTA as probe molecule. Ten normal young adults and 11 children served as controls. After oral administration of (/sup 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 lessmore » than 0.001).« less

  6. Cystic fibrosis chronic rhinosinusitis: A comprehensive review

    PubMed Central

    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

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

    PubMed

    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.

  8. A Study of the Safety and Tolerability of Inhaled SNSP113 in Healthy Subjects and Subjects With Stable Cystic Fibrosis

    ClinicalTrials.gov

    2017-10-12

    Lung Diseases; Pulmonary Disease; Cystic Fibrosis; Cystic Fibrosis Lung; Cystic Fibrosis Pulmonary Exacerbation; Cystic Fibrosis With Exacerbation; Respiratory Tract Disease; Pulmonary Inflammation; Multi-antibiotic Resistance; Antibiotic Resistant Infection; Lung Infection; Lung Infection Pseudomonal; Lung; Infection, Atypical Mycobacterium; Burkholderia Infections; Burkholderia Cepacia Infection; Lung Inflammation

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

    PubMed

    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

  10. Vitamin K supplementation for cystic fibrosis.

    PubMed

    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

  11. Vitamin K supplementation for cystic fibrosis

    PubMed Central

    Jagannath, Vanitha A; Fedorowicz, Zbys; Thaker, Vidhu; Chang, Anne B

    2015-01-01

    Background 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. Objectives 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. Search methods 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: 08 October 2014. Selection criteria 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). Data collection and analysis Two authors independently screened papers, extracted trial details and assessed their risk of bias. Main results 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 crossover 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

  12. Nasal potential difference outcomes support diagnostic decisions in cystic fibrosis.

    PubMed

    Tridello, Gloria; Menin, Laura; Pintani, Emily; Bergamini, Gabriella; Assael, Baroukh Maurice; Melotti, Paola

    2016-09-01

    When cystic fibrosis (CF) is suspected Nasal Potential Difference (NPD) measurements are proposed to support controversial diagnosis: we investigated appropriate outcomes at the CF Centre of Verona. NPD were measured in 196 subjects: 50 non-CF, 65 classical CF (the reference group) and 81 with uncertain CF (case group). Discriminating power was determined by comparison between several outcomes from the CF reference group versus non-CF: basal, amiloride, 0Cl, isoproterenol, ATP, Delta-amiloride, Delta-0Cl, Delta-isoproterenol, Delta-ATP, Delta-isoproterenol+Delta-0Cl, Wilschanski Index (WI) and Sermet score (SS). The most appropriate cut-off values for variables with the best discriminating power were then applied to the case group. Descriptive statistics, logistic regression models and ROC curve analysis were applied. WI and SS were the most powerful in discriminating CF from non-CF subjects. In the reference group sensitivity of the 0.82 WI cut-off was 98%, specificity 96%; both sensitivity and specificity of the -0.44 SS cut-off value were 100%. For the case group, WI and SS were, respectively, consistent with CF diagnosis in 94% and 92% of the cases. Formulae have the highest discriminating power and can support the diagnosis in uncertain cases; they should be utilized for standardized interpretation of NPD for diagnosis and possibly for clinical research. Copyright © 2016. Published by Elsevier B.V.

  13. Inhaled mannitol for cystic fibrosis.

    PubMed

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

    2015-10-09

    Several agents are used to clear secretions from the airways of people with cystic fibrosis. Inhaled dry powder mannitol is now available in Australia and some countries in Europe. The exact mechanism of action of mannitol is unknown, but it increases mucociliary clearance. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. 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: 16 April 2015. 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 searches identified nine separate studies (45 publications), of which four studies (36 publications) were included with a total of 667 participants, one study (only available as an abstract) is awaiting assessment and two studies are ongoing. Duration of treatment in the included studies ranged from two weeks to six months with open-label treatment for an additional six months in two of the studies. Three studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol); two of these were parallel studies with a similar design and data could be pooled, where data for a particular outcome and time point were available; also, one short

  14. Glucosylceramide Critically Contributes to the Host Defense of Cystic Fibrosis Lungs.

    PubMed

    Kovacic, Barbara; Sehl, Carolin; Wilker, Barbara; Kamler, Markus; Gulbins, Erich; Becker, Katrin Anne

    2017-01-01

    Cystic fibrosis (CF) is the most common autosomal-recessive disorder in western countries. Previous studies have demonstrated an important role of sphingolipids in the pathophysiology of cystic fibrosis. It has been shown that ceramide has a central role in various pulmonary infections, including those with Pseudomonas aeruginosa (P. aeruginosa). Ceramide is accumulated in the airways of CF mice and patients. However, little is known about a potential role of glucosylceramide in cystic fibrosis. We investigated the expression of glucosylceramide and lactosylceramide in the respiratory tract of murine and human CF samples by immunohistochemistry and analyzed effects of glucosylceramide on P. aeruginosa in vitro. We performed pulmonary infections with P. aeruginosa and tested inhalation with glucosylceramide. We demonstrate that glucosylceramide is down-regulated on the apical surface of bronchial and tracheal epithelial cells in cystic fibrosis mice. Although glucosylceramide did not have a direct bactericidal effect on Pseudomonas aeruginosa in vitro, inhalation of CF mice with glucosylceramide protected these mice from infection with P. aeruginosa, while non-inhaled CF mice developed severe pneumonia. Our data suggest that glucosylceramide acts in vivo in concert with ceramide and sphingosine to determine the pulmonary defense against P. aeruginosa. © 2017 The Author(s)Published by S. Karger AG, Basel.

  15. Applying the Transtheoretical Model to Physical Activity Behavior in Individuals With Non-Cystic Fibrosis Bronchiectasis.

    PubMed

    Wilson, Jason J; Kirk, Alison; Hayes, Kate; Bradbury, Ian; McDonough, Suzanne; Tully, Mark A; O'Neill, Brenda; Bradley, Judy M

    2016-01-01

    The transtheoretical model has been successful in promoting health behavior change in general and clinical populations. However, there is little knowledge about the application of the transtheoretical model to explain physical activity behavior in individuals with non-cystic fibrosis bronchiectasis. The aim was to examine patterns of (1) physical activity and (2) mediators of behavior change (self-efficacy, decisional balance, and processes of change) across stages of change in individuals with non-cystic fibrosis bronchiectasis. Fifty-five subjects with non-cystic fibrosis bronchiectasis (mean age ± SD = 63 ± 10 y) had physical activity assessed over 7 d using an accelerometer. Each component of the transtheoretical model was assessed using validated questionnaires. Subjects were divided into groups depending on stage of change: Group 1 (pre-contemplation and contemplation; n = 10), Group 2 (preparation; n = 20), and Group 3 (action and maintenance; n = 25). Statistical analyses included one-way analysis of variance and Tukey-Kramer post hoc tests. Physical activity variables were significantly (P < .05) higher in Group 3 (action and maintenance) compared with Group 2 (preparation) and Group 1 (pre-contemplation and contemplation). For self-efficacy, there were no significant differences between groups for mean scores (P = .14). Decisional balance cons (barriers to being physically active) were significantly lower in Group 3 versus Group 2 (P = .032). For processes of change, substituting alternatives (substituting inactive options for active options) was significantly higher in Group 3 versus Group 1 (P = .01), and enlisting social support (seeking out social support to increase and maintain physical activity) was significantly lower in Group 3 versus Group 2 (P = .038). The pattern of physical activity across stages of change is consistent with the theoretical predictions of the transtheoretical model. Constructs of the transtheoretical model that appear to be

  16. Effects of puberty on cystic fibrosis related pulmonary exacerbations in women versus men.

    PubMed

    Sutton, Shelby; Rosenbluth, Daniel; Raghavan, Deepa; Zheng, Jie; Jain, Raksha

    2014-01-01

    Epidemiologic data from studies of airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis indicate a gender disparity where women have worse outcomes. The explanation for this is largely unknown. We hypothesize that female sex hormones play a role in this gender disparity, predisposing women to more exacerbations and decreased lung function post-puberty. In Cystic Fibrosis, to determine if puberty marks a point of increasing exacerbations and decreasing lung function in women relative to men. Using the United States Cystic Fibrosis Foundation Patient Registry, we used linear regression to compare lung function and rate of pulmonary exacerbations in men versus women before and after puberty. Of 5,137 subjects who met inclusion criteria, 2,689 were male and 2,448 were female. Average age of puberty was found to be 13.2 ± 2.2 years in men and 11.2 ± 2.0 years of age in women. Percent predicted FEV1 pre- and post-puberty were no different between males versus females (P = 0.44 pre-puberty and P = 0.16 post-puberty). In contrast, women had a significantly higher rate of pulmonary exacerbations post-puberty than men (1.17 ± 1.35 exacerbations per year in women versus 0.95 ± 1.27 in men; P < 0.001) despite controlling for morphometrics, co-morbidities, and microbiologic variables. After puberty, the rate of pulmonary exacerbations increased in adolescent women relative to men with cystic fibrosis, supporting a role for sex hormones in the disease process. Further understanding of the mechanisms that modulate sex hormone receptors in airway disease may serve as future targets for therapy. © 2013 Wiley Periodicals, Inc.

  17. Effects of Puberty on Cystic Fibrosis Related Pulmonary Exacerbations in Women Versus Men

    PubMed Central

    Sutton, Shelby; Rosenbluth, Daniel; Raghavan, Deepa; Zheng, Jie; Jain, Raksha

    2014-01-01

    Summary Background Epidemiologic data from studies of airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis indicate a gender disparity where women have worse outcomes. The explanation for this is largely unknown. We hypothesize that female sex hormones play a role in this gender disparity, predisposing women to more exacerbations and decreased lung function post-puberty. Objective In Cystic Fibrosis, to determine if puberty marks a point of increasing exacerbations and decreasing lung function in women relative to men. Methods Using the United States Cystic Fibrosis Foundation Patient Registry, we used linear regression to compare lung function and rate of pulmonary exacerbations in men versus women before and after puberty. Results Of 5,137 subjects who met inclusion criteria, 2,689 were male and 2,448 were female. Average age of puberty was found to be 13.2 ± 2.2 years in men and 11.2 ± 2.0 years of age in women. Percent predicted FEV1 pre-and post-puberty were no different between males versus females (P = 0.44 pre-puberty and P = 0.16 post-puberty). In contrast, women had a significantly higher rate of pulmonary exacerbations post-puberty than men (1.17 ± 1.35 exacerbations per year in women versus 0.95 ± 1.27 in men; P < 0.001) despite controlling for morphometrics, co-morbidities, and microbiologic variables. Conclusion After puberty, the rate of pulmonary exacerbations increased in adolescent women relative to men with cystic fibrosis, supporting a role for sex hormones in the disease process. Further understanding of the mechanisms that modulate sex hormone receptors in airway disease may serve as future targets for therapy. PMID:23460461

  18. Diagnosis and Treatment of Endocrine Co-Morbidities in Patients with Cystic Fibrosis

    PubMed Central

    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

  19. Anti-inflammatory drugs and analgesics for managing symptoms in people with cystic fibrosis-related arthritis.

    PubMed

    Thornton, Judith; Rangaraj, Satyapal

    2016-01-21

    Arthritis remains a relatively infrequent complication of cystic fibrosis, but is a cause of significant morbidity when it does occur. Two distinct types of arthritis are described in cystic fibrosis: cystic fibrosis-related arthropathy (CFA) and hypertrophic pulmonary osteoarthropathy (HPO). Management of arthritis in people with cystic fibrosis is uncertain and complex because of the underlying disease and its intense treatment. This is an update of a previously published review. To review the effectiveness and safety of pharmacological agents for the symptomatic management of cystic fibrosis-related arthritis in adults and children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.Date of most recent search: 19 January 2016. Randomised controlled studies which compared the efficacy and safety of anti-inflammatory and analgesic agents (e.g. non-steroidal anti-inflammatory agents, systemic corticosteroids, intra-articular corticosteroids) with each other, with no treatment or with placebo for CFA and HPO. No relevant studies were identified. No studies were included in this review. Although it is generally recognised that CFA may be episodic and resolve spontaneously, treatment with analgesics and anti-inflammatory agents may be needed. While this approach may be sufficient to manage symptoms, it is disappointing that no randomised controlled trials to rigorously evaluate these agents were found, nor could the authors identify any quasi-randomised. This systematic review has identified the need for a well-designed adequately-powered randomised controlled trial to assess the efficacy and safety of pharmacological agents for the symptomatic management of cystic fibrosis-related arthritis (CFA and HPO) in adults and children with cystic fibrosis

  20. Electrolyte abnormalities in cystic fibrosis: systematic review of the literature.

    PubMed

    Scurati-Manzoni, Elisabetta; Fossali, Emilio F; Agostoni, Carlo; Riva, Enrica; Simonetti, Giacomo D; Zanolari-Calderari, Maura; Bianchetti, Mario G; Lava, Sebastiano A G

    2014-06-01

    Cystic fibrosis per se can sometimes lead to hyponatremia, hypokalemia, hypochloremia or hyperbicarbonatemia. This tendency was first documented 60 years ago and has subsequently been confirmed in single case reports or small case series, most of which were retrospective. However, this issue has not been addressed analytically. We have therefore systematically reviewed and analyzed the available literature on this subject. This was a systematic review of the literature. The reports included in this review cover 172 subacute and 90 chronic cases of electrolyte imbalances in patients with cystic fibrosis. The male:female ratio was 1.57. Electrolyte abnormalities were mostly associated with clinically inapparent fluid volume depletion, mainly affected patients aged ≤2.5 years, frequently tended to recur and often were found before the diagnosis of cystic fibrosis was established. Subacute presentation often included an history of heat exposure, vomiting, excessive sweating and pulmonary infection. History of chronic presentation, in contrast, was often inconspicuous. The tendency to hypochloremia, hypokalemia and metabolic alkalosis was similar between subacute and chronic patients, with hyponatremia being more pronounced (P < 0.02) in subacute compared to chronic presentations. Subacute cases were treated parenterally; chronic ones were usually managed with oral salt supplementation. Retention of urea and creatinine was documented in 38 % of subacute cases. The findings of our review suggest that physicians should be aware that electrolyte abnormalities can occur both as a presenting and a recurring feature of cystic fibrosis.

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

    PubMed Central

    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

  2. Cystic Fibrosis Related Liver Disease—Another Black Box in Hepatology

    PubMed Central

    Staufer, Katharina; Halilbasic, Emina; Trauner, Michael; Kazemi-Shirazi, Lili

    2014-01-01

    Due to improved medical care, life expectancy in patients with cystic fibrosis (CF) has veritably improved over the last decades. Importantly, cystic fibrosis related liver disease (CFLD) has become one of the leading causes of morbidity and mortality in CF patients. However, CFLD might be largely underdiagnosed and diagnostic criteria need to be refined. The underlying pathomechanisms are largely unknown, and treatment strategies with proven efficacy are lacking. This review focuses on current invasive and non-invasive diagnostic standards, the current knowledge on the pathophysiology of CFLD, treatment strategies, and possible future developments. PMID:25093717

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

    PubMed Central

    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

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

    PubMed

    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 lethal autosomal 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 discovery of the disease-causing gene.

  5. Association of growth and nutritional parameters with pulmonary function in cystic fibrosis: a literature review.

    PubMed

    Mauch, Renan Marrichi; Kmit, Arthur Henrique Pezzo; Marson, Fernando Augusto de Lima; Levy, Carlos Emilio; Barros-Filho, Antonio de Azevedo; Ribeiro, José Dirceu

    2016-12-01

    To review the literature addressing the relationship of growth and nutritional parameters with pulmonary function in pediatric patients with cystic fibrosis. A collection of articles published in the last 15 years in English, Portuguese and Spanish was made by research in electronic databases - PubMed, Cochrane, Medline, Lilacs and Scielo - using the keywords cystic fibrosis, growth, nutrition, pulmonary function in varied combinations. Articles that addressed the long term association of growth and nutritional parameters, with an emphasis on growth, with pulmonary disease in cystic fibrosis, were included, and we excluded those that addressing only the relationship between nutritional parameters and cystic fibrosis and those in which the aim was to describe the disease. Seven studies were included, with a total of 12,455 patients. Six studies reported relationship between growth parameters and lung function, including one study addressing the association of growth parameters, solely, with lung function, and all the seven studies reported relationship between nutritional parameters and lung function. The review suggests that the severity of the lung disease, determined by spirometry, is associated with body growth and nutritional status in cystic fibrosis. Thus, the intervention in these parameters can lead to the better prognosis and life expectancy for cystic fibrosis patients. Copyright © 2016 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

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

    PubMed

    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 < 0.0001). Vaccines

  7. Cystic Fibrosis Revisited - a Review Study.

    PubMed

    Klimova, Blanka; Kuca, Kamil; Novotny, Michal; Maresova, Petra

    2017-01-01

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

  8. Sodium channel blockers for cystic fibrosis.

    PubMed

    Burrows, E; Southern, K W; Noone, P

    2006-07-19

    People with cystic fibrosis (CF) have increased transport of the salt, sodium across their airway lining. Over-absorption of sodium results in the dehydration of the liquid that lines the airway surface and is a primary defect in people with CF. To determine whether the topical administration of drugs that block sodium transport improves the respiratory condition of people with CF. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We contacted principal investigators known to work in the field, previous authors and pharmaceutical companies who manufacture ion transport agents for unpublished or follow-up data. Most recent search of the Group's register: March 2006 Published or unpublished randomised controlled trials (RCTs) or quasi-randomised controlled trials of sodium channel blockers compared to placebo or another sodium channel blocker or the same sodium channel blocker at a different dosing regimen. Two authors independently extracted data. Meta-analysis was limited due to differing study designs. Four RCTs, with a total of 205 participants, examining the topical administration of the short-acting sodium channel blocker, amiloride, compared to placebo were identified as eligible for inclusion in the review. For three studies, interventions for six months were completed and it was possible to calculate relative change in respiratory function (FVC). There was a significant difference found in relative change in FVC in favour of placebo (GIV analysis of weighted mean difference for FVC; 1.51% (95% confidence interval -2.77 to -0.25). There were no significant differences identified in other clinically relevant outcomes. We found no evidence that the topical administration of a short-acting sodium channel blocker improves respiratory condition in people with cystic

  9. [Cystic fibrosis gene mutations in the West of France: clinical application].

    PubMed

    Verlingue, C; Travert, G; Le Roux, M G; Laroche, D; Audrézet, M P; Mercier, B; Moisan, J P; Férec, C

    1994-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) gene, responsible for the cystic fibrosis phenotype when both alleles are mutated, was cloned and sequenced in 1989. Since then, more than 400 mutations have been reported in the gene, although most of these are rare. We have systematically analysed the entire coding sequence of the CFTR gene in a cohort of patients originating from the West of France (Caen, Brest and Nantes). More than 450 CF children, 914 chromosomes in all, have been exhaustively studied in the three centers. We have been able to characterize more than 90% of the mutations, respectively 93.5%, 99% and 95.8%. Despite the large diversity in the CFTR mutations occurring in CF patients from this area, these results can help to improve genetic counselling, prenatal diagnosis as well as our understanding of the molecular basis of the pathophysiology of cystic fibrosis.

  10. Dornase alfa: a new option in the management of cystic fibrosis.

    PubMed

    Witt, D M; Anderson, L

    1996-01-01

    Recombinant human DNase I, or dornase alfa, is the first new therapy developed specifically for cystic fibrosis in almost 30 years. It selectively digests extracellular DNA and reduces the viscosity of purulent sputum. In clinical trials dornase alfa modestly improved pulmonary function, slightly decreasing the number of respiratory exacerbations requiring parenteral antibiotics compared with placebo. Phase III studies suggest that patients receiving dornase alfa also spend slightly fewer days in the hospital than those treated with placebo. The aerosolized preparation is safe and generally well tolerated. Voice alteration and sore throat are the most commonly reported adverse effects. Further research is necessary to determine the optimum time to initiate therapy and to evaluate the agent's pharmacoeconomic impact on the treatment of cystic fibrosis. Aerosolized dornase alfa should always be given in conjunction with standard cystic fibrosis therapies including antibiotics, chest physiotherapy, and pancreatic enzyme supplementation.

  11. Mast cell tryptase changes with Aspergillus fumigatus - Host crosstalk in cystic fibrosis patients.

    PubMed

    Gomez, Carine; Carsin, Ania; Gouitaa, Marion; Reynaud-Gaubert, Martine; Dubus, Jean-Christophe; Mège, Jean-Louis; Ranque, Stéphane; Vitte, Joana

    2018-02-15

    Pulmonary and systemic antifungal immunity influences quality of life and survival of people with cystic fibrosis. Aspergillus fumigatus (Af) induces specific IgG and IgE. Mast cells respond to IgE, IgG and direct interactions with Af. Mast cells are the source of the protease tryptase. We aimed at evaluating serum baseline tryptase as a potential biomarker of the Af-host interaction in cystic fibrosis patients. Serum baseline tryptase, IgE and IgG directed to Af extract and Af molecular allergens were measured in 76 cystic fibrosis patients. The main findings were (i) lower levels of serum baseline tryptase in patients displaying specific IgE to Af (p < 0.0001) and (ii) an association between tryptase levels and IgE or IgG responses to Af and ribotoxin (Asp f 1). These findings suggest that serum baseline tryptase is influenced by Af-host interactions and thus might be a marker for mast cell regulation and pulmonary immune defenses. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  12. CFTR-dependent defect in alternatively-activated macrophages in cystic fibrosis.

    PubMed

    Tarique, Abdullah A; Sly, Peter D; Holt, Patrick G; Bosco, Anthony; Ware, Robert S; Logan, Jayden; Bell, Scott C; Wainwright, Claire E; Fantino, Emmanuelle

    2017-07-01

    The role of the macrophages in cystic fibrosis (CF) lung disease has been poorly studied. We hypothesized that alternatively activated M2 macrophages are abnormal in CF lung disease. Blood samples were collected from adults (n=13) children (n=27) with CF on admission for acute pulmonary exacerbation and when clinically stable. Monocytes were differentiated into macrophages and polarized into classical (M1) and alternatively-activated (M2) phenotypes, function determined ex-vivo and compared with healthy controls. In the absence of functional cystic fibrosis trans-membrane conductance regulator (CFTR), either naturally in patients with CF or induced with CFTR inhibitors, monocyte-derived macrophages do not respond to IL-13/IL-4, fail to polarize into M2s associated with a post-transcriptional failure to produce and express IL-13Rα1 on the macrophage surface Polarization to the M1 phenotype was unaffected. CFTR-dependent imbalance of macrophage phenotypes and functions could contribute to the exaggerated inflammatory response seen in CF lung disease. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  13. Cystic Fibrosis: Brazilian ENT Experience

    PubMed Central

    Sih, Tania; Godinho, Ricardo; Franco, Leticia Paiva; Piltcher, Otávio

    2012-01-01

    Most published studies about Cystic Fibrosis (CF) are European or North American. There are still few publications about the characteristics of fibrocystic populations in developing countries. The incidence of cystic fibrosis (CF) in Brazil varies among different regions (1 : 10,000 in Minas Gerais, 1 : 9,500 in Paraná, 1 : 8,700 in Santa Catarina, and 1 : 1600 in Rio Grande do Sul). The prevalence of the DF508 mutation also varies according to population: 33% in Sao Paulo, 49% in Rio Grande do Sul, 27% in Santa Catarina, and 52% in Minas Gerais. Cough and nasal obstruction are the most common symptoms. The variation in nasal polyposis prevalence may be explained by population genotypic characteristics in a country that spans a continent. Findings on nasal endoscopy and computed tomography (CT) have better correlation than do this information compared with surgical and clinical history. Microbiologic studies suggest a high level of early contamination of the airways. Sensorineural hearing loss (SNHL) occurs in these patients as a result of ototoxic antibiotics. The data compiled in this paper is useful, but also lead to the general agreement that more research would be welcome due to the unique characteristics of this country. PMID:22611403

  14. Timing of dornase alfa inhalation for cystic fibrosis.

    PubMed

    Dentice, Ruth; Elkins, Mark

    2016-07-26

    Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane review. To determine the effect of timing of dornase alfa inhalation on measures of clinical efficacy in people with cystic fibrosis (in relation to airway clearance techniques or time of day). Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), and international cystic fibrosis conference proceedings.Date of the most recent search: 25 April 2016. Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the study with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation. Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. We identified 115 trial reports representing 55 studies, of which five studies (providing data on 122 participants) met our inclusion criteria. All five studies used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second. Similarly, forced vital capacity and quality of life were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small studies in children (seven to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.In one trial

  15. Dornase alfa as postoperative therapy in cystic fibrosis sinonasal disease.

    PubMed

    Cimmino, Mariano; Nardone, Massimiliano; Cavaliere, Matteo; Plantulli, Angela; Sepe, Angela; Esposito, Valeria; Mazzarella, Giuseppina; Raia, Valeria

    2005-12-01

    To determine the benefit of nasally inhaled dornase alfa in patients with cystic fibrosis and nasal symptoms. Double-blind placebo-controlled trial. Cystic Fibrosis Regional Center of Campania at the University of Naples "Federico II." A total of 24 patients with cystic fibrosis and chronic sinusitis. Patients underwent sinonasal surgery during a 3-year period and received once-daily doses of either dornase alfa (2.5 mg) or hypotonic saline solution (5 mL) beginning 1 month after surgery and for a 12-month period. Primary outcomes were nasal-related symptoms and nasal endoscopic appearance; secondary outcomes were forced expiratory volume in 1 second, nasal computed tomography findings, and saccharine clearance test results. Patients were evaluated before and after treatment. After surgery, all outcomes were significantly improved for each treatment at 1 month (P<.05); primary outcomes were improved at 24 and 48 weeks in the group receiving dornase alfa (P<.05), and at 12 weeks in the group receiving placebo. Secondary outcomes were better in the dornase alfa group (P<.01) than in the placebo group at 12 months except for the saccharine clearance test results. In particular, median relative difference in forced expiratory volume in 1 second between dornase alfa and placebo was significantly improved in the dornase alfa group (P<.01). Nasally inhaled dornase alfa can be effective in patients with cystic fibrosis and sinonasal disease who do not respond to conventional therapy after surgical treatment. Further studies should be carried out to determine the long-term effect on sinus disease, recurrence of polyps, and quality of life.

  16. [Improvement of intestinal function in cystic fibrosis patients using probiotics].

    PubMed

    Infante Pina, D; Redecillas Ferreiro, S; Torrent Vernetta, A; Segarra Cantón, O; Maldonado Smith, M; Gartner Tizziano, L; Hidalgo Albert, E

    2008-12-01

    In some cases, cystic fibrosis may include intestinal inflammation and bacterial overgrowth. Probiotics are considered as immunomodulatory, anti-inflammatory and microbiotic regulator substances. The aim of our study is to determine the prevalence of bacterial overgrowth in cystic fibrosis patients and try to improve the intestinal function with the administration of probiotics. We examined 20 patients with cystic fibrosis (mean age 10.33, range 5 to 17 years). The expired hydrogen test with a 2 g/kg of 20% dextrose overload was performed on 10 patients. After the test, Lactobacillus rhamnosus LGG 10(11) CFU was administered twice daily for four weeks. Faecal near infrared spectroscopy (FENIR) of water, fat, nitrogen and sugar content in faeces was performed before and after probiotics administration. Five patients (50%) showed bacterial overgrowth. We obtained a positive correlation between the hydrogen test and steatorrhea (R = 0.57) and sugar in faeces (R = 0.52). The FENIR results pre-treatment vs post-treatment were: fat 6.2 g +/- 3.3 g vs. 4.9 g +/- 2.1 g (p < 0.05), sugar 6.7 +/- g 3.6 g vs. 5 g +/- 2.6 g (p < 0.05) and nitrogen 0.87 g +/- 0.27 g vs. 0.91 g +/- 0.14 g (NS) respectively. Thirteen patients (81.25%) had improved stool appearance and intestinal comfort and nine (56.25%) decreased the number of daily stools. Probiotics improved not only clinical but also biochemical intestinal function in cystic fibrosis patients. These could be given as a regular treatment in this type of patients and in those with bacterial overgrowth.

  17. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene

    PubMed Central

    Sosnay, Patrick R; Siklosi, Karen R; Van Goor, Fredrick; Kaniecki, Kyle; Yu, Haihui; Sharma, Neeraj; Ramalho, Anabela S; Amaral, Margarida D; Dorfman, Ruslan; Zielenski, Julian; Masica, David L; Karchin, Rachel; Millen, Linda; Thomas, Philip J; Patrinos, George P; Corey, Mary; Lewis, Michelle H; Rommens, Johanna M; Castellani, Carlo; Penland, Christopher M; Cutting, Garry R

    2013-01-01

    Allelic heterogeneity in disease-causing genes presents a substantial challenge to the translation of genomic variation to clinical practice. Few of the almost 2,000 variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have empirical evidence that they cause cystic fibrosis. To address this gap, we collected both genotype and phenotype data for 39,696 cystic fibrosis patients in registries and clinics in North America and Europe. Among these patients, 159 CFTR variants had an allele frequency of ≥0.01%. These variants were evaluated for both clinical severity and functional consequence with 127 (80%) meeting both clinical and functional criteria consistent with disease. Assessment of disease penetrance in 2,188 fathers of cystic fibrosis patients enabled assignment of 12 of the remaining 32 variants as neutral while the other 20 variants remained indeterminate. This study illustrates that sourcing data directly from well-phenotyped subjects can address the gap in our ability to interpret clinically-relevant genomic variation. PMID:23974870

  18. Longevity of Patients With Cystic Fibrosis in 2000 to 2010 and Beyond: Survival Analysis of the Cystic Fibrosis Foundation Patient Registry

    PubMed Central

    MacKenzie, Todd; Gifford, Alex H.; Sabadosa, Kathryn A.; Quinton, Hebe B.; Knapp, Emily A.; Goss, Christopher H.; Marshall, Bruce C.

    2015-01-01

    Background Advances in treatments for cystic fibrosis (CF) continue to extend survival. An updated estimate of survival is needed for better prognostication and to anticipate evolving adult care needs. Objective To characterize trends in CF survival between 2000 and 2010 and to project survival for children born and diagnosed with the disease in 2010. Design Registry-based study. Setting 110 Cystic Fibrosis Foundation–accredited care centers in the United States. Patients All patients represented in the Cystic Fibrosis Foundation Patient Registry (CFFPR) between 2000 and 2010. Measurements Survival was modeled with respect to age, age at diagnosis, gender, race or ethnicity, F508del mutation status, and symptoms at diagnosis. Results Between 2000 and 2010, the number of patients in the CFFPR increased from 21 000 to 26 000, median age increased from 14.3 to 16.7 years, and adjusted mortality decreased by 1.8% per year (95% CI, 0.5% to 2.7%). Males had a 19% (CI, 13% to 24%) lower adjusted risk for death than females. Median survival of children born and diagnosed with CF in 2010 is projected to be 37 years (CI, 35 to 39 years) for females and 40 years (CI, 39 to 42 years) for males if mortality remains at 2010 levels and more than 50 years if mortality continues to decrease at the rate observed between 2000 and 2010. Limitations The CFFPR does not include all patients with CF in the United States, and loss to follow-up and missing data were observed. Additional analyses to address these limitations suggest that the survival projections are conservative. Conclusion Children born and diagnosed with CF in the United States in 2010 are expected to live longer than those born earlier. This has important implications for prognostic discussions and suggests that the health care system should anticipate greater numbers of adults with CF. Primary Funding Source Cystic Fibrosis Foundation. PMID:25133359

  19. Autogenic drainage for airway clearance in cystic fibrosis.

    PubMed

    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

  20. Lung transplantation for non-cystic fibrosis bronchiectasis: analysis of a 13-year experience.

    PubMed

    Beirne, Paul Adrian; Banner, Nicholas R; Khaghani, Asghar; Hodson, Margaret E; Yacoub, Magdi H

    2005-10-01

    Lung transplantation is a well-established treatment for end-stage cystic fibrosis, and there are considerable data on medium- and long-term results. However, less information exists about transplantation for non-cystic fibrosis bronchiectasis. Between December 1988 and June 2001, 22 patients (12 men, 10 women) underwent transplantation for bronchiectasis not due to cystic fibrosis. Procedures were bilateral sequential single-lung transplants (BSSLTX) in 4 patients, en bloc double lung transplants (DLTX) in 5, heart-lung transplants (HLTX) in 6, and single-lung transplants (SLTX) in 7. Lifelong outpatient follow-up was continued at a minimum of every 6 months. One-year Kaplan-Meier survival for all patients was 68% (95% confidence interval [CI], 54%-91%), and 5-year survival was 62% (95% CI, 41-83%). One-year survival after SLTX was 57% (95% CI, 20%-94%) vs 73% (95% CI, 51-96%) for those receiving 2 lungs. At 6 months, mean forced expiratory volume in 1 second was 73% predicted (range, 58%-97%), and mean forced vital capacity was 68% predicted (range, 53%-94%) after receiving 2 lungs (n = 10); in the SLTX group at 6 months, mean forced expiratory volume in 1 second was 50% predicted (range, 34%-61%), and mean forced vital capacity was 53% predicted (range 46-63%) (n = 4). Survival and lung function after transplantation for non-cystic fibrosis bronchiectasis was similar to that after transplantation for cystic fibrosis. A good outcome is possible after single lung transplantation in selected patients.

  1. Zinc supplementation in children with cystic fibrosis

    USDA-ARS?s Scientific Manuscript database

    Cystic fibrosis (CF) leads to malabsorption of macro- and micronutrients. Symptomatic zinc deficiency has been reported in CF but little is known about zinc homeostasis in children with CF. Zinc supplementation (Zn suppl) is increasingly common in children with CF but it is not without theoretcial r...

  2. Dornase alfa for cystic fibrosis.

    PubMed

    Yang, Connie; Chilvers, Mark; Montgomery, Mark; Nolan, Sarah J

    2016-04-04

    Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review. To determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other medications that improve airway clearance, and to identify any adverse events associated with its use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Group's Cystic Fibrosis Register: 30 November 2015.Clinicaltrials.gov was also searched to identify unpublished or ongoing trials. Date of most recent search: 28 November 2015. All randomised and quasi-randomised controlled trials comparing dornase alfa to placebo, standard therapy or other medications that improve airway clearance. Authors independently assessed trials against the inclusion criteria; two authors carried out analysis of methodological quality and data extraction. The searches identified 54 trials, of which 19 (including a total of 2565 participants) met our inclusion criteria. Three additional papers examined the healthcare cost from one of the clinical trials. Fifteen trials compared dornase alfa to placebo or no dornase alfa treatment (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa with hypertonic saline and alternate day dornase alfa (48 participants); one compared dornase alfa to mannitol and the combination of both drugs (38 participants). Trial duration varied from six days to three years.Compared to placebo, forced expiratory volume at one second improved in the intervention groups, with

  3. Changing epidemiology of non-cystic fibrosis bronchiectasis.

    PubMed

    Bahçeci, Semiha; Karaman, Sait; Nacaroğlu, Hikmet Tekin; Yazıcı, Selçuk; Girit, Saniye; Ünsal-Karkıner, Şule; Can, Demet

    2016-01-01

    Non-cystic fibrosis bronchiectasis again becomes a major health problem due to inappropriate antibiotic use and increasing frequency of protracted bacterial bronchitis. The aim was to determine the changes in etiology of bronchiectasis. Patients who admitted to Behçet Uz Children Hospital between 2005 and 2015 (n=110) were retrospectively examined. The etiology of bronchiectasis was detected as; primary ciliary dyskinesia 26.4%, protracted bacterial bronchitis 22.8%, primary immune deficiency 11.8%, bronchiolitis obliterans 8.2%, lung disease secondary to gastro-esophageal reflux 3.7%, foreign body aspiration 2.7%, tuberculosis %2.7, congenital malformation 1.8% and asthma 1.8%, respectively. In 15.4% of cases, etiology was not identified clearly. 91% of the patients were medically treated. In ten years, the frequency of asthma and tuberculosis in etiology had decreased but primary ciliary dyskinesia and primary immune deficiency had increased. Non-cystic fibrosis bronchiectasis can be followed up for a long time with medical treatment.

  4. Lung transplantation in patients with cystic fibrosis.

    PubMed

    Morton, Judith; Glanville, Allan R

    2009-10-01

    Cystic fibrosis is one of the most common indications for lung transplantation worldwide and certainly the most common indication for all pediatric lung transplants and for bilateral lung transplantation irrespective of age. Outcomes are outstanding when compared with other indications for lung transplantation, and an increasing number of centers now report mean survival of greater than 10 years posttransplant. Hence it is important to concentrate on the broad panoply of potential systemic complications of cystic fibrosis and address proactively issues that may be associated with adverse outcomes. Optimum management of infectious, nutritional, diabetic, renal, bone, and gut complications is critical to long-term success so that recipients may realize their full potential. Timing of referral for consideration of active listing should allow sufficient time for the patient and lung transplant team to develop a productive working relationship based on best available evidence and mutual trust, which will culminate in a long-term successful outcome. Copyright Thieme Medical Publishers.

  5. Breakdown in Breathing: The Complexities of Cystic Fibrosis

    MedlinePlus

    ... very important so we can intervene early.” Early diagnosis and treatment can help raise the life expectancy for people living with ... Wise Choices Living with Cystic Fibrosis In between checkups, practice good self-care and ...

  6. Ion Channel Modulators in Cystic Fibrosis.

    PubMed

    Gentzsch, Martina; Mall, Marcus A

    2018-05-08

    Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and remains one of the most common life-shortening genetic diseases affecting the lung and other organs. CFTR functions as a cAMP-dependent anion channel that transports chloride and bicarbonate across epithelial surfaces and disruption of these ion transport processes plays a central role in the pathogenesis of CF. These findings provided the rationale for pharmacological modulation of ion transport, either by targeting mutant CFTR or alternative ion channels that can compensate for CFTR dysfunction, as a promising therapeutic approach. High throughput screening has supported the development of CFTR modulator compounds. CFTR correctors are designed to improve defective protein processing, trafficking and cell surface expression, whereas potentiators increase the activity of mutant CFTR at the cell surface. The approval of the first potentiator ivacaftor for the treatment of patients with specific CFTR mutations and, more recently the corrector lumacaftor in combination with ivacaftor for patients homozygous for the common F508del mutation, were major breakthroughs on the path to causal therapies for all patients with CF. In this review, we focus on recent developments and remaining challenges of CFTR-directed therapies, as well as modulators of other ion channels such as alternative chloride channels and the epithelial sodium channel (ENaC) as additional targets in CF lung disease. Further, we discuss how patient-derived precision medicine models may aid the translation of emerging next generation ion channel modulators from the laboratory to the clinic and tailor their use for optimal therapeutic benefits in individual patients with CF. Copyright © 2018. Published by Elsevier Inc.

  7. Cystic Fibrosis Gene Therapy in the UK and Elsewhere

    PubMed Central

    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. Immunological mechanisms behind the cystic fibrosis-ABPA link.

    PubMed

    Hartl, Dominik

    2009-01-01

    Allergic bronchopulmonary aspergillosis (ABPA), a pulmonary hypersensitivity disease mediated by an allergic response to Aspergillus fumigatus (A. fumigatus), occurs preferentially in disease conditions with an impaired pulmonary immunity, especially in cystic fibrosis (CF) and allergic asthma. The pathophysiological mechanisms underlying the link between CF and ABPA are poorly understood. Animal and human data support a critical role for chemokines, especially CCL17 and its receptor CCR4, in ABPA. A summary and discussion of the immunological mechanism involved in the pathogenesis of ABPA with a focus on CF lung disease and the role of chemokines is presented here.

  9. CFTR Modulators for the Treatment of Cystic Fibrosis.

    PubMed

    Pettit, Rebecca S; Fellner, Chris

    2014-07-01

    Defects in a single gene lead to the defective proteins that cause cystic fibrosis, making the disease an ideal candidate for mutation-targeted therapy. Although ivacaftor is currently the only FDA-approved CFTR modifier, others are in development.

  10. Point shear wave elastography of the pancreas in patients with cystic fibrosis: a comparison with healthy controls.

    PubMed

    Pfahler, Matthias Hermann Christian; Kratzer, Wolfgang; Leichsenring, Michael; Graeter, Tilmann; Schmidt, Stefan Andreas; Wendlik, Inka; Lormes, Elisabeth; Schmidberger, Julian; Fabricius, Dorit

    2018-02-19

    Manifestations of cystic fibrosis in the pancreas are gaining in clinical importance as patients live longer. Conventional ultrasonography and point shear wave elastography (pSWE) imaging are non-invasive and readily available diagnostic methods that are easy to perform. The aim of this study was to perform conventional ultrasonography and obtain pSWE values in the pancreases of patients with cystic fibrosis and to compare the findings with those of healthy controls. 27 patients with cystic fibrosis (13 women/14 men; mean age 27.7 ± 13.7 years; range 9-58 years) and 60 healthy control subjects (30 women/30 men; mean age 30.3 ± 10.0 years; range 22-55 years) underwent examinations of the pancreas with conventional ultrasound and pSWE imaging. Patients with cystic fibrosis have an echogenic pancreatic parenchyma. We found cystic lesions of the pancreas in six patients. pSWE imaging of the pancreatic parenchyma gave significantly lower shear wave velocities in patients with cystic fibrosis than in the control group (1.01 m/s vs 1.30 m/s; p < 0.001). Using pSWE imaging in vivo, we have shown that the pancreas is considerably softer in patients with cystic fibrosis than in a healthy control population.

  11. Cystic fibrosis presenting with neonatal cholestasis simulating biliary atresia in a patient with a novel mutation.

    PubMed

    Eminoglu, Tuba Fatma; Polat, Emine; Gökçe, Selim; Ezgü, Fatih Süheyl; Senel, Saliha; Apaydin, Sema

    2013-06-01

    Neonatal cholestasis is a rare presenting feature of cystic fibrosis which usually cannot be differentiated from other types of cholestasis. Herein, the authors report a 63 d-old boy with cystic fibrosis presenting with neonatal cholestasis mimicking biliary atresia. A new mutation in CFTR gene resulting in severe phenotype has been described. The cystic fibrosis patients with c.3871 G > T mutation may have acholic gaita mimicking biliary atresia in the absence of insipissated bile with minimal histologic findings in the liver.

  12. Heart-lung transplantation in cystic fibrosis: predictions for the next decade in England and Wales.

    PubMed

    Elborn, J S; Shale, D J; Britton, J R

    1994-02-01

    Heart-lung transplantation has become an established treatment for end stage respiratory failure secondary to cystic fibrosis. The success of this form of treatment, and the increasing survival of such patients, suggests there will be an increased need for transplantation over the next decade. We have used cystic fibrosis population predictions and all cause mortality data to estimate the number of cardio-pulmonary deaths, due to cystic fibrosis, over the next decade and to estimate the number of such patients who are likely to benefit from heart-lung transplantation. We estimate that there will be between 85 and 127 potential transplant recipients with cystic fibrosis each year over the next decade. During 1990, 1991 and 1992 there were less than 40 transplants each year in such patients. These data emphasize the need to expand transplantation services and to maintain the availability of donor organs.

  13. Multiplex PCR reveals that viruses are more frequent than bacteria in children with cystic fibrosis.

    PubMed

    Miró-Cañís, Sílvia; Capilla-Rubio, Sílvia; Marzo-Checa, Laura; Fontanals-Aymerich, Dionisia; Sanfeliu-Sala, Isabel; Espasa-Soley, Mateu; Asensio-de-la-Cruz, Oscar

    2017-01-01

    Cystic fibrosis is a degenerative disease characterized by progressive epithelial secretory gland dysfunction associated with repeated respiratory infections. Bacterial infections are very frequent in children with cystic fibrosis, but because rapid METHODS: for screening for the wide variety of potentially involved viruses were unavailable until recently, the frequency of viral presence is unknown. Multiplex PCR enables screening for many viruses involved in respiratory infections. This study aimed to evaluate the frequency of viruses and bacteria in respiratory specimens from children with cystic fibrosis and to clarify the incidence and characteristics (seasonality and age of patients) of different viruses detected in children with cystic fibrosis. In this 2-year prospective study, we obtained paired nasopharyngeal-swab and sputum specimens from children with cystic fibrosis during clinical respiratory examinations separated by at least 14days. We analyzed viruses in nasopharyngeal-swab specimens with multiplex PCR and bacteria in sputum with standard methods. We analyzed 368 paired specimens from 33 children. We detected viruses in 154 (41.8%) and bacteria in 132 (35.9%). Bacteria were commoner in spring and summer; viruses were commoner in autumn and winter. In every season, Staphylococcus aureus was the commonest bacteria and rhinovirus was the commonest virus. Nearly all infections with Haemophilus influenzae occurred in autumn and winter. Viruses were more prevalent in children <5 years old, and bacteria were more prevalent in children ≥12 years old. Multiplex PCR screening for respiratory viruses is feasible in children with cystic fibrosis; the clinical implications of screening warrant further study. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Customer satisfaction survey to improve the European cystic fibrosis external quality assessment scheme.

    PubMed

    Berwouts, Sarah; Dequeker, Elisabeth

    2011-08-01

    The Cystic Fibrosis European Network, coordinated from within the Katholieke Universiteit Leuven, is the provider of the European cystic fibrosis external quality assessment (EQA) scheme. The network aimed to seek feedback from laboratories that participated in the cystic fibrosis scheme in order to improve services offered. In this study we analysed responses to an on-line customer satisfaction survey conducted between September and November 2009. The survey was sent to 213 laboratories that participated in the cystic fibrosis EQA scheme of 2008; 69 laboratories (32%) responded. Scores for importance and satisfaction were obtained from a five-point Likert scale for 24 attributes. A score of one corresponded to very dissatisfied/very unimportant and five corresponded to very satisfied/very important. Means were calculated and placed in a two-dimensional grid (importance-satisfaction analysis). Means were subtracted from each other to obtain gap values (gap-analysis). No attribute had a mean score below 3.63. The overall mean of satisfaction was 4.35. Opportunities for improvement enclosed clarity, usefulness and completeness of the general report and individual comments, and user-friendliness of the electronic datasheet. This type of customer satisfaction survey was a valuable instrument to identify opportunities to improve the cystic fibrosis EQA scheme. It should be conducted on a regular basis to reveal new opportunities in the future and to assess effectiveness of actions taken. Moreover, it could be a model for other EQA providers seeking feedback from participants. Overall, the customer satisfaction survey provided a powerful quality of care improvement tool.

  15. [Cystic Fibrosis Cloud database: An information system for storage and management of clinical and microbiological data of cystic fibrosis patients].

    PubMed

    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.

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

    PubMed

    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.

  17. Vocational Rehabilitation of the Person with Cystic Fibrosis.

    ERIC Educational Resources Information Center

    Isralsky, Marc; And Others

    1979-01-01

    Explored vocational development, self-concept, and vocational adjustment of persons with cystic fibrosis. The following measures of vocational development correlated with work adjustment: vocational plans, educational plans, initiative, occupational information, and average vocational development score. Vocational development did not correlate…

  18. Uncertain diagnosis after newborn screening for cystic fibrosis: An ethics-based approach to a clinical dilemma.

    PubMed

    Massie, John; Gillam, Lynn

    2014-01-01

    There is uncertainty about the diagnosis of cystic fibrosis after newborn screening (NBS) for some babies, either because of an intermediate sweat chloride test or inconclusive gene mutation analysis. There is considerable difficulty knowing how best to manage these babies, some of whom will develop cystic fibrosis, but many not. This article offers an ethics-based approach to this clinical dilemma that should be helpful to clinicians managing the baby with an uncertain diagnosis of cystic fibrosis after NBS. © 2013 Wiley Periodicals, Inc.

  19. Evaluation of respiratory dynamics by volumetric capnography during submaximal exercise protocol of six minutes on treadmill in cystic fibrosis patients.

    PubMed

    Parazzi, Paloma L F; Marson, Fernando A L; Ribeiro, Maria A G O; Schivinski, Camila I S; Ribeiro, José D

    2017-11-29

    Volumetric capnography provides the standard CO 2 elimination by the volume expired per respiratory cycle and is a measure to assess pulmonary involvement. Thus, the objective of this study was to evaluate the respiratory dynamics of healthy control subjects and those with cystic fibrosis in a submaximal exercise protocol for six minutes on the treadmill, using volumetric capnography parameters (slope 3 [Slp3], Slp3/tidal volume [Slp3/TV], and slope 2 [Slp2]). This was a cross-sectional study with 128 subjects (cystic fibrosis, 64 subjects; controls, 64 subjects]. Participants underwent volumetric capnography before, during, and after six minutes on the treadmill. Statistical analysis was performed using the Friedman, Mann-Whitney, and Kruskal-Wallis tests, considering age and sex. An alpha=0.05 was considered. Six minutes on the treadmill evaluation: in cystic fibrosis, volumetric capnography parameters were different before, during, and after six minutes on the treadmill; the same was observed for the controls, except for Slp2. Regarding age, an Slp3 difference was observed in cystic fibrosis patients regardless of age, at all moments, and in controls for age≥12 years; a difference in Slp3/TV was observed in cystic fibrosis and controls, regardless of age; and an Slp2 difference in the cystic fibrosis, regardless of age. Regarding sex, Slp3 and Slp3/TV differences were observed in cystic fibrosis regardless of sex, and in controls in male participants; an Slp2 difference was observed in the cystic fibrosis and female participants. The analysis between groups (cystic fibrosis and controls) indicated that Slp3 and Slp3/TV has identified the CF, regardless of age and sex, while the Slp2 showed the CF considering age. Cystic fibrosis showed greater values of the parameters before, during, and after exercise, even when stratified by age and sex, which may indicate ventilation inhomogeneity in the peripheral pathways in the cystic fibrosis. Copyright © 2017

  20. Disease disclosure in individuals with cystic fibrosis: Association with psychosocial and health outcomes.

    PubMed

    Borschuk, Adrienne P; Everhart, Robin S; Eakin, Michelle N; Rand-Giovannetti, Devin; Borrelli, Belinda; Riekert, Kristin A

    2016-09-01

    This study aimed to quantify cystic fibrosis (CF) disclosure and examine associations between disclosure and psychosocial and health outcomes. Participants completed measures assessing disease disclosure and psychosocial outcomes. Data from chart reviews and pharmacy records were obtained. Participants (N=128; ages 16-63) were more likely to disclose to romantic partners (97%) and close friends (94%) than to casual friends (79%), bosses (71%), or co-workers (53%). Participants reported more comfort discussing CF with and doing treatments in front of romantic partners and close friends than other groups. Disclosure was associated with higher social support, social functioning, and medication adherence self-efficacy. Lower lung-function was associated with disclosure to bosses and co-workers. Clinicians should consider discussing disclosure with patients, as limited disclosure may have a negative impact on psychosocial outcomes. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  1. Sodium channel blockers for cystic fibrosis.

    PubMed

    Burrows, Elinor F; Southern, Kevin W; Noone, Peadar G

    2014-04-09

    People with cystic fibrosis (CF) have increased transport of the salt, sodium across their airway lining. Over-absorption of sodium results in the dehydration of the liquid that lines the airway surface and (along with defective chloride secretion) is a primary defect in people with CF. To determine whether the topical administration of drugs that block sodium transport improves the respiratory condition of people with CF. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We contacted principal investigators known to work in the field, previous authors and pharmaceutical companies who manufacture ion transport agents for unpublished or follow-up data.Most recent search of the Group's register: 19 December 2013. Published or unpublished randomised controlled trials (RCTs) or quasi-randomised controlled trials of sodium channel blockers compared to placebo or another sodium channel blocker or the same sodium channel blocker at a different dosing regimen. Two authors independently extracted data. Meta-analysis was limited due to differing study designs. Five RCTs, with a total of 226 participants, examining the topical administration of the short-acting sodium channel blocker, amiloride, compared to placebo were identified as eligible for inclusion in the review. In three studies over six months, there was a significant difference found in the difference in relative change in FVC in favour of placebo (weighted mean difference 1.51% (95% confidence interval -2.77 to -0.25), although heterogeneity was evident. A two-week study demonstrated that hypertonic saline with amiloride pre-treatment did not result in a significant improvement in respiratory function or mucus clearance, in contrast to pre-treatment with placebo. There were no significant differences identified in other

  2. Sodium channel blockers for cystic fibrosis.

    PubMed

    Burrows, Elinor F; Southern, Kevin W; Noone, Peadar G

    2012-03-14

    People with cystic fibrosis (CF) have increased transport of the salt, sodium across their airway lining. Over-absorption of sodium results in the dehydration of the liquid that lines the airway surface and is a primary defect in people with CF. To determine whether the topical administration of drugs that block sodium transport improves the respiratory condition of people with CF. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We contacted principal investigators known to work in the field, previous authors and pharmaceutical companies who manufacture ion transport agents for unpublished or follow-up data.Most recent search of the Group's register: 22nd August 2011. Published or unpublished randomised controlled trials (RCTs) or quasi-randomised controlled trials of sodium channel blockers compared to placebo or another sodium channel blocker or the same sodium channel blocker at a different dosing regimen. Two authors independently extracted data. Meta-analysis was limited due to differing study designs. Five RCTs, with a total of 226 participants, examining the topical administration of the short-acting sodium channel blocker, amiloride, compared to placebo were identified as eligible for inclusion in the review. In three studies over six months, there was a significant difference found in the difference in relative change in FVC in favour of placebo (weighted mean difference 1.51% (95% confidence interval -2.77 to -0.25), although heterogeneity was evident. A two-week study demonstrated that hypertonic saline with amiloride pre-treatment did not result in a significant improvement in respiratory function or mucus clearance, in contrast to pre-treatment with placebo. There were no significant differences identified in other clinically relevant outcomes. We found no

  3. Calcium Stone Growth in Urine from Cystic Fibrosis Patients and Healthy Controls

    NASA Astrophysics Data System (ADS)

    McSorley, Anita; Jones, Andrew M.; Webb, A. Kevin; Rao, P. Nagaraj; Kavanagh, John P.

    2007-04-01

    Cystic fibrosis patients have an increased risk of renal stone disease. There is some evidence that this may be related to a different excretory pattern of stone risk factors, but an alternative hypothesis, that the urine of cystic fibrosis patients is deficient in urinary inhibitors of crystallization and stone formation has not been tested. Here we have grown calcium stones, in vitro, in the presence of urine from healthy controls and compared this with growth in the presence of urine from cystic fibrosis patients. A stone farm was used to grow twelve calcium stones simultaneously, firstly in artificial urine for about 200 hours and then in 90% whole human urine for another 500 hours. Six of the stones received urine from healthy controls and six received urine from adult cystic fibrosis patients. There were no significant differences in stone mass at any of the key time points or in the overall growth pattern (p>0.05) between stones destined for, or treated with, urine from CF patients and the controls. Human urine greatly inhibited stone growth in vitro but there was no difference in the growth rate in urine from healthy controls and CF patients. This refutes the hypothesis that a tendency for a higher prevalence of urinary stones in CF patients is related to a deficiency in inhibitory activity.

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

    PubMed

    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, p<0.0012; 75 μM: 32% fall, p<0.0001). Samples from cystic fibrosis patients (n = 3) showed similar results (150 μM: 55% fall, p = 0.001). Ciliary beat frequency inhibition was not due to loss of cell viability and was reversible. The inhibitory mechanism was independent of ATP levels. KCN also significantly inhibited ciliary beat frequency in ALI cultures, albeit to a lesser extent. Ciliary beat frequency measurements on ALI cultures treated with culture supernatants from P. aeruginosa mutants defective in virulence factor production implicated cyanide 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.

  5. Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis and non-cystic fibrosis bronchiectasis.

    PubMed

    Alyasin, Soheila; Moghtaderi, Mozhgan; Farjadian, Shirin; Babaei, Maryam; Teshnizi, Saeed Hosseini

    2018-01-01

    Aspergillus sensitization (AS) and allergic bronchopulmonary aspergillosis (ABPA) can occur as a cause of permanent lung damage in patients with cystic fibrosis (CF) and non-CF bronchiectasis. The aim of this study was to determine the frequency of AS and ABPA in patients with CF and non-CF bronchiectasis in southwestern Iran. This cross-sectional study was conducted on 33 patients with CF and 27 patients with non-CF bronchiectasis from southwestern Iran who were referred to Namazi Hospital affiliated to Shiraz University of Medical Sciences from July 2015 to February 2016. Skin prick test to Aspergillus fumigatus, peripheral blood eosinophil count, total serum IgE, specific IgE and IgG against Aspergillus fumigatus as well as radiologic chest studies were done for each patient. Statistical analysis was done by Mann-Whitney U test, Fisher Exact test, and Kappa weighted in SPSS software version 18. Level of significance was set at p<0.05. Nine patients with CF (27.3%) and one patient with non-CF bronchiectasis (3.7%) had positive skin tests to Aspergillus. There was 81.2% agreement between positive skin test and specific IgE to Aspergillus fumigatus (p<0.001). Three patients with CF (9%) met the diagnostic criteria for ABPA, whereas ABPA was not seen in patients with non-CF bronchiectasis. ABPA was low in this study, considering more frequency of AS in patients with cystic fibrosis, clinicians should keep in mind the diagnosis of ABPA for those CF patients that do not respond to usual medical therapy and have positive skin tests to Aspergillus allergens.

  6. Chronic Rhinosinusitis in Patients with Cystic Fibrosis.

    PubMed

    Hamilos, Daniel L

    2016-01-01

    Chronic rhinosinusitis (CRS) is highly prevalent in patients with cystic fibrosis (CF) and accounts for significant morbidity and contribution to CF lung disease. Mutations of the cystic fibrosis transmembrane regulator gene occur with increased prevalence in patients with CRS without CF, suggesting some contribution to CRS pathophysiology. Nasal polyps (NPs) occur with increased prevalence in patients with CF of all ages and have a more neutrophilic appearance with fewer eosinophils and increased submucosal glandular elements in comparison to NPs from patients without CF. Mainstays of medical treatment include isotonic saline irrigations and topical intranasal glucocorticoids, with some evidence that topical intranasal glucocorticoids reduce NP size. Although inhaled hypertonic saline (7%) has been widely studied as a mucolytic agent for CF lung disease, there are no reports of its use in CF CRS. Mucolytics have also not been studied as a treatment for CRS in CF, and most evidence does not support their use for CF lung disease. Nasally nebulized dornase alfa (recombinant human deoxyribonuclease) following sinus surgery shows promise for treatment. Other unproven therapies include addition of baby shampoo to isotonic saline to potentially thin mucus and help prevent biofilm formation. There are no data to support the use of low-dose oral macrolide antibiotics or the use of prophylactic oral antibiotics for CRS in patients with CF. However, there is some support for the use of topical antibiotics, including colistimethate sodium or tobramycin, administered as a sinus irrigation or antral lavage in patients following sinus surgery when susceptible bacteria are cultured. Key components of CF sinus surgical management include extensive surgery to ensure that the maxillary, frontal, sphenoid, and ethmoid sinuses are all widely opened with smoothing of bony overhangs to prevent mucus retention and bacterial recolonization, postoperative meticulous daily nasal irrigations

  7. [Pancreatic infringement exocrine and endocrine in cystic fibrosis].

    PubMed

    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

  8. Effect of amiloride and saline on nasal mucociliary clearance and potential difference in cystic fibrosis and normal subjects.

    PubMed Central

    Middleton, P. G.; Geddes, D. M.; Alton, E. W.

    1993-01-01

    BACKGROUND--Mucociliary clearance is an important component of pulmonary defence. Maximum clearance is thought to depend on an optimal depth of the sol layer, allowing the most efficient interaction between the cilia and the overlying mucus layer. Sodium absorption, the major ion transport in human airways, is thought to be important in the regulation of the depth of the sol layer. In the airways of patients with cystic fibrosis sodium absorption is increased and mucociliary clearance decreased. Amiloride, a sodium channel blocker, has been shown to improve pulmonary mucociliary clearance in patients with cystic fibrosis. However, its effects on nasal mucociliary clearance in either normal subjects or those with cystic fibrosis are unknown. A study was therefore performed to investigate whether nebulised amiloride improves nasal mucociliary clearance in normal or cystic fibrosis subjects. METHODS--Nasal mucociliary clearance was measured by the saccharin clearance technique in 12 normal subjects and 12 with cystic fibrosis. For the control study measurements were made on two consecutive days and the mean time for each subject averaged. For the drug study measurements were also made on two consecutive days, after administration of nasally nebulised amiloride or placebo (saline) in a double blind manner. Nasal potential difference was measured in eight patients with cystic fibrosis after the administration of amiloride or placebo to assess the efficacy of deposition and duration of action. RESULTS--Baseline values of mucociliary clearance were significantly faster in the normal subjects than in those with cystic fibrosis. In both groups mucociliary clearance was increased after both saline and amiloride, with no significant difference between either treatment. As previously reported, baseline nasal potential difference was significantly more negative in the subjects with cystic fibrosis. Amiloride significantly reduced the potential difference for at least 60 minutes

  9. Cystic Fibrosis Heterozygote Resistance to Cholera Toxin in the Cystic Fibrosis Mouse Model

    NASA Astrophysics Data System (ADS)

    Gabriel, Sherif E.; Brigman, Kristen N.; Koller, Beverly H.; Boucher, Richard C.; Stutts, M. Jackson

    1994-10-01

    The effect of the number of cystic fibrosis (CF) alleles on cholera toxin (CT)-induced intestinal secretion was examined in the CF mouse model. CF mice that expressed no CF transmembrane conductance regulator (CFTR) protein did not secrete fluid in response to CT. Heterozygotes expressed 50 percent of the normal amount of CFTR protein in the intestinal epithelium and secreted 50 percent of the normal fluid and chloride ion in response to CT. This correlation between CFTR protein and CT-induced chloride ion and fluid secretion suggests that CF heterozygotes might possess a selective advantage of resistance to cholera.

  10. Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis.

    PubMed

    Furlan, Larissa Lazzarini; Ribeiro, José Dirceu; Bertuzzo, Carmen Sílvia; Salomão Junior, João Batista; Souza, Dorotéia Rossi Silva; Marson, Fernando Augusto Lima

    Interleukin 8 protein promotes inflammatory responses, even in airways. The presence of interleukin 8 gene variants causes altered inflammatory responses and possibly varied responses to inhaled bronchodilators. Thus, this study analyzed the interleukin 8 variants (rs4073, rs2227306, and rs2227307) and their association with the response to inhaled bronchodilators in cystic fibrosis patients. Analysis of interleukin 8 gene variants was performed by restriction fragment length polymorphism of polymerase chain reaction. The association between spirometry markers and the response to inhaled bronchodilators was evaluated by Mann-Whitney and Kruskal-Wallis tests. The analysis included all cystic fibrosis patients, and subsequently patients with two mutations in the cystic fibrosis transmembrane conductance regulator gene belonging to classes I to III. This study included 186 cystic fibrosis patients. There was no association of the rs2227307 variant with the response to inhaled bronchodilators. The rs2227306 variant was associated with FEF 50% in the dominant group and in the group with two identified mutations in the cystic fibrosis transmembrane conductance regulator gene. The rs4073 variant was associated with spirometry markers in four genetic models: co-dominant (FEF 25-75% and FEF 75% ), dominant (FEV 1 , FEF 50% , FEF 75% , and FEF 25-75% ), recessive (FEF 75% and FEF 25-75% ), and over-dominant (FEV 1 /FVC). 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. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  11. Clinical presentation of cystic fibrosis at the time of diagnosis: a multicenter study in a region without newborn screening.

    PubMed

    Farahmand, Fatemeh; Khalili, Manijeh; Shahbaznejad, Leila; Hirbod-Mobarakeh, Armin; Najafi Sani, Mehri; Khodadad, Ahmad; Motamed, Farzaneh; Rezaei, Nima

    2013-01-01

    Cystic fibrosis is the most common inherited lethal disease, which could be frequently identified late in regions without newborn screening. There are dramatically better outcomes in the early diagnosis of cystic fibrosis patients. This study aimed to evaluate the spectrum of manifestations of cystic fibrosis at first admission leading to diagnosis. This study was performed in a multi-referral pediatrics center in Iran. Data of patients with cystic fibrosis at the time of diagnosis were recorded based on a checklist denoting demographic characteristics, clinical and laboratory features. All of the patients had two documented sweat chloride tests. One hundred and ninety seven patients with cystic fibrosis were enrolled in this study. Among them, 119 patients (74%) were less than six months and 34 patients (21%) were between 6 and 12 months of age. The most common clinical findings were failure to thrive, recurrent pulmonary infections, and steatorrhea in 178 (90%), 139 (71%), and 135 (69%) patients, respectively. The most common radiologic abnormality was hyperaeration. In patients with salty tasting skin, steatorrhea, metabolic alkalosis, radiologic findings, and liver function abnormalities, the mean age at the time of diagnosis was significantly low than in the subjects without these findings. This study suggests that some conditions such as failure to thrive, recurrent respiratory infections, steatorrhea, metabolic alkalosis, and salty tasting skin should be considered as clinical screening tools for cystic fibrosis, especially in regions with high rate of cystic fibrosis. In these regions, awareness and clinical suspicion of medical professionals are crucial for early diagnosis of cystic fibrosis patients in the pre-diagnostic period.

  12. Nutritional assessment in children with cystic fibrosis

    USDA-ARS?s Scientific Manuscript database

    Optimal nutrition, including consuming 35–40% of calories (kcal) as fat, is a vital part of the management of cystic fibrosis (CF), and involves accurate assessment of dietary intake. We compared 3 methods of nutritional assessment in 8– to 14-year-old children (n=20) with CF: 1) a 24-h Dietary Reca...

  13. Fungi in cystic fibrosis and non-cystic fibrosis bronchiectasis.

    PubMed

    Moss, Richard B

    2015-04-01

    Bronchiectasis is a pathologic bronchial dilatation with loss of function that can result from multiple inflammatory and infectious injuries to the conducting airways of the lung. Molds, particularly the filamentous fungus Aspergillus fumigatus, have been implicated as a common cause of both cystic fibrosis (CF) and non-CF bronchiectasis, the latter primarily in patients with severe asthma. The pathogenesis of mold-associated bronchiectasis is usually due to atopic sensitization to mold allergens in the presence of active chronic endobronchial fungal infection with host innate and adaptive immune deviation to a Th2-dominated inflammation, a condition known as allergic bronchopulmonary aspergillosis (ABPA) (or allergic bronchopulmonary mycosis if a non-Aspergillus mold is implicated). Diagnostic criteria of ABPA continue to evolve, while treatment relies upon downregulation of the allergic inflammatory response with immunomodulatory agents and antifungal pharmacotherapy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  14. Pediatric and adult lung transplantation for cystic fibrosis.

    PubMed

    Mendeloff, E N; Huddleston, C B; Mallory, G B; Trulock, E P; Cohen, A H; Sweet, S C; Lynch, J; Sundaresan, S; Cooper, J D; Patterson, G A

    1998-02-01

    This paper was undertaken to review the experience at our institution with bilateral sequential lung transplantation for cystic fibrosis. Since 1989, 103 bilateral sequential lung transplants for cystic fibrosis have been performed (46 pediatric, 48 adult, 9 redo); the mean age was 21 +/- 10 years. Cardiopulmonary bypass was used in all but one pediatric (age <18) transplant, and in 15% of adults. Hospital mortality was 4.9%, with 80% of early deaths related to infection. Bronchial anastomotic complications occurred with equal frequency in the pediatric and the adult populations (7.3%). One- and 3-year actuarial survival are 84% and 61%, respectively (no significant difference between pediatric and adult age groups; average follow-up 2.1 +/- 1.6 years). Mean forced expiratory volume in 1 second increased from 25% +/- 9% before transplantation to 79% +/- 35% 1 year after transplantation. Acute rejection occurred 1.7 times per patient-year, with most episodes taking place within the first 6 months after transplantation. The need for treatment of lower respiratory tract infections occurred 1.2 times per patient in the first year after transplantation. Actuarial freedom from bronchiolitis obliterans was 63% at 2 years and 43% at 3 years. Redo transplantation was performed only in the pediatric population and was associated with an early mortality of 33%. Eight living donor transplants (four primary transplants, four redo transplants) were performed with an early survival of 87.5%. Patients with end-stage cystic fibrosis can undergo bilateral lung transplantation with morbidity and mortality comparable to that seen in pulmonary transplantation for other disease entities.

  15. Association of High-Dose Ibuprofen Use, Lung Function Decline, and Long-Term Survival in Children with Cystic Fibrosis.

    PubMed

    Konstan, Michael W; VanDevanter, Donald R; Sawicki, Gregory S; Pasta, David J; Foreman, Aimee J; Neiman, Evgueni A; Morgan, Wayne J

    2018-04-01

    Cystic fibrosis deaths result primarily from lung function loss, so chronic respiratory therapies, intended to preserve lung function, are cornerstones of cystic fibrosis care. Although treatment-associated reduction in rate of lung function loss should ultimately improve cystic fibrosis survival, no such relationship has been described for any chronic cystic fibrosis therapy. In part, this is because the ages of most rapid lung function decline-early adolescence-precede the median age of cystic fibrosis deaths by more than a decade. To study associations of high-dose ibuprofen treatment with the rate of forced expiratory volume in 1 second decline and mortality among children followed in the Epidemiologic Study of Cystic Fibrosis and subsequently in the U.S. Cystic Fibrosis Foundation Patient Registry. We performed a matched cohort study using data from Epidemiologic Study of Cystic Fibrosis. Exposure was defined as high-dose ibuprofen use reported at ≥80% of encounters over 2 years. Unexposed children were matched to exposed children 5:1 using propensity scores on the basis of demographic, clinical, and treatment covariates. The rate of decline of percent predicted forced expiratory volume in 1 second during the 2-year follow-up period was estimated by mixed-effects modeling with random slopes and intercepts. Survival over 16 follow-up years in the U.S. Cystic Fibrosis Foundation Patient Registry was compared between treatment groups by using proportional hazards modeling controlling for matching and covariates. We included 775 high-dose ibuprofen users and 3,665 nonusers who were well matched on demographic, clinical, and treatment variables. High-dose ibuprofen users declined on average 1.10 percent predicted forced expiratory volume in 1 second/yr (95% confidence interval; 0.51, 1.69) during the 2-year treatment period, whereas nonusers declined at a rate of 1.76% percent predicted forced expiratory volume in 1 second/yr (95% confidence interval; 1.48, 2

  16. Dual core quantum dots for highly quantitative ratiometric detection of trypsin activity in cystic fibrosis patients

    NASA Astrophysics Data System (ADS)

    Castelló Serrano, Iván; Stoica, Georgiana; Matas Adams, Alba; Palomares, Emilio

    2014-10-01

    We present herein two colour encoded silica nanospheres (2nanoSi) for the fluorescence quantitative ratiometric determination of trypsin in humans. Current detection methods for cystic fibrosis diagnosis are slow, costly and suffer from false positives. The 2nanoSi proved to be a highly sensitive, fast (minutes), and single-step approach nanosensor for the screening and diagnosis of cystic fibrosis, allowing the quantification of trypsin concentrations in a wide range relevant for clinical applications (25-350 μg L-1). Furthermore, as trypsin is directly related to the development of cystic fibrosis (CF), different human genotypes, i.e. CF homozygotic, CF heterozygotic, and unaffected, respectively, can be determined using our 2nanoSi nanospheres. We anticipate the 2nanoSi system to be a starting point for non-invasive, easy-to-use and cost effective ratiometric fluorescent biomarkers for recessive genetic diseases like human cystic fibrosis. In a screening program in which the goal is to detect disease and also the carrier status, early diagnosis could be of great help.We present herein two colour encoded silica nanospheres (2nanoSi) for the fluorescence quantitative ratiometric determination of trypsin in humans. Current detection methods for cystic fibrosis diagnosis are slow, costly and suffer from false positives. The 2nanoSi proved to be a highly sensitive, fast (minutes), and single-step approach nanosensor for the screening and diagnosis of cystic fibrosis, allowing the quantification of trypsin concentrations in a wide range relevant for clinical applications (25-350 μg L-1). Furthermore, as trypsin is directly related to the development of cystic fibrosis (CF), different human genotypes, i.e. CF homozygotic, CF heterozygotic, and unaffected, respectively, can be determined using our 2nanoSi nanospheres. We anticipate the 2nanoSi system to be a starting point for non-invasive, easy-to-use and cost effective ratiometric fluorescent biomarkers for

  17. [Molecular diagnosis of two Chinese cystic fibrosis children and literature review].

    PubMed

    Xu, B P; Wang, H; Zhao, Y H; Liu, J; Yao, Y; Feng, X L; Shen, K L

    2016-05-01

    To investigate the clinical manifestations and molecular features of cystic fibrosis in Chinese children. A retrospective analysis of two pediatric cystic fibrosis cases diagnosed by gene test in Beijing Children's Hospital, Capital Medical University from 2010 to 2015, and Chinese cystic fibrosis reported patients searched of"cystic fibrosis, Chinese"on Chinese databases (CNKI, Wanfang Data) and PubMed from 1975 to 2015.The clinical manifestations and molecular features were analyzed. One of the two newly diagnosed cystic fibrosis cases was a 10-year old girl who suffered from reccurent cough with expectoration and associated with cirrhosis.Sweat tests showed increased chloride twice with the lower level of 306.82 mmol/L.The other was an 8-month old boy with reccurent pneumonia from neonate, failure to thrive and fatty diarrhea.Two children had various degrees of bronchiectasis and massive sticky secretion on the bronchoscopy.They had no family history and their parents had no consanguineous marriage.CFTR mutations of c. 595C>T and c. 2290C>T were found in gene tests.On the database, twenty-one reports involving thirty-six Chinese patients (16 males and 20 females) were retrieved.Together with this group of 2 cases, a total of 38 cases were involved.The age at diagnosis was 4 months to 28 years with a median age of 10 years.All patients had reccurent respiratory infections, twenty-seven cases (71%) had malnutrition, fifteen (39%)had chronic diarrhea, and 16 cases (42%) had other digestive manifestations, including jaundice (4 cases), hepatomegaly (11 cases), ascites (2 cases) and pancreatic atrophy (3 cases). Five cases had a positive family history and six cases had a suspicious family history.Consanguineous marriage was found in three families.Sweat test revealed elevated chloride (52-327 mmol/L) in 28 cases.Eight of the 16 patients who performed pancreatic exocrine function examination showed pancreatic insufficiency.Eighteen of the 20 patients described the

  18. The porcine lung as a potential model for cystic fibrosis

    PubMed Central

    Rogers, Christopher S.; Abraham, William M.; Brogden, Kim A.; Engelhardt, John F.; Fisher, John T.; McCray, Paul B.; McLennan, Geoffrey; Meyerholz, David K.; Namati, Eman; Ostedgaard, Lynda S.; Prather, Randall S.; Sabater, Juan R.; Stoltz, David Anthony; Zabner, Joseph; Welsh, Michael J.

    2008-01-01

    Airway disease currently causes most of the morbidity and mortality in patients with cystic fibrosis (CF). However, understanding the pathogenesis of CF lung disease and developing novel therapeutic strategies have been hampered by the limitations of current models. Although the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) has been targeted in mice, CF mice fail to develop lung or pancreatic disease like that in humans. In many respects, the anatomy, biochemistry, physiology, size, and genetics of pigs resemble those of humans. Thus pigs with a targeted CFTR gene might provide a good model for CF. Here, we review aspects of porcine airways and lung that are relevant to CF. PMID:18487356

  19. Heritability of Respiratory Infection with Pseudomonas aeruginosa in Cystic Fibrosis

    PubMed Central

    Green, Deanna M.; Collaco, J. Michael; McDougal, Kathryn E.; Naughton, Kathleen M.; Blackman, Scott M.; Cutting, Garry R.

    2013-01-01

    Objective To quantify the relative contribution of factors other than cystic fibrosis transmembrane conductance regulator genotype and environment on the acquisition of Pseudomonas aeruginosa (Pa) by patients with cystic fibrosis. Study design Lung infection with Pa and mucoid Pa was assessed using a co-twin study design of 44 monozygous (MZ) and 17 dizygous (DZ) twin pairs. Two definitions were used to establish infection: first positive culture and persistent positive culture. Genetic contribution to infection (ie, heritability) was estimated based on concordance analysis, logistic regression, and age at onset of infection through comparison of intraclass correlation coefficients. Results Concordance for persistent Pa infection was higher in MZ (0.83; 25 of 30 pairs) than DZ twins (0.45; 5 of 11 pairs), generating a heritability of 0.76. Logistic regression adjusted for age corroborated genetic control of persistent Pa infection. The correlation for age at persistent Pa infection was higher in MZ twins (0.589; 95% CI, 0.222-0.704) than in DZ twins (0.162; 95% CI, −0.352 to 0.607), generating a heritability of 0.85. Conclusion Genetic modifiers play a significant role in the establishment and timing of persistent Pa infection in individuals with cystic fibrosis. PMID:22364820

  20. Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.

    PubMed

    Jat, Kana R; Walia, Dinesh K; Khairwa, Anju

    2018-03-18

    Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review. To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. 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. Last search: 29 September 2017.We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 24 January 2018. Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager. Only one

  1. Lung Infections Associated with Cystic Fibrosis

    PubMed Central

    Lyczak, Jeffrey B.; Cannon, Carolyn L.; Pier, Gerald B.

    2002-01-01

    While originally characterized as a collection of related syndromes, cystic fibrosis (CF) is now recognized as a single disease whose diverse symptoms stem from the wide tissue distribution of the gene product that is defective in CF, the ion channel and regulator, cystic fibrosis transmembrane conductance regulator (CFTR). Defective CFTR protein impacts the function of the pancreas and alters the consistency of mucosal secretions. The latter of these effects probably plays an important role in the defective resistance of CF patients to many pathogens. As the modalities of CF research have changed over the decades from empirical histological studies to include biophysical measurements of CFTR function, the clinical management of this disease has similarly evolved to effectively address the ever-changing spectrum of CF-related infectious diseases. These factors have led to the successful management of many CF-related infections with the notable exception of chronic lung infection with the gram-negative bacterium Pseudomonas aeruginosa. The virulence of P. aeruginosa stems from multiple bacterial attributes, including antibiotic resistance, the ability to utilize quorum-sensing signals to form biofilms, the destructive potential of a multitude of its microbial toxins, and the ability to acquire a mucoid phenotype, which renders this microbe resistant to both the innate and acquired immunologic defenses of the host. PMID:11932230

  2. CFTR Genotype and Maximal Exercise Capacity in Cystic Fibrosis: A Cross-sectional Study.

    PubMed

    Radtke, Thomas; Hebestreit, Helge; Gallati, Sabina; Schneiderman, Jane E; Braun, Julia; Stevens, Daniel; Hulzebos, Erik Hj; Takken, Tim; Boas, Steven R; Urquhart, Don S; Lands, Larry C; Tejero, Sergio; Sovtic, Aleksandar; Dwyer, Tiffany; Petrovic, Milos; Harris, Ryan A; Karila, Chantal; Savi, Daniela; Usemann, Jakob; Mei-Zahav, Meir; Hatziagorou, Elpis; Ratjen, Felix; Kriemler, Susi

    2018-02-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in human skeletal muscle cells. Variations of CFTR dysfunction among patients with cystic fibrosis may be an important determinant of maximal exercise capacity in cystic fibrosis. Previous studies on the relationship between CFTR genotype and maximal exercise capacity are scarce and contradictory. This study was designed to explore factors influencing maximal exercise capacity, expressed as peak oxygen uptake (V.O2peak), with a specific focus on CFTR genotype in children and adults with cystic fibrosis. In an international, multicenter, cross-sectional study, we collected data on CFTR genotype and cardiopulmonary exercise tests in patients with cystic fibrosis who were ages 8 years and older. CFTR mutations were classified into functional classes I–V. The final analysis included 726 patients (45% females; age range, 8–61 yr; forced expiratory volume in 1 s, 16 to 123% predicted) from 17 cystic fibrosis centers in North America, Europe, Australia, and Asia, all of whom had both valid maximal cardiopulmonary exercise tests and complete CFTR genotype data. Overall, patients exhibited exercise intolerance (V.O2peak, 77.3 ± 19.1% predicted), but values were comparable among different CFTR classes. We did not detect an association between CFTR genotype functional classes I–III and either V.O2peak (percent predicted) (adjusted β = −0.95; 95% CI, −4.18 to 2.29; P = 0.57) or maximum work rate (Wattmax) (adjusted β = −1.38; 95% CI, −5.04 to 2.27; P = 0.46) compared with classes IV–V. Those with at least one copy of a F508del-CFTR mutation and one copy of a class V mutation had a significantly lower V.O2peak (β = −8.24%; 95% CI, −14.53 to −2.99; P = 0.003) and lower Wattmax (adjusted β = −7.59%; 95% CI, −14.21 to −0.95; P = 0.025) than those with two copies of a class II mutation. On the basis of linear regression analysis adjusted for

  3. Lack of harmonization in sweat testing for cystic fibrosis - a national survey.

    PubMed

    Christiansen, Anne Lindegaard; Nybo, Mads

    2014-11-01

    Sweat testing is used in the diagnosis of cystic fibrosis. Interpretation of the sweat test depends, however, on the method performed since conductivity, osmolality and chloride concentration all can be measured as part of a sweat test. The aim of this study was to investigate how performance of the test is organized in Denmark. Departments conducting the sweat test were contacted and interviewed following a premade questionnaire. They were asked about methods performed, applied NPU (Nomenclature for Properties and Units) code, reference interval, recommended interpretation and referred literature. 14 departments performed the sweat test. One department measured chloride and sodium concentration, while 13 departments measured conductivity. One department used a non-existing NPU code, two departments applied NPU codes inconsistent with the method performed, four departments applied no NPU code and seven applied a correct NPU code. Ten of the departments measuring conductivity applied reference intervals. Nine departments measuring conductivity had recommendations of a normal area, a grey zone and a pathological value, while four departments only applied a normal and grey zone or a pathological value. Cut-off values for normal, grey and pathological areas were like the reference intervals inconsistent. There is inconsistent use of NPU codes, reference intervals and interpretation of sweat conductivity used in the process of diagnosing cystic fibrosis. Because diagnosing cystic fibrosis is a combined effort between local pediatric departments, biochemical and genetic departments and cystic fibrosis centers, a national harmonization is necessary to assure correct clinical use.

  4. Bronchocele density in cystic fibrosis as an indicator of allergic broncho-pulmonary aspergillosis: A preliminary study.

    PubMed

    Occelli, Aurélie; Soize, Sébastien; Ranc, Caroline; Giovannini-Chami, Lisa; Bailly, Carole; Leloutre, Béatrice; Boyer, Corinne; Baque-Juston, Marie

    2017-08-01

    Allergic broncho-pulmonary aspergillosis (ABPA) is a severe and under-diagnosed complication of cystic fibrosis (CF). The aim of the study was to determine whether the mucus content of bronchoceles in cystic fibrosis complicated with ABPA reveals a higher density than the mucus content of non-ABPA cystic fibrosis. We studied retrospectively 43 computed tomography scans (CT scans) of a pediatric population of cystic fibrosis patients. We measured the mucus attenuation in Hounsfield Units (HU) of all bronchoceles >5mm in diameter. We found bronchoceles >5mm in 13/43 patients. 5/13 patients had a positive diagnosis of ABPA. The median HU value of bronchoceles was higher in patients with than without ABPA [98 HU (26-135) vs 28 HU (10-36); P=0,02]. Moreover, all patients with a bronchocele density >36HU were ABPA positive. CF complicated with ABPA shows higher attenuation bronchoceles on CT scans of the chest. Systematic density measurements of bronchoceles could help to raise the difficult diagnosis of ABPA in patients suffering from cystic fibrosis. Larger series could confirm a threshold in HU which could become a new imaging criterion for the diagnosis of ABPA. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Severe Achromobacter xylosoxidans infection and loss of sputum bacterial diversity in an adult patient with cystic fibrosis.

    PubMed

    Talbot, Nick P; Flight, William G

    2016-08-01

    Achromobacter spp. are emerging pathogens in the lungs of patients with cystic fibrosis. We report the case of an adult patient with cystic fibrosis and chronic A. xylosoxidans infection who experienced rapid, progressive clinical deterioration. Metagenomic analysis of the sputum revealed that the airway microbiota was almost entirely dominated by A. xylosoxidans. We review the impact of this organism on lung function and the airway microbiome in cystic fibrosis, and discuss the potential for cross-infection between patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Psychosocial distress and functioning of Greek youth with cystic fibrosis: a cross-sectional study.

    PubMed

    Kostakou, Konstantina; Giannakopoulos, George; Diareme, Stavroula; Tzavara, Chara; Doudounakis, Stavros; Christogiorgos, Stelios; Bakoula, Chryssa; Kolaitis, Gerasimos

    2014-01-01

    To assess psychosocial functioning and distress of children and adolescents with cystic fibrosis compared to healthy controls. Thirty-six patients with cystic fibrosis aged 8-18 years (24 boys, mean age ± SD: 11.5 ± 2.6 years) and 31 sex- and age-matched healthy control subjects (18 boys, mean age ± SD: 12 ± 2.5 years) were enrolled in the study. In order to assess the self-esteem, social adjustment, and family functioning of these young people, the Culture-free Self-esteem Inventory, the Social Adjustment Scale-Self-Report, and the Family Assessment Device were administered. Emotional/ behavioral problems were assessed through the Youth Self Report and the Child Behavior Checklist given to both the subjects and their parents. No significant differences were found for self-esteem between the two study groups. Regarding social adjustment, children with cystic fibrosis reported significantly worse friendship and overall adjustment (P < 0.05). Moreover, no difference was found in the levels of family functioning between the two groups. No significant differences between the groups were found in emotional/ behavioral problems from the self-reports. On the contrary, parents of children with cystic fibrosis reported significantly higher levels of withdrawal/ depression, thought problems, and delinquent behavior (P ≤ 0.01) as compared to controls. Children and adolescents with cystic fibrosis appear to be a psychosocially vulnerable group. A biopsychosocial approach should emphasize the assessment and treatment of the psychosocial distress of these patients alongside multiple somatic treatments.

  7. Exploring the need for Transition Readiness Scales within cystic fibrosis services: A qualitative descriptive study.

    PubMed

    Bourke, Mary; Houghton, Catherine

    2018-07-01

    To explore healthcare professionals' and patients' perceptions of the potential use of a Transition Readiness Scale in cystic fibrosis care. This included an examination of barriers and facilitators to its implementation along with the identification of key items to include in a Transition Readiness Scale. Due to increasing life expectancy and improved quality of life, more adolescents with cystic fibrosis are transitioning from paediatric to adult health care. To assess and correctly manage this transition, a more structured approach to transition is advocated. This can be achieved using a Transition Readiness Scale to potentially identify or target areas of care in which the adolescent may have poor knowledge. These key items include education, developmental readiness taking into account relationships, reproduction, future plans and self-management skills. Existing tools to gauge readiness concentrate mainly on education and self-care needs assessment as their key items. Currently, there is no specific cystic fibrosis Transition Readiness Scale in use in Ireland or internationally. The study used a descriptive qualitative design. Data were collected using semi-structured interviews (n = 8) and analysed using a thematic approach. The findings identified the potential benefits of this tool and second the resources which need to be in place before its development and implementation into cystic fibrosis services. Transition Readiness Scales have substantial relevance with cystic fibrosis services emphasising the importance of establishing the necessary resources prior to its implementation. These were identified as more staff, a dedicated private space and staff training and education. Significant resources are needed to fully integrate Transition Readiness Scales in practice. The study findings suggest multidisciplinary collaborations, and patient engagement is pivotal in planning and easing the transition process for adolescents with cystic fibrosis. © 2018 The

  8. Self-Efficacy, Pulmonary Function, Perceived Health and Global Quality of Life of Cystic Fibrosis Patients

    ERIC Educational Resources Information Center

    Wahl, Astrid K.; Rustoen ,Tone; Hanestad, Berit R.; Gjengedal, Eva; Moum, Torbjorn

    2005-01-01

    This study examined the extent that pulmonary function is related to perceived health status and global quality of life in adults suffering from cystic fibrosis, and the extent that self-efficacy modifies these relationships. Our sample comprised 86 adults (48% female; mean age, 29 years; age range, 18-54 years) with cystic fibrosis, recruited…

  9. Cystic fibrosis-related diabetes compared with type 1 and type 2 diabetes in adults.

    PubMed

    Konrad, Katja; Scheuing, Nicole; Badenhoop, Klaus; Borkenstein, Martin H; Gohlke, Bettina; Schöfl, Christof; Seufert, Jochen; Thon, Angelika; Holl, Reinhard W

    2013-10-01

    With increasing life expectancy of patients with cystic fibrosis (CF), secondary diabetes becomes more prevalent. It appears to be the most common co-morbidity in persons with cystic fibrosis. Therefore, the objective of our study was to describe characteristics of cystic fibrosis-related diabetes compared with type 1 and 2 diabetes (T1DM/T2DM) in adults. Data from 218 436 patients >18 years with cystic fibrosis (n = 401), T1DM (n = 32,409) or T2DM (n = 185 626) in the multicenter Diabetes-Patienten-Verlaufsdokumentation or prospective documentation of diabetes patients registry were analysed. Diabetes onset [median (interquartile range)] in cystic fibrosis [18.70 (15.50-25.30) years] was between T1DM [16.40 (10.50-31.80) years] and T2DM [58.50 (48.80-68.00) years], with female preponderance. Body mass index (BMI) and glycosylated haemoglobin (HbA1c ) were lowest (19.6 [18.1-21.5] kg/m(2) )/50 mmol/mol (6.73%) versus T1DM (24.4 [22.1-27.4])/62 mmol/mol (7.83%) vs. T2DM (29.6 [26.1-33.9])/54 mmol/mol (7.06%); all p < 0.01. A total of 78.6% of cystic fibrosis patients with diabetes received insulin. Insulin dose (0.74 IE/kg bodyweight) was not significantly different from T1DM (0.73) and T2DM (0.76). Frequency of vascular complications, adjusted for confounding effects, across the groups was different: Hypertension (CFRD 16.1% vs. T1DM 24.0% vs. T2DM 32.2%; all p < 0.01), retinopathy (CFRD 10.7% vs. T1DM 10.4% vs. T2DM 10.5%, not significant), nephropathy (CFRD 25.2% vs. T1DM 17.2% vs. T2DM 24.7%; only T1DM/T2DM; p < 0.01). CFRD is a uniquely complex entity with clear differences from T1DM and T2DM in adults. Copyright © 2013 John Wiley & Sons, Ltd.

  10. Survival Comparison of Patients With Cystic Fibrosis in Canada and the United States: A Population-Based Cohort Study.

    PubMed

    Stephenson, Anne L; Sykes, Jenna; Stanojevic, Sanja; Quon, Bradley S; Marshall, Bruce C; Petren, Kristofer; Ostrenga, Josh; Fink, Aliza K; Elbert, Alexander; Goss, Christopher H

    2017-04-18

    In 2011, the median age of survival of patients with cystic fibrosis reported in the United States was 36.8 years, compared with 48.5 years in Canada. Direct comparison of survival estimates between national registries is challenging because of inherent differences in methodologies used, data processing techniques, and ascertainment bias. To use a standardized approach to calculate cystic fibrosis survival estimates and to explore differences between Canada and the United States. Population-based study. 42 Canadian cystic fibrosis clinics and 110 U.S. cystic fibrosis care centers. Patients followed in the Canadian Cystic Fibrosis Registry (CCFR) and U.S. Cystic Fibrosis Foundation Patient Registry (CFFPR) between 1990 and 2013. Cox proportional hazards models were used to compare survival between patients followed in the CCFR (n = 5941) and those in the CFFPR (n = 45 448). Multivariable models were used to adjust for factors known to be associated with survival. Median age of survival in patients with cystic fibrosis increased in both countries between 1990 and 2013; however, in 1995 and 2005, survival in Canada increased at a faster rate than in the United States (P < 0.001). On the basis of contemporary data from 2009 to 2013, the median age of survival in Canada was 10 years greater than in the United States (50.9 vs. 40.6 years, respectively). The adjusted risk for death was 34% lower in Canada than the United States (hazard ratio, 0.66 [95% CI, 0.54 to 0.81]). A greater proportion of patients in Canada received transplants (10.3% vs. 6.5%, respectively [standardized difference, 13.7]). Differences in survival between U.S. and Canadian patients varied according to U.S. patients' insurance status. Ascertainment bias due to missing data or nonrandom loss to follow-up might affect the results. Differences in cystic fibrosis survival between Canada and the United States persisted after adjustment for risk factors associated with survival, except for private

  11. Adult cystic fibrosis: postprandial response of gut regulatory peptides.

    PubMed

    Allen, J M; Penketh, A R; Adrian, T E; Lee, Y C; Sarson, D L; Hodson, M E; Batten, J C; Bloom, S R

    1983-12-01

    Responses of 11 gastrointestinal regulatory peptides to a standard test meal were assessed in 10 adult patients with cystic fibrosis. The basal plasma neurotensin was significantly elevated in patients with cystic fibrosis, being 31.5 +/- 6.1 pmol/L compared with a control value of 10.3 +/- 1.5 pmol/L (p less than 0.005). Plasma neurotensin remained elevated throughout the test period. Basal plasma enteroglucagon was similarly elevated, the patients with fibrocystic disease having levels of 51.3 +/- 4.6 pmol/L compared to controls with levels of 33.2 +/- 6.7 pmol/L (p less than 0.02). There was, however, no significant difference in postprandial levels of plasma enteroglucagon. Postprandial motilin was significantly elevated in the patients with cystic fibrosis; this elevation is in contrast with previous findings in children. Release of gastric inhibitory polypeptide was impaired, while release of cholecystokinin showed no significant difference in control values, although there was a tendency for delay. There was no significant postprandial rise of pancreatic polypeptide in the patients, whose levels were grossly lower than controls. Insulin showed a delayed response. No significant differences were observed between patients and controls in levels of gastrin, pancreatic glucagon, somatostatin, or vasoactive intestinal peptide. The elevation of plasma neurotensin and enteroglucagon in the basal state may reflect an adaptive response and may be part of the improved digestive function in adults compared with children with fibrocystic disease.

  12. Caregivers’ perspectives on decision making about lung transplantation in cystic fibrosis

    PubMed Central

    Dellon, Elisabeth P.; Shores, Mitchell D.; Nelson, Katherine I.; Wolfe, Joanne; Noah, Terry L.; Hanson, Laura C.

    2013-01-01

    Context Lung transplantation extends survival for some patients with advanced cystic fibrosis, but it is complicated, has many potential risks, and its outcomes are difficult to predict. No standards exist for informed decision making about transplantation. Objective To assess decision making from the perspective of caregivers of patients who faced the transplant decision before dying of cystic fibrosis or transplant complications. Design Semistructured interviews with descriptive and qualitative content analysis. Participants Twenty-eight caregivers of patients with cystic fibrosis who received care at our center and died between 1996 and 2006. Results Of 28 patients who considered lung transplantation, 19 (68%) received transplants, 6 (21%) died while waiting for transplant, and 3 (11%) declined transplant. Three caregivers (11%) thought that the patient did not fully understand the reason for transplant referral. Five (18%) thought that the patient did not fully understand potential risks. Ten (36%) thought that alternatives were not fully understood. The only alternatives to transplant identified, progressive illness and the possibility of earlier death without transplant, were unacceptable to most. Thirteen caregivers (46%) reported that the patient thought that declining transplant was not an option. Caregivers described the decision as “easy” for 19 (68%), often expressing a sentiment of “do or die.” Those who described the decision as “easy” recalled fewer elements of informed decision making. Conclusions From caregivers’ reports, patients with cystic fibrosis may not fully understand risks of and alternatives to lung transplantation. Because a strong desire to prolong life necessitates honest communication about potential outcomes, interventions are needed to facilitate high-quality decision making. PMID:20050454

  13. Chloride and sodium ion concentrations in saliva and sweat as a method to diagnose cystic fibrosis.

    PubMed

    Gonçalves, Aline Cristina; Marson, Fernando Augusto Lima; Mendonça, Regina Maria Holanda; Bertuzzo, Carmen Sílvia; Paschoal, Ilma Aparecida; Ribeiro, José Dirceu; Ribeiro, Antônio Fernando; Levy, Carlos Emílio

    2018-05-19

    Cystic fibrosis diagnosis is dependent on the chloride ion concentration in the sweat test (≥60mEq/mL - recognized as the gold standard indicator for cystic fibrosis diagnosis). Moreover, the salivary glands express the CFTR protein in the same manner as sweat glands. Given this context, the objective was to verify the correlation of saliva chloride concentration and sweat chloride concentration, and between saliva sodium concentration and sweat sodium concentration, in patients with cystic fibrosis and healthy control subjects, as a tool for cystic fibrosis diagnosis. There were 160 subjects enrolled: 57/160 (35.70%) patients with cystic fibrosis and two known CFTR mutations and 103/160 (64.40%) healthy controls subjects. Saliva ion concentration was analyzed by ABL 835 Radiometer ® equipment and, sweat chloride concentration and sweat sodium concentration, respectively, by manual titration using the mercurimetric procedure of Schales & Schales and flame photometry. Statistical analysis was performed by the chi-squared test, the Mann-Whitney test, and Spearman's correlation. Alpha=0.05. Patients with cystic fibrosis showed higher values of sweat chloride concentration, sweat sodium concentration, saliva chloride concentration, and saliva sodium concentration than healthy controls subjects (p-value<0.001). The correlation between saliva chloride concentration and sweat chloride concentration showed a positive Spearman's Rho (correlation coefficient)=0.475 (95% CI=0.346 to 0.587). Also, the correlation between saliva sodium concentration and sweat sodium concentration showed a positive Spearman's Rho=0.306 (95% CI=0.158 to 0.440). Saliva chloride concentration and saliva sodium concentration are candidates to be used in cystic fibrosis diagnosis, mainly in cases where it is difficult to achieve the correct sweat amount, and/or CFTR mutation screening is difficult, and/or reference methods for sweat test are unavailable to implement or are not easily accessible by

  14. Glucose trajectories in cystic fibrosis and their association with pulmonary function.

    PubMed

    Reynaud, Quitterie; Rabilloud, Muriel; Roche, Sylvain; Poupon-Bourdy, Stéphanie; Iwaz, Jean; Nove-Josserand, Raphaële; Blond, Emilie; Laville, Martine; Llerena, Cathy; Quetant, Sébastien; Reix, Philippe; Touzet, Sandrine; Durieu, Isabelle

    2018-05-01

    The prevalence of cystic fibrosis-related diabetes is increasing. This condition is potentially responsible for respiratory decline. At inclusion, then yearly (over three years), 111 children and 117 adults with cystic fibrosis had oral glucose tolerance and insulin tests at one (G1) and 2h (G2). KmL analysis identified homogeneous G1 and G2 glucose trajectories. A linear mixed model quantified the relationships between trajectories and FEV1 changes. In children, there were three G1 and four G2 trajectories and FEV1 decrease was not significantly different between G1 or G2 trajectories. In adults, two G1 and four G2 trajectories were identified and FEV1 change was estimated at -0.85/year (95% CI: [-1.54; -0.17], p=0.01) whatever the G1 trajectory and found significantly faster in the high and increasing G2 trajectory (-2.1/year, [-3.9; -0.2], p=0.03). In case of persistent G2 abnormality, physicians should be alert for clinical deterioration and intensify patient surveillance. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  15. Liver and lung transplantation in cystic fibrosis: an adult cystic fibrosis centre's experience.

    PubMed

    Sivam, S; Al-Hindawi, Y; Di Michiel, J; Moriarty, C; Spratt, P; Jansz, P; Malouf, M; Plit, M; Pleass, H; Havryk, A; Bowen, D; Haber, P; Glanville, A R; Bye, P T P

    2016-07-01

    Liver disease develops in one-third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation. © 2016 Royal Australasian College of Physicians.

  16. Analysis of 16 cystic fibrosis mutations in Mexican patients

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Villalobos-Torres, C.; Rojas-Martinez, A.; Barrera-Saldana, H.A.

    1997-04-14

    We carried out molecular analysis of 80 chromosomes from 40 unrelated Mexican patients with a diagnosis of cystic fibrosis. The study was performed in two PCR steps: a preliminary one to identify mutation AF508, the most frequent cause of cystic fibrosis worldwide, and the second a reverse dot-blot with allele-specific oligonucleotide probes to detect 15 additional common mutations in the Caucasian population. A frequency of 45% for AF508 was found, making it the most common in our sample of Mexican patients. Another five mutations (G542X, 3849 + 10 kb C{r_arrow}T, N1303K, S549N, and 621 + 1 G{r_arrow}T) were detected, andmore » these accounted for 11.25%. The remaining mutations (43.75%) were undetectable with the methodology used. 20 refs., 2 tabs.« less

  17. Bowel ultrasound imaging in patients with cystic fibrosis: Relationship with clinical symptoms and CFTR genotype.

    PubMed

    Fraquelli, Mirella; Baccarin, Alessandra; Corti, Fabiola; Conti, Clara Benedetta; Russo, Maria Chiara; Della Valle, Serena; Pozzi, Roberta; Cressoni, Massimo; Conte, Dario; Colombo, Carla

    2016-03-01

    Ultrasound imaging is used to assess bowel abnormalities in gastrointestinal diseases. We aimed to assess the rate of predefined bowel ultrasound signs and their relationship with gastrointestinal symptoms and the cystic fibrosis transmembrane conductance regulator (CFTR) genotype in cystic fibrosis patients in regular follow-up. Prospective study of 70 consecutive patients with cystic fibrosis and 45 controls who underwent abdominal ultrasound; pertinent findings were related to gastrointestinal symptoms and, in cystic fibrosis patients, to pancreatic status, malabsorption degree, lipase intake, CFTR genotype (classified as severe or mild against functional class of CFTR mutations). 96% patients showed at least one abnormal bowel ultrasound sign. Most frequent signs were lymph node enlargement (64%), bowel loop dilatation (55%), thick corpuscular intraluminal content (49%), bowel wall hypervascularization (26%), thickened bowel wall (22%) and intussusception (17%). Patients with recurrent abdominal pain showed more bowel wall hypervascularization than patients without recurrent pain (47% vs. 19%, respectively; p = 0.02) and intussusception (58% vs. 17%, respectively; p < 0.01). Genotype was not associated to specific bowel ultrasound signs. Patients with bowel loop intussusception showed greater lipase intake than those without intussusception (8.118 ± 2.083 vs. 5.994 ± 4.187, respectively; p < 0.01). Cystic fibrosis patients present a higher rate of bowel ultrasound abnormalities than controls. Bowel ultrasound abnormalities are associated with abdominal symptoms. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  18. Active cycle of breathing technique for cystic fibrosis.

    PubMed

    Mckoy, Naomi A; Wilson, Lisa M; Saldanha, Ian J; Odelola, Olaide A; Robinson, Karen A

    2016-07-05

    People with cystic fibrosis experience chronic airway infections as a result of mucus build up within the lungs. Repeated infections often cause lung damage and disease. Airway clearance therapies aim to improve mucus clearance, increase sputum production, and improve airway function. The active cycle of breathing technique (also known as ACBT) is an airway clearance method that uses a cycle of techniques to loosen airway secretions including breathing control, thoracic expansion exercises, and the forced expiration technique. This is an update of a previously published review. To compare the clinical effectiveness of the active cycle of breathing technique with other airway clearance therapies in cystic fibrosis. 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.Date of last search: 25 April 2016. Randomised or quasi-randomised controlled clinical studies, including cross-over studies, comparing the active cycle of breathing technique with other airway clearance therapies in cystic fibrosis. Two review authors independently screened each article, abstracted data and assessed the risk of bias of each study. Our search identified 62 studies, of which 19 (440 participants) met the inclusion criteria. Five randomised controlled studies (192 participants) were included in the meta-analysis; three were of cross-over design. The 14 remaining studies were cross-over studies with inadequate reports for complete assessment. The study size ranged from seven to 65 participants. The age of the participants ranged from six to 63 years (mean age 22.33 years). In 13 studies, follow up lasted a single day. However, there were two long-term randomised controlled studies with follow up of one to three years. Most of the studies did not report on key quality items, and therefore, have an unclear risk of

  19. [FRENCH CYSTIC FIBROSIS EPIDEMIOLOGY AFTER A DECADE OF NEONATAL SCREENING].

    PubMed

    Durieu, Isabelle

    2015-10-01

    Since its description in 1938, the life expectancy of cystic fibrosis patients has increased from a few months to nearly 50 years in most Western countries. This significant improvement was related to new symptomatic treatments, for nutritional and respiratory cares in specialized multidisciplinary teams. Systematic neonatal screening for the disease avoides the diagnostic delays that have very deleterious impact on the prognosis of the disease. It allows early optimal management; their nutritional benefit has been demonstrated. The French registry of cystic fibrosis shows that adult patients outnumber children. The median age of death remains under thirty years and the prognosis is very closely linked to the progression chronic respiratory insufficiency. About one hundred patients were annually treated by lung transplant

  20. CF-related diabetes: Containing the metabolic miscreant of cystic fibrosis.

    PubMed

    Moheet, Amir; Moran, Antoinette

    2017-11-01

    Cystic fibrosis-related diabetes (CFRD) is associated with both an increase in morbidity and mortality in people with cystic fibrosis (CF). With increased screening and improved life expectancy of people with CF, the prevalence of CFRD is expected to rise further. The underlying pathophysiological mechanisms causing glucose intolerance and diabetes in patients with CF are not well understood but both functional and structural abnormalities in islet cells are likely to have key roles. Insulin therapy improves health outcomes in patients with CF. Future research is needed to better understand the mechanisms underlying the development of CFRD and to develop new screening and treatment strategies to minimize the detrimental impact of CFRD on health outcomes in people with CF. © 2017 Wiley Periodicals, Inc.

  1. Inhaled mannitol for cystic fibrosis.

    PubMed

    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

  2. Dental enamel defects in Italian children with cystic fibrosis: an observational study.

    PubMed

    Ferrazzano, G F; Sangianantoni, G; Cantile, T; Amato, I; Orlando, S; Ingenito, A

    2012-03-01

    The relationship between cystic fibrosis (CF) and caries experience has already been explored, but relatively little information is available on dental enamel defects prevalence among children affected by cystic fibrosis. The aim of this study was to investigate this issue in deciduous and permanent teeth of children with CF resident in southern Italy. This cross sectional observational study was undertaken between October 2009 and March 2010. 88 CF patients and 101 healthy age-matched participated in this study. The prevalence of dental enamel defects was calculated using a modified Developmental Defects of Enamel (DDE) index. The comparison of dental enamel defects prevalence among groups was carried out using regression binary logistic analysis. In the CF subjects there was a higher prevalence (56%) of enamel defects in comparison to the healthy group (22%). The most prevalent enamel defect was hypoplasia with loss of enamel (23% of CF patients vs 1 1/2% of control group) in permanent teeth. This study confirms that children with cystic fibrosis are at increased risk of developing hypoplastic defects on their permanent teeth.

  3. Active video games as an exercise tool for children with cystic fibrosis.

    PubMed

    O'Donovan, Cuisle; Greally, Peter; Canny, Gerard; McNally, Paul; Hussey, Juliette

    2014-05-01

    Active video games are used in many hospitals as exercise tools for children with cystic fibrosis. However, the exercise intensity associated with playing these games has not been examined in this population. Children with cystic fibrosis [n=30, aged 12.3 (2.6) years, 17 boys, BMI 17.7 (2.8) kg/m(2)] were recruited from outpatient clinics in Dublin hospitals. Age and gender matched control children were recruited from local schools. Oxygen consumption, metabolic equivalents (METs) calculated from resting V˙O2, and heart rate were measured while playing Nintendo Wii™ (Nintendo Co. Ltd., Tokyo, Japan) Sports Boxing and Nintendo Wii Fit Free Jogging using a portable indirect calorimeter (Oxycon Mobile). Playing Wii Boxing resulted in light intensity activity (2.46METs) while playing Wii Fit Free Jogging resulted in moderate intensity physical activity (4.44METs). No significant difference was seen between groups in the energy cost of playing active video games. Active video games are a useful source of light to moderate intensity physical activity in children with cystic fibrosis. © 2013.

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-07

    ... 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..., Social Security Administration, 6401 Security Boulevard, Baltimore, Maryland 21235-6401, (410) 965-1020...

  5. Students as Technicians: Screening Newborns for Cystic Fibrosis

    ERIC Educational Resources Information Center

    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…

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

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

    1983-10-01

    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.

  7. Vitamin E supplementation in people with cystic fibrosis.

    PubMed

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

    2014-12-09

    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. 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 February 2014. Date of last search of international trial registers: 30 August 2014. 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 interval 10.59 to 24.74); at three months, one

  8. Vitamin E supplementation in people with cystic fibrosis.

    PubMed

    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

  9. High usability of a smartphone application for reporting symptoms in adults with cystic fibrosis.

    PubMed

    Wood, Jamie; Jenkins, Sue; Putrino, David; Mulrennan, Siobhain; Morey, Sue; Cecins, Nola; Hill, Kylie

    2017-01-01

    Introduction In cystic fibrosis, exacerbations impair lung function and health-related quality of life, increase healthcare costs and reduce survival. Delayed reporting of worsening symptoms can result in more severe exacerbations and worse clinical outcomes; therefore there is a need for a novel approach to facilitate the early identification and treatment of exacerbations in this population. This study investigated the usability of a smartphone application to report symptoms in adults with cystic fibrosis, and the observer agreement in clinical decision-making between senior clinicians interpreting smartphone application responses. Methods Adults with cystic fibrosis used the smartphone application weekly for four weeks. The application comprised 10 yes/no questions regarding respiratory symptoms and two regarding emotional well-being. Usability was measured with the System Usability Scale; Observer agreement was tested by providing a cystic fibrosis physician and a nurse practitioner with 45 clinical scenarios. For each scenario the clinicians, who were blinded to each other's responses, were asked to indicate whether or not they would: (i) initiate telephone contact, and/or (ii) request a clinic visit for the individual. Results Ten participants (five female), aged mean (SD) 33 (11) years, FEV1 49 (27)% predicted completed the study. The mean (SD) System Usability Scale score was 94 (6). There was perfect agreement between clinicians for initiating contact with the participant ( κ = 1.0, p < 0.001), and near-perfect for requesting a clinic visit ( κ = 0.86, p < 0.001). Discussion The use of a smartphone application for reporting symptoms in adults with cystic fibrosis has excellent usability and near-perfect agreement between senior clinicians when interpreting the application responses.

  10. Regulation of Chloride Channels by Protein Kinase C in Normal and Cystic Fibrosis Airway Epithelia

    NASA Astrophysics Data System (ADS)

    Li, Ming; McCann, John D.; Anderson, Matthew P.; Clancy, John P.; Liedtke, Carole M.; Nairn, Angus C.; Greengard, Paul; Welsh, Michael J.

    1989-06-01

    Apical membrane chloride channels control chloride secretion by airway epithelial cells. Defective regulation of these channels is a prominent characteristic of cystic fibrosis. In normal intact cells, activation of protein kinase C (PKC) by phorbol ester either stimulated or inhibited chloride secretion, depending on the physiological status of the cell. In cell-free membrane patches, PKC also had a dual effect: at a high calcium concentration, PKC inactivated chloride channels; at a low calcium concentration, PKC activated chloride channels. In cystic fibrosis cells, PKC-dependent channel inactivation was normal, but activation was defective. Thus it appears that PKC phosphorylates and regulates two different sites on the channel or on an associated membrane protein, one of which is defective in cystic fibrosis.

  11. Respiratory syncytial virus infection disrupts monolayer integrity and function in cystic fibrosis airway cells.

    PubMed

    Kong, Michele; Maeng, Patrick; Hong, Jeong; Szczesniak, Rhonda; Sorscher, Eric; Sullender, Wayne; Clancy, John Paul

    2013-09-19

    Respiratory Syncytial Virus (RSV) infection is a common contributor to pulmonary symptoms in children with cystic fibrosis (CF). Here we examined RSV infection in immortalized bronchial epithelial cells (CFBE41o-) expressing wild-type (wt) or F508del cystic fibrosis transmembrane conductance regulator (CFTR), for monolayer integrity and RSV replication. CFBE41o- monolayers expressing wt or F508del CFTR were grown on permeable supports and inoculated with RSV A2 strain. Control experiments utilized UV-inactivated RSV and heat-killed RSV. Monolayer resistance and RSV production was monitored for up to six days post-infection. Within 24 h, a progressive decrease in monolayer resistance was observed in RSV infected F508del CFBE41o- cells, while the monolayer integrity of RSV infected wt CFTR CFBE41o- cells remained stable. RSV replication was necessary to disrupt F508del CFBE41o- monolayers as UV-irradiated and heat killed RSV had no effect on monolayer integrity, with an earlier and much more pronounced peak in RSV titer noted in F508del relative to wt CFTR-expressing cells. RSV infection of wt CFBE41o- monolayers also resulted in blunting of CFTR response. These findings identify an enhanced sensitivity of CFBE41o- cells expressing F508del CFTR to RSV infection, replication and monolayer disruption independent of the cellular immune response, and provide a novel mechanism by which cystic fibrosis airway epithelia are susceptible to RSV-dependent injury.

  12. Management of male infertility due to congenital bilateral absence of vas deferens should not ignore the diagnosis of cystic fibrosis.

    PubMed

    Grzegorczyk, V; Rives, N; Sibert, L; Dominique, S; Macé, B

    2012-10-01

    Microsurgical or percutaneous epididymal sperm aspiration and intracytoplasmic sperm injection (ICSI) are proposed to overcome male infertility due to congenital bilateral absence of vas deferens (CBAVD). CBAVD has been associated with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and consequently, genetic counselling has to be addressed before beginning ICSI procedure. However, management of male infertility due to CBAVD should not ignore a mild form of cystic fibrosis. We describe the case of cystic fibrosis late diagnosis performed in a 49-year-old infertile men with CBAVD. CFTR molecular testing detected two mutations F508del and A455E corresponding to a cystic fibrosis genotype. Pneumological evaluation revealed a severe obstructive respiratory disease, bronchiectasis and high sweat chloride levels. Symptoms consistent with a cystic fibrosis have to be identified in infertile men with CBAVD before beginning assisted reproductive procedures. © 2012 Blackwell Verlag GmbH.

  13. The Cystic Fibrosis Database: Content and Research Opportunities.

    ERIC Educational Resources Information Center

    Shaw, William M., Jr.; And Others

    1991-01-01

    Describes the files contained in the Cystic Fibrosis (CF) database and discusses educational and research opportunities using this database. Topics discussed include queries, evaluating the relevance of items retrieved, and use of the database in an online searching course in the School of Information and Library Science at the University of North…

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

    PubMed

    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.

  15. Deficient Vasoactive Intestinal Peptide Innervation in the Sweat Glands of Cystic Fibrosis Patients

    NASA Astrophysics Data System (ADS)

    Heinz-Erian, Peter; Dey, Richard D.; Flux, Marinus; Said, Sami I.

    1985-09-01

    The innervation of acini and ducts of eccrine sweat glands by immunoreactive, vasoactive intestinal peptide--containing nerve fibers was sharply reduced in seven patients with cystic fibrosis compared to eight normal subjects. The decrease in innervation by this neuropeptide, which has been shown to promote blood flow and the movement of water and chloride across epithelial surfaces in other systems, may be a basic mechanism for the decreased water content and relative impermeability of the epithelium to chloride and other ions that characterize cystic fibrosis.

  16. Early severe anemia as the first sign of cystic fibrosis.

    PubMed

    Sismanlar, Tugba; Aslan, Ayşe Tana; Köse, Mehmet; Pekcan, Sevgi; Ezgü, Fatih Süheyl; Budakoğlu, Işıl İrem; Yenicesu, İdil

    2016-09-01

    Severe anemia is reported to occur rarely in patients with cystic fibrosis (CF). This study aimed to determine the factors associated with early severe anemia in infants with CF. This study included 231 infants with CF from 3 pediatric CF centers ten year period that were retrospectively reviewed in terms of severe anemia as the first sign of CF. Factors that could affect anemia, such as age, pancreatic insufficiency, mutations, vitamin A and E, and albumin level were evaluated. Clinical and laboratory findings in CF patients that presented with severe anemia and no respiratory symptoms were compared to those in CF patients that did not present with severe anemia. Severe anemia as the first sign of CF was noted in 17 of 231 patients. Patient age, prolonged PT/INR and the albumin level differed significantly between the 2 groups of patients (P < 0.001). Feeding pattern, pancreatic insufficiency, vitamin E and A levels, and the types of genetic mutations did not differ between the 2 groups. The mean hemoglobin level was 5.59 ± 0.21 g/dL and respiratory symptoms began a mean 6.3 months after diagnosis of CF in the anemia group. In early infancy severe anemia in the absence of respiratory symptoms can be the first sign of CF. CF should be considered in the differential diagnosis of severe anemia in infants. Anemia can occur several months before respiratory symptoms in patients with CF and may be caused due to several reasons. • Severe anemia as a first sign is reported to occur rarely in patients with cystic fibrosis. • Although anemia is well known in cystic fibrosis, factors that cause severe anemia are not known clearly. What is New: • This study shows the importance of severe anemia as the first sign of cystic fibrosis. • Anemia can occur several months before respiratory symptoms in patients with CF.

  17. Probiotic supplementation in children with cystic fibrosis-a systematic review.

    PubMed

    Ananthan, Anitha; Balasubramanian, Haribalakrishna; Rao, Shripada; Patole, Sanjay

    2016-10-01

    Probiotics may benefit in cystic fibrosis (CF) as gut dysbiosis is associated with gastrointestinal symptoms and exacerbation of respiratory symptoms in CF. We conducted a systematic review of randomized controlled trials (RCTs) and non-RCTs of probiotic supplementation in children with CF, using the Cochrane methodology, preferred reporting items for systematic reviews (PRISMA) statement, and meta-analysis of observational studies in epidemiology (MOOSE) guidelines. Primary outcomes were pulmonary exacerbations, duration of hospitalization and antibiotics, and all-cause mortality. Secondary outcomes included gastrointestinal symptoms, markers of gut inflammation, and intestinal microbial balance. A total of nine studies (RCTs, 6, non-RCTs, 3; N = 275) with some methodological weaknesses were included in the review. The pooled estimate showed significant reduction in the rate of pulmonary exacerbation (fixed effects model, two parallel group RCTs and one cross-over trial: relative risk (RR) 0.25, (95 % confidence interval (95 % CI) 0.15,0.41); p < 0.00001; level of evidence: low) and decrease in fecal calprotectin (FCLP) levels (fixed effect model, three RCTs: mean difference (MD) -16.71, 95 % CI -27.30,-6.13); p = 0.002; level of evidence: low) after probiotic supplementation. Probiotic supplementation significantly improved gastrointestinal symptoms (one RCT, one non-RCT) and gut microbial balance (decreased Proteobacteria, increased Firmicutes, and Bacteroides in one RCT, one non-RCT). Limited low-quality evidence exists on the effects of probiotics in children with CF. Well-designed adequately powered RCTs assessing clinically meaningful outcomes are required to study this important issue. • Gut dysbiosis is frequent in children with cystic fibrosis due to frequent exposure to pathogens and antibiotics. • Probiotics decrease gut dysbiosis and improve gut maturity and function. What is New: • This comprehensive systematic review shows that current

  18. Cystic Fibrosis and the Nervous System.

    PubMed

    Reznikov, Leah R

    2017-05-01

    Cystic fibrosis (CF) is a life-shortening autosomal recessive disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is an anion channel that conducts bicarbonate and chloride across cell membranes. Although defective anion transport across epithelial cells is accepted as the basic defect in CF, many of the features observed in people with CF and organs affected by CF are modulated by the nervous system. This is of interest because CFTR expression has been reported in both the peripheral and central nervous systems, and it is well known that the transport of anions, such as chloride, greatly modulates neuronal excitability. Thus it is predicted that in CF, lack of CFTR in the nervous system affects neuronal function. Consistent with this prediction, several nervous system abnormalities and nervous system disorders have been described in people with CF and in animal models of CF. The goal of this special feature article is to highlight the expression and function of CFTR in the nervous system. Special emphasis is placed on nervous system abnormalities described in people with CF and in animal models of CF. Finally, features of CF that may be modulated by or attributed to faulty nervous system function are discussed. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  19. Frequency of 8 CFTR gene mutations in cystic fibrosis patients in Minas Gerais, Brazil, diagnosed by neonatal screening.

    PubMed

    Perone, C; Medeiros, G S; del Castillo, D M; de Aguiar, M J B; Januário, J N

    2010-02-01

    The nature and frequency of cystic fibrosis mutations in Brazil is not uniform due to the highly varied ethnic composition of the population. The average frequency of the F508del mutation has been reported to be 48.6%. Other common mutations in Brazil are G542X, R1162X, and N1303K. The aim of this study was to analyze the frequency of 8 mutations (F508del, G542X, R1162X, N1303K, W1282X, G85E, 3120+1G>A, and 711+1G>T) in a sample of 111 newborn patients with cystic fibrosis diagnosed by the Cystic Fibrosis Neonatal Screening Program of Minas Gerais State. The mutations were tested by allele-specific oligonucleotide PCR with specially designed primers. An allele frequency of 48.2% was observed for the F508del mutation, and allele frequencies of 5.41, 4.50, 4.05, and 3.60% were found for the R1162X, G542X, 3120+1G>A, and G85E mutations, respectively. The genotypes obtained were in Hardy-Weinberg equilibrium. These data demonstrate that the 8-mutation panel studied here has extensive coverage (68%) for the cystic fibrosis mutations in Minas Gerais. These data improve our knowledge of cystic fibrosis in Brazil, particularly in this region. In addition, this investigation contributed to the establishment of a sensitive and population-specific mutation panel, which can be helpful for molecular diagnosis of cystic fibrosis.

  20. Oral anti-pseudomonal antibiotics for cystic fibrosis.

    PubMed

    Remmington, Tracey; Jahnke, Nikki; Harkensee, Christian

    2016-07-14

    Pseudomonas aeruginosa is the most common bacterial pathogen causing lung infections in people with cystic fibrosis and appropriate antibiotic therapy is vital. Antibiotics for pulmonary exacerbations are usually given intravenously, and for long-term treatment, via a nebuliser. Oral anti-pseudomonal antibiotics with the same efficacy and safety as intravenous or nebulised antibiotics would benefit people with cystic fibrosis due to ease of treatment and avoidance of hospitalisation. This is an update of a previous review. To determine the benefit or harm of oral anti-pseudomonal antibiotic therapy for people with cystic fibrosis, colonised with Pseudomonas aeruginosa, in the:1. treatment of a pulmonary exacerbation; and2. long-term treatment of chronic infection. 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.We contacted pharmaceutical companies and checked reference lists of identified trials.Date of last search: 08 July 2016. Randomised or quasi-randomised controlled trials comparing any dose of oral anti-pseudomonal antibiotics, to other combinations of inhaled, oral or intravenous antibiotics, or to placebo or usual treatment for pulmonary exacerbations and long-term treatment. Two authors independently selected the trials, extracted data and assessed quality. We contacted trial authors to obtain missing information. We included three trials examining pulmonary exacerbations (171 participants) and two trials examining long-term therapy (85 participants). We regarded the most important outcomes as quality of life and lung function. The analysis did not identify any statistically significant difference between oral anti-pseudomonal antibiotics and other treatments for these outcome measures for either pulmonary exacerbations or long-term treatment. One of the

  1. Cystic fibrosis.

    PubMed

    Bye, M R; Ewig, J M; Quittell, L M

    1994-01-01

    While the care of cystic fibrosis (CF) patients has been mainly the province of pediatricians, great improvements in the therapy and life span of CF patients often results in their transition to care by adult physicians. In this review of CF, we begin with an overview of the epidemiology and genetics of the disease, with a discussion of the recently found ion abnormalities that lead to the clinical manifestations. This is followed by a discussion of the pathophysiology. Methods of diagnosis, ranging from the gold standard, the sweat test, to recent advances based on a greater understanding of the genetics of the disease are reviewed. This is followed by a discussion of therapy primarily geared to the treatment of the respiratory complications, as they are the most common lethal factors of the disease. We point out controversies where they exist. Newer forms of therapy such as lung transplantation are discussed, and we finish with a discussion about future therapeutic modalities, some of which are being approved as the paper is in print.

  2. Carrier screening for cystic fibrosis.

    PubMed

    Dungan, Jeffrey S

    2010-03-01

    Cystic fibrosis is the first genetic disorder for which universal screening of preconceptional or prenatal patients became a component of standard prenatal care. The molecular genetics and mutation profile of the CFTR gene are complex, with a wide range of phenotypic consequences. Carrier screening can facilitate risk assessment for prospective parents to have an affected offspring, although there remains a small residual risk for carrying a mutation even with a negative screening result. There are ethnic differences with respect to disease incidence and effectiveness of carrier testing, which may complicate counseling. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  3. Strength and Conditioning for the Person with Cystic Fibrosis.

    ERIC Educational Resources Information Center

    Waller, Mike

    2001-01-01

    Discusses how a strength and conditioning program can be safety incorporated into the daily life of people with cystic fibrosis as a complementary therapy to medications, regular checkups, bronchial drainage, and respiratory therapy, examining physical restrictions and guidelines, exercise prescriptions, and exercise applications, and explaining…

  4. Strategies for the etiological therapy of cystic fibrosis.

    PubMed

    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.

  5. Strategies for the etiological therapy of cystic fibrosis

    PubMed Central

    Maiuri, Luigi; Raia, Valeria; Kroemer, Guido

    2017-01-01

    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. PMID:28937684

  6. Investigating self-efficacy, disease knowledge and adherence to treatment in adolescents with cystic fibrosis.

    PubMed

    Faint, Nicholas R; Staton, Janelle M; Stick, Stephen M; Foster, Juliet M; Schultz, André

    2017-05-01

    Patient adherence is integral to the effectiveness of prescribed treatment, and is associated with beneficial disease outcomes, yet in adolescents with cystic fibrosis, adherence is often sub-optimal. Multiple factors may contribute to treatment adherence, including disease knowledge and self-efficacy. In adolescents with cystic fibrosis: (i) to compare the disease knowledge of adolescents and their parents before transition to adult care; (ii) to determine the relationship between disease knowledge (adolescent, parent) and adherence; and (iii) to evaluate self-efficacy and its association with disease knowledge and adherence. Adolescents with cystic fibrosis and their parents were recruited from a tertiary children's hospital. Disease knowledge and self-efficacy was assessed using the Knowledge of Disease Management-CF and General Self-Efficacy Scales respectively. Using pharmacy records, medication possession ratio was calculated to measure treatment adherence in the preceding year. Thirty-nine adolescent (aged 12-17 (median 14) years) and parent pairs were recruited. Adherence to hypertonic saline, but not other medications, was significantly associated with disease knowledge in adolescents (r 2  = 0.40, P = 0.029). Mean (SD) adolescent self-efficacy was 30.8 (4.0), and not associated with disease knowledge or adherence. Mean (SD) disease knowledge was less in adolescents than parents (55 (16)% and 72 (14)% respectively, P < 0.001). Disease knowledge is sub-optimal in adolescents with cystic fibrosis, even in the 2 years immediately before transition to adult care. Given that adherence with some treatments has been associated with disease knowledge our results suggest the need for educational interventions in adolescents with cystic fibrosis to optimise self-management and health outcomes. © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  7. Tracking Polymicrobial Metabolism in Cystic Fibrosis Airways: Pseudomonas aeruginosa Metabolism and Physiology Are Influenced by Rothia mucilaginosa-Derived Metabolites.

    PubMed

    Gao, Bei; Gallagher, Tara; Zhang, Ying; Elbadawi-Sidhu, Mona; Lai, Zijuan; Fiehn, Oliver; Whiteson, Katrine L

    2018-04-25

    Due to a lack of effective immune clearance, the airways of cystic fibrosis patients are colonized by polymicrobial communities. One of the most widespread and destructive opportunistic pathogens is Pseudomonas aeruginosa ; however, P. aeruginosa does not colonize the airways alone. Microbes that are common in the oral cavity, such as Rothia mucilaginosa , are also present in cystic fibrosis patient sputum and have metabolic capacities different from those of P. aeruginosa Here we examine the metabolic interactions of P. aeruginosa and R. mucilaginosa using stable-isotope-assisted metabolomics. Glucose-derived 13 C was incorporated into glycolysis metabolites, namely, lactate and acetate, and some amino acids in R. mucilaginosa grown aerobically and anaerobically. The amino acid glutamate was unlabeled in the R. mucilaginosa supernatant but incorporated the 13 C label after P. aeruginosa was cross-fed the R. mucilaginosa supernatant in minimal medium and artificial-sputum medium. We provide evidence that P. aeruginosa utilizes R. mucilaginosa -produced metabolites as precursors for generation of primary metabolites, including glutamate. IMPORTANCE Pseudomonas aeruginosa is a dominant and persistent cystic fibrosis pathogen. Although P. aeruginosa is accompanied by other microbes in the airways of cystic fibrosis patients, few cystic fibrosis studies show how P. aeruginosa is affected by the metabolism of other bacteria. Here, we demonstrate that P. aeruginosa generates primary metabolites using substrates produced by another microbe that is prevalent in the airways of cystic fibrosis patients, Rothia mucilaginosa These results indicate that P. aeruginosa may get a metabolic boost from its microbial neighbor, which might contribute to its pathogenesis in the airways of cystic fibrosis patients.

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

    PubMed Central

    Lambiase, Antonietta; Raia, Valeria; Pezzo, Mariassunta Del; Sepe, Angela; Carnovale, Vincenzo; Rossano, Fabio

    2006-01-01

    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-resistant. Multiresistant

  9. [The concept of transition applied to patients with cystic fibrosis].

    PubMed

    Becher, Christine

    2013-09-04

    The transfer from pediatric to adult care of adolescents with a chronic condition like cystic fibrosis is a great challenge for the patients, their parents and the health care professionals. Therefore it is very important to prepare the families well in advance by coaching the self-management skills of the adolescents and by supporting their parents in letting go. Transition clinics have proved to be the best instruments in the process of handing-over the patients. They guarantee for the continuity of care and they have a positive effect on the satisfaction of adolescents and their parents in the transition process.

  10. Revisiting sweat chloride test results based on recent guidelines for diagnosis of cystic fibrosis.

    PubMed

    Pagaduan, Jayson V; Ali, Mahesheema; Dowlin, Michael; Suo, Liye; Ward, Tabitha; Ruiz, Fadel; Devaraj, Sridevi

    2018-03-01

    Recent sweat chloride guidelines published by the Cystic Fibrosis Foundation changed the intermediate sweat chloride concentration range from 40-59 mmol/L to 30-59 mmol/L for age > 6 months. We wanted to know how this new guideline would impact detection of cystic fibrosis among patients who previously had sweat tests done at Texas Children's Hospital. We revisited sweat chloride test results (n = 3012) in the last 5 years at Texas Children's Hospital based on the new guidelines on diagnosis of cystic fibrosis from the Cystic Fibrosis Foundation. We identified 125 patients that would be reclassified in the intermediate sweat chloride value with the new guidelines that were classified as "unlikely to have CF" in the previous guidelines. 8 (32%) patients with CFTR gene testing were positive for CFTR gene mutation(s). 4 (50%) of these patients were identified to have 2 CFTR mutations. One had variant combination that was reported to cause CF but all were diagnosed with CFTR-related metabolic syndrome. Our findings concur with the new CF diagnosis guidelines that changing the intermediate cut-off to 30-59 mmol/L sweat chloride concentration in combination with CFTR genetic analysis enhances the probability of identifying individuals that have risk of developing CF or have CF and enables for earlier therapeutic intervention.

  11. Impact of Pseudomonas aeruginosa Infection on Respiratory Muscle Function in Adult Cystic Fibrosis Patients.

    PubMed

    Magnet, Friederike Sophie; Callegari, Jens; Dieninghoff, Doris; Spielmanns, Marc; Storre, Jan Hendrik; Schmoor, Claudia; Windisch, Wolfram

    2017-01-01

    Pseudomonas aeruginosa infection impairs respiratory muscle function in adolescents with cystic fibrosis, but its impact on adult patients has not been characterised. To investigate respiratory muscle function in adult cystic fibrosis patients according to P. aeruginosa status (repetitive samples over 12 months). The pressure-time index of the respiratory muscles (PTImus), a measure of their efficiency, served as the primary outcome. In addition, respiratory load and maximal respiratory muscle strength were assessed. In 51 patients examined (65% female; median age 32 years, IQR 24-40), a median of 3.0 (IQR 2-4) different pathogens was found in each patient. The PTImus was 0.113 and 0.126 in Pseudomonas-positive (n = 33) and -negative (n = 18) patients, respectively (p = 0.53). Univariate analysis showed a lower PTImus in male than in female patients (p = 0.006). Respiratory muscle load and strength were otherwise comparable, with the exception of higher nasal sniff pressures in Pseudomonas-positive patients who were chronically infected (>50% of positive samples). Quality of Life (according to the Cystic Fibrosis Questionnaire-Revised) was higher if both respiratory load and the PTImus were low (high respiratory muscle efficiency). Chronic P. aeruginosa infection does not influence respiratory muscle efficiency in adult cystic fibrosis patients with otherwise multiple co-infections. In addition, patients with reduced respiratory muscle efficiency had worse Quality of Life. © 2016 S. Karger AG, Basel.

  12. Impaired Cell Volume Regulation in Intestinal Crypt Epithelia of Cystic Fibrosis Mice

    NASA Astrophysics Data System (ADS)

    Valverde, M. A.; O'Brien, J. A.; Sepulveda, F. V.; Ratcliff, R. A.; Evans, M. J.; Colledge, W. H.

    1995-09-01

    Cystic fibrosis is a disease characterized by abnormalities in the epithelia of the lungs, intestine, salivary and sweat glands, liver, and reproductive systems, often as a result of inadequate hydration of their secretions. The primary defect in cystic fibrosis is the altered activity of a cAMP-activated Cl^- channel, the cystic fibrosis transmembrane conductance regulator (CFTR) channel. However, it is not clear how a defect in the CFTR Cl^- channel function leads to the observed pathological changes. Although much is known about the structural properties and regulation of the CFTR, little is known of its relationship to cellular functions other than the cAMP-dependent Cl^- secretion. Here we report that cell volume regulation after hypotonic challenge is also defective in intestinal crypt epithelial cells isolated from CFTR -/- mutant mice. Moreover, the impairment of the regulatory volume decrease in CFTR -/- crypts appears to be related to the inability of a K^+ conductance to provide a pathway for the exit of this cation during the volume adjustments. This provides evidence that the lack of CFTR protein may have additional consequences for the cellular function other than the abnormal cAMP-mediated Cl^- secretion.

  13. Defining palliative care in cystic fibrosis: A Delphi study.

    PubMed

    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. Cystic fibrosis transmembrane conductance regulator-emerging regulator of cancer.

    PubMed

    Zhang, Jieting; Wang, Yan; Jiang, Xiaohua; Chan, Hsiao Chang

    2018-05-01

    Mutations of cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis, the most common life-limiting recessive genetic disease among Caucasians. CFTR mutations have also been linked to increased risk of various cancers but remained controversial for a long time. Recent studies have begun to reveal that CFTR is not merely an ion channel but also an important regulator of cancer development and progression with multiple signaling pathways identified. In this review, we will first present clinical findings showing the correlation of genetic mutations or aberrant expression of CFTR with cancer incidence in multiple cancers. We will then focus on the roles of CFTR in fundamental cellular processes including transformation, survival, proliferation, migration, invasion and epithelial-mesenchymal transition in cancer cells, highlighting the signaling pathways involved. Finally, the association of CFTR expression levels with patient prognosis, and the potential of CFTR as a cancer prognosis indicator in human malignancies will be discussed.

  15. Employment and work disability in adults with cystic fibrosis.

    PubMed

    Laborde-Castérot, Hervé; Donnay, Carole; Chapron, Jeanne; Burgel, Pierre-Régis; Kanaan, Reem; Honoré, Isabelle; Dusser, Daniel; Choudat, Dominique; Hubert, Dominique

    2012-03-01

    As a result of prolonged survival, more patients with cystic fibrosis (CF) participate in the labour force. The aim of this study was to evaluate their education, occupation levels and risk factors for work disability. 207 patients answered a self-administered questionnaire about their educational level and work status. Independently, medical records were reviewed for illness severity indicators. 39 patients (19%) were students, 117 (57%) were in the labour force, 13 (6%) were seeking employment and 38 (18%) were inactive. CF patients had a higher educational level and were more likely to hold skilled jobs and to work part time than the general population. FEV1 and educational level were the strongest predictive factors of disability. Many CF patients have access to professional life. Their higher educational levels improve the chances of attaining employment, which highlights the need for career counselling. Working part time helps to maintain employment despite declining health. Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  16. Molecular epidemiology of Aspergillus collected from cystic fibrosis patients.

    PubMed

    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. Advances in Cell and Gene-based Therapies for Cystic Fibrosis Lung Disease

    PubMed Central

    Oakland, Mayumi; Sinn, Patrick L; McCray Jr, Paul B

    2012-01-01

    Cystic fibrosis (CF) is a disease characterized by airway infection, inflammation, remodeling, and obstruction that gradually destroy the lungs. Direct delivery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to airway epithelia may offer advantages, as the tissue is accessible for topical delivery of vectors. Yet, physical and host immune barriers in the lung present challenges for successful gene transfer to the respiratory tract. Advances in gene transfer approaches, tissue engineering, and novel animal models are generating excitement within the CF research field. This review discusses current challenges and advancements in viral and nonviral vectors, cell-based therapies, and CF animal models. PMID:22371844

  18. Open randomised prospective comparative multi-centre intervention study of patients with cystic fibrosis and early diagnosed diabetes mellitus

    PubMed Central

    2014-01-01

    Background Diabetes mellitus may be present in patients with cystic fibrosis starting in the second decade of life. The prevalence increases rapidly with increasing age. As life-expectancy increases in cystic fibrosis, cystic fibrosis related diabetes will be diagnosed more frequently in the future. Up to date, no data are available to answer the question if cystic fibrosis related diabetes should always initially be treated by insulin therapy. Missing data regarding oral antidiabetic treatment of newly diagnosed cystic fibrosis related diabetes are an important reason to recommend insulin treatment. Several centres report the successful management of cystic fibrosis related diabetes using oral anti-diabetic drugs at least for some years. Oral therapies would be less invasive for a patient group which is highly traumatized by a very demanding therapy. Based on an initiative of the German Mukoviszidosis-Foundation, the present study tries to answer the question, whether oral therapy with repaglinide is as effective as insulin therapy in cystic fibrosis patients with early diagnosed diabetes mellitus. Methods/Design In all cystic fibrosis patients with an age of 10 years or older, an oral glucose tolerance test is recommended. The result of this test is classified according to the WHO cut off values. It is required to have two diabetes positive oral glucose tolerance tests for the diagnosis of diabetes mellitus. This study is a multi-national, multicentre, open labelled, randomized and prospective controlled parallel group’s trial, with 24 months treatment. The primary objective of this trial is to compare the glycaemic control of oral therapy with Repaglinide with insulin injections in patients with cystic fibrosis related diabetes after 2 years of treatment. The trial should include 74 subjects showing cystic fibrosis related diabetes newly diagnosed by oral glucose tolerance test during annual screening for cystic fibrosis related diabetes. Patients are

  19. Nutritional intervention in patients with Cystic Fibrosis: a systematic review.

    PubMed

    Woestenenk, J W; Castelijns, S J A M; van der Ent, C K; Houwen, R H J

    2013-03-01

    To systematically assess the literature published after 1997 describing the effectiveness of nutritional interventions in Cystic Fibrosis patients. An online search in PUBMED, EMBASE and COCHRANE databases was conducted. Original studies with 4 patients or more, describing a nutritional intervention and giving at least weight as an outcome parameter were included. The inclusion criteria were met by 17 articles, focusing on respectively behavioural interventions (n=6), oral supplementation (n=4) or enteral tube feeding (n=7). This latter intervention was universally successful to induce weight gain. One behavioural study and 2 oral supplementation studies also reported significant weight gain. Enteral tube feeding is effective to improve nutritional status, while the described effects of behavioural intervention and oral supplementation are not consistent at present. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  20. Chronic Rhinovirus Infection in an Adult with Cystic Fibrosis

    PubMed Central

    Bright-Thomas, Rowland J.; Tilston, Peter; Mutton, Kenneth J.; Guiver, Malcolm; Webb, A. Kevin; Jones, Andrew M.

    2013-01-01

    Rhinovirus is a common cause of exacerbations of cystic fibrosis (CF) and is usually considered a self-limiting infection. We report a case of chronic infection with rhinovirus A type 33 in a 43-year-old male with CF which has persisted for over 2 years. PMID:23966488

  1. Psychological Concomitants of Cystic Fibrosis in Children and Adolescents.

    ERIC Educational Resources Information Center

    Kashani, Javad H.; And Others

    1988-01-01

    Administered several psychiatric inventories to 30 cystic fibrosis and 30 matched control children and their parents. Data analysis revealed few differences in either psychopathological symptoms or psychiatric diagnoses between groups. Differences were either physical in nature or did not depart enough from normal scores to merit label of high…

  2. Applications of microscopy to genetic therapy of cystic fibrosis and other human diseases.

    PubMed

    Moninger, Thomas O; Nessler, Randy A; Moore, Kenneth C

    2006-01-01

    Gene therapy has become an extremely important and active field of biomedical research. Microscopy is an integral component of this effort. This chapter presents an overview of imaging techniques used in our facility in support of cystic fibrosis gene therapy research. Instrumentation used in these studies includes light and confocal microscopy, transmission electron microscopy, and scanning electron microscopy. Techniques outlined include negative staining, cryo-electron microscopy, three-dimentional reconstruction, enzyme cytochemistry, immunocytochemistry, and fluorescence imaging.

  3. Predictors and variation of routine home discharge in critically ill adults with cystic fibrosis.

    PubMed

    Oud, Lavi; Chan, Yiu Ming

    2018-06-01

    The short-term outcomes of patients with cystic fibrosis (CF) surviving critical illness were not examined systematically. To determine the factors associated with and variation in rates of routine home discharge among ICU-managed adult CF patients. Predictors of routine home discharge and its hospital-level variation were examined in ICU-managed adults with cystic fibrosis in Texas during 2004-2013. Older age, rural residence, and severity of illness decreased odds of routine home discharge, while hospitalization in facilities accredited as part of the Cystic Fibrosis Foundation Care Center Network nearly doubled the odds of routine home discharge. The median (interquartile) adjusted rate of routine home discharge was 62.0% (31.5-82.5). The identified determinants of routine home discharge can inform clinical decision-making, while the demonstrated wide variation in adjusted across-hospital rates of routine home discharge of ICU-managed adults with CF can provide benchmark data for future quality improvement efforts. Published by Elsevier Inc.

  4. DNase and atelectasis in non-cystic fibrosis pediatric patients

    PubMed Central

    Hendriks, Tom; de Hoog, Matthijs; Lequin, Maarten H; Devos, Annick S; Merkus, Peter JFM

    2005-01-01

    Introduction No evidence based treatment is available for atelectasis. We aimed to evaluate the clinical and radiologic changes in pediatric patients who received DNase for persistent atelectasis that could not be attributed to cardiovascular causes, and who were unresponsive to treatment with inhaled bronchodilators and physiotherapy. Methods All non-cystic fibrosis pediatric patients who received nebulised or endotracheally instilled DNase for atelectasis between 1998 and 2002, with and without mechanical ventilation, were analysed in a retrospective descriptive study. The endpoints were the blood pCO2, the heart rate, the respiratory rate, the FiO2 and the chest X-ray scores before and after treatment. Results In 25 of 30 patients (median [range] age, 1.6 [0.1–11] years) who met inclusion criteria, paired data of at least three endpoints were available. All clinical parameters improved significantly within 2 hours (P < 0.01), except for the heart rate (P = 0.06). Chest X-ray scores improved significantly within 24 hours after DNase treatment (P < 0.001). Individual improvement was observed in 17 patients and no clinical change was observed in five patients. Temporary deterioration (n = 3) was associated with increased airway obstruction and desaturations. No other complications were observed. Conclusion After treatment with DNase for atelectasis of presumably infectious origin in non-cystic fibrosis pediatric patients, rapid clinical improvement was observed within 2 hours and radiologic improvement was documented within 24 hours in the large majority of children, and increased airway obstruction and ventilation–perfusion mismatch occurred in three children, possibly due to rapid mobilisation of mucus. DNase may be an effective treatment for infectious atelectasis in non-cystic fibrosis pediatric patients. PMID:16137347

  5. Cystic Fibrosis Patents: A Case Study of Successful Licensing

    PubMed Central

    Minear, Mollie A.; Kapustij, Cristina; Boden, Kaeleen; Chandrasekharan, Subhashini; Cook-Deegan, Robert

    2013-01-01

    From 2006–2010, Duke University’s Center for Public Genomics prepared eight case studies examining the effects of gene patent licensing practices on clinical access to genetic testing for ten clinical conditions. One of these case studies focused on the successful licensing practices employed by the University of Michigan and the Hospital for Sick Children in Toronto for patents covering the CFTR gene and its ΔF508 mutation that causes a majority of cystic fibrosis cases. Since the licensing of these patents has not impeded clinical access to genetic testing, we sought to understand how this successful licensing model was developed and whether it might be applicable to other gene patents. We interviewed four key players who either were involved in the initial discussions regarding the structure of licensing or who have recently managed the licenses and collected related documents. Important features of the licensing planning process included thoughtful consideration of potential uses of the patent; anticipation of future scientific discoveries and technological advances; engagement of relevant stakeholders, including the Cystic Fibrosis Foundation; and using separate licenses for in-house diagnostics versus kit manufacture. These features led to the development of a licensing model that has not only allowed the patent holders to avoid the controversy that has plagued other gene patents, but has also allowed research, development of new therapeutics, and wide-spread dissemination of genetic testing for cystic fibrosis. Although this licensing model may not be applicable to all gene patents, it serves as a model in which gene patent licensing can successfully enable innovation, investment in therapeutics research, and protect intellectual property while respecting the needs of patients, scientists, and public health. PMID:24231943

  6. Current strategies for the long-term assessment, monitoring, and management of cystic fibrosis patients treated with CFTR modulator therapy.

    PubMed

    Elborn, J Stuart; Davies, Jane; Mall, Marcus A; Flume, Patrick A; Plant, Barry

    2017-01-01

    The content for this activity is based on the satellite symposium, "Current Strategies for the Long-term Assessment, Monitoring, and Management for Cystic Fibrosis Patients Treated with CFTR Modulator Therapy" that was presented at the 39th European Cystic Fibrosis Society Conference on June 10, 2016 (Online access: http://courses.elseviercme.com/ecfs2016e/619e). The emergence of novel targeted agents, that directly correct CFTR loss function alleles, has created new treatment opportunities for patients with cystic fibrosis with advanced disease. Knowledge of the role of these agents in the clinical setting is quickly evolving and will require physicians to stay acquainted with the latest data as well as evidence-based treatment guidelines in order to achieve optimized cystic fibrosis patient care. Ideally, after diagnosis, a personalized approach would be adapted and tailored to the patient through genome-informed medicine. However, due to the relative recentness of genomic-based therapeutics, physicians may have a limited knowledge base regarding these new treatment options and how to best incorporate these agents into patient management plans. Although cystic fibrosis is still largely regarded as a pediatric disease, the median survival for patients is 35years of age. Consequently, pediatric-to-adult cystic fibrosis care programs would allow suitable preparation time for this transition and develop a standardized group of self-care and management skills. Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  7. Congruence Between Pulmonary Function and Computed Tomography Imaging Assessment of Cystic Fibrosis Severity.

    PubMed

    Rybacka, Anna; Goździk-Spychalska, Joanna; Rybacki, Adam; Piorunek, Tomasz; Batura-Gabryel, Halina; Karmelita-Katulska, Katarzyna

    2018-05-04

    In cystic fibrosis, pulmonary function tests (PFTs) and computed tomography are used to assess lung function and structure, respectively. Although both techniques of assessment are congruent there are lingering doubts about which PFTs variables show the best congruence with computed tomography scoring. In this study we addressed the issue by reinvestigating the association between PFTs variables and the score of changes seen in computed tomography scans in patients with cystic fibrosis with and without pulmonary exacerbation. This retrospective study comprised 40 patients in whom PFTs and computed tomography were performed no longer than 3 weeks apart. Images (inspiratory: 0.625 mm slice thickness, 0.625 mm interval; expiratory: 1.250 mm slice thickness, 10 mm interval) were evaluated with the Bhalla scoring system. The most frequent structural abnormality found in scans were bronchiectases and peribronchial thickening. The strongest relationship was found between the Bhalla sore and forced expiratory volume in 1 s (FEV1). The Bhalla sore also was related to forced vital capacity (FVC), FEV1/FVC ratio, residual volume (RV), and RV/total lung capacity (TLC) ratio. We conclude that lung structural data obtained from the computed tomography examination are highly congruent to lung function data. Thus, computed tomography imaging may supersede functional assessment in cases of poor compliance with spirometry procedures in the lederly or children. Computed tomography also seems more sensitive than PFTs in the assessment of cystic fibrosis progression. Moreover, in early phases of cystic fibrosis, computed tomography, due to its excellent resolution, may be irreplaceable in monitoring pulmonary damage.

  8. Detection of hyphomycetes in the upper respiratory tract of patients with cystic fibrosis.

    PubMed

    Horré, R; Marklein, G; Siekmeier, R; Reiffert, S-M

    2011-11-01

    The respiratory tract of cystic fibrosis patients is colonised by bacteria and fungi. Although colonisation by slow growing fungi such as Pseudallescheria, Scedosporium and Exophiala species has been studied previously, the colonisation rate differs from study to study. Infections caused by these fungi have been recognised, especially after lung transplants. Monitoring of respiratory tract colonisation in cystic fibrosis patients includes the use of several semi-selective culture media to detect bacteria such as Pseudomonas aeruginosa and Burkholderia cepacia as well as Candida albicans. It is relevant to study whether conventional methods are sufficient for the detection of slow growing hyphomycetes or if additional semi-selective culture media should be used. In total, 589 respiratory specimens from cystic fibrosis patients were examined for the presence of slow growing hyphomycetes. For 439 samples from 81 patients, in addition to conventional methods, erythritol-chloramphenicol agar was used for the selective isolation of Exophiala dermatitidis and paraffin-covered liquid Sabouraud media for the detection of phaeohyphomycetes. For 150 subsequent samples from 42 patients, SceSel+ agar was used for selective isolation of Pseudallescheria and Scedosporium species,and brain-heart infusion bouillon containing a wooden stick for hyphomycete detection. Selective isolation techniques were superior in detecting non-Aspergillus hyphomycetes compared with conventional methods. Although liquid media detected fewer strains of Exophiala, Pseudallescheria and Scedosporium species, additional hyphomycete species not detected by other methods were isolated. Current conventional methods are insufficient to detect non-Aspergillus hyphomycetes, especially Exophiala, Pseudallescheria and Scedosporium species, in sputum samples of cystic fibrosis patients. © 2010 Blackwell Verlag GmbH.

  9. Chronic Azithromycin Use in Cystic Fibrosis and Risk of Treatment-Emergent Respiratory Pathogens.

    PubMed

    Cogen, Jonathan D; Onchiri, Frankline; Emerson, Julia; Gibson, Ronald L; Hoffman, Lucas R; Nichols, David P; Rosenfeld, Margaret

    2018-02-23

    Azithromycin has been shown to improve lung function and reduce the number of pulmonary exacerbations in cystic fibrosis patients. Concerns remain, however, regarding the potential emergence of treatment-related respiratory pathogens. To determine if chronic azithromycin use (defined as thrice weekly administration) is associated with increased rates of detection of eight specific respiratory pathogens. We performed a new-user, propensity-score matched retrospective cohort study utilizing data from the Cystic Fibrosis Foundation Patient Registry. Incident azithromycin users were propensity-score matched 1:1 with contemporaneous non-users. Kaplan-Meier curves and Cox proportional hazards regression were used to evaluate the association between chronic azithromycin use and incident respiratory pathogen detection. Analyses were performed separately for each pathogen, limited to patients among whom that pathogen had not been isolated in the two years prior to cohort entry. After propensity score matching, mean age of the cohorts was ~12 years. Chronic azithromycin users had a significantly lower risk of detection of new methicillin-resistant Staphylococcus aureus, non-tuberculous mycobacteria, and Burkholderia cepacia complex compared to non-users. The risk of acquiring the remaining five pathogens was not significantly different between users and non-users. Using an innovative new-user, propensity-score matched study design to minimize indication and selection biases, we found in a predominantly pediatric cohort that chronic azithromycin users had a lower risk of acquiring several cystic fibrosis-related respiratory pathogens. These results may ease concerns that chronic azithromycin exposure increases the risk of acquiring new respiratory pathogens among pediatric cystic fibrosis patients.

  10. A new method to improve the clinical evaluation of cystic fibrosis patients by mucus viscoelastic properties.

    PubMed

    Tomaiuolo, Giovanna; Rusciano, Giulia; Caserta, Sergio; Carciati, Antonio; Carnovale, Vincenzo; Abete, Pasquale; Sasso, Antonio; Guido, Stefano

    2014-01-01

    In cystic fibrosis (CF) patients airways mucus shows an increased viscoelasticity due to the concentration of high molecular weight components. Such mucus thickening eventually leads to bacterial overgrowth and prevents mucus clearance. The altered rheological behavior of mucus results in chronic lung infection and inflammation, which causes most of the cases of morbidity and mortality, although the cystic fibrosis complications affect other organs as well. Here, we present a quantitative study on the correlation between cystic fibrosis mucus viscoelasticity and patients clinical status. In particular, a new diagnostic parameter based on the correlation between CF sputum viscoelastic properties and the severity of the disease, expressed in terms of FEV1 and bacterial colonization, was developed. By using principal component analysis, we show that the types of colonization and FEV1 classes are significantly correlated to the elastic modulus, and that the latter can be used for CF severity classification with a high predictive efficiency (88%). The data presented here show that the elastic modulus of airways mucus, given the high predictive efficiency, could be used as a new clinical parameter in the prognostic evaluation of cystic fibrosis.

  11. Activation of chloride channels in normal and cystic fibrosis airway epithelial cells by multifunctional calcium/calmodulin-dependent protein kinase

    NASA Astrophysics Data System (ADS)

    Wagner, John A.; Cozens, Alison L.; Schulman, Howard; Gruenert, Dieter C.; Stryer, Lubert; Gardner, Phyllis

    1991-02-01

    CYSTIC fibrosis is associated with defective regulation of apical membrane chloride channels in airway epithelial cells. These channels in normal cells are activated by cyclic AMP-dependent protein kinase1,2 and protein kinase C3,4. In cystic fibrosis these kinases fail to activate otherwise normal Cl- channels1-4. But Cl- flux in cystic fibrosis cells, as in normal cells, can be activated by raising intracellular Ca2+ (refs 5-10). We report here whole-cell patch clamp studies of normal and cystic fibrosis-derived airway epithelial cells showing that Cl- channel activation by Ca2+ is mediated by multifunctional Ca2+/calmodulin-dependent protein kinase. We find that intracellular application of activated kinase and ATP activates a Cl- current similar to that activated by a Ca2+ ionophore, that peptide inhibitors of either the kinase or calmodulin block Ca2+-dependent activation of Cl- channels, and that a peptide inhibitor of protein kinase C does not block Ca2+-dependent activation. Ca2+/calmodulin activation of Cl- channels presents a pathway with therapeutic potential for circumventing defective regulation of Cl- channels in cystic fibrosis.

  12. New horizons for cystic fibrosis treatment.

    PubMed

    Fajac, Isabelle; De Boeck, Kris

    2017-02-01

    Cystic fibrosis is an inherited multi-system disease associated with chronic lung infection, malabsorption, salt loss syndromes, male infertility and leading to numerous comorbidities. The landscape in cystic fibrosis care has changed markedly with currently more adult patients than children in many countries. Over 2000 different mutations in the CFTR gene have been reported and the majority are extremely rare. Understanding how CFTR mutations translate to disturbed synthesis or function of the CFTR protein has opened the way to 'personalized' treatments to correct the basic defect. The first 2 drugs have reached the clinic: a CFTR potentiator to augment CFTR channel function, and the combination of this potentiator with a corrector to increase CFTR expression at the cell membrane. To obtain robust correction of CFTR expression at the cell membrane, combinations of correctors with additive efficacy are under investigation. Other mutation type-specific treatments under clinical investigation are premature stop codon-read through drugs and antisense oligonucleotides that correct the basic defect at the mRNA level. Restoring the defective gene by gene editing can already be achieved ex vivo. Mutation agnostic treatments are explored as well: stabilizing CFTR expression at the cell membrane, circumventing the CFTR channel by blocking or activating other ion channels, and gene therapy. Combinations of these therapies can be anticipated. The pipeline of corrective strategies under clinical investigation is increasing continuously and a rising number of pharmaceutical companies are entering the field. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Cystic fibrosis: psychological issues.

    PubMed

    Götz, I; Götz, M

    2000-06-01

    To most parents the diagnosis of cystic fibrosis (CF) in their child represents a severe blow because they are confronted with an unwanted and unexpected disease that completely changes their whole life. Common reactions such as shock, denial, sadness and anger have to be mastered before a gradual adaptation to reality will be possible. The provision of support by a multidisciplinary team, including a psychologist, that offers its services from diagnosis and puts an emphasis on preventive care may help to achieve, maintain and improve physical and mental health, and social functioning in both patients and parents. CF not only affects the individual but the whole family, and the presence of biopsychosocial stressors may add to the burden caused by the disease. CF does not necessarily cause long-term serious family dysfunction, but it changes family structures and often taxes the family system beyond its strength. Even if there is only partial adherence to the demanding and complex treatment regimen, health professionals need to acknowledge the tremendous underlying effort on the part of the families. As a consequence of their continuous endeavours, many individuals with CF do lead remarkably normal lives with the prospect of gene therapy and lung transplantation, maintaining hope in case of severe deterioration.

  14. Oscillating devices for airway clearance in people with cystic fibrosis.

    PubMed

    Morrison, Lisa; Agnew, Jennifer

    2014-07-20

    Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis. Oscillating devices generate intra- or extra-thoracic oscillations orally or external to the chest wall. Internally they create variable resistances within the airways, generating controlled oscillating positive pressure which mobilises mucus. Extra-thoracic oscillations are generated by forces outside the respiratory system, e.g. high frequency chest wall oscillation. To identify whether oscillatory devices, oral or chest wall, are effective for mucociliary clearance and whether they are equivalent or superior to other forms of airway clearance in the successful management of secretions in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and hand searches of relevant journals and abstract books of conference proceedings. Latest search of the Cystic Fibrosis Trials Register: 13 January 2014. Randomised controlled studies and controlled clinical studies of oscillating devices compared with any other form of physiotherapy in people with cystic fibrosis. Single-treatment interventions (therapy technique used only once in the comparison) were excluded. Two authors independently applied the inclusion criteria to publications and assessed the quality of the included studies. The searches identified 68 studies with a total of 288 references; 35 studies (total of 1050 participants) met the inclusion criteria. Studies varied in duration from up to one week to one year; 20 of the studies were cross-over in design. The studies also varied in type of intervention and the outcomes measured, furthermore data were not published in sufficient detail in most of these studies, so meta-analysis was limited. Few studies were considered to have a low risk of bias in any domain. It is not possible to blind participants and

  15. Risk of gastrointestinal cancers in patients with cystic fibrosis: a systematic review and meta-analysis.

    PubMed

    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; p<0·0001; log SIR 2·10, 95% CI 1·87-2·32; p<0·0001, I 2 =93·93%). Subgroup analyses showed that the risk of gastrointestinal cancer among patients

  16. Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.

    PubMed

    Hussein, Norita; Weng, Stephen F; Kai, Joe; Kleijnen, Jos; Qureshi, Nadeem

    2015-08-12

    Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 25 June 2015.Date of latest search of all other sources: 10 December 2014. Any randomised or quasi-randomised control trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease

  17. Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.

    PubMed

    Hussein, Norita; Weng, Stephen F; Kai, Joe; Kleijnen, Jos; Qureshi, Nadeem

    2018-03-14

    Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. This is an update of a previously published review. To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 20 June 2017.Date of latest search of all other sources: 16 November 2017. Any randomised or quasi-randomised controlled trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle

  18. Endocrine Disorders in Cystic Fibrosis.

    PubMed

    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.

  19. Role of Mutant CFTR in Hypersusceptibility of Cystic Fibrosis Patients to Lung Infections

    NASA Astrophysics Data System (ADS)

    Pier, Gerald B.; Grout, Martha; Zaidi, Tanweer S.; Olsen, John C.; Johnson, Larry G.; Yankaskas, James R.; Goldberg, Joanna B.

    1996-01-01

    Cystic fibrosis (CF) patients are hypersusceptible to chronic Pseudomonas aeruginosa lung infections. Cultured human airway epithelial cells expressing the ΔF508 allele of the cystic fibrosis transmembrane conductance regulator (CFTR) were defective in uptake of P. aeruginosa compared with cells expressing the wild-type allele. Pseudomonas aeruginosa lipopolysaccharide (LPS)-core oligosaccharide was identified as the bacterial ligand for epithelial cell ingestion; exogenous oligosaccharide inhibited bacterial ingestion in a neonatal mouse model, resulting in increased amounts of bacteria in the lungs. CFTR may contribute to a host-defense mechanism that is important for clearance of P. aeruginosa from the respiratory tract.

  20. Aspergillus fumigatus in cystic fibrosis: An update on immune interactions and molecular diagnostics in allergic bronchopulmonary aspergillosis.

    PubMed

    Carsin, A; Romain, T; Ranque, S; Reynaud-Gaubert, M; Dubus, J-C; Mège, J-L; Vitte, J

    2017-11-01

    A wide spectrum of pathological conditions may result from the interaction of Aspergillus fumigatus and the immune system of its human host. Allergic bronchopulmonary aspergillosis is one of the most severe A. fumigatus-related diseases due to possible evolution toward pleuropulmonary fibrosis and respiratory failure. Allergic bronchopulmonary aspergillosis occurs almost exclusively in cystic fibrosis or asthmatic patients. An estimated 8%-10% of patients with cystic fibrosis experience this condition. The diagnosis of allergic bronchopulmonary aspergillosis relies on criteria first established in 1977. Progress in the understanding of host-pathogen interactions in A. fumigatus and patients with cystic fibrosis and the ongoing validation of novel laboratory tools concur to update and improve the diagnosis of allergic bronchopulmonary aspergillosis. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  1. Diagnosis, follow-up and treatment of cystic fibrosis-related liver disease.

    PubMed

    van de Peppel, Ivo P; Bertolini, Anna; Jonker, Johan W; Bodewes, Frank A J A; Verkade, Henkjan J

    2017-11-01

    To provide an insight and overview of the challenges in the diagnosis, follow-up and treatment of cystic fibrosis-related liver disease (CFLD). The variable pathophysiology of CFLD complicates its diagnosis and treatment. A 'gold standard' for CFLD diagnosis is lacking. Over the past years, new techniques to diagnose features of CFLD, such as transient elastography, have been investigated. Although most of these tests confirm cystic fibrosis-related liver involvement (CFLI), they are, however, not suitable to distinguish various phenotypical presentations or predict progression to clinically relevant cirrhosis or portal hypertension. A combined initiative from the European and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has been started, aimed to obtain consensus on CFLD criteria and definitions. Currently, only ursodeoxycholic acid is used in CFLD treatment, although it has not been convincingly demonstrated to change the natural course of the disease. Drugs that directly target cystic fibrosis transmembrane conductance regulator protein dysfunction show promising results; however, more long-term follow-up and validation studies are needed. CFLD is an umbrella term referring to a wide variety of liver manifestations with variable clinical needs and consequences. CFLD with portal hypertension is the most severe form of CFLD due to its significant implications on morbidity and mortality. The clinical relevance of other CFLI is uncertain. Consensus on CFLD definitions is essential to validate new diagnostic tools and therapeutic outcome measures.

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

    PubMed

    Somaraju, Usha Rani; Solis-Moya, Arturo

    2014-10-13

    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. 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: 14 August 2014.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: 12 May 2014. 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 parallel trial and 11 cross-over trials of children and

  3. Newborn bloodspot screening for cystic fibrosis: What do antenatal and postnatal women know about cystic fibrosis?

    PubMed

    Fitzgerald, C; Linnane, B; Heery, E; Conneally, N; George, S; Fitzpatrick, P

    2016-07-01

    The Republic of Ireland has one of the highest reported incidences of cystic fibrosis (CF) in the world (1/1353) with an estimated carrier rate of 1/20. No cure exists, however there have been significant advances in available treatments. Newborn bloodspot screening (NBS) for CF was added to the NBS programme in Ireland in July 2011. Little is known about antenatal or postnatal women's knowledge about CF. This was a cross-sectional study of 662 antenatal (≥36weeks gestation) and 480 postnatal women (post NBS). Women were asked to self-complete a questionnaire including 14 CF knowledge questions. Among the respondents significantly more postnatal than antenatal women were aware that CF is included on the NBS (81.8% vs 63.5%; p<0.001). 92.7% believe that there are health consequences to being a carrier and 33.6% believe there is a cure for CF. In the multivariate analysis, lower educational status (OR 2.13; 95% CI 1.31, 3.46) being an antenatal mother (OR 1.51; 95% CI 1.04, 2.18), having no family history of CF (OR 5.82; 95% CI 1.62, 20.90) were associated with poor CF knowledge, while increasing age was found to be protective against poor CF knowledge (OR 0.96; 95% CI 0.92, 0.99). Results from this study provide a useful insight into women's preexisting knowledge about CF, which could be used to inform initial discussions with parents about their child's diagnosis. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  4. Rare association between cystic fibrosis, Chiari I malformation, and hydrocephalus in a baby: a case report and review of the literature

    PubMed Central

    2011-01-01

    Introduction Cystic fibrosis, an epithelial cell transport disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator gene, is not generally associated with malformations of the central nervous system. We review eight previously published reports detailing an infrequent association between cystic fibrosis and Chiari I malformation. Case presentation To the best of our knowledge, our report describes only the ninth case of a baby presenting with a new diagnosis of cystic fibrosis and Chiari I malformation, in this case in a 10-month-old, full-term Caucasian baby boy from the United States of America. Neurosurgical consultation was obtained for associated developmental delay, macrocephaly, bulging anterior fontanel, and papilledema. An MRI scan demonstrated an extensive Chiari I malformation with effacement of the fourth ventricle, obliteration of the outlets of the fourth ventricle and triventricular hydrocephalus without aqueductal stenosis. Our patient was taken to the operating room for ventriculoperitoneal shunt placement. Conclusions It is possible that the cystic fibrosis transmembrane conductance regulator gene may play a previously unrecognized role in central nervous system development; alternatively, this central nervous system abnormality may have been acquired due to constant valsalva from recurrent coughing or wheezing or metabolic and electrolyte imbalances that occur characteristically in cystic fibrosis. PMID:21838874

  5. [Isonymy analysis in a sample of parents of cystic fibrosis patients from Antioquia, Colombia].

    PubMed

    Rodríguez-Acevedo, Astrid; Morales, Olga; Durango, Harold; Pineda-Trujillo, Nicolás

    2012-01-01

    Cystic fibrosis (CTFR) is one of the most common autosomal recessive disorders in European descendants. Geographic distribution of CFTR gene mutations vary worldwide. The degree of isonimy was evaluated in a sample of parents with children affected by cystic fibrosis. Observed and expected isonimy as well as endogamy components (Fr, Fn, Ft, and the values α and B) were calculated for 35 parents of children diagnosed with cystic fibrosis. These parameters were calculated for both the total population of Antioquia Province and for an eastern subpopulation of Antioquia. The values obtained for Fr, Fn, Ft, α and B were 0.01, 0.007, 0.019, 268 and 0.44, respectively for the total population of Antioquia. For the eastern subpopulation, the values were 0.026, 0.0017, 0.027, 135 and 0.62. The most frequent last-names in the total sample (n=70) were Gómez (6%), Alzate (4%), and González (3.7 %), whilst for the eastern subpopulation (n=32) were Gómez (8%) and Marín (6%). A high percentage of last-names was shared, as is reflected in the isonimy values. Similarly, the presence of a reduced number of last-names in an important percentage of the population is reflected in the Fr values obtained for both analyses, which suggest homogeneity. Thus, it is expected a low number of CFTR mutations in the children from Antioquia with cystic fibrosis.

  6. Distal intestinal obstruction syndrome and colonic pathologies in cystic fibrosis.

    PubMed

    Canny, J D; Brookes, A; Bowley, D B

    2017-01-02

    The management of abdominal pain in cystic fibrosis can be complicated. Distal intestinal obstruction syndrome is a common cause of pain and obstruction in these patients. Knowledge of the diagnosis and management and of similar presenting symptoms is essential for the hospital doctor.

  7. Recent Progress in CFTR Interactome Mapping and Its Importance for Cystic Fibrosis.

    PubMed

    Lim, Sang Hyun; Legere, Elizabeth-Ann; Snider, Jamie; Stagljar, Igor

    2017-01-01

    Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride channel found in secretory epithelia with a plethora of known interacting proteins. Mutations in the CFTR gene cause cystic fibrosis (CF), a disease that leads to progressive respiratory illness and other complications of phenotypic variance resulting from perturbations of this protein interaction network. Studying the collection of CFTR interacting proteins and the differences between the interactomes of mutant and wild type CFTR provides insight into the molecular machinery of the disease and highlights possible therapeutic targets. This mini review focuses on functional genomics and proteomics approaches used for systematic, high-throughput identification of CFTR-interacting proteins to provide comprehensive insight into CFTR regulation and function.

  8. New possibilities for population control of cystic fibrosis.

    PubMed Central

    Dodge, J. A.; Boulyjenkov, V.

    1992-01-01

    Cystic fibrosis (CF), which is caused exclusively by mutation of a single gene, is inherited in autosomal recessive fashion and is the commonest such disorder in populations of Caucasian origin. Although much progress has been made during the last 50 years in its clinical management, with a corresponding improvement in the mean life expectancy in developed countries from a few months to a few decades, it remains incurable and a complete understanding of its biochemical basis is still being sought. Consequently, attention has been given to the possibility of screening for carriers of the defective gene, who represent up to 5% in some populations, so that they may be given appropriate genetic counselling. Whereas previously carriers were identified only when they became parents of affected children, in recent years carriers who were more distantly related to CF patients have often been identified by means of genetic linkage techniques. A new strategy for the control of CF at the population level is now proposed. It is based on the report of a joint WHO/ICF(M)A (International Cystic Fibrosis (Mucoviscidosis) Association) Task Force on CF which met in November 1990. PMID:1464143

  9. Molecular typing of Mycobacterium Abscessus isolated from cystic fibrosis patients.

    PubMed

    Trovato, Alberto; Baldan, Rossella; Costa, Danila; Simonetti, Tullia M; Cirillo, Daniela M; Tortoli, Enrico

    2017-01-01

    The possibility of inter-human transmission of Mycobacterium abscessus in cystic fibrosis centres has been recently hypothesized suggesting the need for the molecular characterization of strains isolated from such patients. One hundred and forty one isolates of M. abscessus grown from sputum samples of 29 patients with cystic fibrosis were genotyped resorting to variable number of tandem repeats (VNTR) determination and whole genome sequencing (WGS). Out of 29 VNTR profiles, 15 were unique to the same number of patients while seven were shared by multiple patients. WGS showed that only two of the patients sharing common VNTR patterns were indeed infected by the same strain. The shared VNTR patterns were mostly present among the isolates of M. abscessus subsp. abscessus. As expected WGS showed a clearly higher discriminatory power in comparison with VNTR and appeared the only molecular epidemiology tool suitable to effectively discriminate the isolates of M. abscessus subsp. abscessus.

  10. Stem cell-derived organoids to model gastrointestinal facets of cystic fibrosis

    PubMed Central

    Hohwieler, Meike; Perkhofer, Lukas; Liebau, Stefan; Seufferlein, Thomas; Müller, Martin

    2016-01-01

    Cystic fibrosis (CF) is one of the most frequently occurring inherited human diseases caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) which lead to ample defects in anion transport and epithelial fluid secretion. Existing models lack both access to early stages of CF development and a coeval focus on the gastrointestinal CF phenotypes, which become increasingly important due increased life span of the affected individuals. Here, we provide a comprehensive overview of gastrointestinal facets of CF and the opportunity to model these in various systems in an attempt to understand and treat CF. A particular focus is given on forward-leading organoid cultures, which may circumvent current limitations of existing models and thereby provide a platform for drug testing and understanding of disease pathophysiology in gastrointestinal organs. PMID:28815024

  11. Body fat assessed from body density and estimated from skinfold thickness in normal children and children with cystic fibrosis.

    PubMed

    Johnston, J L; Leong, M S; Checkland, E G; Zuberbuhler, P C; Conger, P R; Quinney, H A

    1988-12-01

    Body density and skinfold thickness at four sites were measured in 140 normal boys, 168 normal girls, and 6 boys and 7 girls with cystic fibrosis, all aged 8-14 y. Prediction equations for the normal boys and girls for the estimation of body-fat content from skinfold measurements were derived from linear regression of body density vs the log of the sum of the skinfold thickness. The relationship between body density and the log of the sum of the skinfold measurements differed from normal for the boys and girls with cystic fibrosis because of their high body density even though their large residual volume was corrected for. However the sum of skinfold measurements in the children with cystic fibrosis did not differ from normal. Thus body fat percent of these children with cystic fibrosis was underestimated when calculated from body density and invalid when calculated from skinfold thickness.

  12. Structural Changes Fundamental to Gating of the Cystic Fibrosis Transmembrane Conductance Regulator Anion Channel Pore.

    PubMed

    Linsdell, Paul

    2017-01-01

    Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial cell anion channel. Potentiator drugs used in the treatment of cystic fibrosis act on the channel to increase overall channel function, by increasing the stability of its open state and/or decreasing the stability of its closed state. The structure of the channel in either the open state or the closed state is not currently known. However, changes in the conformation of the protein as it transitions between these two states have been studied using functional investigation and molecular modeling techniques. This review summarizes our current understanding of the architecture of the transmembrane channel pore that controls the movement of chloride and other small anions, both in the open state and in the closed state. Evidence for different kinds of changes in the conformation of the pore as it transitions between open and closed states is described, as well as the mechanisms by which these conformational changes might be controlled to regulate normal channel gating. The ways that key conformational changes might be targeted by small compounds to influence overall CFTR activity are also discussed. Understanding the changes in pore structure that might be manipulated by such small compounds is key to the development of novel therapeutic strategies for the treatment of cystic fibrosis.

  13. Disseminated Trichosporon mycotoxinivorans, Aspergillus fumigatus, and Scedosporium apiospermum coinfection after lung and liver transplantation in a cystic fibrosis patient.

    PubMed

    Hirschi, Sandrine; Letscher-Bru, Valérie; Pottecher, Julien; Lannes, Béatrice; Jeung, Mi Young; Degot, Tristan; Santelmo, Nicola; Sabou, Alina Marcela; Herbrecht, Raoul; Kessler, Romain

    2012-12-01

    Trichosporon mycotoxinivorans is a novel pathogen recently found in cystic fibrosis patients. We report the first case of a disseminated fatal infection with T. mycotoxinivorans associated with invasive Aspergillus fumigatus and Scedosporium apiospermum infection after lung and liver transplantation in a cystic fibrosis patient.

  14. A new compound heterozygous CFTR mutation in a Chinese family with cystic fibrosis.

    PubMed

    Xie, Yingjun; Huang, Xueqiong; Liang, Yujian; Xu, Lingling; Pei, Yuxin; Cheng, Yucai; Zhang, Lidan; Tang, Wen

    2017-11-01

    Cystic fibrosis (CF) is the most common autosomal recessive disease among Caucasians but is rarer in the Chinese population, because mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. To elucidate the causative role of a novel compound heterozygous mutation of CF. In this study, clinical samples were obtained from two siblings with recurrent airway infections, clubbed fingers, salt-sweat and failure to gain weight in a non-consanguineous Chinese family. Next-generation sequencing was performed on the 27 coding exons of CFTR in both children, with confirmation by Sanger sequencing. Next-generation sequencing showed the same compound heterozygous CFTR mutation (c.865A>T p.Arg289X and c.3651_3652insAAAT p.Tyr1219X) in both children. As this mutation is consistent with the clinical manifestations of CF and no other mutations were detected after scanning the gene sequence, we suggest that the CF phenotype is caused by compound heterozygosity for c.865A>T and c.3651_3652insAAAT. As c865A>T is not currently listed in the "Cystic Fibrosis Mutation Database", this information about CF in a Chinese population is of interest. © 2015 John Wiley & Sons Ltd.

  15. Using bacterial biomarkers to identify early indicators of cystic fibrosis pulmonary exacerbation onset

    PubMed Central

    Rogers, Geraint B; Hoffman, Lucas R; Johnson, Matt W; Mayer-Hamblett, Nicole; Schwarze, Jürgen; Carroll, Mary P; Bruce, Kenneth D

    2011-01-01

    Acute periods of pulmonary exacerbation are the single most important cause of morbidity in cystic fibrosis patients, and may be associated with a loss of lung function. Intervening prior to the onset of a substantially increased inflammatory response may limit the associated damage to the airways. While a number of biomarker assays based on inflammatory markers have been developed, providing useful and important measures of disease during these periods, such factors are typically only elevated once the process of exacerbation has been initiated. Identifying biomarkers that can predict the onset of pulmonary exacerbation at an early stage would provide an opportunity to intervene before the establishment of a substantial immune response, with major implications for the advancement of cystic fibrosis care. The precise triggers of pulmonary exacerbation remain to be determined; however, the majority of models relate to the activity of microbes present in the patient's lower airways of cystic fibrosis. Advances in diagnostic microbiology now allow for the examination of these complex systems at a level likely to identify factors on which biomarker assays can be based. In this article, we discuss key considerations in the design and testing of assays that could predict pulmonary exacerbations. PMID:21405970

  16. Comparative biology of cystic fibrosis animal models.

    PubMed

    Fisher, John T; Zhang, Yulong; Engelhardt, John F

    2011-01-01

    Animal models of human diseases are critical for dissecting mechanisms of pathophysiology and developing therapies. In the context of cystic fibrosis (CF), mouse models have been the dominant species by which to study CF disease processes in vivo for the past two decades. Although much has been learned through these CF mouse models, limitations in the ability of this species to recapitulate spontaneous lung disease and several other organ abnormalities seen in CF humans have created a need for additional species on which to study CF. To this end, pig and ferret CF models have been generated by somatic cell nuclear transfer and are currently being characterized. These new larger animal models have phenotypes that appear to closely resemble human CF disease seen in newborns, and efforts to characterize their adult phenotypes are ongoing. This chapter will review current knowledge about comparative lung cell biology and cystic fibrosis transmembrane conductance regulator (CFTR) biology among mice, pigs, and ferrets that has implications for CF disease modeling in these species. We will focus on methods used to compare the biology and function of CFTR between these species and their relevance to phenotypes seen in the animal models. These cross-species comparisons and the development of both the pig and the ferret CF models may help elucidate pathophysiologic mechanisms of CF lung disease and lead to new therapeutic approaches.

  17. Long-term clearance from small airways in patients with cystic fibrosis.

    PubMed

    Lindström, M; Camner, P; Falk, R; Hjelte, L; Philipson, K; Svartengren, M

    2005-02-01

    Impaired mucociliary clearance is a hallmark of cystic fibrosis (CF). Early morphological changes first appear in the small airways. Lung clearance was investigated in 11 young CF adults with mild-to-moderate lung disease using a method depositing particles mainly in the small airways. Radiolabelled Teflon particles (6 microm) were inhaled with an extremely slow inhalation flow, 0.05 L x s(-1). Lung retention was measured immediately following inhalations and, on four occasions up to 21 days. The results were compared with data from healthy subjects. The lung retention at 24 h in % of deposition was 67% (95% confidence interval 58-76) in the CF patients, compared to 48% (42-53) in the healthy subjects. Clearance on days 1-7 was larger in the CF patients, 22% (15-29) compared to the healthy subjects, 14% (12-16). No difference was observed between the CF patients and the healthy subjects in the slow clearance phase at day 7 to day 21, representing small airway clearance. Impaired mucociliary clearance in CF patients results in increased 24-h retention and a prolonged rapid clearance phase. The results of the study do not support the current authors' hypothesis that clearance from small airways is slower in cystic fibrosis patients compared to healthy subjects. Furthermore, the data suggest that mucociliary transport is not the dominant clearance mechanism in small airways.

  18. A randomized placebo-controlled trial of miglustat in cystic fibrosis based on nasal potential difference.

    PubMed

    Leonard, Anissa; Lebecque, Patrick; Dingemanse, Jasper; Leal, Teresinha

    2012-05-01

    Preclinical data suggest that miglustat could restore the function of the cystic fibrosis transmembrane conductance regulator gene in cystic fibrosis cells. Single-center, randomized, double-blind, placebo-controlled, crossover Phase II study in 11 patients (mean±SD age, 26.3±7.7 years) homozygous for the F508del mutation received oral miglustat 200 mgt.i.d. or placebo for two 8-day cycles separated by a 14-day washout period. The primary endpoint was the change in total chloride secretion (TCS) assessed by nasal potential difference. No statistically significant changes in TCS, sweat chloride values or FEV(1) were detected. Pharmacokinetic and safety were similar to those observed in patients with other diseases exposed to miglustat. There was no evidence of a treatment effect on any nasal potential difference variable. Further studies with miglustat need to adequately address criteria for assessment of nasal potential difference. Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  19. R248G cystic fibrosis transmembrane conductance regulator mutation in three siblings presenting with recurrent acute pancreatitis and reproductive issues: a case series.

    PubMed

    Villalona, Seiichi; Glover-López, Guillermo; Ortega-García, Juan Antonio; Moya-Quiles, Rosa; Mondejar-López, Pedro; Martínez-Romero, Maria C; Rigabert-Montiel, Mariano; Pastor-Vivero, María D; Sánchez-Solís, Manuel

    2017-02-15

    Mutational combinations of the cystic fibrosis transmembrane conductance regulator, CFTR, gene have different phenotypic manifestations at the molecular level with varying clinical consequences for individuals possessing such mutations. Reporting cystic fibrosis transmembrane conductance regulator mutations is important in understanding the genotype-phenotype correlations and associated clinical presentations in patients with cystic fibrosis. Understanding the effects of mutations is critical in developing appropriate treatments for individuals affected with cystic fibrosis, non-classic cystic fibrosis, or cystic fibrosis transmembrane conductance regulator-related disorders. This is the first report of related individuals possessing the R248G missense cystic fibrosis transmembrane conductance regulator mutation and we present their associated clinical histories. All three patients are of Spanish descent. Deoxyribonucleic acid analysis revealed that all three siblings possessed a novel c.742A>G mutation, resulting in a p.Arg248Gly (R248G) amino acid change in exon 6 in trans with the known N1303K mutant allele. Case 1 patient is a 39-year-old infertile man presenting with congenital unilateral absence of the vas deferens and recurrent episodes of epigastric pain. Case 2 patient is a 32-year-old woman presenting with periods of infertility, two previous spontaneous abortions, recurrent epigastric pain, and recurrent pancreatitis. Case 3 patient is a 29-year-old woman presenting with recurrent pancreatitis and epigastric pain. We report the genotype-phenotype correlations and clinical manifestations of a novel R248G cystic fibrosis transmembrane conductance regulator mutation: congenital unilateral absence of the vas deferens in males, reduced female fertility, and recurrent acute pancreatitis. In addition, we discuss the possible functional consequences of the mutations at the molecular level.

  20. Progress in cystic fibrosis and the CF Therapeutics Development Network

    PubMed Central

    Rowe, Steven M; Borowitz, Drucy S; Burns, Jane L; Clancy, John P; Donaldson, Scott H; Retsch-Bogart, George; Sagel, Scott D; Ramsey, Bonnie W

    2013-01-01

    Cystic fibrosis (CF), the most common life-shortening genetic disorder in Caucasians, affects approximately 70 000 individuals worldwide. In 1998, the Cystic Fibrosis Foundation (CFF) launched the CF Therapeutics Development Network (CF-TDN) as a central element of its Therapeutics Development Programme. Designed to accelerate the clinical evaluation of new therapies needed to fulfil the CFF mission to control and cure CF, the CF-TDN has conducted 75 clinical trials since its inception, and has contributed to studies as varied as initial safety and proof of concept trials to pivotal programmes required for regulatory approval. This review highlights recent and significant research efforts of the CF-TDN, including a summary of contributions to studies involving CF transmembrane conductance regulator (CFTR) modulators, airway surface liquid hydrators and mucus modifiers, anti-infectives, anti-inflammatories, and nutritional therapies. Efforts to advance CF biomarkers, necessary to accelerate the therapeutic goals of the network, are also summarised. PMID:22960984

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Progress in cystic fibrosis and the CF Therapeutics Development Network.

    PubMed

    Rowe, Steven M; Borowitz, Drucy S; Burns, Jane L; Clancy, John P; Donaldson, Scott H; Retsch-Bogart, George; Sagel, Scott D; Ramsey, Bonnie W

    2012-10-01

    Cystic fibrosis (CF), the most common life-shortening genetic disorder in Caucasians, affects approximately 70 000 individuals worldwide. In 1998, the Cystic Fibrosis Foundation (CFF) launched the CF Therapeutics Development Network (CF-TDN) as a central element of its Therapeutics Development Programme. Designed to accelerate the clinical evaluation of new therapies needed to fulfil the CFF mission to control and cure CF, the CF-TDN has conducted 75 clinical trials since its inception, and has contributed to studies as varied as initial safety and proof of concept trials to pivotal programmes required for regulatory approval. This review highlights recent and significant research efforts of the CF-TDN, including a summary of contributions to studies involving CF transmembrane conductance regulator (CFTR) modulators, airway surface liquid hydrators and mucus modifiers, anti-infectives, anti-inflammatories, and nutritional therapies. Efforts to advance CF biomarkers, necessary to accelerate the therapeutic goals of the network, are also summarised.

  3. Cystic fibrosis carrier screening in Veneto (Italy): an ethical analysis.

    PubMed

    Bruni, Tommaso; Mameli, Matteo; Pravettoni, Gabriella; Boniolo, Giovanni

    2012-08-01

    A recent study by Castellani et al. (JAMA 302(23):2573-2579, 2009) describes the population-level effects of the choices of individuals who underwent molecular carrier screening for cystic fibrosis (CF) in Veneto, in the northeastern part of Italy, between 1993 and 2007. We discuss some of the ethical issues raised by the policies and individual choices that are the subject of this study. In particular, (1) we discuss the ethical issues raised by the acquisition of genetic information through antenatal carrier testing; (2) we consider whether by choosing to procreate naturally these couples can harm the resulting child and/or other members of society, and what the moral implications of such harm would be; (3) we consider whether by choosing to avoid natural procreation carrier couples can harm current or future individuals affected by cystic fibrosis; (4) we discuss whether programs that make carrier testing available can be considered eugenic programs.

  4. Host-pathogen interplay in the respiratory environment of cystic fibrosis.

    PubMed

    Yonker, Lael M; Cigana, Cristina; Hurley, Bryan P; Bragonzi, Alessandra

    2015-07-01

    Significant advances have been made in the understanding of disease progression in cystic fibrosis (CF), revealing a complex interplay between host and pathogenic organisms. The diverse CF microbiota within the airway activates an aberrant immune response that is ineffective in clearing infection. An appreciation of how the CF host immune system interacts with these organisms is crucial to understanding the pathogenesis of CF pulmonary disease. Here we discuss the microbial complexity present in the lungs of individuals with CF, review emerging concepts of innate and adaptive immune responses to pathogens that chronically inhabit the CF lung, and discuss therapies that target the aberrant inflammatory response that characterizes CF. A greater understanding of the underlying mechanisms will shed light on pathogenesis and guide more targeted therapies in the future that serve to reduce infection, minimize lung pathology, and improve the quality of life for patients with CF. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  5. Matrix metalloproteinase activation by free neutrophil elastase contributes to bronchiectasis progression in early cystic fibrosis.

    PubMed

    Garratt, Luke W; Sutanto, Erika N; Ling, Kak-Ming; Looi, Kevin; Iosifidis, Thomas; Martinovich, Kelly M; Shaw, Nicole C; Kicic-Starcevich, Elizabeth; Knight, Darryl A; Ranganathan, Sarath; Stick, Stephen M; Kicic, Anthony

    2015-08-01

    Neutrophil elastase is the most significant predictor of bronchiectasis in early-life cystic fibrosis; however, the causal link between neutrophil elastase and airway damage is not well understood. Matrix metalloproteinases (MMPs) play a crucial role in extracellular matrix modelling and are activated by neutrophil elastase. The aim of this study was to assess if MMP activation positively correlates with neutrophil elastase activity, disease severity and bronchiectasis in young children with cystic fibrosis.Total MMP-1, MMP-2, MMP-7, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-1 levels were measured in bronchoalveolar lavage fluid collected from young children with cystic fibrosis during annual clinical assessment. Active/pro-enzyme ratio of MMP-9 was determined by gelatin zymography. Annual chest computed tomography imaging was scored for bronchiectasis.A higher MMP-9/TIMP-1 ratio was associated with free neutrophil elastase activity. In contrast, MMP-2/TIMP-2 ratio decreased and MMP-1 and MMP-7 were not detected in the majority of samples. Ratio of active/pro-enzyme MMP-9 was also higher in the presence of free neutrophil elastase activity, but not infection. Across the study cohort, both MMP-9/TIMP-1 and active MMP-9 were associated with progression of bronchiectasis.Both MMP-9/TIMP-1 and active MMP-9 increased with free neutrophil elastase and were associated with bronchiectasis, further demonstrating that free neutrophil elastase activity should be considered an important precursor to cystic fibrosis structural disease. Copyright ©ERS 2015.

  6. Year to year change in FEV1 in patients with cystic fibrosis and different mutation classes.

    PubMed

    De Boeck, K; Zolin, A

    2017-03-01

    In patients with cystic fibrosis, most treatments addressing the underlying basic defect are mutation or mutation class specific. These treatments are disease modifying if they lower the year to year change in lung function. We therefore calculated the current loss of lung function, measured by year to year change in forced expired volume in 1s in 11,417 patients included in the European Cystic Fibrosis Society Patient Registry. Whereas patients with at least one mutation of class IV or V have on average a lower year to year change, we did not find a difference between patients with a stop codon mutation, homozygous for F508del or at least one class III mutation. These data are useful background information to discuss the impact of different disease modifying treatments. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  7. Nasal polyposis in cystic fibrosis: follow-up of children and adolescents for a 3-year period.

    PubMed

    Weber, Silke Anna Theresa; Iyomasa, Renata Mizusaki; Corrêa, Camila de Castro; Florentino, Wellington Novais Mafra; Ferrari, Giesela Fleischer

    Nasal polyposis is often found in patients with cystic fibrosis. To assess the incidence of nasal polyposis, the response to medical treatment, recurrence and the need for surgical intervention in children and adolescents with cystic fibrosis during a three-year follow-up. Clinical symptoms (pulmonary, pancreatic insufficiency, malnutrition, nasal obstruction), two positive sweat chloride tests, and genotype findings in 23 patients with cystic fibrosis were analyzed. All patients underwent nasal endoscopy every 12 months from January 2005 to December 2007, to assess the presence and grade of Nasal Polyps. Nasal polyposis, when present, were treated with topical corticosteroids for 6-12 months, with progress being evaluated within the 3 years of follow-up. In the first evaluation, nasal polyposis was diagnosed in 30.43% of patients (3 bilateral and 4 unilateral), recurrent pneumonia in 82.6%, pancreatic insufficiency in 87%, and malnutrition in 74%. The presence of nasal polyposis was not associated with chloride values in the sweat, genotype, clinical signs of severity of cystic fibrosis, or nasal symptoms. In the three-year period of follow up, 13 patients (56.52%) had at least one event of polyposis, with the youngest being diagnosed at 32 months of age. Only one patient underwent surgery (polypectomy), and there was one diagnosis of nasopharyngeal carcinoma. The study showed a high incidence of nasal polyposis. Monitoring through routine endoscopy in patients with cystic fibrosis, even in the absence of nasal symptoms, is highly recommended. The therapy with topical corticosteroids achieved good results. Thus, an interaction between pediatricians and otolaryngologists is necessary. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  8. Technological advances shed light on left ventricular cardiac disturbances in cystic fibrosis.

    PubMed

    Sayyid, Zahra N; Sellers, Zachary M

    2017-07-01

    Cystic fibrosis (CF), the most common autosomal recessive lethal disease in Caucasians, causes chronic pulmonary disease and can lead to cor pulmonale with right ventricular dysfunction. The presence of the cystic fibrosis transmembrane conductance regulator (CFTR) in cardiac myocardia has prompted debate regarding possible defective ion channel-induced cardiomyopathy. Clinical heart disease in CF is considered rare and is restricted to case reports. It has been unclear if this is due to the lack of physiological importance of CFTR in the heart, the relatively short lifespan of those with CF, or a technical inability to detect subclinical disease. Extensive echocardiographic investigations have yielded contradictory results, leading to the dogma that left ventricular defects in CF occur secondary to lung disease. In this review, we consider why studies examining heart function in CF have not provided clarity on this topic. We then focus on data from new echocardiographic and magnetic resonance imaging technology, which are providing greater insight into cardiac function in CF and demonstrating that, in addition to secondary effects from pulmonary disease, there may be an intrinsic primary defect in the CF heart. With advancing lifespans and activity levels, understanding the risk of cardiac disease is vital to minimizing morbidity in adults with CF. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  9. Diagnosis of biofilm infections in cystic fibrosis patients.

    PubMed

    Høiby, Niels; Bjarnsholt, Thomas; Moser, Claus; Jensen, Peter Østrup; Kolpen, Mette; Qvist, Tavs; Aanaes, Kasper; Pressler, Tanja; Skov, Marianne; Ciofu, Oana

    2017-04-01

    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 dominated by alginate and the pathogenesis of tissue damage is immune complex-mediated chronic inflammation dominated by polymorphonuclear leukocytes and their products (DNA, oxygen radicals and proteases). The P. aeruginosa biofilm infection can be diagnosed by microscopy of lung tissue, sputum and mucus from the paranasal sinuses, where aggregates of the bacteria are found surrounded by the abundant alginate matrix. Specific PNA-FISH probes can be used to identify P. aeruginosa and other pathogens in situ in the biofilms. Growth of mucoid colonies from the locations mentioned above is also diagnostic for biofilm infection. Rise of specific anti-P. aeruginosa antibodies is likewise diagnostic, IgG in serum in case of lung infection, sIgA in saliva or nasal secretions in case of paranasal sinus infection. Similar approaches have been developed to diagnose chronic biofilm infections in cystic fibrosis caused by other pathogens e.g., Stenotrophomonas, Burkholderia multivorans, Achromobacter xylosoxidans and Mycobacterium abscessus complex. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  10. Liver disease in patients with cystic fibrosis.

    PubMed

    Kamal, Natasha; Surana, Pallavi; Koh, Christopher

    2018-05-01

    The aim of this study was to provide an overview of the current understanding of the pathophysiology, diagnosis and management of cystic fibrosis-liver disease (CFLD). CFLD has a variety of manifestations. Previously, it was thought that patients progressed from mild cholestatic disease to cirrhosis to decompensated cirrhosis with portal hypertension. Newer evidence suggests that some patients may develop cirrhosis while others develop noncirrhotic portal hypertension. Advances in our understanding of the pathophysiology of disease necessitate modifications to the current diagnostic criteria. Both fibroscan and noninvasive biomarkers can be used to identify patients with cirrhosis and portal hypertension. Ursodeoxycholic acid remains the mainstay of therapy despite a paucity of rigorous studies supporting its use. Novel therapeutic agents such as CF transmembrane conductance regulator (CFTR) modulators and potentiators are encouraging but need to be evaluated specifically in CFLD. A better understanding of the pathophysiology of disease is critical to developing more disease-specific diagnostics and therapeutics.

  11. Assessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Spino, M.; Chai, R.P.; Isles, A.F.

    1985-07-01

    A study was conducted to examine renal function in 10 healthy control subjects and eight patients with cystic fibrosis in stable condition. Sequential bolus injections of /sup 99m/Tc-DTPA and /sup 125/I-OIH were administered to assess glomerular filtration rate and effective renal plasma flow, respectively. Blood was subsequently collected for 3 hours, and urine for 24 hours. Renal clearances of both radioisotope markers were virtually identical in patients and controls. Inasmuch as neither glomerular filtration rate nor effective renal plasma flow was enhanced in patients with cystic fibrosis, increased clearance of drugs in these patients is unlikely to be the resultmore » of enhanced glomerular filtration or tubular secretion.« less

  12. A cystic fibrosis patient who is homozygous for the A559T mutation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McDowell, T.; Shackleton, S.; Dear, S.

    1995-09-01

    We have recently defined a cystic fibrosis (CF) patient who is homozygous for the A559T mutation in exon 11 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This mutation was detected by direct sequence analysis and confirmed to be carried by both parents (of West Indian origin) of the index case. The A559T mutation has not been detected in any Caucasian CF patients. The presence of this mutation in North American black CF patients and a British CF patient of West Indian origin is clearly of interest in designing CF screening tests that are tailored to specific ethnic groups.more » 1 ref.« less

  13. Cystic fibrosis: Beyond the airways. Report on the meeting of the basic science working group in Loutraki, Greece.

    PubMed

    Amaral, Margarida D; Boj, Sylvia F; Shaw, James; Leipziger, Jens; Beekman, Jeffrey M

    2018-06-01

    The European Cystic Fibrosis Society (ECFS) Basic Science Working Group (BSWG) organized a session on the topic "Cystic Fibrosis: Beyond the Airways", within the 15th ECFS Basic Science Conference which gathered around 200 researchers working in the basic science of CF. The session was organized and chaired by Margarida Amaral (BioISI, University of Lisboa, Portugal) and Jeffrey Beekman (University Medical Centre Utrecht, Netherlands) as Chair and Vice-Chair of the BSWG and its purpose was to bring attention of participants of the ECFS Basic Science Conference to "more forgotten" organs in CF disease. In this report we attempt to review and integrate the ideas that emerged at the session. Copyright © 2018 European Cystic Fibrosis Society. All rights reserved.

  14. Consequences of Expiratory Flow Limitation at Rest in Subjects with Cystic Fibrosis.

    PubMed

    Vilozni, Daphna; Lavie, Moran; Ofek, Miryam; Sarouk, Ifat; Bar-Aluma, Bat-El; Dagan, Adi; Ashkenazi, Moshe; Segel, Michael J; Efrati, Ori

    2016-06-01

    Expiratory flow limitation at resting tidal volume (EFLTV) presents a severe mechanical constraint in chronic lung diseases and has not yet been studied longitudinally in cystic fibrosis. To study the effect of EFLTV as it emerged from simple spirometry on lung function and clinical status in cystic fibrosis. Best year spirometry that included tidal flow/volume curves and the related clinical data were retrospectively collected over 12 ± 3.0 yr/person from 108 subjects with cystic fibrosis. The year in which forced expiratory flow, midexpiratory phase (FEF25-75%, L/s) was equal to tidal peak expiratory flow (L/s) was defined as EFLTV-onset year. EFLTV occurred in 55 (51%) subjects, at age 23 ± 6 years. At EFLTV onset, tidal peak expiratory flow and FEF25-75% values were 1.44 ± 0.23 L/s and FEV1 was 62 ± 10% predicted. Within the following 2 years, FEV1 dropped to 48 ± 11% predicted, and 35 (63%) of the subjects reported shortness of breath at rest. Hospital days increased from 5.3 ± 24.6 to 24.12 ± 9.0 d/yr (P = 0.0001). Of the 55 subjects, 29 (53%) received transplant or died, with survival time being 6.9 ± 3.9 years. EFLTV onset may be an important pathophysiological event that could influence the natural history of lung function decline in subjects with cystic fibrosis. This may lead to a significant deterioration in lung function in the following 2 years alongside an increase in the number of hospitalization days. The monitoring of FEV1 alone does not offer as good a threshold signal, because values are only moderately reduced. Therefore, identifying EFLTV appearance is potentially a signal for therapeutic intervention. Further studies are warranted to confirm our findings.

  15. Validation of a Nutrition Screening Tool for Pediatric Patients with Cystic Fibrosis.

    PubMed

    Souza Dos Santos Simon, Miriam Isabel; Forte, Gabriele Carra; da Silva Pereira, Juliane; da Fonseca Andrade Procianoy, Elenara; Drehmer, Michele

    2016-05-01

    In cystic fibrosis (CF), nutrition diagnosis is of critical relevance because the early identification of nutrition-related compromise enables early, adequate intervention and, consequently, influences patient prognosis. Up to now, there has not been a validated nutrition screening tool that takes into consideration clinical variables. To validate a specific nutritional risk screening tool for patients with CF based on clinical variables, anthropometric parameters, and dietary intake. Cross-sectional study. The nutrition screening tool was compared with a risk screening tool proposed by McDonald and the Cystic Fibrosis Foundation criteria. Patients aged 6 to 18 years, with a diagnosis of CF confirmed by two determinations of elevated chloride level in sweat (sweat test) and/or by identification of two CF-associated genetic mutations who were receiving follow-up care through the outpatient clinic of a Cystic Fibrosis Treatment Center. Earlier identification of nutritional risk in CF patients aged 6 to 18 years when a new screening tool was applied. Agreement among the tested methods was assessed by means of the kappa coefficient for categorical variables. Sensitivity, specificity, and accuracy values were calculated. The significance level was set at 5% (P<0.05). Statistical analyses were carried out in PASW Statistics for Windows version 18.0 (2009, SPSS Inc). Eighty-two patients (49% men, aged 6 to 18 years) were enrolled in the study. The agreement between the proposed screening tool and the tool for screening nutritional risk for CF by the McDonald method was good (κ=0.804; P<0.001) and the sensitivity and specificity was 85% and 95%, respectively. Agreement with the Cystic Fibrosis Foundation criteria was lower (κ=0.418; P<0.001), and the sensitivity and specificity were both 72%. The proposed screening tool with defined clinical variables promotes earlier identification of nutritional risk in pediatric patients with CF. Copyright © 2016 Academy of Nutrition

  16. Family-centred care for families living with cystic fibrosis in a rural setting: A qualitative study.

    PubMed

    Jessup, Melanie; Smyth, Wendy; Abernethy, Gail; Shields, Linda; Douglas, Tonia

    2018-02-01

    To explore experiences of family-centred care among parents of children with cystic fibrosis living far from tertiary treatment centres and to understand what such distances mean to their care. Australia is a large continent. However, many families with a child with cystic fibrosis live in regional areas, often thousands of kilometres away from the primary treatment centres located in Australia's coastal capital cities. A qualitative, phenomenological design using a Van Manen () approach. Individual, semi-structured interviews were conducted with parents (n = 7) of a child with cystic fibrosis who lived in regional Australia. Thematic content data analysis was used. The essence of the participants' experience was their seeking certainty and continuity in the changeable realm of cystic fibrosis while negotiating a collaborative approach to their child's care. Five core themes and two subthemes were identified: "Daily care: a family affair," including the subtheme "Accessing expert care"; "Family-centred care: seeking inclusion"; "Control versus collaboration: seeking mutual trust," with the subtheme "The team who grows with you"; "Future projections"; and "The CF circle." Some concerns are not unlike those of their city counterparts, but can be intensified by their sense of distance and isolation. Insight into this unique milieu from the parents' perspective is requisite so that care is appropriate to such a challenging environment and incorporates the whole family. © 2017 John Wiley & Sons Ltd.

  17. Expression of the cystic fibrosis transmembrane conductance regulator gene in the respiratory tract of normal individuals and individuals with cystic fibrosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Trapnell, B.C.; Chinshyan Chu; Paakko, P.K.

    1991-08-01

    The most common mutation of the cystic fibrosis transmembrane conductance regulator gene, CFTR, associated with the clinical disorder cystic fibrosis (CF) is called {Delta}Phe{sup 508}, a triple-base deletion resulting in loss of phenylalanine at residue 508 of the predicted 1480-amino acid CFTR protein. In the context that the lung is the major site of morbidity and mortality in CF, the authors evaluated airway epithelial cells for CFTR mRNA transcripts in normal individuals, normal-{Delta}Phe{sup 508} heterozygotes, and {Delta}Phe{sup 508} homozygotes to determine if the normal and {Delta}Phe{sup 508} CFTR alleles are expressed in the respiratory epithelium, to what extent they aremore » expressed, and whether there are relative differences in the expression of the normal and abnormal alleles at the mRNA level. Respiratory tract epithelial cells recovered by fiberoptic bronchoscopy with a cytology brush demonstrated CFTR mRNA transcripts with sequences appropriately reflecting the normal and {Delta}Phe{sup 508} CFTR alleles of the various study groups. CFTR gene expression quantified by limited polymerase chain reaction amplification showed that in normal individuals, CFTR mRNA transcripts are expressed in nasal, tracheal, and bronchial epithelial cells.« less

  18. The changing epidemiology and demography of cystic fibrosis.

    PubMed

    Stephenson, Anne L; Stanojevic, Sanja; Sykes, Jenna; Burgel, Pierre-Regis

    2017-06-01

    Once considered a pediatric disease with a poor prognosis, individuals born with cystic fibrosis (CF) today can expect to live well into adulthood. The implementation of multidisciplinary care, novel treatments and newborn screening has resulted in the rapid evolution in the demographics of the CF population. The purpose of this review is to highlight the evolving epidemiology and demographics of the CF population internationally. Copyright © 2017. Published by Elsevier Masson SAS.

  19. Is bronchoscopy an obsolete tool in cystic fibrosis? The role of bronchoscopy in cystic fibrosis and its clinical use

    PubMed Central

    2017-01-01

    Cystic fibrosis (CF) is a progressive life threatening multisystem genetic disease which affects the CF transmembrane conductance regulator channel. Respiratory causes remain the most common mortality in CF. With the onset of newborn screening, initiating treatments both for prophylaxis and disease management, optimizing nutritional support, and developing therapies targeting CF transmembrane conductance regulator protein, this has significantly changed the face of managing this devastating disease. Bronchoscopy and related procedures such as bronchoalveolar lavage (BAL), transbronchial biopsies, and protected brush sampling have been looked at in the management of CF as patients with CF continue to live longer with the help of newer therapies, the microbiome in the lung becomes less diverse along with increased occurrences for noninfectious causes of airway diseases. Though bronchoscopy has been used in conjunction with other modalities such as computed tomography and sputum induction providing a better understanding of the progression of the disease, it still remains valuable in the diagnosis and management of CF. PMID:29214071

  20. Parent Interview Findings Regarding the Impact of Cystic Fibrosis on Families.

    ERIC Educational Resources Information Center

    Phillips, Sheridan

    1985-01-01

    An assessment of the impact of cystic fibrosis (CF) was conducted with 43 families. The impact of hospitalization upon parents was the most prevalent major problem. Parental communication was a "major problem" for 28% of the mothers but only one father. (Author/CL)

  1. Newborn screening for cystic fibrosis with the chloride electrode and neutron activation analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Guerson, C.T.; Sertel, H.; Guerkan, M.

    From third annual meeting of the European Working Group of Cystic Fibrosis; Erbach, Germany (6 Sep 1972). In 6,061 newborns, the chloride electrode technique was used for the detection of cystic fibrosis. The electrolyte values obtained were found to vary with the type of electrode used (45.9 plus or minus 9.9 mEq/l Beckman and 22.3 plus or minus 12 mEq/l Orion), and in both cases a value greater than the mean + 2 standard deviation was held as suspect and retested. In the group studied, the incidence of cystic fibrosis was calculated to be 1 in 3,000. In 590 ofmore » these cases the sodium values of nail clippings were measured by neutron activation analysis and were found to differ according to the washing method used; wash in vivo with ethanol 211.26 plus or minus 85.9 mEq/ kg water wash and acetone rinse 93.00 plus or minus 47.24 mEq/ kg; washing with H/sub 2/O/sub 2/ + absolute ethanol + diethyl ether, 183.42 plus or minus 61.26 mEq/k g. In addition, no correlation was found between chloride in sweat and the sodium content of nails. (auth)« less

  2. Best practices in the treatment of early cystic fibrosis lung disease.

    PubMed

    Proesmans, Marijke

    2017-02-01

    For many years, management of cystic fibrosis (CF) lung disease was focused on symptomatic treatment of chronic lung infection, which is characterized by cough and sputum production, leading to progressive lung damage. With increasing survival and better knowledge of the pathogenesis of CF lung disease, it has become clear that treatment has to start very early because lung damage occurs in young patients, often before obvious symptoms appear. The arrival of new cystic fibrosis transmembrane conductance-regulator (CFTR)-correcting therapies will bring more opportunities to prevent the disease, apart from only treating chronic lung infection. In this review, a summary of the current knowledge of early CF lung disease is provided, based on animal model studies, as well as on data obtained from well structured follow-up programs after newborn screening (NBS). The most important clinical guidelines for treating young CF patients are also summarized.

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

    PubMed

    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

  4. Fatal Disseminated Aspergillus penicillioides Infection in a 3-Month-Old Infant with Suspected Cystic Fibrosis: Autopsy Case Report with Review of Literature.

    PubMed

    Gupta, Kirti; Gupta, Parikshaa; Mathew, Joseph L; Bansal, Arun; Singh, Gangandeep; Singh, Meenu; Chakrabarti, Arunaloke

    Patients with cystic fibrosis (CF) often are colonized by Aspergillus species in their respiratory tract, but invasive aspergillosis is a rare complication. We describe the autopsy findings of an infant with cystic fibrosis who had fatal disseminated aspergillosis. The causative agent was identified as A. penicillioides by molecular technique. To our knowledge, this is the first report of disseminated aspergillosis caused by A. penicillioides in any type of patient. The literature on invasive aspergillosis in patients with cystic fibrosis also is reviewed.

  5. The Epidemiology and Management of Lung Diseases in Sickle Cell Disease: Lessons Learned from Acute and Chronic Lung Disease in Cystic Fibrosis.

    PubMed

    Willen, Shaina M; DeBaun, Michael R

    2018-06-01

    Although sickle cell disease and cystic fibrosis are two of the most common monogenic diseases presenting in childhood worldwide, cystic fibrosis and sickle cell disease enjoy vastly different funding and collaborative research efforts. Pulmonary complications in cystic fibrosis have well established guidelines and multidisciplinary involvement focusing on comorbidities, routine monitoring, infectious complications, nutrition, and treatment recommendations. These guidelines can provide a framework on which to build knowledge of lung disease in sickle cell disease. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Urinary incontinence in patients with cystic fibrosis.

    PubMed

    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 (< 12 or ≥ 12 years). The different characteristics of 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.

  7. Postnatal airway growth in cystic fibrosis piglets.

    PubMed

    Adam, Ryan J; Abou Alaiwa, Mahmoud H; Bouzek, Drake C; Cook, Daniel P; Gansemer, Nicholas D; Taft, Peter J; Powers, Linda S; Stroik, Mallory R; Hoegger, Mark J; McMenimen, James D; Hoffman, Eric A; Zabner, Joseph; Welsh, Michael J; Meyerholz, David K; Stoltz, David A

    2017-09-01

    Mutations in the gene encoding the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) anion channel cause CF. The leading cause of death in the CF population is lung disease. Increasing evidence suggests that in utero airway development is CFTR-dependent and that developmental abnormalities may contribute to CF lung disease. However, relatively little is known about postnatal CF airway growth, largely because such studies are limited in humans. Therefore, we examined airway growth and lung volume in a porcine model of CF. We hypothesized that CF pigs would have abnormal postnatal airway growth. To test this hypothesis, we performed CT-based airway and lung volume measurements in 3-wk-old non-CF and CF pigs. We found that 3-wk-old CF pigs had tracheas of reduced caliber and irregular shape. Their bronchial lumens were reduced in size proximally but not distally, were irregularly shaped, and had reduced distensibility. Our data suggest that lack of CFTR results in aberrant postnatal airway growth and development, which could contribute to CF lung disease pathogenesis. NEW & NOTEWORTHY This CT scan-based study of airway morphometry in the cystic fibrosis (CF) postnatal period is unique, as analogous studies in humans are greatly limited for ethical and technical reasons. Findings such as reduced airway lumen area and irregular caliber suggest that airway growth and development are CF transmembrane conductance regulator-dependent and that airway growth defects may contribute to CF lung disease pathogenesis. Copyright © 2017 the American Physiological Society.

  8. Four case reports of Chinese cystic fibrosis patients and literature review.

    PubMed

    Xu, Juan; Yin, Yong; Zhang, Lei; Zhang, Jing; Yuan, Shuhua; Zhang, Hao

    2017-08-01

    Cystic fibrosis (CF) is an extremely rare disease in Asians. Here, we report four Chinese children with CF and review the literature about Chinese CF patients. The cystic fibrosis transmembrane conductance regulator (CFTR) gene testing was performed on four suspected patients for CF screening. We also reviewed the literature about Chinese CF patients from 1970s. The clinical data of all these CF patients were summarized. We diagnosed four CF patients who had mutations in the CFTR gene. We identified six different mutations in the four patients. The c.1766+5G>T, c.595C>T, c.2909G>A, and c.4056G>C had been reported already. The two splicing mutations of c.579+1_579+2insACAT and c.1117-1G>C were novel mutations. There have been 46 Chinese CF patients reported in literature from 1974 up to present (2016.12). The clinical manifestations of CF involved several systems. The most common symptom was recurrent pulmonary infections. Thirty-three different mutations were identified; c.1766 + 5G>T was the most common mutation among Chinese CF patients. Only one of these mutations (R553X) was in the Caucasian CF screening panel. The spectrum of CFTR mutations in Chinese was highly different from that of Caucasian. There was a high risk of misdiagnosis or delayed diagnosis of CF even in suspected cases in China. It is necessary to educate Chinese clinicians about the signs, symptoms, and diagnosis of cystic fibrosis and promote the implementation of the sweat chloride test. © 2017 Wiley Periodicals, Inc.

  9. Increased apical Na+ permeability in cystic fibrosis is supported by a quantitative model of epithelial ion transport

    PubMed Central

    O’Donoghue, Donal L; Dua, Vivek; Moss, Guy W J; Vergani, Paola

    2013-01-01

    Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes an anion channel. In the human lung CFTR loss causes abnormal ion transport across airway epithelial cells. As a result CF individuals produce thick mucus, suffer persistent bacterial infections and have a much reduced life expectancy. Trans-epithelial potential difference (Vt) measurements are routinely carried out on nasal epithelia of CF patients in the clinic. CF epithelia exhibit a hyperpolarised basal Vt and a larger Vt change in response to amiloride (a blocker of the epithelial Na+ channel, ENaC). Are these altered bioelectric properties solely a result of electrical coupling between the ENaC and CFTR currents, or are they due to an increased ENaC permeability associated with CFTR loss? To examine these issues we have developed a quantitative mathematical model of human nasal epithelial ion transport. We find that while the loss of CFTR permeability hyperpolarises Vt and also increases amiloride-sensitive Vt, these effects are too small to account for the magnitude of change observed in CF epithelia. Instead, a parallel increase in ENaC permeability is required to adequately fit observed experimental data. Our study provides quantitative predictions for the complex relationships between ionic permeabilities and nasal Vt, giving insights into the physiology of CF disease that have important implications for CF therapy. PMID:23732645

  10. Practical Guidelines: Lung Transplantation in Patients with Cystic Fibrosis

    PubMed Central

    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

  11. Implementation of newborn screening for cystic fibrosis in Norway. Results from the first three years.

    PubMed

    Lundman, Emma; Gaup, H Junita; Bakkeheim, Egil; Olafsdottir, Edda J; Rootwelt, Terje; Storrøsten, Olav Trond; Pettersen, Rolf D

    2016-05-01

    Norway introduced newborn screening for cystic fibrosis (CF) March 1, 2012. We present results from the first three years of the national newborn CF screening program. Positive primary screening of immunoreactive trypsinogen (IRT) was followed by DNA testing of the Cystic fibrosis transmembrane conductance regulator (CFTR) gene. Infants with two CFTR mutations were reported for diagnostic follow-up. Of 181,859 infants tested, 1454 samples (0.80%) were assessed for CFTR mutations. Forty children (1:4546) had two CFTR mutations, of which only 21 (1:8660) were confirmed to have a CF diagnosis. The CFTR mutations differed from previously clinically diagnosed CF patients, and p.R117H outnumbered p.F508del as the most frequent mutation. One child with a negative IRT screening test was later clinically diagnosed with CF. The CF screening program identified fewer children with a conclusive CF diagnosis than expected. Our data suggest a revision of the IRT/DNA protocol. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  12. Cystic Fibrosis: Microbiology and Host Response.

    PubMed

    Zemanick, Edith T; Hoffman, Lucas R

    2016-08-01

    The earliest descriptions of lung disease in people with cystic fibrosis (CF) showed the involvement of 3 interacting pathophysiologic 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, increased longevity, and increasingly sophisticated laboratory techniques. This article reviews the current understanding of infection and inflammation and their roles in CF lung disease. It also discusses how this constantly evolving information is used to inform current therapeutic strategies, measures and predictors of disease severity, and research priorities. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. CYSTIC FIBROSIS: MICROBIOLOGY AND HOST RESPONSE

    PubMed Central

    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

  14. Cystic Fibrosis Diagnosis and Newborn Screening.

    PubMed

    Rosenfeld, Margaret; Sontag, Marci K; Ren, Clement L

    2016-08-01

    The diagnosis of cystic fibrosis (CF) has evolved over the past decade as newborn screening has become universal in the United States and elsewhere. The heterogeneity of phenotypes associated with CF transmembrane conductance regulator (CFTR) dysfunction and mutations in the CFTR gene has become clearer, ranging from classic pancreatic-insufficient CF to manifestations in only 1 organ system to indeterminate diagnoses identified by newborn screening. The tools available for diagnosis have also expanded. This article reviews the newest diagnostic criteria for CF, newborn screening, prenatal screening and diagnosis, and indeterminate diagnoses in newborn-screened infants and symptomatic adults. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. [Autosomal-recessive renal cystic disease and congenital hepatic fibrosis: clinico-anatomic case].

    PubMed

    Rostol'tsev, K V; Burenkov, R A; Kuz'micheva, I A

    2012-01-01

    Clinico-anatomic observation of autosomal-recessive renal cystic disease and congenital hepatic fibrosis at two fetuses from the same family was done. Mutation of His3124Tyr in 58 exon of PKHD1 gene in heterozygous state was found out. The same pathomorphological changes in the epithelium of cystic renal tubules and bile ducts of the liver were noted. We suggest that the autopsy research of fetuses with congenital abnormalities, detected after prenatal ultrasonic screening, has high diagnostic importance.

  16. Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor.

    PubMed

    Bessonova, Leona; Volkova, Nataliya; Higgins, Mark; Bengtsson, Leif; Tian, Simon; Simard, Christopher; Konstan, Michael W; Sawicki, Gregory S; Sewall, Ase; Nyangoma, Stephen; Elbert, Alexander; Marshall, Bruce C; Bilton, Diana

    2018-05-10

    Ivacaftor is the first cystic fibrosis transmembrane conductance regulator (CFTR) modulator demonstrating clinical benefit in patients with cystic fibrosis (CF). As ivacaftor is intended for chronic, lifelong use, understanding long-term effects is important for patients and healthcare providers. This ongoing, observational, postapproval safety study evaluates clinical outcomes and disease progression in ivacaftor-treated patients using data from the US and the UK CF registries following commercial availability. Annual analyses compare ivacaftor-treated and untreated matched comparator patients for: risks of death, transplantation, hospitalisation, pulmonary exacerbation; prevalence of CF-related complications and microorganisms and lung function changes in a subset of patients who initiated ivacaftor in the first year of commercial availability. Results from the 2014 analyses (2 and 3 years following commercial availability in the UK and USA, respectively) are presented here. Analyses included 1256 ivacaftor-treated and 6200 comparator patients from the USA and 411 ivacaftor-treated and 2069 comparator patients from the UK. No new safety concerns were identified based on the evaluation of clinical outcomes included in the analyses. As part of safety evaluations, ivacaftor-treated US patients were observed to have significantly lower risks of death (0.6% vs 1.6%, p=0.0110), transplantation (0.2% vs 1.1%, p=0.0017), hospitalisation (27.5% vs 43.1%, p<0.0001) and pulmonary exacerbation (27.8% vs 43.3%, p<0.0001) relative to comparators; trends were similar in the UK. In both registries, ivacaftor-treated patients had a lower prevalence of CF-related complications and select microorganisms and had better preserved lung function. While general limitations of observational research apply, analyses revealed favourable results for clinically important outcomes among ivacaftor-treated patients, adding to the growing body of literature supporting disease modification by

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

    PubMed

    Meng, Xin; Clews, Jack; Kargas, Vasileios; Wang, Xiaomeng; Ford, Robert C

    2017-01-01

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

  18. Glutamine supplementation in cystic fibrosis: A randomized placebo-controlled trial.

    PubMed

    Forrester, Doug L; Knox, Alan J; Smyth, Alan R; Barr, Helen L; Simms, Rebecca; Pacey, Sarah J; Pavord, Ian D; Honeybourne, David; Dewar, Jane; Clayton, Andy; Fogarty, Andrew W

    2016-03-01

    Pulmonary infection and malnutrition in cystic fibrosis are associated with decreased survival. Glutamine has a possible anti-microbial effect, with a specific impact against Pseudomonas aeruginosa. We aimed to test the hypothesis that oral glutamine supplementation (21 g/day) for 8 weeks in adults with cystic fibrosis would decrease pulmonary inflammation and improve clinical status. The study design was a randomized double-blind placebo-controlled study design with an iso-nitrogenous placebo. The primary analysis was intention to treat, and the primary outcome was change in induced sputum neutrophils. Thirty-nine individuals were recruited and thirty-six completed the study. Glutamine supplementation had no impact on any of the outcome measures in the intention-to-treat analysis. In the per protocol analysis, glutamine supplementation was associated with an increase in induced sputum neutrophils (P = 0.046), total cells (P = 0.03), and in Pseudomonas isolation agar colony forming units (P = 0.04) compared to placebo. There was no effect of glutamine supplementation on markers of pulmonary inflammation in the intention-to-treat analysis. © 2015 Wiley Periodicals, Inc.

  19. Optical Coherence Tomography Identifies Lower Labial Salivary Gland Surface Density in Cystic Fibrosis

    PubMed Central

    Nowak, Jan K.; Grulkowski, Ireneusz; Karnowski, Karol; Wojtkowski, Maciej; Walkowiak, Jaroslaw

    2015-01-01

    The labial minor salivary glands (LSGs) are easily accessible mucus-secreting structures of the alimentary tract that may provide new information on the basis of gastrointestinal complications of cystic fibrosis (CF). It was shown that they are destructed in the course of cystic fibrosis. We employed wide-field, micrometer resolution in vivo optical coherence tomography to assess the surface density of LSGs in 18 patients with CF and 18 healthy subjects. The median LSGs’ surface densities in CF patients, and in the control group were 4.32 glands/cm2 and 6.58 glands/cm2, respectively (p = 0.006; Mann-Whitney U test). A lower LSG surface density is a previously unrecognized CF-related pathology of the alimentary tract. PMID:25622042

  20. Nutritional state and lung disease in cystic fibrosis.

    PubMed

    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.

  1. Iron accumulates in the lavage and explanted lungs of cystic fibrosis patients.

    EPA Science Inventory

    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 ...

  2. Managing central venous obstruction in cystic fibrosis recipients--lung transplant considerations.

    PubMed

    Otani, Shinji; Westall, Glen P; Levvey, Bronwyn J; Marasco, Silvana; Lyon, Stuart; Snell, Gregory I

    2015-03-01

    The superior vena cava (SVC) syndrome in cystic fibrosis (CF) patients is rare, but presents unique challenges in the peri-transplant period. We reviewed our experience of SVC syndrome in CF recipients undergoing lung transplantation. This is a retrospective case series from a single center chart-review. SVC obstruction is defined by clinically significant stenosis or obstruction of the SVC as detected by contrast studies. We identified SVC obstruction in seven post-transplant cases and one pre-transplant case. All eight patients had previous or current history of indwelling central venous catheters. Three recipients experienced operative complications. Five of the seven recipients suffered at least one episode of post-operative SVC obstruction or bleeding despite prophylactic anticoagulation. At a median follow-up of 29 months, six of the seven patients transplanted are well. Strategies are available to minimize the risks of intra/peri-operative acute life-threatening SVC obstruction in CF patients. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  3. Metabolomic responses to lumacaftor/ivacaftor in cystic fibrosis.

    PubMed

    Kopp, Benjamin T; McCulloch, Scott; Shrestha, Chandra L; Zhang, Shuzhong; Sarzynski, Lisa; Woodley, Frederick W; Hayes, Don

    2018-05-01

    Cystic fibrosis (CF) is a life-limiting disease caused by a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Lumacaftor/Ivacaftor is a novel CFTR modulator approved for patients that are homozygous for Phe508del CFTR, but its clinical effectiveness varies amongst patients, making it difficult to determine clinical responders. Therefore, identifying biochemical biomarkers associated with drug response are clinically important for follow-up studies. Serum metabolomics was performed on twenty patients with CF pre- and 6-month post-Lumacaftor/Ivacaftor response via Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Correlation with clinical variables was performed. Metabolomics analysis demonstrated 188 differentially regulated metabolites between patients pre- and post-Lumacaftor/Ivacaftor initiation, with a predominance of lipid and amino acid alterations. The top 30 metabolites were able to differentiate pre- and post-Lumacaftor/Ivacaftor status in greater than 90% of patients via a random-forest confusion matrix. Alterations in bile acids, phospholipids, and bacteria-associated metabolites were the predominant changes associated with drug response. Importantly, changes in metabolic patterns were associated with clinical responders. Selected key lipid and amino acid metabolic pathways were significantly affected by Lumacaftor/Ivacaftor initiation and similar pathways were affected in clinical responders. Targeted metabolomics may provide useful and relevant biomarkers of CFTR modulator responses. © 2018 Wiley Periodicals, Inc.

  4. Chloride losing diarrhoea and metabolic alkalosis in an infant with cystic fibrosis.

    PubMed Central

    Hochman, H I; Feins, N R; Rubin, R; Gould, J

    1976-01-01

    A case of hypochloraemic metabolic alkalosis in an infant with chloride losing ileostomy drainage and cystic fibrosis is described. It is speculated that intestinal loss of chloride played a major role in the development of metabolic alkalosis. PMID:938082

  5. The outcome of pregnancies in women with cystic fibrosis--single centre experience 1998-2011.

    PubMed

    Thorpe-Beeston, J G; Madge, S; Gyi, K; Hodson, M; Bilton, D

    2013-02-01

    To describe the maternal and fetal outcomes of pregnancies in women with cystic fibrosis. Retrospective study. Single obstetric hospital and adult cystic fibrosis centre. Retrospective case-note review of pregnant women with cystic fibrosis referred for antenatal care and delivery. Maternal and fetal outcomes, mode of delivery, lung function and pregnancy complications. Forty-eight pregnancies were studied in 41 women. There were two miscarriages, 44 singleton pregnancies and two sets of twins. All babies were liveborn and survived. The mean gestational age at delivery was 35.9 ± 3.3 weeks. There were no fetal abnormalities or terminations of pregnancy. The median birthweight centile was 31.9 (interquartile range 14.9-55.6). Twenty-five (52.1%) of the women had pancreatic insufficiency and 17 (35.4%) required insulin. There was a positive correlation between booking predicted forced expiratory volume in 1 second (FEV(1) ) and gestational age at delivery (P < 0.01). Women with FEV(1) ≤60% were more likely to deliver earlier and by caesarean section compared with women with FEV(1) >60% (35.0 ± 3.2 weeks versus 37.1 ± 3.0 weeks; P = 0.02 and 75.0% versus 25.0%; P = 0.01). Three of the seven women with an FEV(1) <40% died within 18 months of delivery. Four of the eight women with FEV(1) 40-50% died between 2 and 8 years after delivery. Pregnancy for women with cystic fibrosis is possible and results in favourable maternal and fetal outcomes, but the incidence of preterm delivery and caesarean section is increased. Women with pre-existing poor lung function should be counselled antenatally to ensure that they understand the implications of their shortened life-expectancy and parenthood. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

  6. A cost description of an adult cystic fibrosis unit and cost analyses of different categories of patients.

    PubMed Central

    Robson, M; Abbott, J; Webb, K; Dodd, M; Walsworth-Bell, J

    1992-01-01

    BACKGROUND: There is little information on the costs of running an adult cystic fibrosis centre. The aim of this study was to provide detailed costs to assist funding and planning for these patients. METHODS: The cost of a regional adult cystic fibrosis centre serving 119 cystic fibrosis patients, categorised according to four treatment regimens, was determined. District health authority, family health service authority, and voluntary resources used from April 1989 to March 1990 were determined, with appropriate bases for allocation of costs and patient based costs from local information. RESULTS: The total annual cost of treating the 119 patients was 980,646 pounds, with an average cost 8241 pounds per patient. An outpatient reviewed at three monthly intervals cost 2792 pounds a year; an outpatient receiving intravenous antibiotics cost 8606 pounds; an inpatient receiving intravenous antibiotics cost 13,501 pounds; and a patient needing a high level of care cost 19,955 pounds. Medication accounted for 57% (561,395 pounds) of the total cost. CONCLUSIONS: This analysis has helped us to secure funding for patients with cystic fibrosis and it facilitates the prediction of future requirements. The study also indicates the limitations of using average patient costs and difficulties as a result of the poorly structured British National Health Service accounting and information systems. PMID:1440461

  7. Evaluation of Inhaled Dornase Alfa Administration in Non-Cystic Fibrosis Patients at a Tertiary Academic Medical Center.

    PubMed

    Torbic, Heather; Hacobian, Gaspar

    2016-10-01

    The use of dornase alfa in a non-cystic fibrosis population has been proposed to help improve atelectasis and secretions. Data evaluating dornase alfa in a non-cystic fibrosis population are limited, and the prescribing practices at a tertiary academic medical center are unknown. Adult patients ≥18 years of age were included if they received inhaled dornase alfa. Patients were excluded if they had cystic fibrosis. Data collected included demographic data, dornase alfa prescribing patterns, concomitant inhaled therapy, blood gas data, and documented efficacy and safety data. Seventy-six orders for dornase alfa therapy were included in the analysis. Of the patients, 18% had asthma and 19% had chronic obstructive pulmonary disease. Seventy-seven percent of the patients received concomitant inhaled therapy. Eighty-three percent of orders were for 2.5 mg of dornase alfa twice daily. The median (interquartile range [IQR]) number of doses received per patient was 6 (4-13) with a median (IQR) duration of 3 (2-7) days. After inhaled dornase alfa administration, 11% of patients were able to cough productively. No safety issues related to inhaled dornase alfa therapy were noted. Inhaled dornase alfa is commonly prescribed to improve atelectasis and secretions in a non-cystic fibrosis patient population at a tertiary academic medical center. © The Author(s) 2015.

  8. Effect of VX-770 in Persons with Cystic Fibrosis and the G551D-CFTR Mutation

    PubMed Central

    Accurso, Frank J.; Rowe, Steven M.; Clancy, J.P.; Boyle, Michael P.; Dunitz, Jordan M.; Durie, Peter R.; Sagel, Scott D.; Hornick, Douglas B.; Konstan, Michael W.; Donaldson, Scott H.; Moss, Richard B.; Pilewski, Joseph M.; Rubenstein, Ronald C.; Uluer, Ahmet Z.; Aitken, Moira L.; Freedman, Steven D.; Rose, Lynn M.; Mayer-Hamblett, Nicole; Dong, Qunming; Zha, Jiuhong; Stone, Anne J.; Olson, Eric R.; Ordoñez, Claudia L.; Campbell, Preston W.; Ashlock, Melissa A.; Ramsey, Bonnie W.

    2010-01-01

    BACKGROUND A new approach in the treatment of cystic fibrosis involves improving the function of mutant cystic fibrosis transmembrane conductance regulator (CFTR). VX-770, a CFTR potentiator, has been shown to increase the activity of wild-type and defective cell-surface CFTR in vitro. METHODS We randomly assigned 39 adults with cystic fibrosis and at least one G551D-CFTR allele to receive oral VX-770 every 12 hours at a dose of 25, 75, or 150 mg or placebo for 14 days (in part 1 of the study) or VX-770 every 12 hours at a dose of 150 or 250 mg or placebo for 28 days (in part 2 of the study). RESULTS At day 28, in the group of subjects who received 150 mg of VX-770, the median change in the nasal potential difference (in response to the administration of a chloride-free isoproterenol solution) from baseline was −3.5 mV (range, −8.3 to 0.5; P = 0.02 for the within-subject comparison, P = 0.13 vs. placebo), and the median change in the level of sweat chloride was −59.5 mmol per liter (range, −66.0 to −19.0; P = 0.008 within-subject, P = 0.02 vs. placebo). The median change from baseline in the percent of predicted forced expiratory volume in 1 second was 8.7% (range, 2.3 to 31.3; P = 0.008 for the within-subject comparison, P = 0.56 vs. placebo). None of the subjects withdrew from the study. Six severe adverse events occurred in two subjects (diffuse macular rash in one subject and five incidents of elevated blood and urine glucose levels in one subject with diabetes). All severe adverse events resolved without the discontinuation of VX-770. CONCLUSIONS This study to evaluate the safety and adverse-event profile of VX-770 showed that VX-770 was associated with within-subject improvements in CFTR and lung function. These findings provide support for further studies of pharmacologic potentiation of CFTR as a means to treat cystic fibrosis. PMID:21083385

  9. Activation of deltaF508 CFTR in a cystic fibrosis respiratory epithelial cell line by 4-phenylbutyrate, genistein and CPX.

    PubMed

    Andersson, C; Roomans, G M

    2000-05-01

    The cellular basis of cystic fibrosis (CF) is a defect in a cyclic adenosine monophosphate (cAMP)-activated chloride channel (CF transmembrane conductance regulator) in epithelial cells that leads to decreased chloride ion transport and impaired water transport across the cell membrane. This study investigated whether it was possible to activate the defective chloride channel in cystic fibrosis respiratory epithelial cells with 4-phenylbutyrate (4PBA), genistein and 8-cyclopentyl-1,3-dipropylxanthine (CPX). The CF bronchial epithelial cell line CFBE41o-, which expresses the deltaF508 mutation, was treated with these agents and loss of Cl-, indicating Cl- efflux, measured by X-ray microanalysis. 8-bromo-cAMP alone did not induce Cl- efflux in CFBE41o- cells, but after incubation with 4PBA a significant efflux of Cl- occurred. Stimulation of cells with a combination of genistein and cAMP also induced Cl- efflux, whereas a combination of pretreatment with 4PBA and a combined stimulation with genistein and cAMP induced an even larger Cl- efflux. Cl- efflux could also be stimulated by CPX, but this effect was not enhanced by 4PBA pretreatment. The deltaF508 mutation leads to impaired processing of the cystic fibrosis transmembrane conductance regulator. The increased efflux of chloride after 4-phenylbutyrate treatment can be explained by the fact that 4-phenylbutyrate allows the deltaF508 cystic fibrosis transmembrane conductance regulator to escape degradation and to be transported to the cell surface. Genistein and 8-cyclopentyl-1,3-dipropylxanthine act by stimulating chloride ion efflux by increasing the probability of the cystic fibrosis transmembrane conductance regulator being open. The combination of 4-phenylbutyrate and genistein may be useful in a potential pharmacological therapy for cystic fibrosis patients with the deltaF508 mutation.

  10. Cystic fibrosis lung transplantation.

    PubMed

    Braun, Andrew T; Merlo, Christian A

    2011-11-01

    This review summarizes recently published investigations on issues pertaining to cystic fibrosis (CF) lung transplantation. We specifically focus on indications and candidate selection as well as infectious and noninfectious issues specific to CF lung transplant recipients. Recent studies have focused on candidate adequacy in high-risk CF patients. We review the current literature on individuals who develop respiratory failure requiring mechanical ventilation and those patients with a pretransplant diagnosis of pulmonary hypertension. Furthermore, the management of peri-operative infectious issues is reviewed including recurrent infections with multidrug-resistant bacterial, mycobacterial, and fungal organisms. Other CF-specific issues addressed include common comorbidities such as CF-related diabetes, gastroesophageal reflux, CF liver disease, and bone metabolism. Lung transplantation is a limited, but potentially life-saving therapeutic option for patients with CF. Optimal candidate selection and awareness of CF-specific issues in the pretransplant and posttransplant setting may lead to better long-term outcomes. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

  11. 21 CFR 866.5900 - Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation detection system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5900 Cystic fibrosis transmembrane conductance regulator (CFTR...

  12. Cystic Fibrosis Transmembrane Conductance Regulator Potentiation as a Therapeutic Strategy for Pulmonary Edema: A Proof-of-Concept Study in Pigs.

    PubMed

    Li, Xiaopeng; Vargas Buonfiglio, Luis G; Adam, Ryan J; Stoltz, David A; Zabner, Joseph; Comellas, Alejandro P

    2017-12-01

    To determine the feasibility of using a cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770/Kalydeco, Vertex Pharmaceuticals, Boston, MA), as a therapeutic strategy for treating pulmonary edema. Prospective laboratory animal investigation. Animal research laboratory. Newborn and 3 days to 1 week old pigs. Hydrostatic pulmonary edema was induced in pigs by acute volume overload. Ivacaftor was nebulized into the lung immediately after volume overload. Grams of water per grams of dry lung tissue were determined in the lungs harvested 1 hour after volume overload. Ivacaftor significantly improved alveolar liquid clearance in isolated pig lung lobes ex vivo and reduced edema in a volume overload in vivo pig model of hydrostatic pulmonary edema. To model hydrostatic pressure-induced edema in vitro, we developed a method of applied pressure to the basolateral surface of alveolar epithelia. Elevated hydrostatic pressure resulted in decreased cystic fibrosis transmembrane conductance regulator activity and liquid absorption, an effect which was partially reversed by cystic fibrosis transmembrane conductance regulator potentiation with ivacaftor. Cystic fibrosis transmembrane conductance regulator potentiation by ivacaftor is a novel therapeutic approach for pulmonary edema.

  13. Bowel adenocarcinoma in a patient with cystic fibrosis.

    PubMed

    Roberts, J A; Tullett, W M; Thomas, J S; Galloway, D; Stack, B H

    1986-04-01

    Cystic fibrosis (CF) is an autosomal recessive condition affecting one in 2,000 live births in the UK. There are few reports of malignant tumours in this condition probably because, until recently, the majority died before the age of 30 years as a result of recurrent and chronic bronchopulmonary infection with impaired growth and development and resistance to infection due to pancreatic malabsorption. We describe an adult male with CF who died from an adenocarcinoma affecting the ileocaecal region of the bowel.

  14. Genetics and epithelial cell dysfunction in cystic fibrosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Riordan, J.R.; Buchwald, M.

    1987-01-01

    This book examines the advances being made in the study of the physiology, cell biology, and molecular genetics of cystic fibrosis. Emphasis is placed on various areas of research that involve epithelial cells (e.g., the CF-specific phenotypes exhibited by epithelial cells, abnormalities in epithelium ion transport, chloride channel regulation in CF epithelial.) Coverage is presented on the current status of CF, including data on the incidence of the disease, its mode of inheritance, chromosomal localization, genetic heterogeneity, and screening and management.

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

    PubMed

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

    PubMed Central

    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 patients. In addition, AST/Platelets-Ratio-Index (APRI), and Forns' score were calculated. Healthy probands and patients with alcoholic liver cirrhosis served as controls. Results Fourteen CF patients met CFLD criteria, six had liver cirrhosis. Elastography acquisition was successful in >89% of cases. Non-cirrhotic CFLD individuals showed elastography values similar to CF patients without liver involvement. Cases with liver cirrhosis differed significantly from other CFLD patients (ARFI: 1.49 vs. 1.13 m/s; p = 0.031; TE: 7.95 vs. 4.16 kPa; p = 0.020) and had significantly lower results than individuals with alcoholic liver cirrhosis (ARFI: 1.49 vs. 2.99 m/s; p = 0.002). APRI showed the best diagnostic performance for CFLD detection (AUROC 0.815; sensitivity 85.7%, specificity 70.7%). Conclusions ARFI, TE, and laboratory based fibrosis indices correlate with each other and reliably detect CFLD related liver cirrhosis in adult CF patients. CF specific cut-off values for cirrhosis in adults are lower than in alcoholic cirrhosis. PMID:22848732

  17. Global impact of bronchiectasis and cystic fibrosis

    PubMed Central

    Redondo, Margarida; Keyt, Holly; Dhar, Raja

    2016-01-01

    Educational aims To recognise the clinical and radiological presentation of the spectrum of diseases associated with bronchiectasis. 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. PMID:28210295

  18. Drug therapies for reducing gastric acidity in people with cystic fibrosis.

    PubMed

    Ng, Sze May; Francini, Angelo J

    2012-04-18

    Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, abstract books and conference proceedings.Most recent search of the Group's Trials Register: 15 February 2012. All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment. Both authors independently selected trials, assessed trial quality and extracted data. Thirty-eight trials were identified from the searches. Sixteen trials, with 256 participants, were suitable for inclusion. Seven trials were limited to children and three trials enrolled only adults. Meta-analysis was not performed. However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures

  19. Adherence Determinants in Cystic Fibrosis: Cluster Analysis of Parental Psychosocial, Religious, and/or Spiritual Factors.

    PubMed

    Grossoehme, Daniel H; Szczesniak, Rhonda D; Britton, LaCrecia L; Siracusa, Christopher M; Quittner, Alexandra L; Chini, Barbara A; Dimitriou, Sophia M; Seid, Michael

    2015-06-01

    Cystic fibrosis is a progressive disease requiring a complex, time-consuming treatment regimen. Nonadherence may contribute to an acceleration of the disease process. Spirituality influences some parental healthcare behaviors and medical decision-making. We hypothesized that parents of children with cystic fibrosis, when classified into groups based on adherence rates, would share certain psychosocial and religious and/or spiritual variables distinguishing them from other adherence groups. We conducted a multisite, prospective, observational study focused on parents of children younger than 13 years old at two cystic fibrosis center sites (Site 1, n= 83; Site 2, n = 59). Religious and/or spiritual constructs, depression, and marital adjustment were measured by using previously validated questionnaires. Determinants of adherence included parental attitude toward treatment, perceived behavioral norms, motivation, and self-efficacy. Adherence patterns were measured with the Daily Phone Diary, a validated instrument used to collect adherence data. Cluster analysis identified discrete adherence patterns, including parents' completion of more treatments than prescribed. For airway clearance therapy, four adherence groups were identified: median adherence rates of 23%, 52%, 77%, and 120%. These four groups differed significantly for parental depression, sanctification of their child's body, and self-efficacy. Three adherence groups were identified for nebulized medications: median adherence rates of 35%, 82%, and 130%. These three groups differed significantly for sanctification of their child's body and self-efficacy. Our results indicated that parents in each group shared psychosocial and religious and/or spiritual factors that differentiated them. Therefore, conversations about adherence likely should be tailored to baseline adherence patterns. Development of efficacious religious and/or spiritual interventions that promote adherence by caregivers of children with

  20. Classification of malnutrition in cystic fibrosis: implications for evaluating and benchmarking clinical practice performance2

    PubMed Central

    HuiChuan, J Lai; Suzanne, M Shoff

    2008-01-01

    Background In 2005, the Cystic Fibrosis Foundation (CFF) revised the nutrition classification guidelines to eliminate the use of percentage of ideal body weight (%IBW) to define “nutritional failure”; the CFF also recommended that children with cystic fibrosis maintain a body mass index percentile (BMIp) ≥ 50th. Objective We assessed the effect of the 2005 CFF nutrition classification guidelines on evaluating the performance of nutritional care practices. Design Data from 14 702 children reported to the 2002 CFF Patient Registry were analyzed to compare malnutrition rates in 113 cystic fibrosis centers in the United States. Nutritional failure was defined according to the 2002 CFF criteria—ie, height < 5th percentile, %IBW < 90%, or BMIp < 10th. “Below BMI goal” was defined according to the 2005 CFF criterion, ie BMIp < 50th. Results Eliminating %IBW resulted in a 6% reduction (from 33% to 27%) in the nutritional failure rate in the United States. The use of BMIp < 50th led to the classification of 57% of children as below the BMI goal. Misclassification of nutritional failure according to %IBW ranged from 1% to 16% among 113 centers and was greater in the centers with a larger proportion of tall patients. After the elimination of %IBW, one-third of centers changed to a different tertile ranking for nutritional failure rates (kappa = 0.50, moderate-to-poor agreement). More than half the centers changed to a different tertile ranking, from nutritional failure to below BMI goal (kappa = 0.22, poor agreement). Conclusion Eliminating misclassification by %IBW and implementing the new BMI goal led to profound and unequal changes in malnutrition rates across cystic fibrosis centers. PMID:18614737

  1. Prenatal intestinal volvulus: look for cystic fibrosis.

    PubMed

    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.

  2. Utility of gram stain in evaluation of sputa from patients with cystic fibrosis.

    PubMed Central

    Sadeghi, E; Matlow, A; MacLusky, I; Karmali, M A

    1994-01-01

    The utility of sputum Gram stain in assessing salivary contamination and in predicting the presence of pathogens on the basis of morphology was investigated in 287 respiratory specimens from patients with cystic fibrosis. Where acceptability for culture was defined as a leukocyte/squamous epithelial cell ratio of > 5, 76.6% (220 of 287) of respiratory specimens received in the laboratory were considered acceptable. Unacceptable specimens were more common in younger patients. The positive predictive value of the Gram stain for growth from acceptable sputum samples was 98% for Pseudomonas aeruginosa, 84.4% for Pseudomonas cepacia, 86.3% for Staphylococcus aureus, and 100% for Haemophilus influenzae. In cystic fibrosis patients, as has been reported for respiratory specimens in general, Gram stain of respiratory specimens in helpful for interpreting culture results. PMID:7510312

  3. Differences between WHO AND CDC early growth measurements in the assessment of Cystic Fibrosis clinical outcomes.

    PubMed

    Usatin, Danielle; Yen, Elizabeth H; McDonald, Catherine; Asfour, Fadi; Pohl, John; Robson, Jacob

    2017-07-01

    Early childhood growth status has been used to predict long-term clinical outcomes in Cystic Fibrosis (CF) patients. Adulthood CF outcomes based on early weight-for-length (WFL) measurements, using either World Health Organization (WHO) or Centers for Disease Control (CDC) scales, have not been compared. Cystic Fibrosis Foundation registry patients were studied (n=3014). Participants were categorized at age two years as WFL <50th percentile on both WHO and CDC scales, ≥50th percentile on WHO but not CDC, or ≥50th percentile on both. Pulmonary function and overall survival were assessed at age 18years. Stepwise gains in pulmonary function and lung transplant-free survival were noted across the three increasing WFL categories. Children with CF who achieve higher WFL at age two years have improved pulmonary and survival outcomes into adulthood. CF providers should continue to utilize current early growth recommendations, with goal WFL ≥50th percentile on CDC growth charts before age two. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

    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.

  5. Burkholderia cepacia, cystic fibrosis and outcomes following lung transplantation: experiences from a single center in Brazil.

    PubMed

    de Souza Carraro, Danila; Carraro, Rafael Medeiros; Campos, Silvia Vidal; Iuamoto, Leandro Ryuchi; Braga, Karina Andrighetti de Oliveira; Oliveira, Lea Campos de; Sabino, Ester Cerdeira; Rossi, Flavia; Pêgo-Fernandes, Paulo Manuel

    2018-03-12

    To evaluate the impact of Burkholderia cepacia complex colonization in cystic fibrosis patients undergoing lung transplantation. We prospectively analyzed clinical data and respiratory tract samples (sputum and bronchoalveolar lavage) collected from suppurative lung disease patients between January 2008 and November 2013. We also subtyped different Burkholderia cepacia complex genotypes via DNA sequencing using primers against the recA gene in samples collected between January 2012 and November 2013. From 2008 to 2013, 34 lung transplants were performed on cystic fibrosis patients at our center. Burkholderia cepacia complex was detected in 13 of the 34 (38.2%) patients. Seven of the 13 (53%) strains were subjected to genotype analysis, from which three strains of B. metallica and four strains of B. cenocepacia were identified. The mortality rate was 1/13 (7.6%), and this death was not related to B. cepacia infection. The results of our study suggest that colonization by B. cepacia complex and even B. cenocepacia in patients with cystic fibrosis should not be considered an absolute contraindication to lung transplantation in Brazilian centers.

  6. Cystic fibrosis transmembrane conductance regulator (CFTR) allelic variants relate to shifts in faecal microbiota of cystic fibrosis patients.

    PubMed

    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.

  7. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Allelic Variants Relate to Shifts in Faecal Microbiota of Cystic Fibrosis Patients

    PubMed Central

    Santangelo, Floriana; Gagliardi, Antonella; De Biase, Riccardo Valerio; Stamato, Antonella; Bertasi, Serenella; Lucarelli, Marco

    2013-01-01

    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. PMID:23613805

  8. Allergic bronchopulmonary aspergillosis and Aspergillus infection in cystic fibrosis.

    PubMed

    Moss, Richard B

    2010-11-01

    Recent literature on Aspergillus fumigatus infection and allergy in cystic fibrosis have expanded our understanding of many aspects of allergic bronchopulmonary aspergillosis, and bring new attention to A. fumigatus airways infection and A. fumigatus allergy without allergic bronchopulmonary aspergillosis (ABPA). ABPA, A. fumigatus infection and A. fumigatus allergy without ABPA all likely worsen cystic fibrosis (CF) lung disease. Studies examining utility of new serologic assays for diagnosing ABPA include evaluations of standardized measurement of A. fumigatus-specific IgG, serum chemokine TARC levels, and recombinant A. fumigatus allergens; as yet, none appear ideal. Although oral glucocorticoids remain primary therapy, toxicity and incomplete control have led to an ongoing search for further safe and effective agents including itraconazole and voriconazole, intravenous pulse methylprednisolone, nebulized amphotericin B and omalizumab. Little controlled treatment data is available. Diagnosis of CF-ABPA remains difficult, but improvements in serologic assays are occurring. Treatment remains in many cases unsatisfactory, and new agents offer promise but await proper controlled trials of safety and efficacy. A. fumigatus airway infection and A. fumigatus allergy without ABPA are emerging as further complications of A. fumigatus respiratory colonization in patients with CF, but prospective studies are needed to corroborate largely retrospective findings.

  9. Dornase Alfa for Non-Cystic Fibrosis Pediatric Pulmonary Atelectasis.

    PubMed

    Thornby, Krisy-Ann; Johnson, Ashley; Axtell, Samantha

    2014-08-01

    To review the literature evaluating the efficacy of dornase alfa for non-cystic fibrosis pediatric patients with pulmonary atelectasis. Articles were retrieved after a search of MEDLINE/PubMed (1946 to April 2014), and International Pharmaceutical Abstracts (1970-April 2014) was performed using the terms dornase alfa, recombinant human deoxyribonuclease, pulmonary, persistent, and atelectasis. Other relevant articles referenced from the MEDLINE search were also utilized. Data sources were limited to English language clinical trials and case studies including only children; 8 clinical trials and 12 case reports met the criteria. Dornase alfa is used as an off-label treatment option for pulmonary atelectasis because limited treatment modalities exist after conventional therapy has failed. We evaluated 8 clinical trials and 12 case reports involving this pediatric population with varying primary diagnoses. The majority of patients experienced improvement in atelectasis, suggesting benefit after receiving treatment with dornase alfa. However, the outcomes were possibly confounded by those receiving combination therapies, varying primary diagnoses, and varying end points evaluated. Dornase alfa was overall well tolerated, with only a few patients experiencing worsening atelectasis posttreatment. Dornase alfa may be considered as a therapeutic option in non-cystic fibrosis pediatric patients with pulmonary atelectasis, who require treatment intervention when conventional therapy is unsuccessful. © The Author(s) 2014.

  10. Evidence for transmission of Pseudomonas cepacia by social contact in cystic fibrosis.

    PubMed

    Govan, J R; Brown, P H; Maddison, J; Doherty, C J; Nelson, J W; Dodd, M; Greening, A P; Webb, A K

    1993-07-03

    Pulmonary colonisation with Pseudomonas cepacia in patients with cystic fibrosis can be associated with increased morbidity and mortality. The modes of transmission of P cepacia are, however, unclear. We used selective media and phenotypic and genomic typing systems to investigate the acquisition of P cepacia by adults with cystic fibrosis. An analysis of isolates from 210 patients attending regional clinics in Edinburgh and Manchester between 1986 and 1992 showed that the main cause of increased isolations of P cepacia from 1989 was the emergence of an epidemic strain that had spread between patients in both clinics. Epidemiological evidence indicated that social contact was important in spread of the epidemic strain within and between clinics. We suggest that guidelines to limit the acquisition of P cepacia should not be restricted to patients in hospital, and that intimate or frequent social contact is associated with a high risk of cross-infection.

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

    PubMed

    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.

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

    PubMed

    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.

  13. Oscillating devices for airway clearance in people with cystic fibrosis.

    PubMed

    Morrison, Lisa; Innes, Stephanie

    2017-05-04

    Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis. Oscillating devices generate intra- or extra-thoracic oscillations orally or external to the chest wall. Internally they create variable resistances within the airways, generating controlled oscillating positive pressure which mobilises mucus. Extra-thoracic oscillations are generated by forces outside the respiratory system, e.g. high frequency chest wall oscillation. This is an update of a previously published review. To identify whether oscillatory devices, oral or chest wall, are effective for mucociliary clearance and whether they are equivalent or superior to other forms of airway clearance in the successful management of secretions in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and hand searches of relevant journals and abstract books of conference proceedings. Latest search of the Cystic Fibrosis Trials Register: 27 April 2017.In addition we searched the trials databases ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Latest search of trials databases: 26 April 2017. Randomised controlled studies and controlled clinical studies of oscillating devices compared with any other form of physiotherapy in people with cystic fibrosis. Single-treatment interventions (therapy technique used only once in the comparison) were excluded. Two authors independently applied the inclusion criteria to publications and assessed the quality of the included studies. The searches identified 76 studies (302 references); 35 studies (total of 1138 participants) met the inclusion criteria. Studies varied in duration from up to one week to one year; 20 of the studies were cross-over in design. The studies also varied in type of intervention and the outcomes measured, data were not

  14. Development and evaluation of a palliative care curriculum for cystic fibrosis healthcare providers.

    PubMed

    Linnemann, Rachel W; O'Malley, Patricia J; Friedman, Deborah; Georgiopoulos, Anna M; Buxton, David; Altstein, Lily L; Sicilian, Leonard; Lapey, Allen; Sawicki, Gregory S; Moskowitz, Samuel M

    2016-01-01

    Primary palliative care refers to basic skills that all healthcare providers can employ to improve quality of life for patients at any stage of disease. Training in these core skills is not commonly provided to clinicians caring for cystic fibrosis (CF) patients. The objective of this study was to assess change in comfort with core skills among care team members after participation in CF-specific palliative care training focused on management of burdensome symptoms and difficult conversations. A qualitative needs assessment was performed to inform the development of an 18-hour curriculum tailored to the chronicity and complexity of CF care. A 32-question pre- and post-course survey assessed CF provider comfort with the targeted palliative care skills in 5 domains using a 5-point Likert scale (1=very uncomfortable, 3=neutral, 5=very comfortable). Among course participants (n=16), mean overall comfort score increased by 0.9, from 3 (neutral) to 3.9 (comfortable) (p<0.001). Mean comfort level increased significantly (range 0.8 to 1.4) in each skill domain: use of supportive care resources, pain management, non-pain symptom management, communication, and psychosocial skills. CF-specific palliative care training was well received by participants and significantly improved self-assessed comfort with core skills. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  15. Analysis of cystic fibrosis gener product (CFTR) function in patients with pancreas divisum and recurrent acute pancreatitis.

    PubMed

    Gelrud, Andres; Sheth, Sunil; Banerjee, Subhas; Weed, Deborah; Shea, Julie; Chuttani, Ram; Howell, Douglas A; Telford, Jennifer J; Carr-Locke, David L; Regan, Meredith M; Ellis, Lynda; Durie, Peter R; Freedman, Steven D

    2004-08-01

    The mechanism by which pancreas divisum may lead to recurrent episodes of acute pancreatitis in a subset of individuals is unknown. Abnormalities of the cystic fibrosis gene product (CFTR) have been implicated in the genesis of idiopathic chronic pancreatitis. The aim of this study was to determine if CFTR function is abnormal in patients with pancreas divisum and recurrent acute pancreatitis (PD/RAP). A total of 69 healthy control subjects, 12 patients with PD/RAP, 16 obligate heterozygotes with a single CFTR mutation, and 95 patients with cystic fibrosis were enrolled. CFTR function was analyzed by nasal transepithelial potential difference testing in vivo. The outcomes of the PD/RAP patients following endoscopic and surgical treatments were concomitantly analyzed. Direct measurement of CFTR function in nasal epithelium in response to isoproterenol demonstrated that the values for PD/RAP were intermediate between those observed for healthy controls and cystic fibrosis patients. The median value was 13 mV for PD/RAP subjects, which was statistically different from healthy controls (22 mV, p= 0.001) and cystic fibrosis pancreatic sufficient (-1 mV, p < 0.0001) and pancreatic insufficient (-3 mV, p < 0.0001) patients. These results suggest a link between CFTR dysfunction and recurrent acute pancreatitis in patients with pancreas divisum and may explain why a subset of patients with pancreas divisum develops recurrent acute pancreatitis. Copyright 2004 American College of Gastroenterology

  16. Microbial colonization and lung function in adolescents with cystic fibrosis.

    PubMed

    Hector, Andreas; Kirn, Tobias; Ralhan, Anjali; Graepler-Mainka, Ute; Berenbrinker, Sina; Riethmueller, Joachim; Hogardt, Michael; Wagner, Marlies; Pfleger, Andreas; Autenrieth, Ingo; Kappler, Matthias; Griese, Matthias; Eber, Ernst; Martus, Peter; Hartl, Dominik

    2016-05-01

    With intensified antibiotic therapy and longer survival, patients with cystic fibrosis (CF) are colonized with a more complex pattern of bacteria and fungi. However, the clinical relevance of these emerging pathogens for lung function remains poorly defined. The aim of this study was to assess the association of bacterial and fungal colonization patterns with lung function in adolescent patients with CF. Microbial colonization patterns and lung function parameters were assessed in 770 adolescent European (German/Austrian) CF patients in a retrospective study (median follow-up time: 10years). Colonization with Pseudomonas aeruginosa and MRSA were most strongly associated with loss of lung function, while mainly colonization with Haemophilus influenzae was associated with preserved lung function. Aspergillus fumigatus was the only species that was associated with an increased risk for infection with P. aeruginosa. Microbial interaction analysis revealed three distinct microbial clusters within the longitudinal course of CF lung disease. Collectively, this study identified potentially protective and harmful microbial colonization patterns in adolescent CF patients. Further studies in different patient cohorts are required to evaluate these microbial patterns and to assess their clinical relevance. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  17. Initiating transitional care for adolescents with cystic fibrosis at the age of 12 is both feasible and promising.

    PubMed

    Skov, M; Teilmann, G; Damgaard, I N; Nielsen, K G; Hertz, P G; Holgersen, M G; Presfeldt, M; Dalager, A M S; Brask, M; Boisen, K A

    2018-05-05

    Adolescence is a vulnerable period in cystic fibrosis, associated with declining lung function. This study described, implemented and evaluated a transition programme for adolescents. We conducted a single centre, non-randomised and non-controlled prospective programme at the cystic fibrosis centre at Copenhagen University Hospital Rigshospitalet from 2010-2011, assessing patients aged 12 to 18 at baseline and after 12 months. Changes implemented included staff training on communication, a more youth friendly feel to the outpatient clinic, the introduction of youth consultations partly alone with the adolescent, and a parents' evening focusing on cystic fibrosis in adolescence. Lung function and body mass index (BMI) were measured monthly and adolescents were assessed for their readiness for transition and quality of life at baseline and 12 months. We found that 40 (98%) of the eligible patients participated and youth consultations were successfully implemented with no dropouts. The readiness checklist score increased significantly over the one-year study period, indicating increased readiness for transfer and self-care. Overall quality of life, lung function and BMI remained stable during the study period. A well structured transition programme for cystic fibrosis patients as young as 12 years of age proved to be both feasible and sustainable. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. eSensor®: A Microarray Technology Based on Electrochemical Detection of Nucleic Acids and Its Application to Cystic Fibrosis Carrier Screening

    NASA Astrophysics Data System (ADS)

    Reed, Michael R.; Coty, William A.

    We have developed a test for identification of carriers for cystic fibrosis using the eSensor® DNA detection technology. Oligonucleotide probes are deposited within self-assembled monolayers on gold electrodes arrayed upon printed circuit boards. These probes allow sequence-specific capture of amplicons containing a panel of mutation sites associated with cystic fibrosis. DNA targets are detected and mutations genotyped using a “sandwich” assay methodology employing electrochemical detection of ferrocene-labeled oligonucleotides for discrimination of carrier and non-carrier alleles. Performance of the cystic fibrosis application demonstrates sufficient accuracy and reliability for clinical diagnostic use, and the procedure can be performed by trained medical technologists available in the hospital laboratory.

  19. Self-reported exercise and longitudinal outcomes in cystic fibrosis: a retrospective cohort study.

    PubMed

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

    2014-10-06

    Cystic fibrosis (CF) is characterized by recurrent respiratory infections and progressive lung disease. Whereas exercise may contribute to preserving lung function, its benefit is difficult to ascertain given the selection bias of healthier patients being more predisposed to exercise. Our objective was to examine the role of self-reported exercise with longitudinal lung function and body mass index (BMI) measures in CF. A total of 1038 subjects with CF were recruited through the U.S. CF Twin-Sibling Study. Questionnaires were used to determine exercise habits. Questionnaires, chart review, and U.S. CF Foundation Patient Registry data were used to track outcomes. Within the study sample 75% of subjects self-reported regular exercise. Exercise was associated with an older age of diagnosis (p = 0.002), older age at the time of ascertainment (p < 0.001), and higher baseline FEV1 (p = 0.001), but not CFTR genotype (p = 0.64) or exocrine pancreatic function (p = 0.19). In adjusted mixed models, exercise was associated with both a reduced decline in FEV1 (p < 0.001) and BMI Z-score (p = 0.001) for adults, but not children aged 10-17 years old. In our retrospective study, self-reported exercise was associated with improved longitudinal nutritional and pulmonary outcomes in cystic fibrosis for adults. Although prospective studies are needed to confirm these associations, programs to promote regular exercise among individuals with cystic fibrosis would be beneficial.

  20. Correlation between sinus and lung cultures in lung transplant patients with cystic fibrosis.

    PubMed

    Choi, Kevin J; Cheng, Tracy Z; Honeybrook, Adam L; Gray, Alice L; Snyder, Laurie D; Palmer, Scott M; Abi Hachem, Ralph; Jang, David W

    2018-03-01

    Lung transplantation has revolutionized the treatment of end-stage pulmonary disease due to cystic fibrosis. However, infection of the transplanted lungs can lead to serious complications, including graft failure and death. Although many of these patients have concurrent sinusitis, it is unclear whether bacteria from the sinuses can infect the allograft. This is a single-institution retrospective study of all patients who underwent lung transplantation for cystic fibrosis from 2005 to 2015 at Duke University Hospital. Pre- and posttransplant nasal and pulmonary cultures obtained via nasal endoscopy and bronchoalveolar lavage (BAL), respectively, were analyzed. A total of 141 patients underwent 144 lung transplants. Sinus cultures were available for 76 patients (12 pretransplant, 42 posttransplant, 22 both pre- and posttransplant). Pretransplant BAL cultures were available for 139 patients, and posttransplant BAL cultures were available for all patients. Pseudomonas aeruginosa (PsA) and methicillin-resistant Staphylococcus aureus (MRSA) were the most common organisms cultured. There was a significant correlation between pretransplant sinus and posttransplant BAL cultures for PsA (p = 0.003), MRSA (p = 0.013), and Burkholderia cepacia (p = 0.001). There was a high correlation between pretransplant sinus cultures and posttransplant BAL cultures for PsA, MRSA, and Burkholderia sp. This suggests that the paranasal sinuses may act as a reservoir for allograft colonization in patients with cystic fibrosis. Further studies are needed to determine whether treatment of sinusitis affects allograft colonization and transplant outcomes. © 2017 ARS-AAOA, LLC.

  1. Aerosolized recombinant human DNase I for the treatment of cystic fibrosis.

    PubMed

    Shak, S

    1995-02-01

    Respiratory symptoms, recurrent infectious exacerbations, and progressive lung destruction in cystic fibrosis can be attributed to bacterial persistence and the accumulation of viscous purulent secretions in the airways. Purulent secretions contain high concentrations of extracellular DNA, a viscous material released by leukocytes. To evaluate the potential clinical utility of recombinant human DNase I (rhDNase or Pulmozyme), the human enzyme was cloned, sequenced, and expressed. In in vitro studies, rhDNase has been shown to reduce the viscoelasticity, reduce the adhesiveness, and improve the mucociliary transportability of cystic fibrosis sputum. In short-term phase 1 and phase 2 clinical trials, rhDNase has been shown to be safely tolerated and to improve the FEV1, FVC, and symptoms of dyspnea. A long-term placebo-controlled phase 3 study was performed in 968 adults and children (> or = 5 years) with cystic fibrosis to determine the effect of rhDNase on the risk of respiratory exacerbations requiring parenteral antibiotics and on the FEV1. Compared with placebo-treated patients, patients treated with rhDNase once daily or twice daily experienced a reduced risk of respiratory exacerbations by 28% (p = 0.04) and 37% (p = 0.01), respectively, and had a mean improvement in FEV1 of 5.8% (p < 0.01) and 5.6% (p < 0.01), respectively. Compared with placebo-treated patients, patients treated with rhDNase spent 2.7 fewer days receiving parenteral antibiotics (p = 0.04) and spent 1.3 fewer days in the hospital (p = 0.06) over the 6-month treatment period. Inhalation of rhDNase did not cause anaphylaxis but was associated with upper airway symptoms (ie, voice alteration, hoarseness, pharyngitis) that were generally mild and transient. In conclusion, aerosol administration of rhDNase was safely tolerated, reduced the risk of infectious exacerbations requiring parenteral antibiotics, and improved pulmonary function and patient well-being.

  2. Impact of Scedosporium apiospermum complex seroprevalence in patients with cystic fibrosis.

    PubMed

    Parize, Perrine; Billaud, Sandrine; Bienvenu, Anne L; Bourdy, Stéphanie; le Pogam, Marie A; Reix, Philippe; Picot, Stéphane; Robert, Raymond; Lortholary, Olivier; Bouchara, Jean-Philippe; Durieu, Isabelle

    2014-12-01

    Species of the Scedosporium apiospermum complex (S. a complex) are emerging fungi responsible for chronic airway colonization in cystic fibrosis (CF) patients. Recent studies performed on Aspergillus fumigatus suggest that the colonization of the airways by filamentous fungi may contribute to the progressive deterioration of lung function. We studied S. a complex seroprevalence, as a marker of close contact between patient and the fungi, in a large monocentric cohort of CF patients attended in a reference centre in Lyon, France. Serum samples from 373 CF patients were analysed. Antibodies against S. a complex were detected in 35 patients (9.4%). In multivariate analysis, S. a complex seropositivity was only associated with seropositivity to A. fumigatus. This study does not suggest an association between sensitization against S. a complex and poorer lung function in CF. Prospective studies are needed to evaluate the impact of both seropositivity and S. a complex colonization on the course of CF. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  3. Chronic Mycobacterium abscessus infection and lung function decline in cystic fibrosis.

    PubMed

    Esther, Charles R; Esserman, Denise A; Gilligan, Peter; Kerr, Alan; Noone, Peadar G

    2010-03-01

    Although nontuberculous mycobacteria (NTM) are recognized pathogens in cystic fibrosis (CF), associations with clinical outcomes remain unclear. Microbiological data was obtained from 1216 CF patients over 8years (481+/-55patients/year). Relationships to clinical outcomes were examined in the subset (n=271, 203+/-23 patients/year) with longitudinal data. Five hundred thirty-six of 4862 (11%) acid-fast bacilli (AFB) cultures grew NTM, with Mycobacterium abscessus (n=298, 55.6%) and Mycobacterium avium complex (n=190, 35.4%) most common. Associated bacterial cultures grew Stenotrophomonas or Aspergillus species more often when NTM were isolated (18.2% vs. 8.4% and 13.9% vs. 7.2%, respectively, p<0.01). After controlling for confounders, patients with chronic M. abscessus infection had greater rates of lung function decline than those with no NTM infection (-2.52 vs. -1.64% predicted FEV(1)/year, p<0.05). NTM infection is common in CF and associated with particular pathogens. Chronic M. abscessus infection is associated with increased lung function decline. Copyright (c) 2009 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  4. Effects of Aspergillus fumigatus colonization on lung function in cystic fibrosis.

    PubMed

    Speirs, Jennifer J; van der Ent, Cornelis K; Beekman, Jeffrey M

    2012-11-01

    Aspergillus fumigatus is frequently isolated from cystic fibrosis (CF) patients and is notorious for its role in the debilitating condition of allergic bronchopulmonary aspergillosis (ABPA). Although CF patients suffer from perpetual microorganism-related lung disease, it is unclear whether A. fumigatus colonization has a role in causing accelerated lung function decline and whether intervention is necessary. A. fumigatus morbidity appears to be related to cystic fibrosis transmembrane conductance regulator-dependant function of the innate immune system. A. fumigatus-colonized patients have a lower lung capacity, more frequent hospitalizations and more prominent radiological abnormalities than noncolonized patients. Treatment with antifungal agents can be of value but has several drawbacks and a direct effect on lung function is yet to be shown. A. fumigatus appears to have an important role in CF lung disease, not exclusive to the context of ABPA. However, a causal relationship still needs to be confirmed. Study observations and trends indicate a need to further elucidate the mechanisms of A. fumigatus interactions with the host innate immune system and its role in CF lung morbidity.

  5. Eradication failure of newly acquired Pseudomonas aeruginosa isolates in cystic fibrosis.

    PubMed

    Cohen-Cymberknoh, Malena; Gilead, Noa; Gartner, Silvia; Rovira, Sandra; Blau, Hannah; Mussaffi, Huda; Rivlin, Joseph; Gur, Michal; Shteinberg, Michal; Bentur, Lea; Livnat, Galit; Aviram, Micha; Picard, Elie; Tenenbaum, Ariel; Armoni, Shoshana; Breuer, Oded; Shoseyov, David; Kerem, Eitan

    2016-11-01

    Eradication of Pseudomonas aeruginosa (PA) is critical in cystic fibrosis (CF) patients. To determine eradication success rate of newly acquired PA and to identify characteristics associated with eradication failure. In an observational study, data from patients with newly acquired PA infection from 2007 to 2013 were collected. Clinical variables were compared in patients with and without successful eradication for ≥1year. Of 183 patients out of 740 (25%) from 7 CF Centers that had newly acquired PA, eradication succeeded in 72%. Patients with the highest risk of failure had multi-resistant PA, fewer sputum cultures taken, were older, and were diagnosed at a later age. The risk of eradication failure increased by 1.3% with each year of delayed CF diagnosis; successful eradication increased by 17% with each additional sputum culture taken. Delayed detection of PA infection leading to delayed treatment and growth of multi-resistant organisms is associated with eradication failure. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  6. Novel short chain fatty acids restore chloride secretion in cystic fibrosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nguyen, Toan D.; Kim, Ug-Sung; Perrine, Susan P.

    2006-03-31

    Phenylalanine deletion at position 508 of the cystic fibrosis transmembrane conductance regulator ({delta}F508-CFTR), the most common mutation in cystic fibrosis (CF), causes a misfolded protein exhibiting partial chloride conductance and impaired trafficking to the plasma membrane. 4-Phenylbutyrate corrects defective {delta}F508-CFTR trafficking in vitro, but is not clinically efficacious. From a panel of short chain fatty acid derivatives, we showed that 2,2-dimethyl-butyrate (ST20) and {alpha}-methylhydrocinnamic acid (ST7), exhibiting high oral bioavailability and sustained plasma levels, correct the {delta}F508-CFTR defect. Pre-incubation ({>=}6 h) of CF IB3-1 airway cells with {>=}1 mM ST7 or ST20 restored the ability of 100 {mu}M forskolin tomore » stimulate an {sup 125}I{sup -} efflux. This efflux was fully inhibited by NPPB, DPC, or glibenclamide, suggesting mediation through CFTR. Partial inhibition by DIDS suggests possible contribution from an additional Cl{sup -} channel regulated by CFTR. Thus, ST7 and ST20 offer treatment potential for CF caused by the {delta}F508 mutation.« less

  7. Current and future molecular approaches in the diagnosis of cystic fibrosis.

    PubMed

    Bergougnoux, Anne; Taulan-Cadars, Magali; Claustres, Mireille; Raynal, Caroline

    2018-05-01

    Cystic Fibrosis is among the first diseases to have general population genetic screening tests and one of the most common indications of prenatal and preimplantation genetic diagnosis for single gene disorders. During the past twenty years, thanks to the evolution of diagnostic techniques, our knowledge of CFTR genetics and pathophysiological mechanisms involved in cystic fibrosis has significantly improved. Areas covered: Sanger sequencing and quantitative methods greatly contributed to the identification of more than 2,000 sequence variations reported worldwide in the CFTR gene. We are now entering a new technological age with the generalization of high throughput approaches such as Next Generation Sequencing and Droplet Digital PCR technologies in diagnostics laboratories. These powerful technologies open up new perspectives for scanning the entire CFTR locus, exploring modifier factors that possibly influence the clinical evolution of patients, and for preimplantation and prenatal diagnosis. Expert commentary: Such breakthroughs would, however, require powerful bioinformatics tools and relevant functional tests of variants for analysis and interpretation of the resulting data. Ultimately, an optimal use of all those resources may improve patient care and therapeutic decision-making.

  8. Pharmacists' perspectives on monitoring adherence to treatment in Cystic Fibrosis.

    PubMed

    Mooney, Karen; Ryan, Cristín; Downey, Damian G

    2016-04-01

    Cystic Fibrosis (CF) management requires complex treatment regimens but adherence to treatment is poor and has negative health implications. There are various methods of measuring adherence, but little is known regarding the extent of adherence measurement in CF centres throughout the UK and Ireland. To determine the adherence monitoring practices in CF centres throughout the UK and Ireland, and to establish CF pharmacists' views on these practices. UK and Ireland Cystic Fibrosis Pharmacists' Group's annual meeting (2014). A questionnaire was designed, piloted and distributed to pharmacists attending the UK and Ireland Cystic Fibrosis Pharmacists' Group's annual meeting (2014). The main outcome measures were the methods of inhaled/nebulised antibiotic supply and the methods used to measure treatment adherence in CF centres. The questionnaire also ascertained the demographic information of participating pharmacists. Closed question responses were analysed using descriptive statistics. Open questions were analysed using content analysis. Twenty-one respondents (84 % response) were included in the analysis and were mostly from English centres (66.7 %). Detailed records of patients receiving their inhaled/nebulised antibiotics were lacking. Adherence was most commonly described to be measured at 'every clinic visit' (28.6 %) and 'occasionally' (28.6 %). Patient self-reported adherence was the most commonly used method of measuring adherence in practice (90.5 %). The availability of electronic adherence monitoring in CF centres did not guarantee its use. Pharmacists attributed an equal professional responsibility for adherence monitoring in CF to Consultants, Nurses and Pharmacists. Seventy-six percent of pharmacists felt that the current adherence monitoring practices within their own unit were inadequate and associated with the absence of sufficient specialist CF pharmacist involvement. Many suggested that greater specialist pharmacist involvement could facilitate

  9. Scoliosis in cystic fibrosis - an appraisal

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Paling, M.R.; Spasovsky-Chernick, M.

    1982-03-01

    An unusually high prevalence (10%) of scoliosis is described in a series of 151 patients aged four years and older with cystic fibrosis. The scolioses were of the late onset (juvenile and adolescent) type, being typically thoracic with the curve convex to the right, although there was no significant preference for either sex. No direct relationship was found between the spinal curvature and the severity or distribution of the lung disease, although the worse scolioses tended to occur in patients with relatively severe pulmonary involvement. There was no evidence of metabolic bone disease as a predisposing cause. Some indication ofmore » a familial tendency towards scoliosis was apparent, and a genetic or constitutional basis is postulated with an unknown precipitating factor.« less

  10. Hyperthyrotropinemia in newly diagnosed cystic fibrosis patients with pancreatic insufficiency reversed by enzyme therapy.

    PubMed

    Giannakopoulos, Aris; Katelaris, Anni; Noni, Maria; Karakonstantakis, Theodore; Kanaka-Gantenbein, Christina; Doudounakis, Stavros

    2018-05-01

    Patients with cystic fibrosis (CF) commonly present with an elevated TSH concentration, suggesting subclinical hypothyroidism. Its relation to concomitant pancreatic insufficiency and its natural course upon initiation of enzyme replacement have not been adequately studied. Herein, we investigated the thyroid function in newly diagnosed infants with CF and monitored the course of thyroid function response to pancreatic enzyme substitution treatment. Fourteen, newly diagnosed infants with CF and pancreatic insufficiency, were followed every 6-8 weeks for 6 months ensuing onset of pancreatic enzyme substitution therapy. All infants had normal TSH values on neonatal screening. Ten out of 14 (71%) had hyperthyrotropinemia and normal freeT4 values at presentation. No patient received thyroxine. Upon follow-up, after 6 months, TSH values normalized in 90% of infants with CF and hyperthyrotropinemia. Serum selenium levels were negatively correlated with TSH levels. Mild TSH elevation is a frequent finding in newly diagnosed cystic fibrosis patients with pancreatic insufficiency during infancy. TSH elevation resolves in most cases after initiation of enzyme substitution and improvement of nutritional status without any substitutive therapy with thyroxine. What is Known: • Newly diagnosed infants with cystic fibrosis often present with a state of hyperthyrotropinemia suggesting subclinical hypothyroidism. What is New: • Pancreatic enzyme substitution and improvement of nutrition restores normal TSH levels without the need of thyroxine therapy.

  11. Radionuclide assessment of the effects of chest physical therapy on ventilation in cystic fibrosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    DeCesare, J.A.; Babchyck, B.M.; Colten, H.R.

    1982-06-01

    This study assesses the use of /sup 81m/Kr scintigraphy as a measurement tool in evaluating the effectiveness of bronchial drainage with percussion and vibration on peripheral ventilation in patients with cystic fibrosis. Ten patients with cystic fibrosis participated. Each patient underwent a /sup 81m/Kr ventilation study and traditional pulmonary function tests. Forty-five minutes later, these studies were repeated before and after a chest physical therapy treatment. Each patient acted as his own control. All /sup 81m/Kr scintiscans were recorded and analyzed visually and numerically using a digital computer to assess distribution of ventilation. Visual analysis of the scintiscans indicated individualmore » variation in treatment response: in some patients ventilation improved with therapy; in others, no change was noted; still others had changes independent of treatment. Numerical data derived from the scintiscans and pulmonary function tests showed no important differences among the three studies of each patient. Airway abnormalities characteristic of cystic fibrosis, progression of the disease, sputum production, or a combination of these factors may account for the individual variation in response to treatment. /sup 81m/Kr scintigraphy is a reliable measure of regional ventilation and should be useful for assessing the efficacy of chest physical therapy because of the consistent, high quality visual data retrieved.« less

  12. Genetic Expression in Cystic Fibrosis Related Bone Disease. An Observational, Transversal, Cross-Sectional Study.

    PubMed

    Ciuca, Ioana M; Pop, Liviu L; Rogobete, Alexandru F; Onet, Dan I; Guta-Almajan, Bogdan; Popa, Zoran; Horhat, Florin G

    2016-09-01

    Cystic fibrosis (CF) is the most frequent monogenic genetic disease with autosomal recessive transmission and characterized by important clinical polymorphism and significant lethal prospective. CF related bone disease occurs frequently in adults with CF. Childhood is the period of bone formation, and therefore, children are more susceptible to low bone density. Several factors like pancreatic insufficiency, hormone imbalance, and physical inactivity contribute to CF bone disease development. Revealing this would be important for prophylactic treatment against bone disease occurrence. The study was observational, transversal, with a cross-sectional design. The study included 68 children with cystic fibrosis, genotyped and monitored in the National CF Centre. At the annual assessment, besides clinical examination, biochemical evaluation for pancreatic insufficiency, and diabetes, they were evaluated for bone mineral density using dual energy X-ray absorptiometry (DXA). Twenty-six patients, aged over 10 years were diagnosed with CF bone disease, without significant gender gap. Bone disease was frequent in patients aged over 10 years with exocrine pancreatic insufficiency, carriers of severe mutations, and CF liver disease. CF carriers of a severe genotype which associates pancreatic insufficiency and CF liver disease, are more likely predisposed to low bone mineral density. Further studies should discover other significant influences in order to prevent the development of CF bone disease and an improved quality of life in cystic fibrosis children.

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

    PubMed

    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

  14. Information needs of parents of infants diagnosed with cystic fibrosis: Results of a pilot study.

    PubMed

    Edwards, Danielle J; Wicking, Kristin; Smyth, Wendy; Shields, Linda; Douglas, Tonia

    2018-01-01

    This study investigated the information needs, priorities and information-seeking behaviours of parents of infants recently diagnosed with cystic fibrosis (CF) following newborn screening, by piloting the 'Care of Cystic Fibrosis Families Survey'. The questionnaires were posted to eligible parents ( n = 66) attending CF clinics in hospitals in two Australian states; reply-paid envelopes were provided for return of the questionnaires. Twenty-six were returned (response rate 39.4%). The most common questions to which parents required answers during their initial education period related to what CF is, how it is treated and how to care for their child. Parents preferred face-to-face consultations to deliver information, and yet all reported using the Internet to search for more information at some point during the education period. Many parents provided negative feedback about being given their child's CF diagnosis via telephone. The timing, content and method of information delivery can all affect the initial education experience. We can deliver education to better suit the information needs and priorities for education of parents of infants recently diagnosed with CF. The Care of Cystic Fibrosis Families Survey was successfully piloted and recommendations for amendments have been made for use in a larger study across Australia.

  15. The prevalence of anxiety and depression in Italian patients with cystic fibrosis and their caregivers.

    PubMed

    Catastini, Paola; Di Marco, Serena; Furriolo, Maria; Genovese, Carmela; Grande, Alessia; Iacinti, Eugenia; Iusco, Danila Rosa; Nobili, Rita Maria Vittoria; Pescini, Rita; Ragni, Roberto; Randazzo, Roberto; Risso, Cristiana; Tabarini, Paola; Braggion, Cesare; De Masi, Salvatore; McGreevy, Kathleen S

    2016-12-01

    Cystic fibrosis, like other chronic diseases, is a risk factor for the development of elevated symptoms of depression and anxiety. The objective of this study was to investigate the prevalence of anxiety and depression in Italian patients with CF and their parents. The Hospital Anxiety and Depression Scale (HADS) and Center for Epidemiologic Studies Depression Scale (CES-D) questionnaires were administered to a sample of patients and their parents recruited at the cystic fibrosis centers in Italy. Elevated levels of anxiety were higher in mothers than in fathers, and also higher in female patients than in male patients. A correlation between elevated levels of anxiety/depression and geographical area also emerged. Patient anxiety (OR 2.33) and depression (OR 4.09) were significantly associated with forced expiratory volume in one second (FEV1) <40% and forced vital capacity (FVC) <80% (OR 1.60 and 1.61, respectively). Cystic fibrosis increases the risk of developing anxiety and depression in female patients and in mothers. Geographical differences were observed, with higher anxiety and depression in southern Italy for parents, but not for patients. Anxiety and depression levels also depend on clinical status. Pediatr Pulmonol. 2016;51:1311-1319. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Early analysis of operative management of Chiari I malformation in pediatric cystic fibrosis patients.

    PubMed

    Samples, Derek C; Thoms, Dewey J; Tarasiewicz, Izabela

    2018-04-02

    Chiari I malformation, defined as herniation of the cerebellar tonsils at least 5 mm below the foramen magnum, can result from congenital or acquired pathology. While the mechanism is not well understood, an association between Chiari I and cystic fibrosis has been described in the literature. The lifelong respiratory status management necessitated by cystic fibrosis creates a greater risk of Chiari symptomatology as well as post-operative CSF-related complications in the setting of duraplasty secondary to recurrent transient increases in intracranial pressure. We will review the literature, describe our experience with these patients, and propose bony decompression as an approach to treatment. A retrospective review of pediatric patients treated at our institution with both cystic fibrosis and Chiari I was performed. Since our first case in 2016, our department has evaluated four patients carrying that dual diagnosis. All four underwent posterior fossa decompression surgery. Two patients had incidental pathology. Two symptomatic patients exhibited headaches and/or coordination difficulty. Half of the patients had associated syringomyelia. All patients were offered posterior fossa decompression utilizing intraoperative ultrasound. All four patients underwent posterior fossa decompression without duraplasty. Average operative time was 128 min. There were no complications post-operatively. Average hospital stay was 3.8 days. Average surgical length of stay was 2.3 days. Morbidity and mortality were 0%. The longest follow-up to date is 20 months. The two asymptomatic patients remained so post-operatively. The child with headaches and imbalance had complete resolution of his symptoms after surgery, as did the toddler with headaches. Both patients with syringomyelia demonstrated significant decrease in the size of their syrinxes on imaging performed at least 3 months post-operatively. Based on the literature and our experience, we recommend considering posterior

  17. Cystic fibrosis epithelial cells are primed for apoptosis as a result of increased Fas (CD95).

    PubMed

    Chen, Qiwei; Pandi, Sudha Priya Soundara; Kerrigan, Lauren; McElvaney, Noel G; Greene, Catherine M; Elborn, J Stuart; Taggart, Clifford C; Weldon, Sinéad

    2018-02-24

    Previous work suggests that apoptosis is dysfunctional in cystic fibrosis (CF) airways with conflicting results. We evaluated the relationship between dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) and apoptosis in CF airway epithelial cells. Apoptosis and associated caspase activity were analysed in non-CF and CF tracheal and bronchial epithelial cell lines. Basal levels of apoptosis and activity of caspase-3 and caspase-8 were significantly increased in CF epithelial cells compared to controls, suggesting involvement of extrinsic apoptosis signalling, which is mediated by the activation of death receptors, such as Fas (CD95). Increased levels of Fas were observed in CF epithelial cells and bronchial brushings from CF patients compared to non-CF controls. Neutralisation of Fas significantly inhibited caspase-3 activity in CF epithelial cells compared to untreated cells. In addition, activation of Fas significantly increased caspase-3 activity and apoptosis in CF epithelial cells compared to control cells. Overall, these results suggest that CF airway epithelial cells are more sensitive to apoptosis via increased levels of Fas and subsequent activation of the Fas death receptor pathway, which may be associated with dysfunctional CFTR. Copyright © 2018 European Cystic Fibrosis Society. All rights reserved.

  18. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR.

    PubMed

    Wainwright, Claire E; Elborn, J Stuart; Ramsey, Bonnie W; Marigowda, Gautham; Huang, Xiaohong; Cipolli, Marco; Colombo, Carla; Davies, Jane C; De Boeck, Kris; Flume, Patrick A; Konstan, Michael W; McColley, Susanna A; McCoy, Karen; McKone, Edward F; Munck, Anne; Ratjen, Felix; Rowe, Steven M; Waltz, David; Boyle, Michael P

    2015-07-16

    Cystic fibrosis is a life-limiting disease that is caused by defective or deficient cystic fibrosis transmembrane conductance regulator (CFTR) protein activity. Phe508del is the most common CFTR mutation. We conducted two phase 3, randomized, double-blind, placebo-controlled studies that were designed to assess the effects of lumacaftor (VX-809), a CFTR corrector, in combination with ivacaftor (VX-770), a CFTR potentiator, in patients 12 years of age or older who had cystic fibrosis and were homozygous for the Phe508del CFTR mutation. In both studies, patients were randomly assigned to receive either lumacaftor (600 mg once daily or 400 mg every 12 hours) in combination with ivacaftor (250 mg every 12 hours) or matched placebo for 24 weeks. The primary end point was the absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV1) at week 24. A total of 1108 patients underwent randomization and received study drug. The mean baseline FEV1 was 61% of the predicted value. In both studies, there were significant improvements in the primary end point in both lumacaftor-ivacaftor dose groups; the difference between active treatment and placebo with respect to the mean absolute improvement in the percentage of predicted FEV1 ranged from 2.6 to 4.0 percentage points (P<0.001), which corresponded to a mean relative treatment difference of 4.3 to 6.7% (P<0.001). Pooled analyses showed that the rate of pulmonary exacerbations was 30 to 39% lower in the lumacaftor-ivacaftor groups than in the placebo group; the rate of events leading to hospitalization or the use of intravenous antibiotics was lower in the lumacaftor-ivacaftor groups as well. The incidence of adverse events was generally similar in the lumacaftor-ivacaftor and placebo groups. The rate of discontinuation due to an adverse event was 4.2% among patients who received lumacaftor-ivacaftor versus 1.6% among those who received placebo. These data show that lumacaftor in

  19. Exopolysaccharides produced by Inquilinus limosus, a new pathogen of cystic fibrosis patients: novel structures with usual components.

    PubMed

    Herasimenka, Yury; Cescutti, Paola; Impallomeni, Giuseppe; Rizzo, Roberto

    2007-11-26

    The major cause of morbidity and mortality in patients with cystic fibrosis, an autosomal recessive disorder, is chronic microbial colonisation of the major airways that leads to exacerbation of pulmonary infection. Several different microbes colonise cystic fibrosis lungs, and Pseudomonas aeruginosa is one of the most threatening, since the establishment of mucoid (alginate producing) strains is ultimately associated with the patient's death. Very recently a new bacterium, named Inquilinus limosus, was repeatedly found infecting the respiratory tract of cystic fibrosis patients. Its multi-resistance characteristic to antibiotics might result in the spreading of I. limosus infection among the cystic fibrosis community, as recently happened with strains of the Burkholderia cepacia complex. Since exopolysaccharides are recognised as important virulence factors in lung infections, the primary structure of the polysaccharide produced by I. limosus strain LMG 20952(T) was investigated as the first step in understanding its role in pathogenesis. The structure was determined by means of methylation analysis, acid degradations, mass spectrometry and NMR spectroscopy. The results showed that the bacterium produced a mixture constituted of the following polymers: [3)-[4,6-O-(1-carboxyethylidene)]-beta-D-Glcp(1-->]n; [2)-[4,6-O-(1-carboxyethylidene)]-alpha-D-Manp(1-->]n. Both polymers were completely substituted with pyruvyl ketal groups, a novel structural characteristic not previously found in bacterial polysaccharides. The absolute configuration of all pyruvyl groups was S. Inspection of possible local conformations assumed by the two polysaccharide chains showed features, which might provide interesting clues for understanding structure-function relationships.

  20. Cystic fibrosis transmembrane conductance regulator regulates epithelial cell response to Aspergillus and resultant pulmonary inflammation.

    PubMed

    Chaudhary, Neelkamal; Datta, Kausik; Askin, Frederic B; Staab, Janet F; Marr, Kieren A

    2012-02-01

    Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) alter epithelial cell (EC) interactions with multiple microbes, such that dysregulated inflammation and injury occur with airway colonization in people with cystic fibrosis (CF). Aspergillus fumigatus frequently colonizes CF airways, but it has been assumed to be an innocent saprophyte; its potential role as a cause of lung disease is controversial. To study the interactions between Aspergillus and EC, and the role of the fungus in evoking inflammatory responses. A. fumigatus expressing green fluorescent protein was developed for in vitro and in vivo models, which used cell lines and mouse tracheal EC. Fungal spores (conidia) are rapidly ingested by ECs derived from bronchial cell lines and murine tracheas, supporting a role for EC in early airway clearance. Bronchial ECs harboring CFTR mutations (ΔF508) or deletion demonstrate impaired uptake and killing of conidia, and ECs with CFTR mutation undergo more conidial-induced apoptosis. Germinated (hyphal) forms of the fungus evoke secretion of inflammatory mediators, with CFTR mutation resulting in increased airway levels of macrophage inflammatory protein 2 and KC, and higher lung monocyte chemotactic protein-1. After A. fumigatus inhalation, CFTR(-/-) mice develop exaggerated lymphocytic inflammation, mucin accumulation, and lung injury. Data demonstrate a critical role for CFTR in mediating EC responses to A. fumigatus. Results suggest that the fungus elicits aberrant pulmonary inflammation in the setting of CFTR mutation, supporting the potential role of antifungals to halt progressive CF lung disease.

  1. Associations between Academic Achievement and Psychosocial Variables in Adolescents with Cystic Fibrosis

    ERIC Educational Resources Information Center

    Grieve, Adam J.; Tluczek, Audrey; Racine-Gilles, Caroline N.; Laxova, Anita; Albers, Craig A.; Farrell, Philip M.

    2011-01-01

    Background: Cystic fibrosis (CF) is a chronic genetic disease that leads to the accumulation of thick mucus in multiple organ systems, leading to chronic lung infection and affecting the body's ability to absorb nutrients necessary for growth and development. This cross-sectional, correlational study examined the potential effects of CF on…

  2. The L441P mutation of cystic fibrosis transmembrane conductance regulator and its molecular pathogenic mechanisms in a Korean patient with cystic fibrosis.

    PubMed

    Gee, Heon Yung; Kim, Chang Keun; Kim, So Won; Lee, Ji Hyun; Kim, Jeong-Ho; Kim, Kyung Hwan; Lee, Min Goo

    2010-01-01

    Cystic fibrosis (CF) is an autosomal recessive disorder usually found in populations of white Caucasian descent. CF is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. A 5-yr-old Korean girl was admitted complaining of coughing and greenish sputum. Chest radiographs and computed tomographic (CT) scan revealed diffuse bronchiectasis in both lungs. The patient had chronic diarrhea and poor weight gain, and the abdominal pancreaticobiliary CT scan revealed atrophy of the pancreas. Finally, CF was confirmed by the repeated analysis of the quantitative pilocarpine iontophoresis test. The chloride concentration of sweat samples taken from both forearms of the pateint was an average of 88.7 mM/L (normal value <40 mM/L). After a comprehensive search for mutations in the CFTR gene, the patient was found to carry the non-synonymous L441P mutation in one allele. Molecular physiologic analysis of the L441P mutation of CFTR revealed that the L441P mutation completely abolished the CFTR Cl(-) channel activity by disrupting proper protein folding and membrane trafficking of CFTR protein. These results confirmed the pathogenicity of the L441P mutation of CFTR circulating in the Korean population. The possibility of CF should be suspected in patients with chronic bronchiectasis, although the frequency of CF is relatively rare in East Asia.

  3. Effect of bronchoalveolar lavage-directed therapy on Pseudomonas aeruginosa infection and structural lung injury in children with cystic fibrosis: a randomized trial.

    PubMed

    Wainwright, Claire E; Vidmar, Suzanna; Armstrong, David S; Byrnes, Catherine A; Carlin, John B; Cheney, Joyce; Cooper, Peter J; Grimwood, Keith; Moodie, Marj; Robertson, Colin F; Tiddens, Harm A

    2011-07-13

    Early pulmonary infection in children with cystic fibrosis leads to increased morbidity and mortality. Despite wide use of oropharyngeal cultures to identify pulmonary infection, concerns remain over their diagnostic accuracy. While bronchoalveolar lavage (BAL) is an alternative diagnostic tool, evidence for its clinical benefit is lacking. To determine if BAL-directed therapy for pulmonary exacerbations during the first 5 years of life provides better outcomes than current standard practice relying on clinical features and oropharyngeal cultures. The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) randomized controlled trial, recruiting infants diagnosed with cystic fibrosis through newborn screening programs in 8 Australasian cystic fibrosis centers. Recruitment occurred between June 1, 1999, and April 30, 2005, with the study ending on December 31, 2009. BAL-directed (n = 84) or standard (n = 86) therapy until age 5 years. The BAL-directed therapy group underwent BAL before age 6 months when well, when hospitalized for pulmonary exacerbations, if Pseudomonas aeruginosa was detected in oropharyngeal specimens, and after P. aeruginosa eradication therapy. Treatment was prescribed according to BAL or oropharyngeal culture results. Primary outcomes at age 5 years were prevalence of P. aeruginosa on BAL cultures and total cystic fibrosis computed tomography (CF-CT) score (as a percentage of the maximum score) on high-resolution chest CT scan. Of 267 infants diagnosed with cystic fibrosis following newborn screening, 170 were enrolled and randomized, and 157 completed the study. At age 5 years, 8 of 79 children (10%) in the BAL-directed therapy group and 9 of 76 (12%) in the standard therapy group had P. aeruginosa in final BAL cultures (risk difference, -1.7% [95% confidence interval, -11.6% to 8.1%]; P = .73). Mean total CF-CT scores for the BAL-directed therapy and standard therapy groups were 3.0% and 2.8%, respectively (mean difference, 0.19% [95

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

    PubMed Central

    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. Association between glucose intolerance and bacterial colonisation in an adult population with cystic fibrosis, emergence of Stenotrophomonas maltophilia.

    PubMed

    Lehoux Dubois, C; Boudreau, V; Tremblay, F; Lavoie, A; Berthiaume, Y; Rabasa-Lhoret, R; Coriati, A

    2017-05-01

    Diabetes is common in cystic fibrosis (CF). Glucose can be detected in the airway when the blood glucose is elevated, which favours bacterial growth. We investigated the relationship between dysglycemia and lung pathogens in CF. Cross-sectional and prospective analysis of CF patients (N=260) who underwent a 2h-oral glucose tolerance test. Clinical data was collected. Stenotrophomonas maltophilia (S. maltophilia) was the sole bacteria increased in dysglycemic (AGT: 20.2%, CFRD: 21.6%) patients compared to normotolerants (NGT: 8.7%). S. maltophilia positive patients with dysglycemia had more pulmonary exacerbation events compared to NGTs (1.22 vs 0.63, P=0.003). The interaction between S. maltophilia colonisation and glucose tolerance status significantly increases the risk of lower lung function (P=0.003). Its growth was not affected by the evolution of the glucose tolerance after three years follow-up. Prevalence of S. maltophilia was higher in dysglycemic patients, supporting the idea that S. maltophilia is a marker of disease severity in CF. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  6. Channel Gating Regulation by the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) First Cytosolic Loop.

    PubMed

    Ehrhardt, Annette; Chung, W Joon; Pyle, Louise C; Wang, Wei; Nowotarski, Krzysztof; Mulvihill, Cory M; Ramjeesingh, Mohabir; Hong, Jeong; Velu, Sadanandan E; Lewis, Hal A; Atwell, Shane; Aller, Steve; Bear, Christine E; Lukacs, Gergely L; Kirk, Kevin L; Sorscher, Eric J

    2016-01-22

    In this study, we present data indicating a robust and specific domain interaction between the cystic fibrosis transmembrane conductance regulator (CFTR) first cytosolic loop (CL1) and nucleotide binding domain 1 (NBD1) that allows ion transport to proceed in a regulated fashion. We used co-precipitation and ELISA to establish the molecular contact and showed that binding kinetics were not altered by the common clinical mutation F508del. Both intrinsic ATPase activity and CFTR channel gating were inhibited severely by CL1 peptide, suggesting that NBD1/CL1 binding is a crucial requirement for ATP hydrolysis and channel function. In addition to cystic fibrosis, CFTR dysregulation has been implicated in the pathogenesis of prevalent diseases such as chronic obstructive pulmonary disease, acquired rhinosinusitis, pancreatitis, and lethal secretory diarrhea (e.g. cholera). On the basis of clinical relevance of the CFTR as a therapeutic target, a cell-free drug screen was established to identify modulators of NBD1/CL1 channel activity independent of F508del CFTR and pharmacologic rescue. Our findings support a targetable mechanism of CFTR regulation in which conformational changes in the NBDs cause reorientation of transmembrane domains via interactions with CL1 and result in channel gating. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Potentiators (specific therapies for class III and IV mutations) for cystic fibrosis.

    PubMed

    Patel, Sanjay; Sinha, Ian P; Dwan, Kerry; Echevarria, Carlos; Schechter, Michael; Southern, Kevin W

    2015-03-26

    placebo in people with cystic fibrosis. In a post hoc change we excluded trials combining CFTR potentiators with other mutation-specific therapies. These will be considered in a separate review. The authors independently extracted data and assessed the risk of bias in included trials; they contacted trial authors for additional data. Meta-analyses were undertaken on outcomes at a number of time points. We included four randomised controlled trials (n = 378), lasting from 28 days to 48 weeks, comparing the potentiator ivacaftor to placebo. Trials differed in terms of design and participant eligibility criteria, which limited the meta-analyses. The phase 2 trial (n = 19) and two phase 3 trials (adult trial (n = 167), paediatric trial (n = 52)), recruited participants with the G551D mutation (class III). The fourth trial (n = 140) enrolled participants homozygous for the ΔF508 mutation (class II).Risks of bias in the trials were moderate. Random sequence generation, allocation concealment and blinding of trial personnel were well-documented. Participant blinding was less clear throughout all trials; in three trials, some participant data were excluded from the analysis. Selective outcome reporting was apparent in three trials. All trials were sponsored by industry and supported by other non-pharmaceutical funding bodies.No trial reported any deaths. Significantly higher quality of life scores in the respiratory domain were reported by the adult phase 3 G551D trial at 24 weeks, mean difference 8.10 (95% confidence interval (CI) 4.77 to 11.43) and 48 weeks, mean difference 8.60 (95% CI 5.27 to 11.93); but not by the paediatric phase 3 G551D trial. The adult phase 3 G551D trial reported improvements in relative change from baseline in forced expiratory volume at one second at 24 weeks, mean difference 16.90% (95% CI 13.60 to 20.20) and 48 weeks, mean difference 16.80% (95% CI 13.50 to 20.10); as did the paediatric G551D trial at 24 weeks, mean difference 17.4% (P < 0

  8. Annual Review Clinic improves care in children with cystic fibrosis.

    PubMed

    Chuang, Sandra; Doumit, Michael; McDonald, Rebecca; Hennessy, Erika; Katz, Tamarah; Jaffe, Adam

    2014-03-01

    It is unclear whether annual multidisciplinary reviews in cystic fibrosis (CF) patients should be conducted in dedicated annual review (AR) clinics or during continuous assessments throughout the year. Our aim was to assess the effect of introducing an AR clinic. A retrospective written and electronic record review of CF patients was carried out for 2007 (no AR Clinic) and 2010 (established AR Clinic) calendar years. An internet-based satisfaction survey was distributed to families attending the AR clinic. In total, 123 children (mean age 9.5 years, range 1.32-18.8 years) and 141 children (8.3 years, 1.1-18.3 years) were included in 2007 and 2010 respectively. There was a significant increase in multidisciplinary reviews (documented annual review 28% vs 85%, P < 0.001; dietary assessment 46% vs 92%, P < 0.001) and investigations (OGTT 2% vs 74%, P < 0.001; abdominal ultrasound 35% vs 85%, P < 0.001) conducted after the introduction of AR clinic. The majority of the families surveyed (85%) were satisfied or very satisfied with the AR clinic. CF AR clinic significantly improves the number of annual investigations and multidisciplinary reviews performed. Families were satisfied with this new process. © 2013. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. All rights reserved.

  9. CFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease.

    PubMed

    Fernandez Fernandez, Elena; de Santi, Chiara; De Rose, Virginia; Greene, Catherine M

    2018-05-11

    Obstructive lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are causes of high morbidity and mortality worldwide. CF is a multiorgan genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is characterized by progressive chronic obstructive lung disease. Most cases of COPD are a result of noxious particles, mainly cigarette smoke but also other environmental pollutants. Areas covered: Although the pathogenesis and pathophysiology of CF and COPD differ, they do share key phenotypic features and because of these similarities there is great interest in exploring common mechanisms and/or factors affected by CFTR mutations and environmental insults involved in COPD. Various molecular, cellular and clinical studies have confirmed that CFTR protein dysfunction is common in both the CF and COPD airways. This review provides an update of our understanding of the role of dysfunctional CFTR in both respiratory diseases. Expert Commentary: Drugs developed for people with CF to improve mutant CFTR function and enhance CFTR ion channel activity might also be beneficial in patients with COPD. A move toward personalized therapy using, for example, microRNA modulators in conjunction with CFTR potentiators or correctors, could enhance treatment of both diseases.

  10. A Comparison of Family Adaptations to Having a Child with Cystic Fibrosis.

    ERIC Educational Resources Information Center

    Johnson, Mark C.; And Others

    1985-01-01

    Examines effect of cystic fibrosis (CF) on structure and social climate of the family using self-report scales and independent observations of family functioning. Families in which the child with CF was not the firstborn were found to be functioning more healthily than those in which the child was firstborn. (Author/NRB)

  11. Anabolic agent use in adults with cystic fibrosis.

    PubMed

    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.

  12. Cystic Fibrosis Transmembrane Conductance Regulator (ABCC7) Structure

    PubMed Central

    Hunt, John F.; Wang, Chi; Ford, Robert C.

    2013-01-01

    Structural studies of the cystic fibrosis transmembrane conductance regulator (CFTR) are reviewed. Like many membrane proteins, full-length CFTR has proven to be difficult to express and purify, hence much of the structural data available is for the more tractable, independently expressed soluble domains. Therefore, this chapter covers structural data for individual CFTR domains in addition to the sparser data available for the full-length protein. To set the context for these studies, we will start by reviewing structural information on model proteins from the ATP-binding cassette (ABC) transporter superfamily, to which CFTR belongs. PMID:23378596

  13. [Analysis of energy expenditure in adults with cystic fibrosis: comparison of indirect calorimetry and prediction equations].

    PubMed

    Fuster, Casilda Olveira; Fuster, Gabriel Olveira; Galindo, Antonio Dorado; Galo, Alicia Padilla; Verdugo, Julio Merino; Lozano, Francisco Miralles

    2007-07-01

    Undernutrition, which implies an imbalance between energy intake and energy requirements, is common in patients with cystic fibrosis. The aim of this study was to compare resting energy expenditure determined by indirect calorimetry with that obtained with commonly used predictive equations in adults with cystic fibrosis and to assess the influence of clinical variables on the values obtained. We studied 21 patients with clinically stable cystic fibrosis, obtaining data on anthropometric variables, hand grip dynamometry, electrical bioimpedance, and resting energy expenditure by indirect calorimetry. We used the intraclass correlation coefficient (ICC) and the Bland-Altman method to assess agreement between the values obtained for resting energy expenditure measured by indirect calorimetry and those obtained with the World Health Organization (WHO) and Harris-Benedict prediction equations. The prediction equations underestimated resting energy expenditure in more than 90% of cases. The agreement between the value obtained by indirect calorimetry and that calculated with the prediction equations was poor (ICC for comparisons with the WHO and Harris-Benedict equations, 0.47 and 0.41, respectively). Bland-Altman analysis revealed a variable bias between the results of indirect calorimetry and those obtained with prediction equations, irrespective of the resting energy expenditure. The difference between the values measured by indirect calorimetry and those obtained with the WHO equation was significantly larger in patients homozygous for the DeltaF508 mutation and in those with exocrine pancreatic insufficiency. The WHO and Harris-Benedict prediction equations underestimate resting energy expenditure in adults with cystic fibrosis. There is poor agreement between the values for resting energy expenditure determined by indirect calorimetry and those estimated with prediction equations. Underestimation was greater in patients with exocrine pancreatic insufficiency and

  14. FOXO1 content is reduced in cystic fibrosis and increases with IGF-I treatment.

    PubMed

    Smerieri, Arianna; Montanini, Luisa; Maiuri, Luigi; Bernasconi, Sergio; Street, Maria E

    2014-10-08

    Cystic fibrosis-related diabetes is to date the most frequent complication in cystic fibrosis (CF). The mechanisms underlying this condition are not well understood, and a possible role of insulin resistance is debated. We investigated insulin signal transduction in CF. Total insulin receptor, IRS1, p85 PI3K, and AKT contents were substantially normal in CF cells (CFBE41o-), whereas winged helix forkhead (FOX)O1 contents were reduced both in baseline conditions and after insulin stimulation. In addition, CF cells showed increased ERK1/2, and reduced β2 arrestin contents. No significant change in SOCS2 was observed. By using a CFTR inhibitor and siRNA, changes in FOXO1 were related to CFTR loss of function. In a CF-affected mouse model, FOXO1 content was reduced in the muscle while no significant difference was observed in liver and adipose tissue compared with wild-type. Insulin-like growth factor 1 (IGF-I) increased FOXO1 content in vitro and in vivo in muscle and adipose tissue. In conclusion; we present the first description of reduced FOXO1 content in CF, which is compatible with reduced gluconeogenesis and increased adipogenesis, both features of insulin insensitivity. IGF-I treatment was effective in increasing FOXO1, thereby suggesting that it could be considered as a potential treatment in CF patients possibly to prevent and treat cystic fibrosis-related diabetes.

  15. Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis.

    PubMed

    Langton Hewer, Simon C; Smyth, Alan R

    2017-04-25

    Respiratory tract infection with Pseudomonas aeruginosa occurs in most people with cystic fibrosis. Once chronic infection is established, Pseudomonas aeruginosa is virtually impossible to eradicate and is associated with increased mortality and morbidity. Early infection may be easier to eradicate.This is an update of a Cochrane review first published in 2003, and previously updated in 2006, 2009 and 2014. To determine whether antibiotic treatment of early Pseudomonas aeruginosa infection in children and adults with cystic fibrosis eradicates the organism, delays the onset of chronic infection, and results in clinical improvement. To evaluate whether there is evidence that a particular antibiotic strategy is superior to or more cost-effective than other strategies and to compare the adverse effects of different antibiotic strategies (including respiratory infection with other micro-organisms). 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: 10 October 2016. We included randomised controlled trials of people with cystic fibrosis, in whom Pseudomonas aeruginosa had recently been isolated from respiratory secretions. We compared combinations of inhaled, oral or intravenous antibiotics with placebo, usual treatment or other combinations of inhaled, oral or intravenous antibiotics. We excluded non-randomised trials, cross-over trials, and those utilising historical controls. Both authors independently selected trials, assessed risk of bias and extracted data. The search identified 60 trials; seven trials (744 participants) with a duration between 28 days and 27 months were eligible for inclusion. Three of the trials are over 10 years old and their results may be less applicable today given the changes in standard treatment. Some of the trials had low

  16. Health-related quality of life of Spanish children with cystic fibrosis.

    PubMed

    Groeneveld, Iris F; Sosa, Elena S; Pérez, Margarita; Fiuza-Luces, Carmen; Gonzalez-Saiz, Laura; Gallardo, Cristian; López-Mojares, Luis M; Ruiz, Jonatan R; Lucia, Alejandro

    2012-12-01

    To investigate (1) the contributions of sex, age, nutritional status- and physical-fitness-related variables on health-related quality of life (HRQOL) in Spanish children with cystic fibrosis, and (2) the agreement on HRQOL between children and their parents. In 28 children aged 6-17 years, body mass index percentile, percentage body fat, physical activity, pulmonary function, cardiorespiratory fitness, functional mobility, and dynamic muscle strength were determined using objective measures. HRQOL was measured using the revised version of the cystic fibrosis questionnaire. Simple and multiple linear regression analyses were performed to determine the variables associated with HRQOL. To assess the agreement on HRQOL between children and parents, intra-class correlation coefficients (ICCs) were calculated. Girls reported worse emotional functioning, a higher treatment burden, and more respiratory problems than boys. Greater functional mobility appeared associated with a less favourable body image and more eating disturbances. Agreement on HRQOL between children and parents was good to excellent, except for the domain of treatment burden. Sex and age were stronger predictors of HRQOL than nutritional status- or physical-fitness-related variables. Children reported a lower treatment burden than their parents perceived them to have.

  17. Gastric emptying and gastro-oesophageal reflux in children with cystic fibrosis.

    PubMed

    Hauser, Bruno; De Schepper, Jean; Malfroot, Anne; De Wachter, Elke; De Schutter, Iris; Keymolen, Kathelijn; Vandenplas, Yvan

    2016-07-01

    Gastro-oesophageal reflux (GOR) is common in patients with cystic fibrosis (CF). The aim of this study was to investigate the relationship between gastric emptying (GE) and GOR in children with CF. Multichannel intraluminal impedance-pH monitoring (MII-pH) to measure GOR and GE breath test (GEBT) to measure GE were performed in 28 children with symptoms suggestive for GOR disease (GORD) (group 1). GEBT was performed in another 28 children with/without GOR symptoms who agreed to undergo GEBT but not MII-pH (group 2). In group 1, we found increased acid GOR (AGOR) in 46.4% and delayed GE (DGE) in 21.4% but no relationship between increased AGOR and DGE. There was no DGE in group 2. We found DGE in 10.7% and rapid GE in 12.5% of the whole group. Almost half of the children with CF and symptoms suggestive for GORD have increased AGOR and almost a quarter has DGE. However, there was no relation between GOR and GE. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  18. Allergic Bronchopulmonary Aspergillosis in Patient with Cystic Fibrosis - a Case Report

    PubMed Central

    IONESCU, Marcela Daniela; BALGRADEAN, Mihaela; MARCU, Veronica

    2014-01-01

    Asthma with allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity disease of the lungs due to an immune response to Aspergillus fumigattus (Af) antigens, is rarely seen in children, other than complicating cystic fibrosis. We present the case of a 14 – year- old female teenager with cystic fibrosis (CF), admitted in our hospital with respiratory failure and persistent cyanosis. Chest X-ray showed perihilar and upper lobes pulmonary infiltrates. Her airway cultures were positive for methicillin resistant staphilococcus aureus (MRSA) and non-mucoid Pseudomonas aeruginosa. She was prescribed intravenous antibiotherapy with ceftazidime and vancomycine (to which MRSA and Pseudomonas aeruginosa were susceptible). Pulmonary function testing (PFT) revealed severe obstructive lung disease. After ten days of intravenous antibiotics and first five days of corticosteroid, the patient's FEV1 was 68% of predicted. Total serum IgE and IgE antibodies to Aspergillus fumigatus were elevated. These results raised the possibility of allergic bronchopulmonary aspergillosis (ABPA). The possibility of ABPA should be considered in all pulmonary exacerbation and in order to determine if ABPA is developing or if an exacerbation is occurring, a serial monitoring of IgE levels should be performed. PMID:25705310

  19. The Multiple Faces of Non-Cystic Fibrosis Bronchiectasis. A Cluster Analysis Approach.

    PubMed

    Martínez-García, Miguel Á; Vendrell, Montserrat; Girón, Rosa; Máiz-Carro, Luis; de la Rosa Carrillo, David; de Gracia, Javier; Olveira, Casilda

    2016-09-01

    The clinical presentation and prognosis of non-cystic fibrosis bronchiectasis are both very heterogeneous. To identify different clinical phenotypes for non-cystic fibrosis bronchiectasis and their impact on prognosis. Using a standardized protocol, we conducted a multicenter observational cohort study at six Spanish centers with patients diagnosed with non-cystic fibrosis bronchiectasis before December 31, 2005, with a 5-year follow-up from the bronchiectasis diagnosis. A cluster analysis was used to classify the patients into homogeneous groups by means of significant variables corresponding to different aspects of bronchiectasis (clinical phenotypes): age, sex, body mass index, smoking habit, dyspnea, macroscopic appearance of sputum, number of exacerbations, chronic colonization with Pseudomonas aeruginosa, FEV1, number of pulmonary lobes affected, idiopathic bronchiectasis, and associated chronic obstructive pulmonary disease. Survival analysis (Kaplan-Meier method and log-rank test) was used to evaluate the comparative survival of the different subgroups. A total of 468 patients with a mean age of 63 (15.9) years were analyzed. Of these, 58% were females, 39.7% had idiopathic bronchiectasis, and 29.3% presented with chronic Pseudomonas aeruginosa colonization. Cluster analysis showed four clinical phenotypes: (1) younger women with mild disease, (2) older women with mild disease, (3) older patients with severe disease who had frequent exacerbations, and (4) older patients with severe disease who did not have frequent exacerbations. The follow-up period was 54 months, during which there were 95 deaths. Mortality was low in the first and second groups (3.9% and 7.6%, respectively) and high for the third (37%) and fourth (40.8%) groups. The third cluster had a higher proportion of respiratory deaths than the fourth (77.8% vs. 34.4%; P < 0.001). Using cluster analysis, it is possible to separate patients with bronchiectasis into distinct clinical phenotypes

  20. [Indoor fungal exposure: What impact on clinical and biological status regarding Aspergillus during cystic fibrosis].

    PubMed

    Pricope, D; Deneuville, E; Frain, S; Chevrier, S; Belaz, S; Roussey, M; Gangneux, J-P

    2015-06-01

    The sources of exposure during diseases due to Aspergillus fungi in cystic fibrosis patients are still poorly explored. We assessed home fungal exposure in patients suffering from cystic fibrosis and analysed its impact on the presence of Aspergillus biological markers, the colonisation of airways, as well as the sensitization and Aspergillus serology. Between March 2012 and August 2012, 34 patients benefited from a visit performed by a home environment medical adviser including sampling for mycological analysis. The number of colonies of Aspergillus was not significantly different in the various sampling sites (P=0.251), but the number of non-Aspergillus colonies was much higher in the kitchen (P=0.0045). Subsequently, home fungal exposure was compared between the groups "absence of Aspergillus-related markers" and "presence of Aspergillus-related markers". Home exposure to Aspergillus (P=0.453) and non-Aspergillus (P=0.972) flora was not significant between the 2 groups. Within this series of 34 patients that should be expanded, we note an absence of clear relationship between home exposure and the Aspergillus-linked markers in patients suffering from cystic fibrosis. This result should be taken into account regarding too restrictive hygiene advices provided to families, given the fact that fungal exposure can also results from activities performed away from home. Copyright © 2015 Elsevier Masson SAS. All rights reserved.