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Sample records for adult cystic fibrosis

  1. Laparoscopic cholecystectomy in adult cystic fibrosis.

    LENUS (Irish Health Repository)

    McGrath, D S

    2012-02-03

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

  2. Diagnosis of Adult Patients with Cystic Fibrosis.

    Science.gov (United States)

    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.

  3. Cystic fibrosis lung disease in adult patients.

    Science.gov (United States)

    Vender, Robert L

    2008-04-01

    As the longevity of all patients with cystic fibrosis (CF) continues to increase (median 2005 survival=36.8 years), more adult patients will be receiving their medical care from nonpediatric adult-care providers. Cystic fibrosis remains a fatal disease, with more than 80% of patients dying after the age of 18 years, and most deaths resulting from pulmonary disease. The changing epidemiology requires adult-care providers to become knowledgeable and competent in the clinical management of adults with CF. Physicians must understand the influence of specific genotype on phenotypic disease presentation and severity, the pathogenic factors determining lung disease onset and progression, the impact of comorbid disease factors such as CF-related diabetes and malnutrition upon lung disease severity, and the currently approved or standard accepted therapies used for chronic management of CF lung disease. This knowledge is critical to help alleviate morbidity and improve mortality for the rapidly expanding population of adults with CF.

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

    Science.gov (United States)

    Cystic Fibrosis Foundation, Atlanta, GA.

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

  5. Nutrient Status of Adults with Cystic Fibrosis

    Science.gov (United States)

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

    2011-01-01

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

  6. Colonic Disorders in Adult Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Hugh Chaun

    2001-01-01

    Full Text Available By 1996, the median survival of patients with cystic fibrosis (CF in North America had increased to 31 years. With the markedly improved life expectancy, many CF patients are now adults. There is an associated increased risk of certain colonic disorders, and the emergence of other previously unrecognized disorders, in adult CF patients. The distal intestinal obstruction syndrome (DIOS, which is more common in older patients, is a frequent cause of abdominal pain. Intussusception may complicate DIOS; other differential diagnoses include appendiceal disease, volvolus, Crohn's disease, fibrosing colonopathy and colonic carcinoma. The diagnosis of acute appendicitis, although uncommon in patients with CF, is often delayed, and appendiceal abscess is a frequent complication. The prevalence of Crohn's disease in CF has been shown to be 17 times that of the general population. Right-sided microscopic colitis is a recently recognized entity in CF of uncertain clinical significance. Fibrosing colonopathy has been confined mostly to children with CF, attributed to the use of high strength pancreatic enzyme supplements, but it has been reported in three adults. Nine cases of carcinoma of the large intestine have been reported worldwide, associated with an apparent excess risk of digestive tract cancers in CF. Despite high carrier rates of Clostridium difficile in patients with CF, pseudomembranous colitis is distinctly rare, but severe cases complicated by toxic megacolon have been reported. In these patients, watery diarrhea is often absent. Adult CF patients with refractory or unexplained intestinal symptoms merit thorough investigations.

  7. Fungal atopy in adult cystic fibrosis.

    LENUS (Irish Health Repository)

    Henry, M

    2012-02-03

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

  8. Learning about Cystic Fibrosis

    Science.gov (United States)

    ... Cystic Fibrosis Consensus Development Conference Statement Learning About Cystic Fibrosis What do we know about heredity and cystic ... Information What do we know about heredity and cystic fibrosis? Cystic fibrosis (CF) is the most common, fatal ...

  9. Osteoporosis in adults with cystic fibrosis.

    OpenAIRE

    Haworth, C S; Selby, P L; Webb, A. K.; Adams, J. E.

    1998-01-01

    Osteoporosis is prevalent in adults with CF Longitudinal data have not been collected and so the natural history is unknown. The aetiology is not known. There are no published randomized controlled trials evaluating treatments for osteoporosis in CF patients.

  10. Cystic Fibrosis and Pregnancy

    Science.gov (United States)

    ... Complications & Loss > Pregnancy complications > Cystic fibrosis and pregnancy Cystic fibrosis and pregnancy E-mail to a friend Please ... this page It's been added to your dashboard . Cystic fibrosis (CF) is a condition that affects breathing and ...

  11. Cystic Fibrosis Research

    Science.gov (United States)

    ... please turn Javascript on. Feature: Steady Advances Against Cystic Fibrosis Cystic Fibrosis Research Past Issues / Fall 2012 Table of Contents "Remarkable strides in cystic fibrosis research over the past two decades have culminated ...

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

    LENUS (Irish Health Repository)

    O'connor, T M

    2012-02-03

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

  13. Paradoxical Embolization in an Adult Cystic Fibrosis Patient

    Directory of Open Access Journals (Sweden)

    Nabil M Al Lawati

    2007-01-01

    Full Text Available Cystic fibrosis patients with an implantable venous access device (IVAD and a patent foramen ovale (PFO are at an increased risk of developing paradoxical embolism. A 33-year-old patient who had a cerebrovascular accident in the above setting is described. She had been anticoagulated because she had thrombosis of the tip of the indwelling catheter, and her PFO was closed percutaneuosly followed by replacement of her IVAD. She made a full neurological recovery. Echocardiography and prophylactic closure of the PFO, when present, as primary prevention for paradoxical embolism may be warranted in cystic fibrosis patients before placement of an IVAD.

  14. What Causes Cystic Fibrosis?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Causes Cystic Fibrosis? A defect in the CFTR gene causes cystic ... in the severity of the disease. How Is Cystic Fibrosis Inherited? Every person inherits two CFTR genes—one ...

  15. Limited Restoration of Cystic Fibrosis Lung Epithelium In Vivo with Adult Bone Marrow–derived Cells

    OpenAIRE

    Loi, Roberto; Beckett, Travis; Goncz, Kaarin K.; Suratt, Benjamin T.; Weiss, Daniel J.

    2005-01-01

    Rationale: Recent literature suggests that adult bone marrow–derived cells can localize to lung and acquire immunophenotypic characteristics of lung epithelial cells. We speculated this might be a potential therapeutic approach for correcting defective lung epithelium in cystic fibrosis.

  16. Chronic rhinovirus infection in an adult with cystic fibrosis.

    Science.gov (United States)

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

    2013-11-01

    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.

  17. Cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Radlović Nedeljko

    2012-01-01

    Full Text Available Cystic fibrosis (CF is a multisystemic autosomal recessive disease caused by a defect in the expression of CFTR protein, i.e. chloride channel present in the apical membrane of respiratory, digestive, reproductive and sweat glands epithelium. It primarily occurs in the Caucasians, while being considerably or exceptionally rare in persons of other races. Absence, deficit or structural and functional abnormalities of CFTR protein lead to mucosal hyperconcentration in the respiratory, digestive and reproductive systems and malabsorption of chloride and sodium in the sweat glands. Thus, the clinical features of patients’ with CF are predominated by respiratory, digestive and reproductive disorders, as well as the tendency to dehydration in the condition of increased sweating. Beside genotype variations, the degree of disease manifestation is also essentially influenced by various exogenous factors, such as the frequency and severity of respiratory infections, the level of aero-pollution, quality of immunoprophylaxis, patients’ nutritional condition and other. Chloride concentration of over 60 mmol/L in sweat, a high level of immunoreactive chymotrypsinogen in blood and the verification of homozygous mutation of CFTR gene are the basic methods in the diagnostics of the disease. CF belongs to the group of severe and complex chronic diseases, and therefore requires multidisciplinary therapeutic approach. Owing to the improvement of healthcare provision, most patients with CF now survive into adulthood. In addition, their quality of life is also considerably improved.

  18. Cystic fibrosis - nutritional considerations

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002437.htm Cystic fibrosis - nutrition To use the sharing features on this page, please enable JavaScript. Cystic fibrosis (CF) is a life-threatening disease that causes ...

  19. Cystic fibrosis: case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Si Hyun; Lee, Hyun Ju; Kim, Ji Hye; Park, Chol Heui [Gachon Medical School, Inchon (Korea, Republic of)

    2002-12-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  2. Assessing disease disclosure in adults with cystic fibrosis: the Adult Data for Understanding Lifestyle and Transitions (ADULT survey Disclosure of disease in adults with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Modi Avani C

    2010-09-01

    Full Text Available Abstract Background As more patients with cystic fibrosis (CF reach adulthood and participate in age-appropriate activities (e.g. employment, dating, disclosure of medical status becomes more important. This study assessed rates of disclosure and its perceived impact on relationships using the Adult Data for Understanding Lifestyle and Transitions (ADULT online survey. Methods Adults with CF participated in the survey via the United States national network of CF Centers. Descriptive and inferential statistics were utilized. Results Participants (n = 865 were more likely to disclose to relatives (94% and close friends (81% than to dating partners (73%, bosses/supervisors/teachers (51% or co-workers (39%. Respondents generally reported a neutral/positive effect on relationships following disclosure. Negative effects of disclosure were infrequent, but more likely with dating partners or bosses/supervisors/teachers. Results also indicated that disclosure may be influenced by severity of lung disease and gender, with those having normal/mild lung disease less likely to disclose their diagnosis to both co-workers (p Conclusions Most adults with CF disclosed their disease to relatives and close friends. Individuals with severe CF lung disease were more likely to disclose their diagnosis to coworkers and supervisors/teachers. It may be helpful to provide support for disclosure of disease in situations such as employment and dating.

  3. How Is Cystic Fibrosis Treated?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. How Is Cystic Fibrosis Treated? Cystic fibrosis (CF) has no cure. However, ... help oral pancreatic enzymes work better. Treatments for Cystic Fibrosis Complications A common complication of CF is diabetes . ...

  4. Cystic Fibrosis: Diet and Nutrition

    Science.gov (United States)

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Cystic Fibrosis: Diet and Nutrition KidsHealth > For Teens > Cystic Fibrosis: ... Food Enzyme Supplements Beating the Frustration What Is Cystic Fibrosis? At lunch, Lindsay often gets bored with having ...

  5. Genetics Home Reference: cystic fibrosis

    Science.gov (United States)

    ... Me Understand Genetics Home Health Conditions cystic fibrosis cystic fibrosis Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Cystic fibrosis is an inherited disease characterized by the buildup ...

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

    Science.gov (United States)

    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.

  7. Neonatal cystic fibrosis screening test

    Science.gov (United States)

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

  8. Using Cystic Fibrosis Therapies for Non-Cystic Fibrosis Bronchiectasis.

    Science.gov (United States)

    ElMaraachli, Wael; Conrad, Douglas J; Wang, Angela C C

    2016-03-01

    Non-cystic fibrosis bronchiectasis (NCFB) is an increasingly prevalent disease that places a significant burden on patients and health systems globally. Although many of the therapies used to treat NCFB were originally developed as cystic fibrosis (CF) therapies, not all of them have been demonstrated to be efficacious in NCFB and some may even be harmful. This article explores the evidence for which therapeutic strategies used to treat CF have been translated into the care of NCFB. The conclusion is that therapies for adult NCFB cannot be simply extrapolated from CF clinical trials, and in some instances, doing so may actually result in harm.

  9. Cystic fibrosis from the gastroenterologist's perspective.

    Science.gov (United States)

    Ooi, Chee Y; Durie, Peter R

    2016-03-01

    Cystic fibrosis is a life-limiting, recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Increased survival outcomes and the multisystem nature of the disease, including the involvement of hepatobiliary and gastrointestinal tracts, now require the need for more extensive knowledge and expertise in cystic fibrosis among gastroenterologists. Manifestations are either a direct consequence of the primary defect in cystic fibrosis or a secondary complication of the disease or therapy. Adult patients with cystic fibrosis also have an increased risk of malignancy in the gastrointestinal and pancreatico-biliary tracts compared with the general population. Novel treatments that target the basic defects in the CFTR protein have emerged, but to date not much is known about their effects on the gastrointestinal and hepatobiliary systems. The introduction of such therapies has provided new opportunities for the application of intestinal endpoints in clinical trials and the understanding of underlying disease mechanisms that affect the gut in cystic fibrosis.

  10. The adult cystic fibrosis patient with abdominal pain: what the radiologist needs to know

    Energy Technology Data Exchange (ETDEWEB)

    Liong, S.Y.; Awad, D. [Department of Radiology, University Hospital of South Manchester, Wythenshawe Hospital, Manchester (United Kingdom); Jones, A.M. [Department of Respiratory Medicine, University Hospital of South Manchester, Wythenshawe Hospital, Manchester (United Kingdom); Manchester Academic Health Science Centre, University of Manchester, Manchester (United Kingdom); Sukumar, S.A., E-mail: Sathi.Sukumar@uhsm.nhs.u [Department of Radiology, University Hospital of South Manchester, Wythenshawe Hospital, Manchester (United Kingdom)

    2011-02-15

    As the life expectancy of cystic fibrosis (CF) patients continues to increase, abdominal manifestations of CF are increasingly being encountered by clinicians and radiologists. Imaging plays an important role in the evaluation of adult CF patients with abdominal pain as a cause is often not discernable clinically. Accurate diagnosis is crucial in these patients as some causes may be managed conservatively, whilst others may require surgical intervention. In this review, we describe clinical presentation, imaging findings, and management of adult CF patients presenting with abdominal pain.

  11. Pseudomembranous colitis in cystic fibrosis.

    Science.gov (United States)

    Nagakumar, Prasad

    2013-05-01

    Cystic fibrosis (CF) patients may require frequent courses of antibiotics and repeated hospital admissions. Although children with CF have high carriage rate for C.difficile, they rarely develop colitis. Pseudomembranous colitis is more common in adult post lung transplant CF patients. Although rare, paseudomembranous colitis should be considered in CF patients presenting with abdominal symptoms even in the absence of diarrhoea.

  12. Associations between adherence, depressive symptoms and health-related quality of life in young adults with cystic fibrosis

    DEFF Research Database (Denmark)

    Knudsen, K. B.; Pressler, T.; Mortensen, L. H.;

    2016-01-01

    was to examine the relationships among treatment adherence, symptoms of depression and health-related quality of life (HRQoL) in a population of young adults with CF.Methods: We administered three standardized questionnaires to 67 patients with CF aged 18–30 years; Morisky Medication Adherence Scale, Major...... Depression Inventory, and Cystic Fibrosis Questionnaire-Revised.Results: There was a response rate of 77 % and a majority of the young adults (84 %) were employed or in an education program. Most participants (74 %) reported low adherence to medications. One third (32.8 %) of the participants reported......Background: Cystic fibrosis (CF) is a life shortening disease, however prognosis has improved and the adult population is growing. Most adults with cystic fibrosis live independent lives and balance the demands of work and family life with a significant treatment burden. The aim of this study...

  13. Cystic fibrosis: addressing the transition from pediatric to adult-oriented health care

    Directory of Open Access Journals (Sweden)

    Kreindler JL

    2013-12-01

    Full Text Available James L Kreindler,1,2 Victoria A Miller1,31The Children’s Hospital of Philadelphia, 2Department of Pediatrics, 3Department of Anesthesiology and Critical Care Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USAAbstract: Survival for patients with cystic fibrosis (CF increased to nearly 40 years in 2012 from the early childhood years in the 1940s. Therefore, patients are living long enough to require transition from pediatric CF centers to adult CF centers. The goal of transition is for the young adult to be engaged in the adult health care system in ways that optimize health, maximize potential, and increase quality of life. A successful transition promotes autonomy and responsibility with respect to one's own health. Currently, there is an information gap in the literature with respect to psychological models that can help guide informed transition processes. In this review, we establish the framework in which transition exists in CF; we review some of the published literature from the last 20 years of experience with transition in CF centers around the world; and we discuss psychological models of pediatric illness that can help to explain the current state of transition to adult-oriented care from pediatric-oriented care and help to formulate new models of ascertaining readiness for transition. Finally, we look at our current knowledge gaps and opportunities for future research endeavors.Keywords: cystic fibrosis, transition, adolescent, social-ecological model of AYA readiness for transition, SMART

  14. Effect of different breathing aids on ventilation distribution in adults with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Markus Wettstein

    Full Text Available BACKGROUND AND OBJECTIVES: We investigated the effect of different breathing aids on ventilation distribution in healthy adults and subjects with cystic fibrosis (CF. METHODS: In 11 healthy adults and 9 adults with CF electrical impedance tomography measurements were performed during spontaneous breathing, continuous positive airway pressure (CPAP and positive expiratory pressure (PEP therapy randomly applied in upright and lateral position. Spatial and temporal ventilation distribution was assessed. RESULTS: The proportion of ventilation directed to the dependent lung significantly increased in lateral position compared to upright in healthy and CF. This effect was enhanced with CPAP but neutralised with PEP, whereas the effect of PEP was larger in the healthy group. Temporal ventilation distribution showed exactly the opposite with homogenisation during CPAP and increased inhomogeneity with PEP. CONCLUSIONS: PEP shows distinct differences to CPAP with respect to its impact on ventilation distribution in healthy adults and CF subjects EIT might be used to individualise respiratory physiotherapy.

  15. Flying the nest: a challenge for young adults with cystic fibrosis and their parents

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke; Boisen, Kirsten A; Schiøtz, Peter Oluf;

    2017-01-01

    Objectives: As young patients with cystic fibrosis (CF) grow up, they are expected to take increasing responsibility for the treatment and care of their disease. The aim of this study was to explore the disease-related challenges faced by young adults with CF and their parents, when they leave home....... Materials and methods: A questionnaire survey of Danish patients with CF aged 18–25 years and their parents was conducted. The questionnaires were based on focus-group interviews with young adults with CF and their parents, and addressed challenges faced in the transition phase between childhood...... and adulthood, including different areas of disease management in everyday life. Results: Among all of the patients invited, 62% (n=58/94) of young adults and 53% (n=99/188) of their parents participated in the study. In total, 40% of the 18- to 25-year-olds were living with their parents, and the parents...

  16. Respiratory bacterial infections in cystic fibrosis

    DEFF Research Database (Denmark)

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

    2013-01-01

    Bacterial respiratory infections are the main cause of morbidity and mortality in patients with cystic fibrosis (CF). Pseudomonas aeruginosa remains the main pathogen in adults, but other Gram-negative bacteria such as Achromobacter xylosoxidans and Stenotrophomonas maltophilia as well...

  17. 78 FR 26681 - Medical Criteria for Evaluating Cystic Fibrosis

    Science.gov (United States)

    2013-05-07

    ... ADMINISTRATION RIN 0960-AF58 Medical Criteria for Evaluating Cystic Fibrosis AGENCY: Social Security....04 to evaluate claims involving cystic fibrosis in adults and children under titles II and XVI of the... information on the disability program. 2. Information for individuals with cystic fibrosis who apply...

  18. Long-Term Effects of Exercise Training and Hyperalimentation in Adult Cystic Fibrosis Patients with Severe Pulmonary Dysfunction.

    Science.gov (United States)

    Heijerman, Harry G. M.; And Others

    1992-01-01

    This study, with 10 adult patients with cystic fibrosis, found that the improvement in lung function and ergometry parameters obtained by a short in-patient training program could be maintained on an out-patient basis through a voluntary self-treatment program. (DB)

  19. Cystic fibrosis. Diagnosis.

    Directory of Open Access Journals (Sweden)

    Luis Ortigosa

    2009-11-01

    Full Text Available Cystic fibrosis (CF is one of the most frequent inherited mortal diseases in Caucasian population. Dysfunction in exocrine glands is described in CF patients, with severe pancreatic insufficiency and chronic lung disease. CF is inherited as an autosomal recessive disorder. More than 1000 disease-associated mutations in the cystic fibrosis transmembrane conductance regulator (CFTR gene have been described. DF508 mutation is the most common mutation in the CF gen. Diagnosis in CF is based on clinical and laboratory tests findings. Meconial ileus, CF in other relatives, chronic lung disease, congenital absence of the vas deferens with azoospermia are among other clinical findings, main criteria in CF patients. Two positive results in sweat chloride test , or demonstration in nasal epithelial ionic transport alteration (nasal potential difference and identification of two CF mutations in the patient are laboratory findings in CF.

  20. Extended nitric oxide measurements in exhaled air of cystic fibrosis and healthy adults.

    Science.gov (United States)

    Hofer, Markus; Mueller, Luzia; Rechsteiner, Thomas; Benden, Christian; Boehler, Annette

    2009-01-01

    In cystic fibrosis (CF) lung disease, exhaled nitric oxide (FeNO) is not raised, but rather is normal or even decreased when measured at a single expiratory flow. FeNO measurements at several flow rates allow differentiation between alveolar and bronchial nitric oxide (NO) production. Extended FeNO measurements therefore should be useful to localize the FeNO deficit in CF airways. FeNO was measured in stable CF adults with moderate lung disease and in healthy controls. Bronchial NO fluxes (J(NO,Br)) and alveolar NO concentrations (C(Alv)) were calculated from FeNO measurements at flow rates of 100, 150 and 200 ml/s using a method previously described. Thirty-two adults were included in the study, 12 of whom had CF. CF adults had significantly lower FeNO values at all flow rates. The median J(NO,Br) was significantly lower in CF adults than in healthy controls [0.31 nl/s (range = 0.11-0.63) vs. 0.70 nl/s (0.27-3.52); P alveolar and bronchial NO outputs in CF adults. The lower FeNO in adults with moderate to severe CF lung disease is likely to be the result of lower bronchial NO output.

  1. Molecular Diagnosis of Cystic Fibrosis.

    Science.gov (United States)

    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.

  2. Flying the nest: a challenge for young adults with cystic fibrosis and their parents

    Directory of Open Access Journals (Sweden)

    Bregnballe V

    2017-02-01

    Full Text Available Vibeke Bregnballe,1 Kirsten A Boisen,2 Peter Oluf Schiøtz,3 Tacjana Pressler,4 Kirsten Lomborg1,5 1Department of Clinical Medicine, Aarhus University, Aarhus, 2Center of Adolescent Medicine, Department of Pediatric and Adolescent Medicine, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, 3Department of Pediatrics, Aarhus University Hospital, Aarhus, 4Cystic Fibrosis Centre, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, 5Department of Public Health, Aarhus University, Aarhus, Denmark Objectives: As young patients with cystic fibrosis (CF grow up, they are expected to take increasing responsibility for the treatment and care of their disease. The aim of this study was to explore the disease-related challenges faced by young adults with CF and their parents, when they leave home.Materials and methods: A questionnaire survey of Danish patients with CF aged 18–25 years and their parents was conducted. The questionnaires were based on focus-group interviews with young adults with CF and their parents, and addressed challenges faced in the transition phase between childhood and adulthood, including different areas of disease management in everyday life.Results: Among all of the patients invited, 62% (n=58/94 of young adults and 53% (n=99/188 of their parents participated in the study. In total, 40% of the 18- to 25-year-olds were living with their parents, and the parents continued to play an active role in the daily care of their offspring’s disease. Among the young adults who had left home, both the patients and their parents reported many difficulties regarding disease management; the young adults reported difficulties in contacting social services and in affording and preparing sufficient CF-focused meals, and their parents reported difficulties in answering questions concerning social rights and CF in general, and in knowing how to give their offspring the best help, how much to interfere, and how to relinquish

  3. Pharmacokinetics of single-dose doripenem in adults with cystic fibrosis.

    Science.gov (United States)

    Cirillo, Iolanda; Vaccaro, Nicole; Redman, Rebecca; Black, Philip L; Kearns, Gregory L

    2012-11-01

    The pharmacokinetics of doripenem and doripenem-M-1 (inactive metabolite) were evaluated in an open-label, 2-period, single-sequence study in which single 1-g and 2-g doses of doripenem were administered intravenously over 4 hours to adult patients with cystic fibrosis (CF). The systemic exposure to doripenem and doripenem-M-1, as measured by observed apparent maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC), increased approximately proportionally to the increase in dose. Other pharmacokinetic parameters of doripenem and doripenem-M-1, including clearance, volume of distribution, and elimination half-life, were similar for the 1-g and 2-g doses. The results from this study were also compared with those from a previous study in adult healthy volunteers (HVs) without CF, from a previously conducted pharmacokinetic study, who received single doses of 500 mg and 1 g doripenem administered over 4 hours. The pharmacokinetics of doripenem in adult patients with CF are similar to those from adult HVs, noting some differences in the disposition when comparing body mass index-adjusted pharmacokinetic parameters.

  4. Barriers to adherence in adolescents and young adults with cystic fibrosis

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke; Schiøtz, Peter Oluf; Boisen, Kirsten A;

    2011-01-01

    Treatment adherence is crucial in patients with cystic fibrosis, but poor adherence is a problem, especially during adolescence. Identification of barriers to treatment adherence and a better understanding of how context shapes barriers is of great importance in the disease. Adolescent reports of...... of barriers to adherence have been studied, but studies of their parents' experience of such barriers have not yet been carried out. The aim of the present study was to explore barriers to treatment adherence identified by young patients with cystic fibrosis and by their parents....

  5. Creatinine clearance as predictor of tobramycin elimination in adult patients with cystic fibrosis

    NARCIS (Netherlands)

    Touw, D.J.; Vinks, A.A.T.M.M.; Jacobs, F.; Heijerman, H.G.M.; Bakker, Wim

    1996-01-01

    Assessment of renal function and relating this parameter to aminoglycoside clearance is important for an appropriate individualization of dosage regimens in patients with impaired renal function. However, it has been suggested that in cystic fibrosis (CF), creatinine clearance (CrCl) is not a good p

  6. Sternum Length and Rib Cage Dimensions Compared with Bodily Proportions in Adults with Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Louis-Philippe Laurin

    2012-01-01

    Full Text Available BACKGROUND: A greater structural expansion of the rib cage in females compared with males has been described in cystic fibrosis (CF patients; however, conflicting data exist as to whether an elongation of the bony ribs and sternum contributes to this expansion.

  7. Respiratory muscle strength in stable adolescent and adult patients with cystic fibrosis

    NARCIS (Netherlands)

    Dunnink, M A; Doeleman, W R; Trappenburg, J C A; de Vries, W R

    2009-01-01

    BACKGROUND: Since available studies have provided conflicting results, this study investigated respiratory muscle function and its relationship with exercise capacity, degree of dyspnoea and leg discomfort, and quality of life in patients with Cystic Fibrosis (CF). METHODS: Using a cross-sectional d

  8. Barriers to adherence in adolescents and young adults with cystic fibrosis: a questionnaire study in young patients and their parents

    Directory of Open Access Journals (Sweden)

    Bregnballe V

    2011-10-01

    Full Text Available Vibeke Bregnballe1, Peter Oluf Schiøtz1, Kirsten A Boisen2, Tacjana Pressler3, Mikael Thastum4 1Department of Paediatrics, Aarhus University Hospital, Aarhus, Denmark; 2Centre of Adolescent Medicine, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark; 3Cystic Fibrosis Centre, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark; 4Department of Psychology, University of Aarhus, Aarhus, Denmark Background: Treatment adherence is crucial in patients with cystic fibrosis, but poor adherence is a problem, especially during adolescence. Identification of barriers to treatment adherence and a better understanding of how context shapes barriers is of great importance in the disease. Adolescent reports of barriers to adherence have been studied, but studies of their parents' experience of such barriers have not yet been carried out. The aim of the present study was to explore barriers to treatment adherence identified by young patients with cystic fibrosis and by their parents. Methods: A questionnaire survey of a cohort of young Danish patients with cystic fibrosis aged 14–25 years and their parents was undertaken. Results: Barriers to treatment adherence were reported by 60% of the patients and by 62% of their parents. Patients and parents agreed that the three most common barriers encountered were lack of time, forgetfulness, and unwillingness to take medication in public. We found a significant positive correlation between reported number of barriers and perceived treatment burden. We also found a statistically significant relationship between the reported number of barriers and treatment adherence. A significant association was found between the number of barriers and the reactions of adolescents/young adults and those of their mothers and fathers, and between the number of barriers and the way the family communicated about cystic fibrosis. Conclusion: The present study showed that the majority of adolescents

  9. Preferences for Prenatal Tests for Cystic Fibrosis: A Discrete Choice Experiment to Compare the Views of Adult Patients, Carriers of Cystic Fibrosis and Health Professionals

    Directory of Open Access Journals (Sweden)

    Melissa Hill

    2014-02-01

    Full Text Available As new technologies enable the development of non-invasive prenatal diagnosis (NIPD for cystic fibrosis (CF, research examining stakeholder views is essential for the preparation of implementation strategies. Here, we compare the views of potential service users with those of health professionals who provide counselling for prenatal tests. A questionnaire incorporating a discrete choice experiment examined preferences for key attributes of NIPD and explored views on NIPD for CF. Adult patients (n = 92 and carriers of CF (n = 50 were recruited from one children’s and one adult NHS specialist CF centre. Health professionals (n = 70 were recruited via an e-mail invitation to relevant professional bodies. The key attribute affecting service user testing preferences was no miscarriage risk, while for health professionals, accuracy and early testing were important. The uptake of NIPD by service users was predicted to be high and includes couples that would currently decline invasive testing. Many service users (47% and health professionals (55.2% thought the availability of NIPD for CF would increase the pressure to undergo prenatal testing. Most service users (68.5% thought NIPD for CF should be offered to all pregnant women, whereas more health professionals (68.2% thought NIPD should be reserved for known carrier couples. The implications for clinical practice are discussed.

  10. Nutritional Issues in Cystic Fibrosis.

    Science.gov (United States)

    Solomon, Missale; Bozic, Molly; Mascarenhas, Maria R

    2016-03-01

    The importance of maintaining adequate nutrition in patients with cystic fibrosis has been well known for the past 3 decades. Achieving normal growth and maintaining optimal nutrition is associated with improved lung function. Comprehensive and consistent nutritional assessments at regular intervals can identify those at risk of nutritional failure and uncover micronutrient deficiencies contributing to malnutrition. Management of malnutrition in cystic fibrosis should follow a stepwise approach to determine the causes and comorbidities and to develop a nutritional plan. Nutritional management is crucial at every stage in a person's life with cystic fibrosis and remains a cornerstone of management.

  11. Determinants of mortality for adults with cystic fibrosis admitted in Intensive Care Unit: a multicenter study

    Directory of Open Access Journals (Sweden)

    Rabbat Antoine

    2006-01-01

    Full Text Available Abstract Background Intensive care unit (ICU admission of adults with cystic fibrosis (CF is controversial because of poor outcome. This appraisal needs re-evaluation following recent changes in both CF management and ICU daily practice. Objectives were to determine long-term outcome of adults with CF admitted in ICU and to identify prognostic factors. Methods Retrospective multicenter study of 60 ICU hospitalizations for 42 adult CF patients admitted between 2000 and 2003. Reason for ICU admission, ventilatory support provided and one-year survival were recorded. Multiple logistic analysis was used to determine predictors of mortality. Results Prior to ICU admission, all patients (mean age 28.1 ± 8 yr had a severe lung disease (mean FEV1 28 ± 12% predicted; mean PaCO2 47 ± 9 mmHg. Main reason for ICU hospitalization was pulmonary infective exacerbation (40/60. At admission, noninvasive ventilation was used in 57% of cases and was successful in 67% of patients. Endotracheal intubation was implemented in 19 episodes. Overall ICU mortality rate was 14%. One year after ICU discharge, 10 of the 28 survivors have been lung transplanted. Among recognized markers of CF disease severity, only the annual FEV1 loss was associated with a poor outcome (HR = 1.47 [1.18–1.85], p = 0.001. SAPSII (HR = 1.08 [1.03–1.12], p Conclusion Despite advanced lung disease, adult patients with CF admitted in ICU have high survival rate. Endotracheal intubation is associated with a poor prognosis and should be used as the last alternative. Although efforts have to be made in selecting patients with CF likely to benefit from ICU resources, ICU admission of these patients should be considered.

  12. Profile of cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Mona M. El-Falaki

    2014-09-01

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

  13. Time course and recovery of arterial blood gases during exacerbations in adults with Cystic Fibrosis.

    LENUS (Irish Health Repository)

    Waterhouse, D F

    2012-02-01

    INTRODUCTION: Hypoxia and hypercapnia are closely linked to morbidity and mortality in patients with Cystic Fibrosis (CF). The aims of this study were to describe the changes in blood gases during and following an acute pulmonary exacerbation in adults with CF. METHODS: We performed a prospective observational study of patients with CF admitted for management of an acute exacerbation. Blood gas and spirometric analysis was performed on admission, throughout the treatment period, and 31 days after discharge (day 45). RESULTS: At presentation, eight of nineteen patients had evidence of either hypoxia (PaO(2)<8 kPa) and\\/or hypercapnia (PaCO(2)>6.6 kPa). Blood gas parameters stabilized following two weeks of intravenous antibiotic therapy, with little difference evident in between treatment completion and subsequent review following discharge. Hypercapnia reversed in three patients, with persistent hypercapnia evident in two patients. CONCLUSION: In our study group, hypoxemia and hypercapnia were frequently observed at presentation of the acute exacerbation. Blood gases stabilized following two weeks of intravenous antibiotic therapy, with arterial PCO(2) one month following hospital discharge generally similar to that at time of discharge.

  14. Antibiotic susceptibility and molecular mechanisms of macrolide resistance in streptococci isolated from adult cystic fibrosis patients.

    Science.gov (United States)

    Thornton, Christina S; Grinwis, Margot E; Sibley, Christopher D; Parkins, Michael D; Rabin, Harvey R; Surette, Michael G

    2015-11-01

    The cystic fibrosis (CF) airways are colonized by polymicrobial communities with high bacterial load and are influenced by frequent antibiotic exposures. This community includes diverse streptococci, some of which have been directly or indirectly associated with pulmonary exacerbations. As many streptococci are naturally competent, horizontal transfer of antibiotic-resistant determinants coupled with frequent and/or chronic antibiotic exposure may contribute to high resistance rates. In this study, we assessed antibiotic resistance in 413 streptococcal isolates from adult CF patients against nine antibiotics relevant in CF treatment. We observed very low rates of cephalosporin resistance [cefepime and ceftriaxone ( resistance to tetracycline (∼34%) and sulfamethoxazole/trimethoprim (∼45%). The highest rate of antibiotic resistance was to the macrolides [azithromycin (56.4%) and erythromycin (51.6%)]. We also investigated the molecular mechanisms of macrolide resistance and found that only half of our macrolide-resistant streptococci isolates contained the mef (efflux pump) or erm (methylation of 23S ribosomal target site) genes. The majority of isolates were, however, found to have point mutations at position 2058 or 2059 of the 23S ribosomal subunit - a molecular mechanism of resistance not commonly reported in the non-pyogenic and non-pneumococcal streptococci, and unique in comparison with previous studies. The high rates of resistance observed here may result in poor outcomes where specific streptococci are contributing to CF airway disease and serve as a reservoir of resistance genes within the CF airway microbiome.

  15. Relationship between body balance, lung function, nutritional status and functional capacity in adults with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Jennifer T. S. Penafortes

    2013-10-01

    Full Text Available BACKGROUND: Cystic fibrosis (CF is a hereditary condition in which lung disease affects all patients. In addition to pulmonary involvement, the multisystemic components of CF cause significant physical limitations. However, the impact of lung function on balance control in CF has not been studied. OBJECTIVE: To assess body balance in adults with CF and to test its possible associations with lung function, nutritional status, and functional capacity. METHOD: This was a cross-sectional study in which 14 adults with CF underwent pulmonary function testing (spirometry, body plethysmography, and carbon monoxide diffusing capacity (DLco, respiratory muscle strength, 6-min walking distance (6MWD, Berg balance scale (BBS, nutritional analysis (body mass index and bioelectrical impedance, and stabilometry. Body balance was quantified using stabilometry; all participants performed the following two trials: opened base, eyes open (OBEO; closed base, eyes closed (CBEC. RESULTS: In stabilometry, the median for the lateral range and anterior-posterior range in the CBEC trial was 0.10 (0.08-0.11 and 0.13 (0.11-0.22, respectively (p<0.05. The maximal inspiratory pressure (MIP correlated inversely with the lateral standard deviation (ρ=–0.61; p<0.05 as the DLco correlated positively with the anterior-posterior range (ρ=0.54; p<0.05. There were significant relationships between body composition indexes and almost all stabilometric variables measured. There were no relationships of the BBS and 6MWD with the stabilometric variables. CONCLUSIONS: In adults with CF, imbalance occurs mainly in the anterior-posterior direction and is especially associated with body composition.

  16. Patient knowledge and pulmonary medication adherence in adult patients with cystic fibrosis

    Science.gov (United States)

    Lin, Ann Hsu-An; Kendrick, Jennifer G; Wilcox, Pearce G; Quon, Bradley S

    2017-01-01

    Background and objectives Patient knowledge of lung function (ie, forced expiratory volume in 1 s [FEV1]% predicted) and the intended benefits of their prescribed pulmonary medications might play an important role in medication adherence, but this relationship has not been examined previously in patients with cystic fibrosis (CF). Methods All patients diagnosed with CF and without prior lung transplantation were invited to complete knowledge and self-reported medication adherence questionnaires during routine outpatient visits to the Adult CF Clinic, St Paul’s Hospital, Vancouver, Canada from June 2013 to August 2014. Results A total of 142 out of 167 (85%) consecutive adults attending CF clinic completed patient knowledge and medication adherence survey questionnaires. Sixty-four percent of the patients recalled their last FEV1% predicted value within 5%, and 70% knew the intended benefits of all their prescribed medications. Self-reported adherence rates were highest for inhaled antibiotics (81%), azithromycin (87%), and dornase alpha (76%) and lowest for hypertonic saline (47%). Individuals who knew their FEV1% predicted value within 5% were more likely to self-report adherence to dornase alpha (84% vs 62%, P=0.06) and inhaled antibiotics (88% vs 64%, P=0.06) compared to those who did not, but these associations were not statistically significant. There were no significant associations observed between patient knowledge of intended medication benefits and self-reported medication adherence. Conclusion Contrary to our hypothesis, disease- and treatment-related knowledge was not associated with self-reported medication adherence. This suggests other barriers to medication adherence should be targeted in future studies aiming to improve medication adherence in adults with CF.

  17. Alveolar inflammation in cystic fibrosis

    DEFF Research Database (Denmark)

    Ulrich, Martina; Worlitzsch, Dieter; Viglio, Simona

    2010-01-01

    BACKGROUND: In infected lungs of the cystic fibrosis (CF) patients, opportunistic pathogens and mutated cystic fibrosis transmembrane conductance regulator protein (CFTR) contribute to chronic airway inflammation that is characterized by neutrophil/macrophage infiltration, cytokine release...... accumulated in type II alveolar epithelial cells, lacking CFTR. P. aeruginosa organisms were rarely present in inflamed alveoli. CONCLUSIONS: Chronic inflammation and remodeling is present in alveolar tissues of the CF lung and needs to be addressed by anti-inflammatory therapies....

  18. Extended-Interval Aminoglycoside Use in Cystic Fibrosis Exacerbation in Children and Young Adults

    Science.gov (United States)

    Safi, Khalid H.; Damiani, Justina M.; Sturza, Julie; Nasr, Samya Z.

    2016-01-01

    This is a prospective quality improvement project for patients with cystic fibrosis who are 5 years of age and older who were admitted for intravenous antibiotic administration as part of treatment of cystic fibrosis exacerbation. The goal of this project was to compare the pharmacokinetics of once-daily versus thrice-daily aminoglycoside use when treating cystic fibrosis exacerbation in different age groups. Of the total of 119 patient encounters, 82.4% were started on once-daily dosing, and the remainder were started on thrice-daily dosing. Patients with pharmacokinetics allowing the continuation of once-daily dosing differed from patients who required a switch to thrice-daily dosing in terms of baseline forced expiratory volume in 1 second, forced expiratory flow from 25% to 75% of vital capacity, age, and body mass index (BMI) but were similar in BMI percentiles. The once-daily dosing group had higher mean 18-hour level, higher mean half-life, higher mean area under the curve, and lower mean elimination constant. This study showed that aminoglycoside clearance is higher in younger children. PMID:27336007

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

    Science.gov (United States)

    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.

  20. What Are the Signs and Symptoms of Cystic Fibrosis?

    Science.gov (United States)

    ... Twitter. What Are the Signs and Symptoms of Cystic Fibrosis? The signs and symptoms of cystic fibrosis (CF) ... respiratory, digestive, or reproductive systems of the body. Cystic Fibrosis Figure A shows the organs that cystic fibrosis ...

  1. Accurate reporting of adherence to inhaled therapies in adults with cystic fibrosis: methods to calculate normative adherence

    Directory of Open Access Journals (Sweden)

    Hoo ZH

    2016-05-01

    Full Text Available Zhe Hui Hoo,1,2 Rachael Curley,1,2 Michael J Campbell,1 Stephen J Walters,1 Daniel Hind,3 Martin J Wildman1,2 1School of Health and Related Research (ScHARR, University of Sheffield, 2Sheffield Adult Cystic Fibrosis Centre, Northern General Hospital, 3Sheffield Clinical Trials Research Unit, University of Sheffield, Sheffield, UK Background: Preventative inhaled treatments in cystic fibrosis will only be effective in maintaining lung health if used appropriately. An accurate adherence index should therefore reflect treatment effectiveness, but the standard method of reporting adherence, that is, as a percentage of the agreed regimen between clinicians and people with cystic fibrosis, does not account for the appropriateness of the treatment regimen. We describe two different indices of inhaled therapy adherence for adults with cystic fibrosis which take into account effectiveness, that is, “simple” and “sophisticated” normative adherence. Methods to calculate normative adherence: Denominator adjustment involves fixing a minimum appropriate value based on the recommended therapy given a person’s characteristics. For simple normative adherence, the denominator is determined by the person’s Pseudomonas status. For sophisticated normative adherence, the denominator is determined by the person’s Pseudomonas status and history of pulmonary exacerbations over the previous year. Numerator adjustment involves capping the daily maximum inhaled therapy use at 100% so that medication overuse does not artificially inflate the adherence level. Three illustrative cases: Case A is an example of inhaled therapy under prescription based on Pseudomonas status resulting in lower simple normative adherence compared to unadjusted adherence. Case B is an example of inhaled therapy under-prescription based on previous exacerbation history resulting in lower sophisticated normative adherence compared to unadjusted adherence and simple normative adherence

  2. Intestinal organoids as model for cystic fibrosis

    NARCIS (Netherlands)

    Dekkers, J.F.

    2015-01-01

    Recent advances in adult stem cell culture technology have enabled long-term in vitro expansion of intestinal organoids or ‘mini-guts’. In this thesis, we used the organoid model to develop a novel assay to measure function of CFTR, the protein mutated in subjects with cystic fibrosis (CF). This met

  3. Tracheomalacia in adults with cystic fibrosis: determination of prevalence and severity with dynamic cine CT.

    LENUS (Irish Health Repository)

    McDermott, Shaunagh

    2012-02-01

    PURPOSE: To determine the prevalence and severity of tracheomalacia in adults with cystic fibrosis (CF) by using dynamic cine multidetector computed tomography (CT) and to correlate these findings with pulmonary function test (PFT) results and the severity of parenchymal lung disease. MATERIALS AND METHODS: In this institutional review board-approved HIPAA-compliant study, 40 patients with CF (22 men, 18 women; mean age, 28 years +\\/- 8 [standard deviation]; age range, 18-54 years) prospectively underwent PFTs, standard thin-section CT, and two dynamic cine multidetector CT acquisitions. Ten control subjects underwent dynamic cine multidetector CT. After standard thin-section CT was completed, dynamic cine multidetector CT was performed during a forced expiratory maneuver and during coughing. Dynamic cine multidetector CT images in nine patients were excluded. Maximal inspiratory, dynamic expiratory, and end-expiratory tracheal luminal areas were compared (Student t test) and correlated (Spearman rank) with PFT results and severity of parenchymal lung disease. RESULTS: Mean predicted forced expiratory volume in 1 second (FEV(1)) was 70.6% +\\/- 20.7, and mean Bhalla CT score was 41.8% +\\/- 13.6. In patients with CF, dynamic cine mean tracheal cross-sectional area reduction was 51.7% +\\/- 18.4 (range, 9%-89%) for forced expiratory maneuvers and 68.8% +\\/- 11.7 (range, 18%-88%) for coughing (P = .001). Tracheomalacia was demonstrated in 24 (69%) patients and no control subjects during forced expiratory maneuvers (P = .001) and in 10 (29%) patients and one (10%) control subject during coughing. For end-expiration images, mean tracheal luminal reduction was 16.1% +\\/- 14.0% (range, 0.0%-53.0%), with one patient demonstrating tracheal luminal reduction of more than 50%. There was no correlation between tracheal cross-sectional luminal reduction and either predicted FEV(1) or CT Bhalla score. CONCLUSION: Tracheomalacia depicted at dynamic cine multidetector CT is a

  4. Cystic Fibrosis (CF): Chloride Sweat Test

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Cystic Fibrosis (CF) Chloride Sweat Test KidsHealth > For Parents > Cystic Fibrosis (CF) Chloride Sweat Test Print A A A ... It Is A chloride sweat test helps diagnose cystic fibrosis (CF) , an inherited disorder that makes kids sick ...

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

    Science.gov (United States)

    ... Emergency Room? What Happens in the Operating Room? Cystic Fibrosis KidsHealth > For Kids > Cystic Fibrosis Print A A A What's in this article? ... with a condition she's known all her life — cystic fibrosis (say: SIS-tik fi-BRO-sus). Her parents ...

  6. Adult non-cystic fibrosis bronchiectasis is characterised by airway luminal Th17 pathway activation.

    Directory of Open Access Journals (Sweden)

    Alice C-H Chen

    Full Text Available Non-cystic fibrosis (CF bronchiectasis is characterised by chronic airway infection and neutrophilic inflammation, which we hypothesised would be associated with Th17 pathway activation.Th17 pathway cytokines were quantified in bronchoalveolar lavage fluid (BALF, and gene expression of IL-17A, IL-1β, IL-8 and IL-23 determined from endobronchial biopsies (EBx in 41 stable bronchiectasis subjects and 20 healthy controls. Relationships between IL-17A levels and infection status, important clinical measures and subsequent Pseudomonas aeruginosa infection were determined.BALF levels of all Th17 cytokines (median (IQR pg/mL were significantly higher in bronchiectasis than control subjects, including IL-17A (1.73 (1.19, 3.23 vs. 0.27 (0.24, 0.35, 95% CI 1.05 to 2.21, p<0.0001 and IL-23 (9.48 (4.79, 15.75 vs. 0.70 (0.43, 1.79, 95% CI 4.68 to 11.21, p<0.0001. However, BALF IL-17A levels were not associated with clinical measures or airway microbiology, nor predictive of subsequent P. aeruginosa infection. Furthermore, gene expression of IL-17A in bronchiectasis EBx did not differ from control. In contrast, gene expression (relative to medians of controls in bronchiectasis EBx was significantly higher than control for IL1β (4.12 (1.24, 8.05 vs 1 (0.13, 2.95, 95% CI 0.05 to 4.07, p = 0.04 and IL-8 (3.75 (1.64, 11.27 vs 1 (0.54, 3.89, 95% CI 0.32 to 4.87, p = 0.02 and BALF IL-8 and IL-1α levels showed significant relationships with clinical measures and airway microbiology. P. aeruginosa infection was associated with increased levels of IL-8 while Haemophilus influenzae was associated with increased IL-1α.Established adult non-CF bronchiectasis is characterised by luminal Th17 pathway activation, however this pathway may be relatively less important than activation of non-antigen-specific innate neutrophilic immunity.

  7. Lactate in cystic fibrosis sputum

    DEFF Research Database (Denmark)

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

    2011-01-01

    Antibiotic therapy is thought to improve lung function in patients with cystic fibrosis (CF) by decreasing neutrophil-derived inflammation. We investigated the origin and clinical significance of lactate in the chronically inflamed CF lung. Methods Lactate was measured in sputa of 18 exacerbated ...

  8. Lung transplantation for cystic fibrosis

    NARCIS (Netherlands)

    Adler, Frederick R; Aurora, Paul; Barker, David H; Barr, Mark L; Blackwell, Laura S; Bosma, Otto H; Brown, Samuel; Cox, D R; Jensen, Judy L; Kurland, Geoffrey; Nossent, George D; Quittner, Alexandra L; Robinson, Walter M; Romero, Sandy L; Spencer, Helen; Sweet, Stuart C; van der Bij, Wim; Vermeulen, J; Verschuuren, Erik A M; Vrijlandt, Elianne J L E; Walsh, William; Woo, Marlyn S; Liou, Theodore G

    2009-01-01

    Lung transplantation is a complex, high-risk, potentially life-saving therapy for the end-stage lung disease of cystic fibrosis (CF). The decision to pursue transplantation involves comparing the likelihood of survival with and without transplantation as well as assessing the effect of wait-listing

  9. New insights into cystic fibrosis-related diabetes in children.

    Science.gov (United States)

    Ode, Katie L; Moran, Antoinette

    2013-09-01

    Cystic fibrosis-related diabetes (CFRD) is the most common complication of cystic fibrosis. It is associated with significantly increased morbidity and mortality in adults and children. Adolescents with cystic fibrosis have a much higher prevalence of diabetes than any other similar age population. Glucose abnormalities that precede diabetes are even more common, especially in children younger than 10 years. The pathophysiology of glucose metabolic abnormalities is poorly understood, but insulin insufficiency is clearly the main component. Findings from animal studies have provided insight into the pathophysiology of CFRD, and imply that carbohydrate metabolic abnormalities might begin at much younger ages than was previously thought in patients with cystic fibrosis, and might be related to the basic cystic fibrosis chloride channel defect. In this Review we explore present knowledge of CFRD in children and adolescents, and new data that indicate that the pathophysiology of CFRD begins in very young patients.

  10. Assessment of nutritional status in adult patients with cystic fibrosis: whole-body bioimpedance vs body mass index, skinfolds, and leg-to-leg bioimpedance

    NARCIS (Netherlands)

    Hollander, F.M.; Roos, de N.M.; Vries, de J.H.M.; Berkhout, van F.T.

    2005-01-01

    Objective: To investigate whether body mass index (BMI) or body fat percentage estimated from BMI, skinfolds, or leg-to-leg bioimpedance are good indicators of nutritional status in adult patients with cystic fibrosis. Body fat percentage measured by whole-body bioimpedance was used as the reference

  11. Normal bone mineral density in cystic fibrosis

    OpenAIRE

    Hardin, D.; R. Arumugam; Seilheimer, D.; Leblanc, A.; Ellis, K.

    2001-01-01

    BACKGROUND—Osteoporosis has been reported as a complication of cystic fibrosis (CF).
AIMS—To measure bone mineral density (BMD) in non-acutely ill adults and bone mineral content (BMC) in children with CF.
METHODS—We analysed data from 28 adults and 13 children with CF. Corticosteroid use was minimal for the year prior to study in both groups. Dual x ray absorptiometry was used to measure total body and regional bone mineral density in adults. In children, whole body BMC was...

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

    DEFF Research Database (Denmark)

    Koch, Lene; Stemerding, Dirk

    1994-01-01

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

  13. Reference percentiles for FEV1 and BMI in European children and adults with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Boëlle Pierre-Yves

    2012-09-01

    Full Text Available Abstract Background The clinical course of Cystic Fibrosis (CF is usually measured using the percent predicted FEV1 and BMI Z-score referenced against a healthy population, since achieving normality is the ultimate goal of CF care. Referencing against age and sex matched CF peers may provide valuable information for patients and for comparison between CF centers or populations. Here, we used a large database of European CF patients to compute CF specific reference equations for FEV1 and BMI, derived CF-specific percentile charts and compared these European data to their nearest international equivalents. Methods 34859 FEV1 and 40947 BMI observations were used to compute European CF specific percentiles. Quantile regression was applied to raw measurements as a function of sex, age and height. Results were compared with the North American equivalent for FEV1 and with the WHO 2007 normative values for BMI. Results FEV1 and BMI percentiles illustrated the large variability between CF patients receiving the best current care. The European CF specific percentiles for FEV1 were significantly different from those in the USA from an earlier era, with higher lung function in Europe. The CF specific percentiles for BMI declined relative to the WHO standard in older children. Lung function and BMI were similar in the two largest contributing European Countries (France and Germany. Conclusion The CF specific percentile approach applied to FEV1 and BMI allows referencing patients with respect to their peers. These data allow peer to peer and population comparisons in CF patients.

  14. Outcome in cystic fibrosis liver disease.

    LENUS (Irish Health Repository)

    Rowland, Marion

    2011-01-01

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

  15. Self-management education for cystic fibrosis.

    LENUS (Irish Health Repository)

    Savage, Eileen

    2011-01-01

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

  16. HOME CARE IN CYSTIC-FIBROSIS PATIENTS

    NARCIS (Netherlands)

    VANAALDEREN, WMC; MANNES, GPM; BOSMA, ES; ROORDA, RJ; HEYMANS, HSA

    1995-01-01

    Intravenous antibiotics and enteral tube feeding at home for the treatment of pulmonary exacerbations and underweight condition in cystic fibrosis (CF) patients have become tools that are used in many cystic fibrosis centres, The experience with home care programmes from different countries is quite

  17. European Cystic Fibrosis Society Standards of Care

    DEFF Research Database (Denmark)

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

    2014-01-01

    Since the earliest days of cystic fibrosis (CF) treatment, patient data have been recorded and reviewed in order to identify the factors that lead to more favourable outcomes. Large data repositories, such as the US Cystic Fibrosis Registry, which was established in the 1960s, enabled successful...

  18. Endocrine Disorders in Cystic Fibrosis.

    Science.gov (United States)

    Blackman, Scott M; Tangpricha, Vin

    2016-08-01

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

  19. Cystic Fibrosis: Brazilian ENT Experience

    Directory of Open Access Journals (Sweden)

    Tania Sih

    2012-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  2. Interspecific small molecule interactions between clinical isolates of Pseudomonas aeruginosa and Staphylococcus aureus from adult cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Alexandre Fugère

    Full Text Available Pseudomonas aeruginosa and Staphylococcus aureus are the most prevalent pathogens in airway infections of cystic fibrosis (CF patients. We studied how these pathogens coexist and interact with each other. Clinical isolates of both species were retrieved from adult CF patients. Culture supernatants from 63 P. aeruginosa isolates triggered a wide range of biofilm-stimulatory activities when added to the culture of a control S. aureus strain. The extent of biofilm formation by S. aureus was positively correlated to the levels of the 2-alkyl-4-(1H-quinolones (AQs Pseudomonas Quinolone Signal (PQS and 2-heptyl-4-hydroxy quinoline N-oxide (HQNO produced by the P. aeruginosa isolates. Supernatants from P. aeruginosa isogenic mutants deficient in PQS and HQNO production stimulated significantly less biofilm formation by S. aureus than that seen with the parental strain PA14. When studying co-isolated pairs of P. aeruginosa and S. aureus retrieved from patients showing both pathogens, P. aeruginosa supernatants stimulated less biofilm production by the S. aureus counterparts compared to that observed using the control S. aureus strain. Accordingly, some P. aeruginosa isolates produced low levels of exoproducts and also some of the clinical S. aureus isolates were not stimulated by their co-isolates or by PA14 despite adequate production of HQNO. This suggests that colonization of the CF lungs promotes some type of strain selection, or that co-existence requires specific adaptations by either or both pathogens. Results provide insights on bacterial interactions in CF.

  3. Dietary intake and nutritional status of micronutrients in adults with cystic fibrosis in relation to current recommendations.

    Science.gov (United States)

    Li, Li; Somerset, Shawn

    2016-08-01

    An increased prevalence of cystic fibrosis (CF) related complications such as impaired bone health and diabetes has accompanied increased survival of patients with CF. This review was conducted to determine the extent to which adults with CF are meeting current nutrition recommendations for micronutrients in association with CF-related complications management. Although dietary intake and nutritional status in CF has improved significantly in recent decades, micronutrient status seems to have diverged. While vitamin A and E intakes appear adequate, frequent vitamin D and K deficiency/insufficiency and compromised bone health in CF, occurs despite supplementation. Although deficiency of water-soluble vitamins and minerals is uncommon, ongoing surveillance will enhance overall health outcomes, particularly in cases of CF-related liver disease and deteriorated lung function and bone health. Salt and fluid status in CF may also need attention due to diminished thirst sensation and voluntary rehydration. Further investigation in micronutrient status optimisation in CF will inform the development of more effective and targeted nutrition therapies to enable integration of more refined recommendations for micronutrient intakes in CF based on individual needs and disease progression.

  4. Development, validation, and implementation of a questionnaire assessing disease knowledge and understanding in adult cystic fibrosis patients.

    LENUS (Irish Health Repository)

    Siklosi, Karen R

    2012-02-01

    BACKGROUND: The number of adults living with cystic fibrosis (CF) is increasing, necessitating an assessment of knowledge in this growing population. METHODS: A questionnaire assessing CF knowledge was completed by 100 CF patients (median age: 26.0 years, range 17-49 years; median FEV: 57.0% predicted, range 20-127% predicted). Level of knowledge was correlated with clinical and sociodemographic characteristics. RESULTS: Questionnaire validation showed acceptable internal consistency (alpha=0.75) and test-retest reliability (0.94). Patients had fair overall understanding of CF (mean=72.4%, SD=13.1), with greater knowledge of lung and gastrointestinal topics (mean=81.6%, SD=11.6) than reproduction and genetics topics (mean=57.9%, SD=24.1). Females and those with post-secondary education scored significantly higher (p<0.05). CONCLUSIONS: This study validated a questionnaire that can be utilized to assess CF knowledge. Although CF patients understand most aspects of their disease, knowledge deficits are common - particularly regarding genetics and reproduction - and should be considered when developing CF education programs.

  5. Ability of device to collect bacteria from cough aerosols generated by adults with cystic fibrosis [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    David N. Ku

    2016-08-01

    Full Text Available Background: Identifying lung pathogens and acute spikes in lung counts remain a challenge in the treatment of patients with cystic fibrosis (CF. Bacteria from the deep lung may be sampled from aerosols produced during coughing. Methods: A new device was used to collect and measure bacteria levels from cough aerosols of patients with CF. Sputum and oral specimens were also collected and measured for comparison. Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus mitis were detected in specimens using Real-Time Polymerase Chain Reaction (RT-PCR molecular assays. Results: Twenty adult patients with CF and 10 healthy controls participated. CF related bacteria (CFRB were detected in 13/20 (65% cough specimens versus 15/15 (100% sputum specimens. Commensal S. mitis was present in 0/17 (0%, p=0.0002 cough specimens and 13/14 (93% sputum samples. In normal controls, no bacteria were collected in cough specimens but 4/10 (40% oral specimens were positive for CFRB. Conclusions: Non-invasive cough aerosol collection may detect lower respiratory pathogens in CF patients, with similar specificity and sensitivity to rates detected by BAL, without contamination by oral CFRB or commensal bacteria.

  6. Symposium 6: Young people, artificial nutrition and transitional care. The nutritional challenges of the young adult with cystic fibrosis: transition.

    LENUS (Irish Health Repository)

    Morton, Alison M

    2012-02-01

    Cystic fibrosis (CF) is a complex multisystem disorder affecting mainly the gastrointestinal tract and respiratory system. Intestinal malabsorption occurs in approximately 90% of patients. In the past, malnutrition was an inevitable consequence of disease progression, leading to poor growth, impaired respiratory muscle function, decreased exercise tolerance and immunological impairment. A positive association between body weight and height and survival has been widely reported. The energy requirements of patients with CF vary widely and generally increase with age and disease severity. For many young adults requirements will be 120-150% of the age-related estimated average requirement. To meet these energy needs patients are encouraged to eat a high-fat high-energy diet with appropriate pancreatic enzyme supplements. Many patients are unable to achieve an adequate intake as a result of a variety of factors including chronic poor appetite, infection-related anorexia, gastro-oesophageal reflux and abdominal pain. Oral energy supplements and enteral tube feeding are widely used. Nutritional support has been shown to improve nutritional status and stabilise or slow the rate of decline in lung function. With such emphasis on nutritional intake and nutritional status throughout life, poor adherence to therapies and issues relating to body image are emerging. The median survival of patients with CF is increasing. CF is now considered a life-limiting disease of adulthood rather than a terminal childhood illness. With increased longevity new challenges are emerging that include the transition of young adults with CF to adult services, CF-related diabetes, disordered eating, osteoporosis, liver disease and transplantation.

  7. Cystic fibrosis-related diabetes

    DEFF Research Database (Denmark)

    Andersen, Henrik U; Lanng, Susanne; Pressler, Tania

    2006-01-01

    of diabetic retinopathy was found in patients with insulin-treated CF-related diabetes, stressing the need for a regular screening program as in type 1 diabetes. Severely impaired kidney function was common in lung transplant patients, probably secondary to cyclosporine treatment.......OBJECTIVE: Cystic fibrosis (CF)-related diabetes has been regarded as a mild form of diabetes with a low risk of severe diabetes complications. The prevalence of CF-related diabetes increases with age, resulting in a 50% prevalence of diabetes at age 30 years. We sought to investigate whether...... microvascular complications in CF-related diabetes appear with a relevant frequency. RESEARCH DESIGN AND METHODS: Thirty-eight patients aged 30 (range 18-55) years with CF-related diabetes for 20 (0-31) years were screened for diabetes complications. Because of chronic pulmonary infections, the majority...

  8. miR-17 overexpression in cystic fibrosis airway epithelial cells decreases interleukin-8 production.

    Science.gov (United States)

    Oglesby, Irene K; Vencken, Sebastian F; Agrawal, Raman; Gaughan, Kevin; Molloy, Kevin; Higgins, Gerard; McNally, Paul; McElvaney, Noel G; Mall, Marcus A; Greene, Catherine M

    2015-11-01

    Interleukin (IL)-8 levels are higher than normal in cystic fibrosis (CF) airways, causing neutrophil infiltration and non-resolving inflammation. Overexpression of microRNAs that target IL-8 expression in airway epithelial cells may represent a therapeutic strategy for cystic fibrosis. IL-8 protein and mRNA were measured in cystic fibrosis and non-cystic fibrosis bronchoalveolar lavage fluid and bronchial brushings (n=20 per group). miRNAs decreased in the cystic fibrosis lung and predicted to target IL-8 mRNA were quantified in βENaC-transgenic, cystic fibrosis transmembrane conductance regulator (Cftr)-/- and wild-type mice, primary cystic fibrosis and non-cystic fibrosis bronchial epithelial cells and a range of cystic fibrosis versus non-cystic fibrosis airway epithelial cell lines or cells stimulated with lipopolysaccharide, Pseudomonas-conditioned medium or cystic fibrosis bronchoalveolar lavage fluid. The effect of miRNA overexpression on IL-8 protein production was measured. miR-17 regulates IL-8 and its expression was decreased in adult cystic fibrosis bronchial brushings, βENaC-transgenic mice and bronchial epithelial cells chronically stimulated with Pseudomonas-conditioned medium. Overexpression of miR-17 inhibited basal and agonist-induced IL-8 protein production in F508del-CFTR homozygous CFTE29o(-) tracheal, CFBE41o(-) and/or IB3 bronchial epithelial cells. These results implicate defective CFTR, inflammation, neutrophilia and mucus overproduction in regulation of miR-17. Modulating miR-17 expression in cystic fibrosis bronchial epithelial cells may be a novel anti-inflammatory strategy for cystic fibrosis and other chronic inflammatory airway diseases.

  9. Gastrointestinal manifestations in cystic fibrosis.

    Science.gov (United States)

    Eggermont, E

    1996-08-01

    CFTR, or cystic fibrosis transmembrane conductance regulator, the gene product that is defective in cystic fibrosis, is present in the apical membrane of the epithelial cells from the stomach to the colon. In the foregut, the clinical manifestations are not directly related to the primary defect of the CFTR chloride channel. The most troublesome complaints and symptoms originate from the oesophagus as peptic oesophagitis or oesophageal varices. In the small intestinal wall, the clinical expression of CF depends largely on the decreased secretion of fluid and chloride ions, the increased permeability of the paracellular space between adjacent enterocytes and the sticky mucous cover over the enterocytes. As a rule, the brush border enzyme activities are normal and there is some enhanced active transport as shown for glucose and alanine. The results of continuous enteral feeding of CF patients clearly show that the small intestinal mucosa, in the daily situation, is not functioning at maximal capacity. Although CFTR expression in the colon is lower, the large intestine may be the site of several serious complications such as rectal prolapse, meconium ileus equivalent, intussusception, volvulus and silent appendicitis. In recent years colonic strictures, after the use of high-dose pancreatic enzymes, are being increasingly reported; the condition has recently been called CF fibrosing colonopathy. The CF gastrointestinal content itself differs mainly from the normal condition by the lower acidity in the foregut and the accretion of mucins and proteins, eventually resulting in intestinal obstruction, in the ileum and colon. Better understanding of the CF gastrointestinal phenotype may contribute to improvement of the overall wellbeing of these patients.

  10. Long-term impact of liver transplantation on respiratory function and nutritional status in children and adults with cystic fibrosis.

    Science.gov (United States)

    Dowman, J K; Watson, D; Loganathan, S; Gunson, B K; Hodson, J; Mirza, D F; Clarke, J; Lloyd, C; Honeybourne, D; Whitehouse, J L; Nash, E F; Kelly, D; van Mourik, I; Newsome, P N

    2012-04-01

    Early liver transplant (LT) has been advocated for patients with cystic fibrosis liver disease (CFLD) and evidence of deterioration in nutritional state and respiratory function to prevent further decline. However, the impact of single LT on long-term respiratory function and nutritional status has not been adequately addressed. We performed a retrospective analysis of the outcomes of 40 (21 adult/19 pediatric) patients with CFLD transplanted between 1987 and 2009 with median follow-up of 47.8 months (range 4-180). One and five-year actuarial survival rates were 85%/64% for adult and 90%/85% for pediatric LT cohorts, respectively. Lung function remained stable until 4 years (FEV(1) % predicted; pretransplant 48.4% vs. 45.9%, 4 years posttransplant) but declined by 5 years (42.4%). Up to 4 years posttransplant mean annual decline in FEV(1) % was lower (0.74%; p = 0.04) compared with the predicted 3% annual decline in CF patients with comorbidity including diabetes. Number of courses of intravenous antibiotics was reduced following LT, from 3.9/year pretransplant to 1.1/year, 5 years posttransplant. Body mass index was preserved posttransplant; 18.0 kg/m(2) (range 15-24.3) pretransplant versus 19.6 kg/m(2) (range 16.4-22.7) 5 years posttransplant. In conclusion, LT is an effective treatment for selected patients with cirrhosis due to CFLD, stabilizing aspects of long-term lung function and preserving nutritional status.

  11. 'A bed in the middle of nowhere': parents' meanings of place of death for adults with cystic fibrosis.

    Science.gov (United States)

    Lowton, Karen

    2009-10-01

    As populations age and chronic conditions become more prevalent, an individual's ability to choose the location of their end-of-life care and death is increasingly considered important in the provision of good healthcare, with home implied as the 'best' place of death through UK government policy and specialist and voluntary palliative care services. However, considering meanings of place of end-of-life care and death is complex for young adults with life-limiting conditions where the disease course is variable and uncertain, and aggressive and palliative treatments are administered both at home and in hospital often until death. Although 'place' is a pivotal element in healthcare practice, research and policy, there has been little attempt to understand the meaning and importance of place in understanding experiences of care at end of life. Through analysis of in-depth interviews and letters received from parents of 27 young adults in England, Scotland and Wales who died from cystic fibrosis from 1999 to 2002 aged 17-36 years, key factors that influence families' meanings of place at end of life are presented. Both home and hospital deaths are reported, with no deaths in hospices. Preferences for possible locations of death are generally limited early in the disease course by choice of aggressive treatment, particularly lung transplantation. Rate of health decline, organisation and delivery of services, and relationships with specialist and general healthcare staff strongly influence parents' experience of death at home or in hospital, although no physical location was regarded a 'better' place of death. Meanings of, and attachment to place are mediated for families through these factors, questioning the appropriateness of a 'home is best' policy for those dying from life-limiting conditions.

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

    Science.gov (United States)

    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…

  13. Pathohistological changes in fetuses with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Đolai Matilda

    2012-01-01

    Full Text Available Introduction. Cystic fibrosis or mucoviscidosis is a genetically caused disease. The intensity of disease and histopathological changes grow throughout the life. According to the literature, pathological changes characteristic of cystic fibrosis become noticeable around the sixth month of life. Case Report. After amniocentesis of a 5-lunar month-old fetus had been done, which confirmed cystic fibrosis, the Ethics Commission approved the preterm labor. The autopsy and histopathological analysis demonstrated the existence of typical histopathological changes in the pancreas and intestines. Discussion. In the late fetal period or during the period around the delivery, cystic fibrosis is usually manifested as meconial cap with or without obstruction of the intestinal lumen. Morphological changes in the exocrine glands usually develop only after birth. In this case, the existence of meconial obstruction, as well as the typical acidofil content in the secretory ducts and acini of the pancreas was confirmed, which is unusual for the fetal age of five months.

  14. Nutrition in Cystic Fibrosis: Macro- and Micronutrients

    NARCIS (Netherlands)

    Oudshoorn, Johanna Hermiena

    2006-01-01

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

  15. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)

    OpenAIRE

    Rosenberg, Mark F.; O'Ryan, Liam P.; Hughes, Guy; Zhao, Zhefeng; Aleksandrov, Luba A.; Riordan, John R.; Ford, Robert C.

    2011-01-01

    Cystic fibrosis affects about 1 in 2500 live births and involves loss of transmembrane chloride flux due to a lack of a membrane protein channel termed the cystic fibrosis transmembrane conductance regulator (CFTR). We have studied CFTR structure by electron crystallography. The data were compared with existing structures of other ATP-binding cassette transporters. The protein was crystallized in the outward facing state and resembled the well characterized Sav1866 transporter. We identified ...

  16. [Nutrition, cystic fibrosis and the digestive tract].

    Science.gov (United States)

    Olveira, Gabriel; Olveira, Casilda

    2008-05-01

    The prevalence of hyponutrition in cystic fibrosis is high although it may vary according to the different studies. Detection of hyponutrition should be done by combining different methods, depending on their availability. However, the simplest and most validated criterion is to measure at each visit the weight (and height in children) in order to calculate the body mass index and categorizing hyponutrition according to absolute criteria: in adults colon disease may also condition malnourishment. In patients with cystic fibrosis, a usual high-fat diet providing 120%-150% of the recommended calories is advised. If the nutritional goals are not achieved or maintained with diet modifications, artificial supplements may be added, although the recommendation for their use has not been endorsed by solid scientific evidences. The most frequently used preparations usually are polymeric or hypercaloric. The indications for enteral (through a tube, especially gastrostomy) or parenteral nutritional support are similar to those used in other pathologies. Dietary and nutritional control should be included in a multidisciplinary program allowing the improvement of the functional capacity and the quality of life and reducing, at least from a theoretical viewpoint, the morbimortality associated to malnourishment in these patients.

  17. Global impact of bronchiectasis and cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Margarida Redondo

    2016-09-01

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

  18. CFTR protein repair therapy in cystic fibrosis.

    Science.gov (United States)

    Quintana-Gallego, Esther; Delgado-Pecellín, Isabel; Calero Acuña, Carmen

    2014-04-01

    Cystic fibrosis is a single gene, autosomal recessive disorder, in which more than 1,900 mutations grouped into 6 classes have been described. It is an example a disease that could be well placed to benefit from personalised medicine. There are currently 2 very different approaches that aim to correct the basic defect: gene therapy, aimed at correcting the genetic alteration, and therapy aimed at correcting the defect in the CFTR protein. The latter is beginning to show promising results, with several molecules under development. Ataluren (PTC124) is a molecule designed to make the ribosomes become less sensitive to the premature stop codons responsible for class i mutations. Lumacaftor (VX-809) is a CFTR corrector directed at class ii mutations, among which Phe508del is the most frequent, with encouraging results. Ivacaftor (VX-770) is a potentiator, the only one marketed to date, which has shown good efficacy for the class iii mutation Gly551Asp in children over the age of 6 and adults. These drugs, or a combination of them, are currently undergoing various clinical trials for other less common genetic mutations. In the last 5 years, CFTR has been designated as a therapeutic target. Ivacaftor is the first drug to treat the basic defect in cystic fibrosis, but only provides a response in a small number of patients. New drugs capable of restoring the CFTR protein damaged by the most common mutations are required.

  19. Impact of osteopathic treatment on pain in adult patients with cystic fibrosis--a pilot randomized controlled study.

    Directory of Open Access Journals (Sweden)

    Dominique Hubert

    Full Text Available Pain is a common complication in patients with cystic fibrosis (CF and is associated with shorter survival. We evaluated the impact of osteopathic manipulative treatment (OMT on pain in adults with CF.A pilot multicenter randomized controlled trial was conducted with three parallel arms: OMT (group A, 16 patients, sham OMT (sham treatment, group B, 8 patients and no treatment (group C, 8 patients. Medical investigators and patients were double-blind to treatment for groups A and B, who received OMT or sham OMT monthly for 6 months. Pain was rated as a composite of its intensity and duration over the previous month. The evolution of chest/back pain after 6 months was compared between group A and groups B+C combined (control group. The evolution of cervical pain, headache and quality of life (QOL were similarly evaluated.There was no statistically significant difference between the treatment and control groups in the decrease of chest/back pain (difference = -2.20 IC95% [-4.81; 0.42], p = 0.098; also, group A did not differ from group B. However, chest/back pain decreased more in groups A (p = 0.002 and B (p = 0.006 than in group C. Cervical pain, headache and QOL scores did not differ between the treatment and control groups.This pilot study demonstrated the feasibility of evaluating the efficacy of OMT to treat the pain of patients with CF. The lack of difference between the group treated with OMT and the control group may be due to the small number of patients included in this trial, which also precludes any definitive conclusion about the greater decrease of pain in patients receiving OMT or sham OMT than in those with no intervention.ClinicalTrials.gov NCT01293019.

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

    NARCIS (Netherlands)

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

    2000-01-01

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

  1. [VITAMIN D AND CHRONIC LUNG COLONIZATION IN PEDIATRIC AND YOUNG ADULTS CYSTIC FIBROSIS PATIENTS].

    Science.gov (United States)

    González Jiménez, David; Muñoz Codoceo, Rosana; Garriga García, María; Molina Arias, Manuel; Alvarez Beltran, Marina; García Romero, Ruth; Martínez Costa, Cecilia; Meavilla Olivas, Silvia María; Peña Quintana, Luis; Gallego Gutierrez, Silvia; Marugan de Miguelsanz, Jose Manuel; Suarez Cortina, Lucrecia; Castejón Ponce, Esperanza Natividad; Leis Trabazo, Rosaura; Martín Cruz, Fayna; Díaz Martín, Juan Jose; Bousoño García, Carlos

    2015-10-01

    Introducción y objetivos: conocer la situación en la que se encuentran los pacientes con fibrosis quística en relación con sus niveles de vitamina D y su asociación con las colonizaciones pulmonares crónicas. Material y métodos: estudio multicéntrico transversal. Participaron 12 hospitales nacionales. De noviembre a abril del 2012 al 2014 se incluyeron 377 pacientes con fibrosis quística. Se consideraron insuficientes niveles de vitamina D vitamina D. Se observó una correlación inversa entre edad y niveles de vitamina D (r = -0,20 p vitamina D más altos. Los niveles de vitamina D presentaron una correlación inversa con el número de colonizaciones pulmonares (r = -0,16 p = 0,0015). Ajustando por edad, función pancreática y diagnóstico mediante cribado, la colonización por S. Aureus en menores de seis años y por Pseudomonas sp. en los mayores de esa edad, incrementaban el riesgo de presentar niveles insuficientes de vitamina D: OR 3,17 (IC95% 1,32-7,61) (p=0,010) y OR 3,77 (IC95% 1,37- 10,37)(p = 0,010), respectivamente. Conclusiones: a pesar de una suplementación adecuada, más de la mitad de nuestros pacientes no alcanzan niveles óptimos de vitamina D. La colonización crónica por Pseudomonas sp. en escolares y adolescentes y por S. Aureus en lactantes y preescolares se asocia de forma independiente con la deficiencia de vitamina D.

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

    Directory of Open Access Journals (Sweden)

    Joshi Deepak

    2008-06-01

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

  3. Parenting adolescents with cystic fibrosis: the adolescents' and young adults' perspectives

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke; Schiøtz, Peter Oluf; Lomborg, Kirsten

    2011-01-01

    and the influence of different parenting styles on the adolescents’ adherence to treatment is still limited. Aim: The aim of this study was to identify the types of parental support that adolescents and young adults with CF want and find helpful in terms of preparing them for adult life. Methods: Sixteen Danish...... was conducted. Results: The adolescents and young adults wanted their parents educated about the adolescent experience. They wanted their parents to learn a pedagogical parenting style, to learn to trust them, and to learn to gradually transfer responsibility for their medical treatment. Additionally......: chronic illness, parenting style, qualitative research, patient preferences, interpretive description...

  4. Factors related to changes in the quality of life among Polish adolescents and adults with cystic fibrosis over a 1-year period

    Directory of Open Access Journals (Sweden)

    Dębska G

    2015-12-01

    Full Text Available Grażyna Dębska,1 Henryk Mazurek2 1Faculty of Health and Medical Studies, Andrzej Frycz Modrzewski Krakow University, Krakow, 2Department of Pneumonology and Cystic Fibrosis, National Tuberculosis and Lung Diseases Research Institute, Rabka, Poland Background: The aim of this study was to determine the effects of clinical factors, physical activity, and sociodemographic variables on 1-year changes in health-related quality of life (HRQoL in Polish adolescents and adults with cystic fibrosis (CF.Method: The study included 67 subjects with CF (mean age 21.1±5.1 years; range 14–37 years; 34 males and 33 females. The Cystic Fibrosis Quality of Life Questionnaire was used at baseline and after 1 year. Lung function data, body weight, and body height were extracted from medical records. Clinical assessment was performed with the Shwachman–Kulczycki scale.Results: The highest scores in both HRQoL examinations came from the domains of physical and social functioning, and the lowest from future concerns, body image, and career concerns. No significant changes of Cystic Fibrosis Quality of Life Questionnaire scores were documented over a period of 1 year. Patients with better baseline spirometry results more frequently reported an improvement in the treatment issues (subjects with FEV1 >50% of predicted, P=0.020 and in the career concerns (patients with FVC >50% of predicted, P=0.039. The improvement in the career concerns also depended upon daily physical activity (P=0.024, which was shown to modulate future concerns (P=0.032, along with place of residence and living conditions (P=0.003. Moreover, the time elapsed from the last pulmonary exacerbation was related to the change in social functioning (P=0.026.Conclusion: When planning treatment, attention should be paid to interventions which may improve HRQoL. Systematic chronic therapy improves lung function, related to treatment issues and career concerns. Maintaining good physical condition and

  5. Male fertility in cystic fibrosis.

    LENUS (Irish Health Repository)

    Chotirmall, S H

    2011-04-05

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

  6. Population structure and characterization of viridans group streptococci (VGS) including Streptococcus pneumoniae isolated from adult patients with cystic fibrosis (CF).

    Science.gov (United States)

    Maeda, Yasunori; Elborn, J Stuart; Parkins, Michael D; Reihill, James; Goldsmith, Colin E; Coulter, Wilson A; Mason, Charlene; Millar, B Cherie; Dooley, James S G; Lowery, Colm J; Ennis, Madeleine; Rendall, Jacqueline C; Moore, John E

    2011-03-01

    A study was undertaken to examine the population structure of viridans group streptococci (VGS) in the sputum of adult patients with cystic fibrosis (CF). Freshly expectorated sputa (n=58) from 45 adult CF patients were examined by selective conventional culture on Mitis-Salivarius agar and yielded 190 isolates of VGS. Sequence analyses of the rpnB and 16-23S rRNA ITS genes identified these isolates to belong to 12 species of VGS and included S. anginosus, S. australis, S. cristatus, S. gordonii, S. infantis, S. mitis, S. mutans, S. oralis, S. parasanguinis, S. pneumoniae, S. salivarius and S. sanguinis. The most frequently VGS organism isolated was S. salivarius (47/190; 24.7%), followed by S. mitis (36/190; 19%), S. sanguinis (25/190; 13.2%), S. oralis (20/190; 11.0%), S. pneumoniae (19/190; 10.0%), S. parasanguinis (16/190; 8.4%), S. infantis (11/190; 5.8%), S. gordonii (7/190; 3.7%), S. anginosus (4/190; 2.1%), S. cristatus (2/190; 1.1%), S. australis (1/190; 0.5%), S. mutans (1/190; 0.5%) and S. agalactiae (1/190; 0.5%). All, but four, patients harboured at least one VGS species, which ranged from one to five streptococcal species, with a mean of 2.85 species per patient. There was no clonality at the subspecies level employing ERIC RAPD PCR. Antibiotic susceptibility was determined by Minimum Inhibitory Concentration (MIC) testing against penicillin, erythromycin and ciprofloxacin. Overall, resistance to penicillin with all VGS was 73/190 (38.4%) and 167/190 (87.9%) for erythromycin. With regard to ciprofloxacin, 27/190 (14.2%) were fully resistant, whilst a further 21/190 (11.1%) showed intermediate resistance, which equated to approximately three quarters (74.7%) of isolates being fully sensitive to this agent. In addition, as a comparator control population, we examined antibiotic susceptibility, as above, in a non-CF population comprising 12 individuals (50 VGS isolates), who were not receiving chronic antibiotics. In comparison, 8% and 38% of VGS

  7. Fibrose cística no adulto: aspectos diagnósticos e terapêuticos Cystic fibrosis in adults: diagnostic and therapeutic aspects

    Directory of Open Access Journals (Sweden)

    Paulo de Tarso Roth Dalcin

    2008-02-01

    Full Text Available A fibrose cística, que já foi considerada uma doença da infância, é agora também uma doença do adulto. O aumento da longevidade resultou em mais problemas médicos relacionados com a idade e com a própria doença. O crescente número de adultos com fibrose cística resultou em aumento da necessidade de cuidados médicos. Essa necessidade tem sido suprida por um crescente número de pneumologistas de adultos e outros especialistas. O objetivo dessa revisão é sumarizar o conhecimento corrente sobre o diagnóstico e tratamento no adulto com fibrose cística. Na maioria dos casos, o diagnóstico é sugerido por manifestações de doença sinopulmonar crônica e insuficiência pancreática exócrina, e, então, confirmado por um teste do suor positivo. Pacientes adultos podem, entretanto, apresentar suficiência pancreática e características clínicas atípicas, às vezes, associadas com teste do suor normal ou limítrofe. Em tais casos, a possibilidade de realizar pesquisa de mutações para fibrose cística e de medir a diferença de potencial nasal pode ser de utilidade diagnóstica. A abordagem terapêutica padrão para a doença pulmonar inclui: antibióticos, higiene das vias aéreas, exercício, mucolíticos, broncodilatadores, oxigênio, agentes anti-inflamatórios e suporte nutricional. A utilização adequada dessas terapias resulta em mais pacientes com fibrose cística sobrevivendo na vida adulta com uma aceitável qualidade de vida.Once considered a childhood disease, cystic fibrosis is now also a disease of adults. Increased longevity has resulted in the aging of the cystic fibrosis population. The consequent age-related medical problems among adults with cystic fibrosis have increased medical care needs. These needs are being met by a growing number of non-pediatric pulmonologists and other non-pediatric specialists. The objective of this review was to summarize the current knowledge about diagnosis and treatment in adult

  8. Cystic fibrosis transmembrane conductance regulator protein expression in the male excretory duct system during development.

    Science.gov (United States)

    Marcorelles, Pascale; Gillet, Danièle; Friocourt, Gaëlle; Ledé, Françoise; Samaison, Laura; Huguen, Geneviève; Ferec, Claude

    2012-03-01

    Sterility due to bilateral destruction in utero or in early infancy resulting in congenital absence of the vas deferens is the rule in male patients with cystic fibrosis. To understand the developmental pattern of this anomaly, the microscopic morphology of the male excretory system was analyzed during development and the expression of the cystic fibrosis transmembrane conductance regulator protein was explored by immunohistochemistry. We observed that cystic fibrosis fetuses had no excretory ducts agenesis or obstruction until 22 weeks of gestation. However, a focal inflammatory pattern and mucinous plugs in the oldest cystic fibrosis case suggested a disruptive mechanism. Immunolabeling of cytoplasmic epithelial cystic fibrosis transmembrane conductance regulator protein was demonstrated in all cystic fibrosis and control cases with a similar pattern of expression of the protein between age-matched controls and cystic fibrosis cases. At midgestation, an apical intensification appeared in both cystic fibrosis and control cases and was stable during the remainder of fetal life. No gradient of intensity could be detected between the different segments of the excretory tract. These findings are different from those reported in adults. The absence of any morphologic anomaly until 22 weeks of gestation, the focal destruction of the epithelial structures during the second trimester, and the chronological pattern of expression of cystic fibrosis transmembrane conductance regulator are of interest for a better understanding of the pathophysiology of this disease.

  9. Genetics of Cystic Fibrosis: Clinical Implications.

    Science.gov (United States)

    Egan, Marie E

    2016-03-01

    Cystic fibrosis (CF) is a common life-shortening autosomal recessive genetic disorder caused by mutations in the gene that encodes for the cystic fibrosis transmembrane conductance regulator protein (CFTR). Almost 2000 variants in the CFTR gene have been identified. The mutational classes are based on the functional consequences on CFTR. New therapies are being developed to target mutant CFTR and restore CFTR function. Understanding specific CF genotypes is essential for providing state-of-the art care to patients. In addition to the variation in CFTR genotype, there are several modifier genes that contribute to the respiratory phenotype.

  10. The cystic fibrosis of exocrine pancreas

    DEFF Research Database (Denmark)

    Wilschanski, Michael; Novak, Ivana

    2013-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) protein is highly expressed in the pancreatic duct epithelia and permits anions and water to enter the ductal lumen. This results in an increased volume of alkaline fluid allowing the highly concentrated proteins secreted by the acinar...... cells to remain in a soluble state. This work will expound on the pathophysiology and pathology caused by the malfunctioning CFTR protein with special reference to ion transport and acid-base abnormalities both in humans and animal models. We will also discuss the relationship between cystic fibrosis...

  11. Pseudomonas infection and mucociliary and absorptive clearance in the cystic fibrosis lung.

    Science.gov (United States)

    Locke, Landon W; Myerburg, Michael M; Weiner, Daniel J; Markovetz, Matthew R; Parker, Robert S; Muthukrishnan, Ashok; Weber, Lawrence; Czachowski, Michael R; Lacy, Ryan T; Pilewski, Joseph M; Corcoran, Timothy E

    2016-05-01

    Airway surface liquid hyperabsorption and mucus accumulation are key elements of cystic fibrosis lung disease that can be assessed in vivo using functional imaging methods. In this study we evaluated experimental factors affecting measurements of mucociliary clearance (MCC) and small-molecule absorption (ABS) and patient factors associated with abnormal absorption and mucus clearance.Our imaging technique utilises two radiopharmaceutical probes delivered by inhalation. Measurement repeatability was assessed in 10 adult cystic fibrosis subjects. Experimental factors were assessed in 29 adult and paediatric cystic fibrosis subjects (51 scans). Patient factors were assessed in a subgroup with optimal aerosol deposition (37 scans; 24 subjects). Paediatric subjects (n=9) underwent initial and 2-year follow-up scans. Control subjects from a previously reported study are included for comparison.High rates of central aerosol deposition influenced measurements of ABS and, to a lesser extent, MCC. Depressed MCC in cystic fibrosis was only detectable in subjects with previous Pseudomonas aeruginosa infection. Cystic fibrosis subjects without P. aeruginosa had similar MCC to control subjects. Cystic fibrosis subjects had consistently higher ABS rates.We conclude that the primary experimental factor affecting MCC/ABS measurements is central deposition percentage. Depressed MCC in cystic fibrosis is associated with P. aeruginosa infection. ABS is consistently increased in cystic fibrosis.

  12. Craniofacial morphology in children with cystic fibrosis.

    Science.gov (United States)

    Hellsing, E; Brattström, V; Strandvik, B

    1992-04-01

    Cystic fibrosis (CF) is a hereditary metabolic disorder with clinical symptoms of abnormal mucus production. This blocks the airways, gives pancreatic insufficiency, and increases sweat electrolytes. The progressive respiratory disease often leads to respiratory insufficiency and cor pulmonale. The aim of the present investigation was to examine the facial morphology in children with cystic fibrosis. The sample comprised 11 children with cystic fibrosis, who were divided in two groups, one with gastrointestinal disorders and the other with predominantly respiratory insufficiency. Eleven healthy children with normal occlusions were selected as controls. Lateral skull radiographs obtained in natural head posture were digitized, and linear and angular variables for the different groups calculated and compared statistically. The cystic fibrosis group showed open bite, decreased posterior facial height, increased mandibular and craniocervical inclination. Additionally, within the CF-group, the children with respiratory insufficiency differed more from the controls than the children with gastrointestinal disorders. Despite the small number of subjects, the facial morphology of the CF children showed a similar pattern to that of children with nasal respiratory obstruction due to enlarged adenoids or tonsils.

  13. Cystic fibrosis : terminology and diagnostic algorithms

    NARCIS (Netherlands)

    De Boeck, K; Wilschanski, M; Castellani, C; Taylor, C; Cuppens, H; Dodge, J; Sinaasappel, M

    2006-01-01

    There is great heterogeneity in the clinical manifestations of cystic fibrosis (CF). Some patients may have all the classical manifestations of CF from infancy and have a relatively poor prognosis, while others have much milder or even atypical disease manifestations and still carry mutations on eac

  14. Inhalation of antibiotics in cystic fibrosis

    NARCIS (Netherlands)

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

    1995-01-01

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

  15. Barriers to adherence in cystic fibrosis

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke; Schiøtz, Peter Oluf

    2012-01-01

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

  16. Nutritional assessment in children with cystic fibrosis

    Science.gov (United States)

    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...

  17. Zinc supplementation in children with cystic fibrosis

    Science.gov (United States)

    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...

  18. Emergence of respiratory Streptococcus agalactiae isolates in cystic fibrosis patients

    OpenAIRE

    Vera Eickel; Barbara Kahl; Beatrice Reinisch; Angelika Dübbers; Peter Küster; Claudia Brandt; Barbara Spellerberg

    2009-01-01

    Streptococcus agalactiae is a well-known pathogen for neonates and immunocompromized adults. Beyond the neonatal period, S. agalactiae is rarely found in the respiratory tract. During 2002-2008 we noticed S. agalactiae in respiratory secretions of 30/185 (16%) of cystic fibrosis (CF) patients. The median age of these patients was 3-6 years older than the median age CF patients not harboring S. agalactiae. To analyze, if the S. agalactiae isolates from CF patients were clonal, further characte...

  19. The cystic fibrosis lower airways microbial metagenome

    Science.gov (United States)

    Moran Losada, Patricia; Chouvarine, Philippe; Dorda, Marie; Hedtfeld, Silke; Mielke, Samira; Schulz, Angela; Wiehlmann, Lutz

    2016-01-01

    Chronic airway infections determine most morbidity in people with cystic fibrosis (CF). Herein, we present unbiased quantitative data about the frequency and abundance of DNA viruses, archaea, bacteria, moulds and fungi in CF lower airways. Induced sputa were collected on several occasions from children, adolescents and adults with CF. Deep sputum metagenome sequencing identified, on average, approximately 10 DNA viruses or fungi and several hundred bacterial taxa. The metagenome of a CF patient was typically found to be made up of an individual signature of multiple, lowly abundant species superimposed by few disease-associated pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus, as major components. The host-associated signatures ranged from inconspicuous polymicrobial communities in healthy subjects to low-complexity microbiomes dominated by the typical CF pathogens in patients with advanced lung disease. The DNA virus community in CF lungs mainly consisted of phages and occasionally of human pathogens, such as adeno- and herpesviruses. The S. aureus and P. aeruginosa populations were composed of one major and numerous minor clone types. The rare clones constitute a low copy genetic resource that could rapidly expand as a response to habitat alterations, such as antimicrobial chemotherapy or invasion of novel microbes. PMID:27730195

  20. Infertility Management in Men with Cystic Fibrosis

    Institute of Scientific and Technical Information of China (English)

    Nikita Rawal; Rafit Gazvani; Roger Mountford

    2009-01-01

    Cystic fibrosis (CF) is a multisystem autosomal recessive disorder. CF has a reported incidence of 1 in 2 500 and a carrier frequency of 1 in 25. It is caused by mutations in a gene located on the long arm of chromosome 7. With almost 50% of patients with CF now in the adult population, and a very high interest in future parenting (78% of men wanting children), there is an increasing need to be proactive in terms of advice about reproductive health. Discussion on reproduction should start in early adolescence and be regularly updated by medical staff. The recent advances in reproductive techniques have allowed the development of sperm aspiration coupled with intra-cytoplasmic sperm injection (ICSI). Spermatozoa can be retrieved from either the epididymis or the testes. Genetic counselling is strongly recommended for both partners when congenital bilateral aplasia of vas deferens (CBA VD) is diagnosed as there is the inevitability of transmitting a mutated CFTR gene, and an increased risk of producing an affected child with serious long-term implications. Most treatment centres, with the introduction of ICSI, routinely screen all males with azoospermia caused by obstruction (other than that caused by vasectomy) or germ cell failure. Protocols usually involve screening for 28 relatively common CFTR mutations. Further advanced testing may be necessary up to a final detection level of approximately 98.5%. Before considering any assisted reproduction treatment, it is pertinent that CF patients receive medical and psychological counselling.

  1. Inflammation and its genesis in cystic fibrosis.

    Science.gov (United States)

    Nichols, David P; Chmiel, James F

    2015-10-01

    The host inflammatory response in cystic fibrosis (CF) lung disease has long been recognized as a central pathological feature and an important therapeutic target. Indeed, many believe that bronchiectasis results largely from the oxidative and proteolytic damage comprised within an exuberant airway inflammatory response that is dominated by neutrophils. In this review, we address the longstanding argument of whether or not the inflammatory response is directly attributable to impairment of the cystic fibrosis transmembrane conductance regulator or only secondary to airway obstruction and chronic bacterial infection and challenge the importance of this distinction in the context of therapy. We also review the centrality of neutrophils in CF lung pathophysiology and highlight more recent data that suggest the importance of other cell types and signaling beyond NF-κB activation. We discuss how protease and redox imbalance are critical factors in CF airway inflammation and end by reviewing some of the more promising therapeutic approaches now under development.

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

    DEFF Research Database (Denmark)

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

    1998-01-01

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

  3. Experiences of physical activity: A phenomenological study of individuals with cystic fibrosis.

    Science.gov (United States)

    Street, Rachael; Mercer, Jenny; Mills-Bennett, Rebekah; O'Leary, Catherine; Thirlaway, Kathryn

    2016-02-01

    Although extensive research has investigated the benefits of physical activity in cystic fibrosis, minimal exploration of the experiences for individuals from a qualitative, phenomenological perspective has been carried out. The aim of this study was to explore the subjective experiences of physical activity for individuals with cystic fibrosis. The health-care team, at an Adult Cystic Fibrosis Unit in the United Kingdom, recruited 12 participants to take part. Interview data were analysed using interpretative phenomenological analysis. A central theme of 'self-monitoring' emerged from the accounts and was embedded in the three super-ordinate themes.

  4. Mycobacterium abscessus and Children with Cystic Fibrosis

    Science.gov (United States)

    Sermet-Gaudelus, Isabelle; Le Bourgeois, Muriel; Pierre-Audigier, Catherine; Offredo, Catherine; Guillemot, Didier; Halley, Sophie; Akoua-Koffi, Chantal; Vincent, Véronique; Sivadon-Tardy, Valérie; Ferroni, Agnès; Berche, Patrick; Scheinmann, Pierre; Lenoir, Gérard

    2003-01-01

    We prospectively studied 298 patients with cystic fibrosis (mean age 11.3 years; range 2 months to 32 years; sex ratio, 0.47) for nontuberculous mycobacteria in respiratory samples from January 1, 1996, to December 31, 1999. Mycobacterium abscessus was by far the most prevalent nontuberculous mycobacterium: 15 patients (6 male, 9 female; mean age 11.9 years; range 2.5–22 years) had at least one positive sample for this microorganism (versus 6 patients positive for M. avium complex), including 10 with >3 positive samples (versus 3 patients for M. avium complex). The M. abscessus isolates from 14 patients were typed by pulsed-field gel electrophoresis: each of the 14 patients harbored a unique strain, ruling out a common environmental reservoir or person-to-person transmission. Water samples collected in the cystic fibrosis center were negative for M. abscessus. This major mycobacterial pathogen in children and teenagers with cystic fibrosis does not appear to be acquired nosocomially. PMID:14720400

  5. [Treatment of Cystic Fibrosis with CFTR Modulators].

    Science.gov (United States)

    Tümmler, B

    2016-05-01

    Personalized medicine promises that medical decisions, practices and products are tailored to the individual patient. Cystic fibrosis, an inherited disorder of chloride and bicarbonate transport in exocrine glands, is the first successful example of customized drug development for mutation-specific therapy. There are two classes of CFTR modulators: potentiators that increase the activity of CFTR at the cell surface, and correctors that either promote the read-through of nonsense mutations or facilitate the translation, folding, maturation and trafficking of mutant CFTR to the cell surface. The potentiator ivacaftor and the corrector lumacaftor are approved in Germany for the treatment of people with cystic fibrosis who carry a gating mutation such as p.Gly551Asp or who are homozygous for the most common mutation p.Phe508del, respectively. This report provides an overview of the basic defect in cystic fibrosis, the population genetics of CFTR mutations in Germany and the bioassays to assess CFTR function in humans together with the major achievements of preclinical research and clinical trials to bring CFTR modulators to the clinic. Some practical information on the use of ivacaftor and lumacaftor in daily practice and an update on pitfalls, challenges and novel strategies of bench-to-bedside development of CFTR modulators are also provided.

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

    Directory of Open Access Journals (Sweden)

    Hauser Jenny

    2010-11-01

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

  7. Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review.

    Science.gov (United States)

    Stallings, Virginia A; Stark, Lori J; Robinson, Karen A; Feranchak, Andrew P; Quinton, Hebe

    2008-05-01

    The Cystic Fibrosis Foundation established a process of systematic review of evidence to inform the development of clinical care guidelines and encourage evidence-based practice. The Subcommittee on Growth and Nutrition reviewed the evidence in two areas: energy intake and dosing for pancreatic enzyme replacement therapy. Evidence-based recommendations are presented here. Also, an ad hoc working group conducted a review of the literature and performed new analyses using the Cystic Fibrosis Foundation Patient Registry to update the recommendations for growth and weight-status monitoring. These Registry data-based recommendations are presented.

  8. Relationship Between Fat-Soluble Vitamin Supplementation and Blood Concentrations in Adolescent and Adult Patients With Cystic Fibrosis.

    Science.gov (United States)

    Siwamogsatham, Oranan; Dong, Wei; Binongo, Jose N; Chowdhury, Ritam; Alvarez, Jessica A; Feinman, Shawna J; Enders, Jessica; Tangpricha, Vin

    2014-08-01

    Background: Pancreatic insufficiency is common in patients with cystic fibrosis (CF) and leads to malabsorption of fat-soluble vitamins. Multivitamins, including vitamins A, D, E, and K, are routinely prescribed to patients with CF to prevent vitamin deficiencies. Our objective was to examine the relationship between fat-soluble vitamin supplements and their impact on blood concentrations. Methods: This was a retrospective chart review of patients with CF who were treated at Emory Clinic and Emory University Hospital during 2008-2012. The amount of fat-soluble vitamin supplementation, serum markers of fat-soluble vitamin concentrations, CF transmembrane conductance regulator genotype, and other demographic information were recorded from electronic medical records. Mixed-effects models were used to investigate the trends over time of fat-soluble vitamin supplements and serum vitamin concentrations. Results: In total, 177 charts were eligible. Mean (SD) age was 26.1 (10.2) years. Ninety-two percent of patients had pancreatic insufficiency and 52% had the homozygous ΔF508 mutation. Recorded fat-soluble vitamin supplementation increased in the past 5 years (P < .001 for all). Serum 25-hydroxyvitamin D increased slightly (3% increase; P < .01); however, there were no changes in the blood concentrations of vitamins A, E, and K (P = .26-.96). Conclusions: Despite a near doubling of recorded fat-soluble vitamin supplementation over the past 5 years, there was no parallel increase in blood concentrations of these vitamins. Potential reasons include suboptimal dosages, low adherence, or ongoing issues with malabsorption.

  9. Lack of correlation between pulmonary disease and cystic fibrosis transmembrane conductance regulator dysfunction in cystic fibrosis: a case report

    Directory of Open Access Journals (Sweden)

    Cleveland Robert H

    2010-04-01

    Full Text Available Abstract Introduction Mutations in both alleles of the cystic fibrosis transmembrane conductance regulator gene result in the disease cystic fibrosis, which usually manifests as chronic sinopulmonary disease, pancreatic insufficiency, elevated sodium chloride loss in sweat, infertility among men due to agenesis of the vas deferens and other symptoms including liver disease. Case presentation We describe a pair of African-American brothers, aged 21 and 27, with cystic fibrosis. They were homozygous for a rare frameshift mutation in the cystic fibrosis transmembrane conductance regulator 3791delC, which would be expected to cause significant morbidity. Although 80% of cystic fibrosis patients are colonized with Pseudomonas aeruginosa by eight years of age, the older brother had no serum opsonic antibody titer to P. aeruginosa by age 13 and therefore would have failed to mount an effective antibody response to the alginate (mucoid polysaccharide capsule of P. aeruginosa. He was not colonized with P. aeruginosa until 24 years of age. Similarly, the younger brother was not colonized with P. aeruginosa until age 20 and had no significant lung disease. Conclusion Despite a prevailing idea in cystic fibrosis research that the amount of functional cystic fibrosis transmembrane conductance regulator predicts clinical status, our results indicated that respiratory disease severity in cystic fibrosis exhibits phenotypic heterogeneity. If this heterogeneity is, in part, genetic, it is most likely derived from genes outside the cystic fibrosis transmembrane conductance regulator locus.

  10. [Cystic fibrosis: new treatments targeting the CFTR protein].

    Science.gov (United States)

    Fajac, I; Sermet-Gaudelus, I

    2013-04-01

    Cystic fibrosis is an autosomal recessive genetic disease due to mutations in the (cystic fibrosis transmembrane conductance regulator) CFTR gene. The CFTR protein is a chloride channel expressed at the surface of several epithelial cells. Defective function of the CFTR protein leads to a severe disease in which lung disease is the leading cause of death. Current treatments are symptomatic. Nevertheless, with specialist and holistic care in dedicated cystic fibrosis centres, the median survival has improved. But the average age of death remains 29 years. Innovative molecules aiming to correct the CFTR protein itself are under development. These will be personalised treatments depending on the genotype or the type of CFTR dysfunction. The first molecule, ivacaftor, has just been approved in Europe and the USA. Adults and children treated with ivacaftor in clinical trials had a 10% improvement in FEV1 that was maintained for more than a year. Although at present ivacaftor is approved for only a small percentage of patients, the therapeutic strategy of correcting CFTR protein has been proved a valid approach. Other molecules targeting other defects in the CFTR protein are under evaluation.

  11. Evidence for a Cystic Fibrosis Enteropathy.

    Directory of Open Access Journals (Sweden)

    Marlou P M Adriaanse

    Full Text Available Previous studies have suggested the existence of enteropathy in cystic fibrosis (CF, which may contribute to intestinal function impairment, a poor nutritional status and decline in lung function. This study evaluated enterocyte damage and intestinal inflammation in CF and studied its associations with nutritional status, CF-related morbidities such as impaired lung function and diabetes, and medication use.Sixty-eight CF patients and 107 controls were studied. Levels of serum intestinal-fatty acid binding protein (I-FABP, a specific marker for enterocyte damage, were retrospectively determined. The faecal intestinal inflammation marker calprotectin was prospectively studied. Nutritional status, lung function (FEV1, exocrine pancreatic insufficiency (EPI, CF-related diabetes (CFRD and use of proton pump inhibitors (PPI were obtained from the medical charts.Serum I-FABP levels were elevated in CF patients as compared with controls (p<0.001, and correlated negatively with FEV1 predicted value in children (r-.734, p<0.05. Faecal calprotectin level was elevated in 93% of CF patients, and correlated negatively with FEV1 predicted value in adults (r-.484, p<0.05. No correlation was found between calprotectin levels in faeces and sputum. Faecal calprotectin level was significantly associated with the presence of CFRD, EPI, and PPI use.This study demonstrated enterocyte damage and intestinal inflammation in CF patients, and provides evidence for an inverse correlation between enteropathy and lung function. The presented associations of enteropathy with important CF-related morbidities further emphasize the clinical relevance.

  12. First Report of Chronic Pulmonary Infection by KPC-3-Producing and Colistin-Resistant Klebsiella pneumoniae Sequence Type 258 (ST258) in an Adult Patient with Cystic Fibrosis

    Science.gov (United States)

    Delfino, Emanuele; Del Bono, Valerio; Coppo, Erika; Marchese, Anna; Manno, Graziana; Morelli, Patrizia; Minicucci, Laura; Viscoli, Claudio

    2015-01-01

    The spread of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae continues to increase, and the possible development of KPC-producing K. pneumoniae infections in cystic fibrosis (CF) patients is a matter of concern. Here, we describe the establishment of a chronic lung infection due to a colistin-resistant KPC-producing K. pneumoniae isolate in an Italian CF patient. PMID:25653395

  13. What is the perceived nature of parental care and support for young people with cystic fibrosis as they enter adult health services?

    Science.gov (United States)

    Iles, Nicola; Lowton, Karen

    2010-01-01

    The majority of those diagnosed with cystic fibrosis (CF) now live to adulthood. In response to increased survival age, transition services have been developed to ensure smooth transfer from paediatric to adult specialist healthcare, although the majority of treatment and care continues to be delivered in the home. However, little is known about how young adults and staff conceptualise the nature of the parental role after young people have left paediatric care. The aim of this study is to explore the nature of parental support that is perceived to be available at this time. As part of a larger study of transitional care, semi-structured interviews were conducted with 50 young people with CF aged 13-24 years (32 with experience of transition and/or adult CF services) and 23 specialist healthcare professionals (14 working in adult care) across two CF centres in Southeast England. Interviews took place in young people's homes or within CF services, using a topic guide and were recorded, transcribed and analysed thematically. Four domains of perceived parental support were identified by the young people interviewed, with varying degrees of continuity into adult care: (1) Providing non-clinical practical and emotional support; (2) Acting as 'troubleshooters' in times of health-related crisis; (3) Working in partnership with offspring in ongoing disease management in the home and clinic; (4) Acting as 'protectors' of their children. Young people and service staff expressed tensions in managing parental involvement in post-paediatric consultations and the degree to which parents should be aware of their offspring's deteriorating health and social concerns. Parental anxiety and over-involvement was perceived by many young people and staff as unsupportive. We suggest that although health and social care providers are mindful of the tensions that arise for those leaving paediatric services, the place of parental support in adult care is currently contentious for these 'new

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    DEFF Research Database (Denmark)

    Fluge, G; Olesen, Hanne Vebert; Gilljam, M

    2009-01-01

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

  16. LUNG TRANSPLANTATION IN PATIENTS WITH CYSTIC-FIBROSIS

    NARCIS (Netherlands)

    MANNES, GPM; VANDERBIJ, W

    1995-01-01

    Worldwide more than 600 heart-lung or lung transplantations have been performed in patients with cystic fibrosis and end-stage respiratory disease. At the University Hospital in Groningen 10 patients with cystic fibrosis underwent bilateral sequential lung transplantation until April 1994. The 1-yea

  17. Microbiological surveillance in patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Paola Gualdi

    2010-06-01

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

  18. Mycobacterium abscessus and Children with Cystic Fibrosis

    OpenAIRE

    Sermet-Gaudelus, Isabelle; Le Bourgeois, Muriel; Pierre-Audigier, Catherine; Offredo, Catherine; Guillemot, Didier; Halley, Sophie; Akoua-Koffi, Chantal; Vincent, Véronique; Sivadon-Tardy, Valérie; Ferroni, Agnès; Berche, Patrick; Scheinmann, Pierre; Lenoir, Gérard; Gaillard, Jean-Louis

    2003-01-01

    We prospectively studied 298 patients with cystic fibrosis (mean age 11.3 years; range 2 months to 32 years; sex ratio, 0.47) for nontuberculous mycobacteria in respiratory samples from January 1, 1996, to December 31, 1999. Mycobacterium abscessus was by far the most prevalent nontuberculous mycobacterium: 15 patients (6 male, 9 female; mean age 11.9 years; range 2.5–22 years) had at least one positive sample for this microorganism (versus 6 patients positive for M. avium complex), including...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  20. [Vitamin E deficiency in cystic fibrosis].

    Science.gov (United States)

    Muñoz, C; Polanco, I; Hernanz, A; Carrasco, S; Barea, I; Murga, M L; Arroba, M L; Codoceo, R

    1987-12-01

    Plasma vitamin E levels were measured by high performance liquid chromatography in 42 children with cystic fibrosis and were correlated with the following parameters: sex, age, time of follow-up, clinical evolution (Schwachman score), vitamin E/cholesterol and faecal fat excretion. All children in this study received oral alfa-tocoferol (50-100 mg daily) from the diagnosis. According to the vitamin E level patients were distributed in two groups. Group I: 27 patients (64.3%) with normal concentrations. Group II: 15 patients (35.7%) with decreases plasma levels but without clinical manifestations. Steatorrhea was present in all children except 4 patients from group I and one patient from group II. On the other hand, vitamin E/cholesterol was normal in 80% of patients with vitamin E deficiency (group II). We did not find any correlation between plasma vitamin E levels and the different clinical and biological parameters studied. Further studies should be carried out to throw more light on the mechanism underlying the pathogenesis of vitamin E deficiency in patients with cystic fibrosis.

  1. Targeting ion channels in cystic fibrosis.

    Science.gov (United States)

    Mall, Marcus A; Galietta, Luis J V

    2015-09-01

    Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause a characteristic defect in epithelial ion transport that plays a central role in the pathogenesis of cystic fibrosis (CF). Hence, pharmacological correction of this ion transport defect by targeting of mutant CFTR, or alternative ion channels that may compensate for CFTR dysfunction, has long been considered as an attractive approach to a causal therapy of this life-limiting disease. The recent introduction of the CFTR potentiator ivacaftor into the therapy of a subgroup of patients with specific CFTR mutations was a major milestone and enormous stimulus for seeking effective ion transport modulators for all patients with CF. In this review, we discuss recent breakthroughs and setbacks with CFTR modulators designed to rescue mutant CFTR including the common mutation F508del. Further, we examine the alternative chloride channels TMEM16A and SLC26A9, as well as the epithelial sodium channel ENaC as alternative targets in CF lung disease, which remains the major cause of morbidity and mortality in patients with CF. Finally, we will focus on the hurdles that still need to be overcome to make effective ion transport modulation therapies available for all patients with CF irrespective of their CFTR genotype.

  2. Imaging the Abdominal Manifestations of Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    C. D. Gillespie

    2017-01-01

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

  3. Cystic fibrosis, molecular genetics for all life

    Directory of Open Access Journals (Sweden)

    Ausilia Elce

    2015-10-01

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

  4. Cystic fibrosis in adults. Short-term and long-term reproducibility of the Brody score for lung morphology in low-dose MDCT scans

    Energy Technology Data Exchange (ETDEWEB)

    Weber, K.; Paolini, M.; Schmitz, M.; Coppenrath, E.; Reiser, M.; Mueller-Lisse, U.G. [Ludwig-Maximilians-Univ. Muenchen (Germany). Inst. fuer Klinische Radiologie; Fischer, R.; Huber, R. [Ludwig-Maximilians-Univ. Muenchen (Germany). Medical Hospital V

    2014-01-15

    Purpose: The semi-quantitative Brody score measures the severity of cystic fibrosis (CF)-related lung disease. We investigated the short-term (28 - 60 days) and long-term (2 - 7 years) intra- and inter-observer reproducibility of the Brody score in low-dose multidetector row computed tomography examinations performed in inspiration (LDCTs) of adult CF patients. Materials and Methods: Composite Brody scores and respective underlying bronchiectasis, mucus plugging, peribronchial thickening, parenchymal opacity, and hyperinflation subscores were evaluated twice (time interval, 1 - 84 months) by each of 3 independent radiologists (1 - 20 years of professional diagnostic radiology experience) in LDCTs (4 - 64 rows, 120 KVp, 10 - 15 mAs/slice, CTDIw approx. 1.0 mGy, effective dose approx. 0.5 mSv) of 15 adult patients with CF-related lung disease (8 female, 7 male, age, 18 - 50 years, mean, 33 years). Results: The average reproducibility of the Brody score was within +/-7 % (range, 2 - 30 %) between radiologists, and +/-6 % (3 - 12 %) within radiologists (short-term, 28 - 60 days, 4 %, 0 - 12 %, long-term, 2 - 7 years, 12 %, 1 - 36 %). For the different subscores, the reproducibility was within +/-25 % (15 - 41 %) between radiologists and +/-23 % (12 - 46 %) within radiologists. Conclusion: The Brody score shows high average inter-observer reproducibility in LDCTs of adult CF patients. The Brody score also demonstrates high average intra-observer reproducibility if subsequent assessments are made within 28 - 61 days. With time intervals of 2 - 7 years between subsequent evaluations, however, intra-observer reproducibility decreases. Respective subscores each demonstrate lower intra- and inter-observer reproducibility than does the composite Brody score. (orig.)

  5. Enteral tube feeding for individuals with cystic fibrosis: Cystic Fibrosis Foundation evidence-informed guidelines.

    Science.gov (United States)

    Schwarzenberg, Sarah Jane; Hempstead, Sarah E; McDonald, Catherine M; Powers, Scott W; Wooldridge, Jamie; Blair, Shaina; Freedman, Steven; Harrington, Elaine; Murphy, Peter J; Palmer, Lena; Schrader, Amy E; Shiel, Kyle; Sullivan, Jillian; Wallentine, Melissa; Marshall, Bruce C; Leonard, Amanda Radmer

    2016-11-01

    Nutrition is integral to the care of individuals with cystic fibrosis (CF). Better nutritional status is associated with improved pulmonary function. In some individuals with CF, enteral tube feeding can be useful in achieving optimal nutritional status. Current nutrition guidelines do not include detailed recommendations for enteral tube feeding. The Cystic Fibrosis Foundation convened an expert panel to develop enteral tube feeding recommendations based on a systematic review of the evidence and expert opinion. These guidelines address when to consider enteral tube feeding, assessment of confounding causes of poor nutrition in CF, preparation of the patient for placement of the enteral feeding tube, management of the tube after placement and education about enteral feeding. These recommendations are intended to guide the CF care team, individuals with CF, and their families through the enteral tube feeding process.

  6. The adult cystic fibrosis airway microbiota is stable over time and infection type, and highly resilient to antibiotic treatment of exacerbations.

    Directory of Open Access Journals (Sweden)

    Anthony A Fodor

    Full Text Available Cystic fibrosis (CF is characterized by defective mucociliary clearance and chronic airway infection by a complex microbiota. Infection, persistent inflammation and periodic episodes of acute pulmonary exacerbation contribute to an irreversible decline in CF lung function. While the factors leading to acute exacerbations are poorly understood, antibiotic treatment can temporarily resolve pulmonary symptoms and partially restore lung function. Previous studies indicated that exacerbations may be associated with changes in microbial densities and the acquisition of new microbial species. Given the complexity of the CF microbiota, we applied massively parallel pyrosequencing to identify changes in airway microbial community structure in 23 adult CF patients during acute pulmonary exacerbation, after antibiotic treatment and during periods of stable disease. Over 350,000 sequences were generated, representing nearly 170 distinct microbial taxa. Approximately 60% of sequences obtained were from the recognized CF pathogens Pseudomonas and Burkholderia, which were detected in largely non-overlapping patient subsets. In contrast, other taxa including Prevotella, Streptococcus, Rothia and Veillonella were abundant in nearly all patient samples. Although antibiotic treatment was associated with a small decrease in species richness, there was minimal change in overall microbial community structure. Furthermore, microbial community composition was highly similar in patients during an exacerbation and when clinically stable, suggesting that exacerbations may represent intrapulmonary spread of infection rather than a change in microbial community composition. Mouthwash samples, obtained from a subset of patients, showed a nearly identical distribution of taxa as expectorated sputum, indicating that aspiration may contribute to colonization of the lower airways. Finally, we observed a strong correlation between low species richness and poor lung function

  7. The adult cystic fibrosis airway microbiota is stable over time and infection type, and highly resilient to antibiotic treatment of exacerbations.

    Science.gov (United States)

    Fodor, Anthony A; Klem, Erich R; Gilpin, Deirdre F; Elborn, J Stuart; Boucher, Richard C; Tunney, Michael M; Wolfgang, Matthew C

    2012-01-01

    Cystic fibrosis (CF) is characterized by defective mucociliary clearance and chronic airway infection by a complex microbiota. Infection, persistent inflammation and periodic episodes of acute pulmonary exacerbation contribute to an irreversible decline in CF lung function. While the factors leading to acute exacerbations are poorly understood, antibiotic treatment can temporarily resolve pulmonary symptoms and partially restore lung function. Previous studies indicated that exacerbations may be associated with changes in microbial densities and the acquisition of new microbial species. Given the complexity of the CF microbiota, we applied massively parallel pyrosequencing to identify changes in airway microbial community structure in 23 adult CF patients during acute pulmonary exacerbation, after antibiotic treatment and during periods of stable disease. Over 350,000 sequences were generated, representing nearly 170 distinct microbial taxa. Approximately 60% of sequences obtained were from the recognized CF pathogens Pseudomonas and Burkholderia, which were detected in largely non-overlapping patient subsets. In contrast, other taxa including Prevotella, Streptococcus, Rothia and Veillonella were abundant in nearly all patient samples. Although antibiotic treatment was associated with a small decrease in species richness, there was minimal change in overall microbial community structure. Furthermore, microbial community composition was highly similar in patients during an exacerbation and when clinically stable, suggesting that exacerbations may represent intrapulmonary spread of infection rather than a change in microbial community composition. Mouthwash samples, obtained from a subset of patients, showed a nearly identical distribution of taxa as expectorated sputum, indicating that aspiration may contribute to colonization of the lower airways. Finally, we observed a strong correlation between low species richness and poor lung function. Taken together, these

  8. Scoliosis in cystic fibrosis - an appraisal

    Energy Technology Data Exchange (ETDEWEB)

    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 of a familial tendency towards scoliosis was apparent, and a genetic or constitutional basis is postulated with an unknown precipitating factor.

  9. Psychosocial problems in children with cystic fibrosis

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  10. Influenza vaccination in children with cystic fibrosis.

    Science.gov (United States)

    Patria, Maria Francesca; Longhi, Benedetta; Esposito, Susanna

    2013-04-01

    Cystic fibrosis (CF) is an inherited autosomal recessive disease characterized by progressive pulmonary damage and respiratory failure. It is known that bacterial infections play a critical role in the development of significant lung damage, whereas the role of respiratory viruses in CF pulmonary exacerbations and the relationship between viral infections and the progression of lung damage are uncertain. Health authorities throughout the world recommend influenza vaccination for CF patients. The aim of this review is to analyze the impact of seasonal and pandemic influenza on CF patients and data concerning influenza vaccination in order to assess the current situation and identify areas for future study. As data are limited, further well-constructed clinical studies of the effectiveness of influenza vaccination on the main clinical outcome measures of pulmonary function and nutritional status in patients with CF are required.

  11. Pseudomonas aeruginosa biofilms in cystic fibrosis

    DEFF Research Database (Denmark)

    Høiby, Niels; Ciofu, Oana; Bjarnsholt, Thomas

    2010-01-01

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

  12. Diabetes mellitus in childhood cystic fibrosis.

    LENUS (Irish Health Repository)

    Rauf, F

    2012-02-03

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

  13. Abdominal manifestations of cystic fibrosis in children

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-03-15

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

  14. Attitudes of potential providers toward preconceptual cystic fibrosis carrier screening.

    NARCIS (Netherlands)

    Poppelaars, F.; Ader, H.J.; Cornel, M.C.; Henneman, L.; Hermens, R.P.M.G.; Wal, G. van der; Kate, L. ten

    2004-01-01

    To determine the attitudes of potential providers (general practitioners and Community Health Service workers) towards preconceptual cystic fibrosis (CF) carrier screening and to determine which factors are associated with a positive attitude. A survey was conducted among 200 general practitioners (

  15. Adeno-associated virus for cystic fibrosis gene therapy

    Directory of Open Access Journals (Sweden)

    S.V. Martini

    2011-11-01

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

  16. Changes in Cystic Fibrosis Airway Microbiota at Pulmonary Exacerbation

    OpenAIRE

    Carmody, Lisa A.; Zhao, Jiangchao; Patrick D. Schloss; Petrosino, Joseph F.; Murray, Susan; Young, Vincent B.; Jun Z Li; LiPuma, John J.

    2013-01-01

    Rationale: In persons with cystic fibrosis (CF), repeated exacerbations of pulmonary symptoms are associated with a progressive decline in lung function. Changes in the airway microbiota around the time of exacerbations are not well understood.

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

    DEFF Research Database (Denmark)

    Johansen, Helle Krogh; Gøtzsche, Peter C

    2013-01-01

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

  18. Increased PIVKA-II concentrations in patients with cystic fibrosis.

    OpenAIRE

    de Montalembert, M; Lenoir, G; Saint-Raymond, A.; Rey, J; Lefrère, J J

    1992-01-01

    Serum vitamin K concentrations and prothrombin induced by absence of vitamin K (PIVK-II) concentrations were assayed in 43 patients with cystic fibrosis. Twenty nine showed a normal PIVKA-II and vitamin K concentrations; 14 showed an increased PIVKA-II concentration, in one of whom serum vitamin K was decreased. Although their vitamin K concentrations were normal, some patients with cystic fibrosis still had an increased PIVKA-II. There was a significant correlation between PIVKA-II concentra...

  19. New insights into cystic fibrosis: molecular switches that regulate CFTR.

    Science.gov (United States)

    Guggino, William B; Stanton, Bruce A

    2006-06-01

    Cystic fibrosis transmembrane conductance regulator (CFTR), a Cl(-)-selective ion channel, is a prototypic member of the ATP-binding cassette transporter superfamily that is expressed in several organs. In these organs, CFTR assembles into large, dynamic macromolecular complexes that contain signalling molecules, kinases, transport proteins, PDZ-domain-containing proteins, myosin motors, Rab GTPases, and SNAREs. Understanding how these complexes regulate the intracellular trafficking and activity of CFTR provides a unique insight into the aetiology of cystic fibrosis and other diseases.

  20. Recent concepts on cystic fibrosis Fibrosis quística

    Directory of Open Access Journals (Sweden)

    William Parra

    1991-01-01

    Full Text Available

    Up to date concepts on Cystic Fibrosis are summarized in this article; the following are included: Incidence, pathogenesis, prenatal and postnatal diagnosis, treatment, genetics and future perspectives. Criteria are given for suspecting the disease and emphasis is made on the fact that its frequency in Colombia may be higher than usually thought.

    En este artículo se actualizan algunos conceptos sobre la Fibrosis Quística y su manejo; se incluyen los siguientes: incidencia, patogénesis, bases para el diagnóstico incluyendo el prenatal, tratamiento, aspectos gen éticos y perspectivas futuras. Se hace énfasis en la necesidad de pensar más a menudo en la enfermedad pues su frecuencia en Colombia puede ser mayor de lo que usualmente se acepta.

  1. Practical Guidelines: Lung Transplantation in Patients with Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    T. O. Hirche

    2014-01-01

    Full Text Available 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.

  2. [Recommendations for the management of bone demineralization in cystic fibrosis].

    Science.gov (United States)

    Sermet-Gaudelus, I; Nove-Josserand, R; Loeille, G-A; Dacremont, G; Souberbielle, J-C; Fritsch, J; Laurans, M; Moulin, P; Cortet, B; Salles, J-P; Ginies, J-L; Guillot, M; Perez-Martin, S; Ruiz, J-C; Montagne, V; Cohen-Solal, M; Cormier, C; Garabédian, M; Mallet, E

    2008-03-01

    A high prevalence of low bone mineralization is documented in adult patients with cystic fibrosis (CF). Osteopenia is present in as much as 85% of adult patients and osteoporosis in 13 to 57% of them. In children, studies are discordant probably because of different control database. Denutrition, inflammation, vitamin D and vitamin K deficiency, altered sex hormone production, glucocorticoid therapy, and physical inactivity are well known risk factors for poor bone health. Puberty is a critical period and requires a careful follow-up for an optimal bone peak mass. This review is a consensus statement established by the national working group of the French Federation of CF Centers to develop practice guidelines for optimizing bone health in patients with CF. Recommendations for screening and for calcium, vitamin D and K supplementation are given. Further work is needed to define indications for treatment with biphosphonates and anabolic agents.

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

    Science.gov (United States)

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

    2016-01-01

    Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with pre-existing inflammatory lung disease, such as cystic fibrosis (CF). Pulmonary disease (PD) 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 a panel of 19 experts to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM-PD in individuals with CF. PICO (population, intervention, comparison, outcome) methodology and systematic literature reviews were employed to inform draft recommendations, which were then modified to achieve consensus and subsequently circulated for public consultation within the USA and European CF communities. We have thus generated a series of pragmatic, evidence-based recommendations as an initial step in optimising management for this challenging condition.

  4. Intestinal Bicarbonate Secretion in Cystic Fibrosis Mice

    Directory of Open Access Journals (Sweden)

    Clarke LL

    2001-07-01

    Full Text Available Gene-targeted disruption of the cystic fibrosis transmembrane conductance regulator (CFTR in mice results in an intestinal disease phenotype that is remarkably similar to bowel disease in cystic fibrosis patients. In the intestinal segment downstream from the stomach (i.e., the duodenum, CFTR plays an important role in bicarbonate secretion that protects the epithelium from acidic gastric effluent. In this report, we examine the role of CFTR in cAMP-stimulated bicarbonate secretion in the murine duodenum and the mechanisms of acid-base transport that are revealed in CFTR knockout (CF mice. Ion substitution, channel blocker and pH stat studies comparing duodena from wild-type and CF mice indicate that CFTR mediates a HCO(3(- conductance across the apical membrane of the epithelium. In the presence of a favorable cell-to-lumen HCO(3(- gradient, the CFTR-mediated HCO(3(- current accounts for about 80% of stimulated HCO(3(- secretion. Exposure of the duodenal mucosa to acidic pH reveals another role of CFTR in facilitating HCO(3(- secretion via an electroneutral, 4,4'-diisothiocyanato-stilbene-2,2' disulfonic acid (DIDS sensitive Cl(-/HCO(3(- exchange process. In CF duodenum, other apical membrane acid-base transporters retain function, thereby affording limited control of transepithelial pH. Activity of a Cl(--dependent anion exchanger provides near-constant HCO(3(- secretion in CF intestine, but under basal conditions the magnitude of secretion is lessened by simultaneous activity of a Na(+/H(+ exchanger (NHE. During cAMP stimulation of CF duodenum, a small increase in net base secretion is measured but the change results from cAMP inhibition of NHE activity rather than increased HCO(3(- secretion. Interestingly, a small inward current that is sensitive to the anion channel blocker, 5-nitro-2(3-phenylpropyl amino-benzoate (NPPB, is also activated during cAMP stimulation of the CFTR-null intestine but the identity of the current is yet to be

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Moore John E

    2004-10-01

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

  7. Vitamin K status in cystic fibrosis patients

    Directory of Open Access Journals (Sweden)

    Patrycja Krzyżanowska

    2010-12-01

    Full Text Available Vitamin K belongs to the family of fat-soluble vitamins and plays an important role in hemostasis, bone metabolism and may affect cerebral sphingolipid synthesis. It is a cofactor necessary for posttranslational γ-carboxylation of glutamyl residues in selected proteins such as the osteocalcin, and procoagulation factors II, VII, IX, X. Vitamin K deficient individuals appear to have more undercarboxylated proteins, which are functionally defective. The vitamin K deficiency has been frequently documented in patients with cystic fibrosis. The main possible causes of this deficiency include: fat malabsorption due to pancreatic exocrine insufficiency, cholestatic or  noncholestatic liver disease, reduced production of vitamin K by colonic flora related to chronic antibiotic treatments, bowel resections and increased mucous accumulation in the bowel. CF patients are more prone to osteopenia, caused by chronic vitamin K shortage, than to coagulopathy. Despite available evidence, which strongly suggests that all CF patients are at risk for developing vitamin K deficiency, its supplementation doses have not been established. Recent recommendations from Europe and the UK have suggested varied doses ranging from 0.3 mg/day to 10 mg/week. Further studies, both cross sectional and longitudinal interventional, are still required to determine routine and therapeutic supplementation doses.

  8. Dermatoglyphic Patterns in Cystic Fibrosis Children

    Science.gov (United States)

    Ezzati, Atefeh; Batoei, Fereshteh; Jafari, Seyed-Ali; Kiyani, Mohammad-Ali; Mahdavi-Shahri, Naser; Ahanchian, Hamid; Tehranian, Shahrzad; Kianifar, Hamid-Reza

    2014-01-01

    Objective: It is believed that fingerprints and palm patterns may represent genetically determined congenital abnormalities in Cystic Fibrosis (CF). The main idea of this paper was to determine differences of fingerprints and palm patterns in CF and normal children. Methods: Forty-six CF children (27 males, 19 females) and 341 (113 males, 228 females) healthy individuals were recruited for this study. Fingerprint patterns, Total ridge count (TRC) of each finger, a-b ridge count, and atd angles of all participants were recorded. Asymmetry of the right and left hand for each value was determined and dissimilarity in fingerprint patterns between homologous fingers was compared using Chi-square analysis, Mann-Whitney U test and Fisher's exact test. Findings: There were significant differences in the mean TRC of the right digit IV (P=0.009), left digit III (P=0.02), left digit IV (P=0.03), and left digit V (P=0.03). Furthermore, we found significant differences in right atd angel (P=0.001), left atd angel (P=0.002), right a-b ridge (P=0.007) and left a-b ridge (P=0.001). In contrast, we found no significant differences in atd angle asymmetry, a-b ridge count asymmetry and pattern dissimilarity score between both groups (P>0.05). Conclusion: Dermatoglyphic characteristics could be used as a supplementary diagnostic method in CF children. PMID:25793070

  9. The genus Prevotella in cystic fibrosis airways.

    Science.gov (United States)

    Field, Tyler R; Sibley, Christopher D; Parkins, Michael D; Rabin, Harvey R; Surette, Michael G

    2010-08-01

    Airway disease resulting from chronic bacterial colonization and consequential inflammation is the leading cause of morbidity and mortality in patients with Cystic Fibrosis (CF). Although traditionally considered to be due to only a few pathogens, recent re-examination of CF airway microbiology has revealed that polymicrobial communities that include many obligate anaerobes colonize lower airways. The purpose of this study was to examine Prevotella species in CF airways by quantitative culture and phenotypic characterization. Expectorated sputum was transferred to an anaerobic environment immediately following collection and examined by quantitative microbiology using a variety of culture media. Isolates were identified as facultative or obligate anaerobes and the later group was identified by 16S rRNA sequencing. Prevotella spp. represented the majority of isolates. Twelve different species of Prevotella were recovered from 16 patients with three species representing 65% of isolates. Multiple Prevotella species were often isolated from the same sputum sample. These isolates were biochemically characterized using Rapid ID 32A kits (BioMérieux), and for their ability to produce autoinducer-2 and beta-lactamases. Considerable phenotypic variability between isolates of the same species was observed. The quantity and composition of Prevotella species within a patients' airway microbiome varied over time. Our results suggest that the diversity and dynamics of Prevotella in CF airways may contribute to airway disease.

  10. Asthma and cystic fibrosis: A tangled web.

    LENUS (Irish Health Repository)

    Kent, Brian D

    2014-03-01

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

  11. Complete Genome Sequence of Achromobacter xylosoxidans MN001, a Cystic Fibrosis Airway Isolate.

    Science.gov (United States)

    Badalamenti, Jonathan P; Hunter, Ryan C

    2015-08-20

    The genome of Achromobacter xylosoxidans MN001, a strain isolated from sputum derived from an adult cystic fibrosis patient, was sequenced using combined single-molecule real-time and Illumina sequencing. Assembly of the complete genome resulted in a 5,876,039-bp chromosome, representing the smallest A. xylosoxidans genome sequenced to date.

  12. Complete Genome Sequence of Achromobacter xylosoxidans MN001, a Cystic Fibrosis Airway Isolate

    OpenAIRE

    2015-01-01

    The genome of Achromobacter xylosoxidans MN001, a strain isolated from sputum derived from an adult cystic fibrosis patient, was sequenced using combined single-molecule real-time and Illumina sequencing. Assembly of the complete genome resulted in a 5,876,039-bp chromosome, representing the smallest A. xylosoxidans genome sequenced to date.

  13. 'A bed in the middle of nowhere': parents' meanings of place of death for adults with cystic fibrosis

    OpenAIRE

    Lowton, Karen

    2009-01-01

    As populations age and chronic conditions become more prevalent, an individual's ability to choose the location of their end-of-life care and death is increasingly considered important in the provision of good healthcare, with home implied as the 'best' place of death through UK government policy and specialist and voluntary palliative care services. However, considering meanings of place of end-of-life care and death is complex for young adults with life-limiting conditions where the disease...

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

    Directory of Open Access Journals (Sweden)

    Nico Derichs

    2013-03-01

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

  15. Infection in cystic fibrosis: impact of the environment and climate.

    Science.gov (United States)

    Ramsay, K A; Stockwell, R E; Bell, S C; Kidd, T J

    2016-01-01

    In many countries numbers of adults with cystic fibrosis (CF) exceed that of children, with median survival predicted to surpass 50 years. Increasing longevity is, in part, due to intensive therapies including eradication of early infection and suppressive therapies and pulmonary exacerbations. Initial infections with common CF pathogens are thought to arise from the natural environment. We review the impact of climate and environment on infection in CF. Specifically, several studies indicate that higher ambient temperatures, proximity to the equator and the summer season may be linked to the increased prevalence of Pseudomonas aeruginosa in people with CF. The environment may also play an important role in the acquisition of Gram negative organisms other than P. aeruginosa. There is emerging data suggesting that climatic and environmental factors are likely to impact on the risk of infection with NTM and fungi in people which are found extensively throughout the natural environment.

  16. Development of a novel PCR assay for the identification of the black yeast, Exophiala (Wangiella) dermatitidis from adult patients with cystic fibrosis (CF).

    Science.gov (United States)

    Nagano, Yuriko; Elborn, J Stuart; Millar, B Cherie; Goldsmith, Colin E; Rendall, Jackie; Moore, John E

    2008-11-01

    Cystic fibrosis (CF) patients may suffer increased morbidity and mortality through colonisation, allergy and invasive infection from fungi. The black yeast, Exophiala dermatitidis (synonym Wangiella dermatitidis) has been found with increasing frequency in sputum specimens of CF patients, with reported isolation rates ranging from 1.1 to 15.7%. At present, no diagnostic PCR exists to aid with the clinical laboratory detection and identification of this organism. A novel species-specific PCR-based assay was developed for the detection of E. dermatitidis, based on employment of rDNA operons and interspacer (ITS) regions between these rDNA operons. Two novel primers, (designated ExdF & ExdR) were designed in silico with the aid of computer-aided alignment software and with the alignment of multiple species of Exophiala, as well as with other commonly described yeasts and filamentous fungi within CF sputum, including Candida, Aspergillus and Scedosporium. An amplicon of approximately 455 bp was generated, spanning the partial ITS1 region - the complete 5.8S rDNA region - partial ITS2 region, employing ExdF (forward primer [16-mer], 5'-CCG CCT ATT CAG GTC C-3' and ExdR (reverse primer [16-mer], 5'-TCT CTC CCA CTC CCG C-3', was employed and optimised on extracted genomic DNA from a well characterised culture of E. dermatitidis, as well as with high quality genomic DNA template from a further 16 unrelated fungi, including Candida albicans, C. dubliniensis, C. parapsilosis, C. glabrata, Scedosporium apiospermum, Penicillium sp., Aspergillus fumigatus, Aspergillus versicolor, Pichia guilliermondii, Rhodotorula sp., Trichosporon sp., Aureobasidium pullulans, Fusarium sp., Mucor hiemalis, Bionectria ochroleuca, Gibberella pulicaris. Results demonstrated that only DNA from E. dermatitidis gave an amplification product of the expected size, whilst none of the other fungi were amplifiable. Subsequent employment of this primer pair detected this yeast from mycological cultures

  17. DeltaF508 heterozygosity in cystic fibrosis and susceptibility to asthma

    DEFF Research Database (Denmark)

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

    1998-01-01

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

  18. Sex Disparities in Effects of Cystic Fibrosis-Related Diabetes on Clinical Outcomes: A Matched Study

    Directory of Open Access Journals (Sweden)

    Robert J Miller

    2008-01-01

    Full Text Available BACKGROUND: Cystic fibrosis-related diabetes (CFRD is an increasingly prevalent comorbidity factor for patients with cystic fibrosis (CF. CFRD has been associated with an accelerated decline in clinical parameters and an increased mortality rate.

  19. Airway Clearance Devices for Cystic Fibrosis

    Science.gov (United States)

    2009-01-01

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

  20. Cystic Fibrosis in the African Diaspora.

    Science.gov (United States)

    Stewart, Cheryl; Pepper, Michael S

    2017-01-01

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

  1. Phagocytosis of Pseudomonas aeruginosa by polymorphonuclear leukocytes and monocytes: effect of cystic fibrosis serum.

    OpenAIRE

    Thomassen, M J; Demko, C A; Wood, R.E.; Sherman, J. M.

    1982-01-01

    It has been shown previously that serum from chronically infected patients with cystic fibrosis inhibits the phagocytosis of Pseudomonas aeruginosa by both normal and cystic fibrosis alveolar macrophages. In the present study, the ability of peripheral monocytes and polymorphonuclear leukocytes from normal volunteers and cystic fibrosis patients to phagocytize P. aeruginosa was shown not to be inhibited in the presence of serum from cystic fibrosis patients.

  2. Draft genome sequences of four Achromobacter ruhlandii strains isolated from cystic fibrosis patients

    Science.gov (United States)

    Rodrigues, Elenice RA; Rocha, Géssica A; Ferreira, Alex G; Leão, Robson S; Albano, Rodolpho M; Marques, Elizabeth A

    2016-01-01

    Achromobacter species are being increasingly isolated from the respiratory tract of cystic fibrosis patients. Recent reports indicate that Achromobacter ruhlandii is a potential human pathogen in cystic fibrosis-related infections. Here we report the draft genome of four A. ruhlandii strains isolated from cystic fibrosis patients in Brazil. This report describes A. ruhlandii as a potential opportunistic pathogen in cystic fibrosis and provides a framework to for additional enquires into potential virulence factors and resistance mechanisms within this species. PMID:27812598

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

    Science.gov (United States)

    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.

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

    LENUS (Irish Health Repository)

    Reeves, Emer P

    2012-01-01

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

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

    DEFF Research Database (Denmark)

    Johansen, Helle Krogh; Gøtzsche, Peter C

    2015-01-01

    BACKGROUND: Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed...... in the vaccine group and 91 (1 severe) in the control group. In this large trial of a vaccine developed against flagella antigens, antibody titres against the epitopes contained in the vaccine were higher in the vaccine group compared to the placebo group (P Vaccines against....... This is an update of a previously published review. OBJECTIVES: To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30...

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

    Directory of Open Access Journals (Sweden)

    Emer P. Reeves

    2012-01-01

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

  7. Cystic fibrosis and pregnancy: counseling, obstetrical management and perinatal outcome.

    Science.gov (United States)

    Grigoriadis, Charalampos; Tympa, Aliki; Theodoraki, Kassiani

    2015-03-01

    The progress in research of in vitro fertilization and fetal-maternal medicine allows more women and men, with fertility problems due to cystic fibrosis, to have a baby. In the majority of cases, pregnancy in women with cystic fibrosis results in favorable maternal and fetal outcomes. However, the incidence of preterm delivery, intrauterine growth restriction, caesarean section and deterioration of the maternal health are increased. Pre-pregnancy counseling is a crucial component of overall obstetric care, especially in women with poor pulmonary function. Additionally, closer monitoring during pregnancy with a multidisciplinary approach is required. The value of serial ultrasound scans and fetal Doppler assessment is important for the control of maternal and fetal wellbeing, as well as for the definition of the appropriate timing of delivery. In this article, clinical issues of pregnant women with cystic fibrosis are reviewed; counseling, obstetrical management and perinatal outcomes are being discussed.

  8. Night blindness in a teenager with cystic fibrosis.

    LENUS (Irish Health Repository)

    Roddy, Marie Frances

    2011-12-01

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

  9. Mechanisms of the noxious inflammatory cycle in cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Freyssinet Jean-Marie

    2009-03-01

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

  10. Facial cystic lymphangioma in adults.

    Science.gov (United States)

    Biasotto, Matteo; Clozza, Emanuele; Tirelli, Giancarlo

    2012-07-01

    Lymphangiomas are uncommon congenital malformations of the lymphatic system, generally diagnosed during childhood. These malformations are rarely seen in adults, and the literature provides poor guidelines for treatment options that must be carefully applied to the facial region. Diagnosis in adult subjects is difficult to achieve, and also management of these conditions is still challenging because they tend to infiltrate adjacent tissues, causing frequent relapses. Radical surgery is the main form of treatment, avoiding the sacrifice of function or aesthetics of the patient. Two cases of cystic lymphangioma of the facial region found in adults are described from a clinical and pathologic point of view. The aim of this article was to point out that an early recognition of cystic lymphangioma is a crucial goal to initiate a prompt treatment avoiding serious complication.

  11. 21 CFR 866.5910 - Quality control material for cystic fibrosis nucleic acid assays.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 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...

  12. Gastroesophageal Reflux Disease in Children with Cystic Fibrosis.

    Science.gov (United States)

    Dziekiewicz, Marcin A; Banaszkiewicz, Aleksandra; Urzykowska, Agnieszka; Lisowska, Aleksandra; Rachel, Marta; Sands, Dorota; Walkowiak, Jaroslaw; Radzikowski, Andrzej; Albrecht, Piotr

    2015-01-01

    Previously published studies have indicated that gastroesophageal reflux (GER) disease is common in pediatric patients with cystic fibrosis. The aim of the present study was to get insight into the incidence of GER and to characterize the nature of reflux episodes in children with cystic fibrosis. This was a multicenter, prospective study of children with cystic fibrosis older than 18 months. Forty four consecutive patients (22 boys, mean age 10.4 ± 3.6, range 3.0-17.8 years) were enrolled into the study. All patients underwent 24 h pH-impedance monitoring. GER were classified according to the widely recognized criteria as an acid, weakly acid, weakly alkaline, or proximal. The pH-impedance trace was considered abnormal when acid exposure was >6 %. GER was diagnosed in 24/44 (54.5 %) children. A total of 1585 (median 35, range 7-128) reflux episodes were detected; 1199 (75.6 %) were acidic, 382 (24.1 %) weakly acidic, and 4 (0.3 %) weakly alkaline. Six hundred and ninety-one (43.6 %) reflux episodes reached the proximal esophagus. In 14/44 patients typical GER symptoms were present. We conclude that the incidence of GER in children with cystic fibrosis is very high. In the majority of patients typical GER symptoms are absent. Therefore, diagnostic procedures should be considered, regardless of lacking symptoms. Although acid reflux episodes predominate in children with cystic fibrosis, classical pH-metry may not constitute a sufficient diagnostic method in this population because of a relatively high number of proximal reflux episodes. Such episodes also indicate an increased risk for aspiration. The pH-impedance diagnostic measurement is advocated when suspecting GER in children with cystic fibrosis.

  13. The Approach to Pseudomonas aeruginosa in Cystic Fibrosis.

    Science.gov (United States)

    Talwalkar, Jaideep S; Murray, Thomas S

    2016-03-01

    There is a high prevalence of Pseudomonas aeruginosa in patients with cystic fibrosis and clear epidemiologic links between chronic infection and morbidity and mortality exist. Prevention and early identification of infection are critical, and stand to improve with the advent of new vaccines and laboratory methods. Once the organism is identified, a variety of treatment options are available. Aggressive use of antipseudomonal antibiotics is the standard of care for acute pulmonary exacerbations in cystic fibrosis, and providers must take into account specific patient characteristics when making treatment decisions related to antibiotic selection, route and duration of administration, and site of care.

  14. Microbial ecology and adaptation in cystic fibrosis airways

    DEFF Research Database (Denmark)

    Yang, Lei; Jelsbak, Lars; Molin, Søren

    2011-01-01

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

  15. Cystic fibrosis transmembrane conductance regulator (CFTR allelic variants relate to shifts in faecal microbiota of cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Serena Schippa

    Full Text Available INTRODUCTION: In this study we investigated the effects of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR gene variants on the composition of faecal microbiota, in patients affected by Cystic Fibrosis (CF. CFTR mutations (F508del is the most common lead to a decreased secretion of chloride/water, and to mucus sticky secretions, in pancreas, respiratory and gastrointestinal tracts. Intestinal manifestations are underestimated in CF, leading to ileum meconium at birth, or small bowel bacterial overgrowth in adult age. METHODS: Thirty-six CF patients, fasting and under no-antibiotic treatment, were CFTR genotyped on both alleles. Faecal samples were subjected to molecular microbial profiling through Temporal Temperature Gradient Electrophoresis and species-specific PCR. Ecological parameters and multivariate algorithms were employed to find out if CFTR variants could be related to the microbiota structure. RESULTS: Patients were classified by two different criteria: 1 presence/absence of F508del mutation; 2 disease severity in heterozygous and homozygous F508del patients. We found that homozygous-F508del and severe CF patients exhibited an enhanced dysbiotic faecal microbiota composition, even within the CF cohort itself, with higher biodiversity and evenness. We also found, by species-specific PCR, that potentially harmful species (Escherichia coli and Eubacterium biforme were abundant in homozygous-F508del and severe CF patients, while beneficial species (Faecalibacterium prausnitzii, Bifidobacterium spp., and Eubacterium limosum were reduced. CONCLUSIONS: This is the first report that establishes a link among CFTR variants and shifts in faecal microbiota, opening the way to studies that perceive CF as a 'systemic disease', linking the lung and the gut in a joined axis.

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

    Energy Technology Data Exchange (ETDEWEB)

    Rozen, R.; Ferreira-Rajabi, L.; Robb, L. [McGill Univ., Montreal, Quebec (Canada)] [and others

    1995-07-03

    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 a cohort of 7 French Canadian probands. 20 refs.

  17. Phylogenetic and metabolic diversity of bacteria associated with cystic fibrosis

    NARCIS (Netherlands)

    Roeselers, G.; Guss, A. M.; Newton, I. L. G.; Klepac-Ceraj, V.; Lory, S.; Cavanaugh, C. M.

    2010-01-01

    In patients afflicted with cystic fibrosis (CF), morbidity and mortality are primarily associated with the adverse consequences of chronic microbial bronchial infections, which are thought to be caused by a few opportunistic pathogens. However, recent evidence suggests the presence of other microorg

  18. THE METABOLIC EFFECTS OF PREGNANCY IN CYSTIC FIBROSIS

    Science.gov (United States)

    Our purpose was to determine glucose tolerance in pregnant women with cystic fibrosis (CF) and to relate glucose tolerance to insulin sensitivity, hepatic glucose production, and protein turnover. We studied 8 CF women during pregnancy (CFPreg). Results were compared with those from 9 pregnant contr...

  19. Cystic fibrosis heterozygotes do not have increased platelet activation

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    DEFF Research Database (Denmark)

    Madsen Sommer, Lea Mette

    of natural environments, the primary obstacle is re-sampling of the samepopulation over time, especially if the population is small.Nevertheless, it has been accomplished: Chronic airway infections of cystic fibrosis (CF) patients have offered a unique view into the adaptationand evolution of Pseudomonas...

  1. Risk of asthma in heterozygous carriers for cystic fibrosis

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  2. Shifting paradigms of nontuberculous mycobacteria in cystic fibrosis

    DEFF Research Database (Denmark)

    Qvist, Tavs; Pressler, Tania; Høiby, Niels;

    2014-01-01

    Important paradigms of pulmonary disease with nontuberculous mycobacteria (NTM) are currently shifting based on an increasing attention within the field of cystic fibrosis (CF). These shifts are likely to benefit the management of all patients with pulmonary NTM, regardless of underlying pathology...

  3. Serodiagnosis of Mycobacterium abscessus complex infection in cystic fibrosis

    DEFF Research Database (Denmark)

    Qvist, Tavs; Pressler, Tania; Taylor-Robinson, David;

    2015-01-01

    Early signs of pulmonary disease with Mycobacterium abscessus complex (MABSC) can be missed in patients with cystic fibrosis (CF). A serological method could help stratify patients according to risk. The objective of this study was to test the diagnostic accuracy of a novel method for investigating...

  4. Inspiratory muscle training in patients with cystic fibrosis

    NARCIS (Netherlands)

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

    2001-01-01

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

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  6. Students as Technicians: Screening Newborns for Cystic Fibrosis

    Science.gov (United States)

    Gusky, Sharon

    2014-01-01

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

  7. New and emerging targeted therapies for cystic fibrosis.

    Science.gov (United States)

    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.

  8. Predictive 5-Year Survivorship Model of Cystic Fibrosis

    Science.gov (United States)

    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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    pumps, bubble traps, gas exchange chip, and cell culture chambers. We have successfully applied this system for studying the antibiotic therapy of Pseudomonas aeruginosa, the bacteria mainly responsible for morbidity and mortality in cystic fibrosis, in different oxygen environments. Furthermore, we...

  10. Systematic review of N-acetylcysteine in cystic fibrosis

    NARCIS (Netherlands)

    Duijvestijn, YCM; Brand, PLP

    1999-01-01

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

  11. Cystic fibrosis gene mutations: evaluation and assessment of disease severity

    Directory of Open Access Journals (Sweden)

    Vallières E

    2014-10-01

    Full Text Available Emilie Vallières, Joseph Stuart ElbornCystic Fibrosis and Airways Microbiology Research Group, Queens University Belfast, Belfast, UKAbstract: The cystic fibrosis transmembrane regulator (CFTR gene encodes an ion channel transporter, the CFTR protein. Since its identification in 1989, more than 1,900 sequence variants have been reported, resulting in a wide spectrum of clinical phenotypes. Cystic fibrosis (CF is associated with many CFTR mutants and there is a continuum of disease severity observed. Recent advances in fundamental research have increased our understanding of the consequent molecular defect arising from CF mutations. This knowledge has resulted in the development of CF-specific therapies, targeting either the genetic or the molecular defect. CF care, previously focused on symptom control, is therefore moving toward a "stratified" or "precision" therapeutic approach. This review outlines normal CFTR physiology, the proposed pathologic mechanism underlying CF associated-lung injury, classification of CF mutations, and the CF-specific therapies recently approved or in clinical trials.Keywords: cystic fibrosis, gene mutations, disease severity, evaluation, assessment

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

    Directory of Open Access Journals (Sweden)

    Rolain Jean-Marc

    2011-09-01

    Full Text Available Abstract Background 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. Case presentation 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. Conclusion 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.

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

    DEFF Research Database (Denmark)

    Fluge, G; Ojeniyi, B; Høiby, N;

    2001-01-01

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

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

    DEFF Research Database (Denmark)

    Willumsen, Niels J.; Boucher, Richard C.

    1991-01-01

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

  15. A functional CFTR assay using primary cystic fibrosis intestinal organoids

    NARCIS (Netherlands)

    Dekkers, J.F.; Wiegerinck, C.L.; de Jonge, H.R.; Bronsveld, I.; Janssens, H.M.; de Winter-de Groot, K.M.; Brandsma, A.M.; de Jong, N.W.; Bijvelds, M.J.; Scholte, B.J.; Nieuwenhuis, E.E.; van den Brink, S.; Clevers, H.; van der Ent, C.K.; Middendorp, S.; Beekman, J.M.

    2013-01-01

    We recently established conditions allowing for long-term expansion of epithelial organoids from intestine, recapitulating essential features of the in vivo tissue architecture. Here we apply this technology to study primary intestinal organoids of people suffering from cystic fibrosis, a disease ca

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

    Energy Technology Data Exchange (ETDEWEB)

    Wilfond, B.S.; Fost, N. (Univ. of Wisconsin School of Medicine, Madison (USA))

    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 to 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.

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

    Science.gov (United States)

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

    2016-01-01

    Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with pre-existing inflammatory lung disease such as cystic fibrosis (CF). Pulmonary disease caused by NTM has emerged as a major threat to the health of individuals with CF but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened an expert panel of specialists to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM pulmonary disease in individuals with CF. Nineteen experts were invited to participate in the recommendation development process. Population, Intervention, Comparison, Outcome (PICO) methodology and systematic literature reviews were employed to inform draft recommendations. An anonymous voting process was used by the committee to reach consensus. All committee members were asked to rate each statement on a scale of: 0, completely disagree, to 9, completely agree; with 80% or more of scores between 7 and 9 being considered 'good' agreement. Additionally, the committee solicited feedback from the CF communities in the USA and Europe and considered the feedback in the development of the final recommendation statements. Three rounds of voting were conducted to achieve 80% consensus for each recommendation statement. Through this process, we have generated a series of pragmatic, evidence-based recommendations for the screening, investigation, diagnosis and treatment of NTM infection in individuals with CF as an initial step in optimising management for this challenging condition.

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

    Science.gov (United States)

    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

  19. Cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis: current perspectives

    Directory of Open Access Journals (Sweden)

    Schmidt BZ

    2016-09-01

    Full Text Available Béla Z Schmidt,1 Jérémy B Haaf,2 Teresinha Leal,2 Sabrina Noel,2 1Stem Cell Biology and Embryology, Department of Development and Regeneration, Katholieke Universiteit Leuven, Leuven, 2Louvain Center for Toxicology and Applied Pharmacology, Université Catholique de Louvain, Brussels, Belgium Abstract: Mutations of the CFTR gene cause cystic fibrosis (CF, the most common recessive monogenic disease worldwide. These mutations alter the synthesis, processing, function, or half-life of CFTR, the main chloride channel expressed in the apical membrane of epithelial cells in the airway, intestine, pancreas, and reproductive tract. Lung disease is the most critical manifestation of CF. It is characterized by airway obstruction, infection, and inflammation that lead to fatal tissue destruction. In spite of great advances in early and multidisciplinary medical care, and in our understanding of the pathophysiology, CF is still considerably reducing the life expectancy of patients. This review highlights the current development in pharmacological modulators of CFTR, which aim at rescuing the expression and/or function of mutated CFTR. While only Kalydeco® and Orkambi® are currently available to patients, many other families of CFTR modulators are undergoing preclinical and clinical investigations. Drug repositioning and personalized medicine are particularly detailed in this review as they represent the most promising strategies for restoring CFTR function in CF. Keywords: high-throughput screening, drug repositioning, personalized medicine, precision medicine, potentiators, correctors

  20. Cystic fibrosis transmembrane conductance regulator modulators in cystic fibrosis: current perspectives

    Science.gov (United States)

    Schmidt, Béla Z; Haaf, Jérémy B; Leal, Teresinha; Noel, Sabrina

    2016-01-01

    Mutations of the CFTR gene cause cystic fibrosis (CF), the most common recessive monogenic disease worldwide. These mutations alter the synthesis, processing, function, or half-life of CFTR, the main chloride channel expressed in the apical membrane of epithelial cells in the airway, intestine, pancreas, and reproductive tract. Lung disease is the most critical manifestation of CF. It is characterized by airway obstruction, infection, and inflammation that lead to fatal tissue destruction. In spite of great advances in early and multidisciplinary medical care, and in our understanding of the pathophysiology, CF is still considerably reducing the life expectancy of patients. This review highlights the current development in pharmacological modulators of CFTR, which aim at rescuing the expression and/or function of mutated CFTR. While only Kalydeco® and Orkambi® are currently available to patients, many other families of CFTR modulators are undergoing preclinical and clinical investigations. Drug repositioning and personalized medicine are particularly detailed in this review as they represent the most promising strategies for restoring CFTR function in CF.

  1. Plasma sCD14 as a Biomarker to Predict Pulmonary Exacerbations in Cystic Fibrosis

    OpenAIRE

    Quon, Bradley S.; Ngan, David A.; Wilcox, Pearce G; S F Paul Man; Don D Sin

    2014-01-01

    BACKGROUND: One in four cystic fibrosis (CF) patients diagnosed with a pulmonary exacerbation will not recover their baseline lung function despite standard treatment. This highlights the importance of preventing such events. Clinical decision-making can be improved through a simple blood test that predicts individuals at elevated short-term risk of an exacerbation. METHODS: We obtained plasma samples from 30 stable CF patients from the St. Paul's Hospital Adult CF Clinic (Vancouver, Canada)....

  2. Hemoglobin oxygen affinity in patients with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Dieter Böning

    Full Text Available In patients with cystic fibrosis lung damages cause arterial hypoxia. As a typical compensatory reaction one might expect changes in oxygen affinity of hemoglobin. Therefore position (standard half saturation pressure P50st and slope (Hill's n of the O2 dissociation curve as well as the Bohr coefficients (BC for CO2 and lactic acid were determined in blood of 14 adult patients (8 males, 6 females and 14 healthy controls (6 males, 8 females. While Hill's n amounted to approximately 2.6 in all subjects, P50st was slightly increased by 1 mmHg in both patient groups (controls male 26.7 ± 0.2, controls female 27.0 ± 0.1, patients male 27.7 ± 0.5, patients female 28.0 ± 0.3 mmHg; mean and standard error, overall p<0.01. Main cause was a rise of 1-2 µmol/g hemoglobin in erythrocytic 2,3-biphosphoglycerate concentration. One patient only, clearly identified as an outlier and with the mutation G551D, showed a reduction of both P50st (24.5 mmHg and [2,3-biphosphoglycerate] (9.8 µmol/g hemoglobin. There were no differences in BCCO2, but small sex differences in the BC for lactic acid in the controls which were not detectable in the patients. Causes for the right shift of the O2 dissociation curve might be hypoxic stimulation of erythrocytic glycolysis and an increased red cell turnover both causing increased [2,3-biphosphoglycerate]. However, for situations with additional hypercapnia as observed in exercising patients a left shift seems to be a more favourable adaptation in cystic fibrosis. Additionally when in vivo PO2 values were corrected to the standard conditions they mostly lay left of the in vitro O2 dissociation curve in both patients and controls. This hints to unknown fugitive factors influencing oxygen affinity.

  3. Imaging of cystic fibrosis lung disease and clinical interpretation

    Energy Technology Data Exchange (ETDEWEB)

    Wielpuetz, M.O.; Eichinger, M.; Kauczor, H.U. [Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology; Translational Lung Research Center Heidelberg (TLRC) (Germany); Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology with Nuclear Medicine; Biederer, J. [Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology; Translational Lung Research Center Heidelberg (TLRC) (Germany); Gross-Gerau Community Hospital (Germany). Radiologie Darmstadt; Wege, S. [Heidelberg University Hospital (Germany). Dept. of Pulmonology and Respiratory Medicine; Stahl, M.; Sommerburg, O. [Translational Lung Research Center Heidelberg (TLRC) (Germany); Heidelberg University Hospital (Germany). Div. of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center; Mall, M.A. [Translational Lung Research Center Heidelberg (TLRC) (Germany); Heidelberg University Hospital (Germany). Div. of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center; Heidelberg University Hospital (Germany). Dept. of Translational Pulmonology; Puderbach, M. [Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology; Translational Lung Research Center Heidelberg (TLRC) (Germany); Heidelberg University Hospital (Germany). Dept. of Diagnostic and Interventional Radiology with Nuclear Medicine; Hufeland Hospital, Bad Langensalza (Germany). Dept. of Diagnostic and Interventional Radiology

    2016-09-15

    Progressive lung disease in cystic fibrosis (CF) is the life-limiting factor of this autosomal recessive genetic disorder. Increasing implementation of CF newborn screening allows for a diagnosis even in pre-symptomatic stages. Improvements in therapy have led to a significant improvement in survival, the majority now being of adult age. Imaging provides detailed information on the regional distribution of CF lung disease, hence longitudinal imaging is recommended for disease monitoring in the clinical routine. Chest X-ray (CXR), computed tomography (CT) and magnetic resonance imaging (MRI) are now available as routine modalities, each with individual strengths and drawbacks, which need to be considered when choosing the optimal modality adapted to the clinical situation of the patient. CT stands out with the highest morphological detail and has often been a substitute for CXR for regular severity monitoring at specialized centers. Multidetector CT data can be post-processed with dedicated software for a detailed measurement of airway dimensions and bronchiectasis and potentially a more objective and precise grading of disease severity. However, changing to CT was inseparably accompanied by an increase in radiation exposure of CF patients, a young population with high sensitivity to ionizing radiation and lifetime accumulation of dose. MRI as a cross-sectional imaging modality free of ionizing radiation can depict morphological hallmarks of CF lung disease at lower spatial resolution but excels with comprehensive functional lung imaging, with time-resolved perfusion imaging currently being most valuable.

  4. Bone mineral density in cystic fibrosis: benefit of exercise capacity.

    Science.gov (United States)

    Dodd, Jonathan D; Barry, Sinead C; Barry, Rupert B M; Cawood, Tom J; McKenna, Malachi J; Gallagher, Charles G

    2008-01-01

    The aim of this study was to evaluate the association between bone mineral density (BMD) and objective maximal exercise measurements in adults with cystic fibrosis (CF). Twenty-five CF patients (19 males, 6 females, mean age 25.5 yr, range: 17-52) underwent BMD assessment and maximal-cycle ergometer exercise testing. We examined the relationship between gas exchange (% peak-predicted O(2) uptake, CO(2) output, O(2) saturation), exercise performance (maximum power, exercise duration), and respiratory mechanics (tidal volume, rate) with lumbar spine and total proximal femur BMD. The strongest clinical correlate with BMD was forced expiratory volume at 1s (lumbar spine Z-score, r=0.36; total proximal femur Z-score, r=0.68, pexercise correlate was % peak-predicted O(2) uptake (lumbar spine Z-score, r=0.44, pexercise parameters and total proximal femur BMD (r=0.43-0.60) than with lumbar spine BMD (r=0.04-0.45). Multiple regression analysis revealed VO(2) to be the strongest independent predictor of BMD (R(2)=0.86, pExercise appears to influence total proximal femur BMD more than lumbar spine BMD in CF. Exercise rehabilitation programs focusing on peripheral strength training may benefit those CF patients with low total proximal femur BMD.

  5. Neuromuscular fatigue after maximal exercise in patients with cystic fibrosis.

    Science.gov (United States)

    Vallier, J M; Gruet, M; Mely, L; Pensini, M; Brisswalter, J

    2011-04-01

    The aim of this study was to determine whether patients with cystic fibrosis (CF), despite their ventilatory limitation, would develop neuromuscular fatigue of quadriceps muscles following a maximal cycling exercise. Eleven adults with CF (age=26.8±6.9years; forced expiratory volume in 1s=54.1±12.8% predicted) and 11 age-matched healthy subjects performed a maximal incremental cycle test with respiratory gas exchange measurements. Maximal voluntary contraction (MVC) and electromyographic (EMG) activity of the vastus medialis muscle were recorded before and after exercise. Neural and contractile properties of the quadriceps were also investigated using femoral nerve electrical stimulation. Patients had lower exercise capacity, peak oxygen uptake and MVC than controls. MVC fell significantly postexercise in both groups (CF: -20±10%, controls: -19±6%; ppattern (-38.4±14.4%, -42.1±14.7% and -15±20.4%) but the statistical significance was not reached for the maximal rate of twitch torque relaxation. In conclusion, CF patients demonstrated lower limb fatigue following symptom-limited cycle exercise, which was comparable to that exhibited by healthy controls. This fatigue may be due to contractile impairments and not to transmission failure. Further studies should be conducted in a larger sample to confirm these preliminary results.

  6. Emergence of respiratory Streptococcus agalactiae isolates in cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Vera Eickel

    Full Text Available Streptococcus agalactiae is a well-known pathogen for neonates and immunocompromized adults. Beyond the neonatal period, S. agalactiae is rarely found in the respiratory tract. During 2002-2008 we noticed S. agalactiae in respiratory secretions of 30/185 (16% of cystic fibrosis (CF patients. The median age of these patients was 3-6 years older than the median age CF patients not harboring S. agalactiae. To analyze, if the S. agalactiae isolates from CF patients were clonal, further characterization of the strains was achieved by capsular serotyping, surface protein determination and multilocus sequence typing (MLST. We found a variety of sequence types (ST among the isolates, which did not substantially differ from the MLST patterns of colonizing strains from Germany. However serotype III, which is often seen in colonizing strains and invasive infections was rare among CF patients. The emergence of S. agalactiae in the respiratory tract of CF patients may represent the adaptation to a novel host environment, supported by the altered surfactant composition in older CF patients.

  7. Intestinal lesions are associated with altered intestinal microbiome and are more frequent in children and young adults with cystic fibrosis and cirrhosis.

    Directory of Open Access Journals (Sweden)

    Thomas Flass

    Full Text Available Cirrhosis (CIR occurs in 5-7% of cystic fibrosis (CF patients. We hypothesized that alterations in intestinal function in CF contribute to the development of CIR.Determine the frequency of macroscopic intestinal lesions, intestinal inflammation, intestinal permeability and characterize fecal microbiome in CF CIR subjects and CF subjects with no liver disease (CFnoLIV.11 subjects with CFCIR (6 M, 12.8 yrs ± 3.8 and 19 matched with CFnoLIV (10 M, 12.6 yrs ± 3.4 underwent small bowel capsule endoscopy, intestinal permeability testing by urinary lactulose: mannitol excretion ratio, fecal calprotectin determination and fecal microbiome characterization.CFCIR and CFnoLIV did not differ in key demographics or CF complications. CFCIR had higher GGT (59±51 U/L vs 17±4 p = 0.02 and lower platelet count (187±126 vs 283±60 p = 0.04 and weight (-0.86 ± 1.0 vs 0.30 ± 0.9 p = 0.002 z scores. CFCIR had more severe intestinal mucosal lesions on capsule endoscopy (score ≥4, 4/11 vs 0/19 p = 0.01. Fecal calprotectin was similar between CFCIR and CFnoLIV (166 μg/g ±175 vs 136 ± 193 p = 0.58, nl <120. Lactulose:mannitol ratio was elevated in 27/28 subjects and was slightly lower in CFCIR vs CFnoLIV (0.08±0.02 vs 0.11±0.05, p = 0.04, nl ≤0.03. Small bowel transit time was longer in CFCIR vs CFnoLIV (195±42 min vs 167±68 p<0.001, nl 274 ± 41. Bacteroides were decreased in relative abundance in CFCIR and were associated with lower capsule endoscopy score whereas Clostridium were more abundant in CFCIR and associated with higher capsule endoscopy score.CFCIR is associated with increased intestinal mucosal lesions, slower small bowel transit time and alterations in fecal microbiome. Abnormal intestinal permeability and elevated fecal calprotectin are common in all CF subjects. Disturbances in intestinal function in CF combined with changes in the microbiome may contribute to the development of hepatic fibrosis and intestinal lesions.

  8. Cystic fibrosis school for 10-year-olds

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke; Schiøtz, Peter Oluf

    2000-01-01

    on which they can make their own choices in order to improve their quality of life. In practical terms we make classes of 4-8 10-year-old children with CF. We give them 6 lessons of 3 hours. One lesson every second month. The lessons substitute a monthly visit. The psysiotherapist and the nurse teach...... give them a good basis on which they can make their own choices about how they want to live their lives with cystic fibrosis and with optimal quality of life.......Compliance or rather lack of compliance has always been a problem when treating patients with cystic fibrosis. The patients tend to drop the treatment more or less if the treatment gets too complicated or laboured. We have attempted a systematical education of our patients in a CF school...

  9. Family structure and mothers' caregiving of children with cystic fibrosis.

    Science.gov (United States)

    Gayer, Debra; Ganong, Lawrence

    2006-11-01

    The purpose of this investigation is to examine differences in the experiences of mothers of children with cystic fibrosis who are in diverse family structures (first-marriage families, stepfamily households, single-parent households). In particular, mothers' perceptions of children's health, adherence to prescribed treatments, and help received from others were compared and predictors of treatment adherence were examined. Children's health and adherence to treatment regimens were not related to family structure. Mothers had the major responsibility for seeing that cystic fibrosis treatments were followed, regardless of family structure. Single mothers received less help than married and repartnered mothers. Married fathers helped with treatments more than nonresidential divorced fathers and stepfathers. Implications for nursing practice and suggestions for future research are offered.

  10. ATPase activity of the cystic fibrosis transmembrane conductance regulator.

    Science.gov (United States)

    Li, C; Ramjeesingh, M; Wang, W; Garami, E; Hewryk, M; Lee, D; Rommens, J M; Galley, K; Bear, C E

    1996-11-08

    The gene mutated in cystic fibrosis codes for the cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic AMP-activated chloride channel thought to be critical for salt and water transport by epithelial cells. Plausible models exist to describe a role for ATP hydrolysis in CFTR channel activity; however, biochemical evidence that CFTR possesses intrinsic ATPase activity is lacking. In this study, we report the first measurements of the rate of ATP hydrolysis by purified, reconstituted CFTR. The mutation CFTRG551D resides within a motif conserved in many nucleotidases and is known to cause severe human disease. Following reconstitution the mutant protein exhibited both defective ATP hydrolysis and channel gating, providing direct evidence that CFTR utilizes ATP to gate its channel activity.

  11. Cystic Fibrosis-Related Diabetes in Children: An Update.

    Science.gov (United States)

    Kim, Roy J

    2016-09-01

    Cystic fibrosis-related diabetes mellitus (CFRD) is the most common endocrine complication of cystic fibrosis (CF), affecting more than 50% of patients by the 4th decade of life. CFRD is often preceded by worsening pulmonary status and nutritional decline. Treatment of CFRD is associated with improvements in body weight and pulmonary function and a reduction in pulmonary exacerbations. Because of the clinical significance of CFRD, diabetes screening with an oral glucose tolerance test (OGTT) is recommended annually for all patients with CF starting at age 10 years. The OGTT detects CFRD with greater sensitivity than random glucose or hemoglobin A1c testing. The first-line treatment for CFRD is insulin. The use of other treatments such as oral medications remains under study. [Pediatr Ann. 2016;45(9):e321-e326.].

  12. MicroRNA Expression in Cystic Fibrosis Airway Epithelium

    Directory of Open Access Journals (Sweden)

    Catherine M. Greene

    2013-02-01

    Full Text Available MicroRNAs (miRs have emerged as major regulators of the protein content of a cell. In the most part, miRs negatively regulate target mRNA expression, with sets of miRs predicted to regulate certain signaling pathways. The miR expression profile of endobronchial brushings is altered in people with cystic fibrosis (CF compared to those without CF. How this impacts on CF has important implications for our growing understanding of the pathophysiology of CF lung disease and the development of new therapeutics to treat its pulmonary manifestations. Herein we discuss the potential consequences of altered miR expression in CF airway epithelium particularly with respect to cystic fibrosis transmembrane conductance regulator (CFTR expression, innate immunity and toll-like receptor signalling and explore how best to exploit these changes for therapeutic benefit.

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

    Science.gov (United States)

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

    2012-10-01

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

  14. Antioxidant supplementation for lung disease in cystic fibrosis

    DEFF Research Database (Denmark)

    Ciofu, Oana; Lykkesfeldt, Jens

    2014-01-01

    BACKGROUND: Airway infection leads to progressive damage of the lungs in cystic fibrosis and oxidative stress has been implicated in the etiology. Supplementation of antioxidant micronutrients (vitamin E, vitamin C, ß-carotene and selenium) or glutathione may therefore potentially help maintain...... an oxidant-antioxidant balance. Current literature suggests a relationship between oxidative status and lung function. OBJECTIVES: To synthesize existing knowledge of the effect of antioxidants such as vitamin C, vitamin E, ß-carotene, selenium and glutathione in cystic fibrosis lung disease. SEARCH METHODS...... COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data and assessed the risk of bias in the included studies. We contacted trial investigators to obtain missing information. Primary outcomes are lung function and quality of life; secondary outcomes are oxidative stress...

  15. Glycosylation and the cystic fibrosis transmembrane conductance regulator

    Directory of Open Access Journals (Sweden)

    Glick Mary Catherine

    2001-08-01

    Full Text Available Abstract The cystic fibrosis transmembrane conductance regulator (CFTR has been known for the past 11 years to be a membrane glycoprotein with chloride channel activity. Only recently has the glycosylation of CFTR been examined in detail, by O'Riordan et al in Glycobiology. Using cells that overexpress wild-type (wtCFTR, the presence of polylactosamine was noted on the fully glycosylated form of CFTR. In the present commentary the results of that work are discussed in relation to the glycosylation phenotype of cystic fibrosis (CF, and the cellular localization and processing of ΔF508 CFTR. The significance of the glycosylation will be known when endogenous CFTR from primary human tissue is examined.

  16. Inflammation in Achromobacter xylosoxidans infected cystic fibrosis patients

    DEFF Research Database (Denmark)

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

    2010-01-01

    BACKGROUND: Achromobacter xylosoxidans infection may cause conspicuous chronic pulmonary inflammation in cystic fibrosis (CF) patients similar to Pseudomonas aeruginosa and the Burkholderia cepacia complex (Bcc). Evolution in lung function was compared in chronically infected patients. Cytokine...... patients. CONCLUSION: A. xylosoxidans can cause a level of inflammation similar to P. aeruginosa in chronically infected CF patients. A. xylosoxidans is a clinically important pathogen in CF and should be treated accordingly....

  17. Cystic Fibrosis%囊性纤维化

    Institute of Scientific and Technical Information of China (English)

    李海潮

    2006-01-01

    囊性纤维化(Cystic Fibrosis,CF)的主要病生理改变为外分泌腺功能紊乱,可引起慢性肺部疾病、胰腺外分泌功能低下以及汗液氯化钠含量增高等特征性病变,好发于白种人.

  18. Inspiratory muscle training in patients with cystic fibrosis

    OpenAIRE

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

    2001-01-01

    Little information is available about the effects of inspiratory muscle training in patients with cystic fibrosis (CF). In this study the effects of inspiratory-threshold loading in patients with CF on strength and endurance of the inspiratory muscles, pulmonary function, exercise capacity, dyspnoea and fatigue were evaluated. Sixteen patients were assigned to one of two groups using the minimization method: eight patients in the training group and eight patients in the control group. The tra...

  19. Immunisation in the current management of cystic fibrosis patients

    DEFF Research Database (Denmark)

    Malfroot, Anne; Adam, Georgios; Ciofu, Oana;

    2005-01-01

    for palivizumab in CF as an alternative but expensive prophylaxis. Anti-bacterial vaccinations protecting directly against Pseudomonas aeruginosa colonisation are promising for the future, potential candidates are currently being assessed in phase III clinical trials. More studies are needed to complete......Although no special recommendations exist, clearly patients with cystic fibrosis (CF) can benefit from immunisation. We reviewed the literature regarding vaccination in CF and other chronic diseases. CF subjects should follow national immunisation programmes without delay to obtain optimal...

  20. Increased Congregational Support for Parents of Children with Cystic Fibrosis

    OpenAIRE

    Szczesniak, Rhonda D.; Zou, Yuanshu; Wetzel, J. Denise; Krause, Neal; Grossoehme, Daniel H.

    2015-01-01

    Positive health outcomes are related to adults’ religious congregational participation. For parents of children with chronic disease, structured daily care routines and or strict infection-control precautions may limit participation. For this exploratory study, we examined the relationship between congregational support and religious coping by parents of children with cystic fibrosis (CF) compared to parents for whom child health issues were not significant stressors. CF parents reported high...

  1. Cystic Fibrosis Gene Therapy in the UK and Elsewhere.

    Science.gov (United States)

    Griesenbach, Uta; Pytel, Kamila M; Alton, Eric W F W

    2015-05-01

    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.

  2. Impaired Pancreatic Ductal Bicarbonate Secretion in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Soleimani M

    2001-07-01

    Full Text Available Patients with cystic fibrosis demonstrate a defect in HCO(3(- secretion by their pancreatic duct cells. However, attempts toward understanding or correcting this defect have been hampered by a lack of knowledge regarding the cellular and molecular mechanisms mediating HCO(3(- transport in these cells. Recent functional and molecular studies indicate a major role for a basolateral electrogenically-driven Na(+:HCO(3(- cotransporter (NBC1 in mediating the transport of HCO(3(- into the duct cells. The HCO(3(- exits at the lumen predominantly via two recently discovered apical HCO(3(- transporters. cAMP, which mediates the stimulatory effect of secretin on pancreatic ductal HCO(3(- secretion, potentiates the basolateral Na(+:HCO(3(- cotransporter due to generation of a favorable electrogenic gradient as a result of membrane depolarization by Cl(--secreting cystic fibrosis transmembrane conductance regulator (CFTR. Two apical HCO(3(- transporters drive the secretion of bicarbonate into the pancreatic duct lumen. Molecular and functional studies indicate that CFTR upregulates the expression of these two apical HCO(3(- transporters. In addition, CFTR may also upregulate the expression of certain water channels and facilitate the secretion of fluid into the duct lumen. In brief, current research suggests that the defect in pancreatic HCO(3(- secretion in patients with cystic fibrosis is multifactorial and involves the alteration in the function/expression of transporters at the basolateral and luminal membrane domains of the duct cells.

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

    LENUS (Irish Health Repository)

    Deighan, M

    2014-02-01

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

  4. CFTR and Ca2+ signaling in cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Fabrice eAntigny

    2011-10-01

    Full Text Available Among the diverse physiological functions exerted by calcium signaling in living cells, its role in the regulation of protein biogenesis and trafficking remains incompletely understood. In cystic fibrosis (CF disease the most common CFTR (Cystic Fibrosis Transmembrane conductance Regulator mutation, F508del-CFTR generates a misprocessed protein that is abnormally retained in the endoplasmic reticulum (ER compartment, rapidly degraded by the ubiquitine/proteasome pathway and hence absent at the plasma membrane of CF epithelial cells. Recent studies have demonstrated that intracellular calcium signals consequent to activation of apical G protein-coupled receptors (GPCRs by different agonists are increased in CF airway epithelia. Moreover, the regulation of various intracellular calcium storage compartments, such as ER is also abnormal in CF cells. Although the molecular mechanism to explain this increase remains puzzling in epithelial cells, the F508del-CFTR mutation is proposed to be the origin of abnormal Ca2+ influx linking the calcium signaling to CFTR pathobiology. This article reviews the relationships between CFTR and calcium signaling in the context of the genetic disease cystic fibrosis.

  5. Acute Muscle Trauma due to Overexercise in an Otherwise Healthy Patient with Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Henning Neubauer

    2012-01-01

    Full Text Available Cystic fibrosis (CF is one of the most common inherited diseases and is caused by mutations in the CFTR gene. Although the pulmonary and gastrointestinal manifestations of the disease remain in the focus of treatment, recent studies have shown expression of the CFTR gene product in skeletal muscle cells and observed altered intramuscular Ca2+ release dynamics in CFTR-deficient animal models. Physical exercise is beneficial for maintaining fitness and well-being in CF patients and constitutes one aspect of modern multimodal treatment, which has considerably increased life span and reduced morbidity. We report on a case of acute muscle trauma resulting from excessive dumbbell exercise in a young adult with cystic fibrosis and describe clinical, laboratory and imaging characteristics of acute exercise-induced muscle injury.

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

    OpenAIRE

    Coutinho, Henrique Douglas M.; Falcão-Silva,Vivyanne S.; Gonçalves, Gregório Fernandes

    2008-01-01

    Cystic fibrosis is the most common and best known genetic disease involving a defect in transepithelial Cl- transport by mutations in the CF gene on chromosome 7, which codes for the cystic fibrosis transmembrane conductance regulator protein (CFTR). The most serious symptoms are observed in the lungs, augmenting the risk of bacterial infection. The objective of this review was to describe the bacterial pathogens colonizing patients with cystic fibrosis. A systematic search was conducted usin...

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

    Science.gov (United States)

    Prieto, Claudia I; Palau, María J; Martina, Pablo; Achiary, Carlos; Achiary, Andrés; Bettiol, Marisa; Montanaro, Patricia; Cazzola, María L; Leguizamón, Mariana; Massillo, Cintia; Figoli, Cecilia; Valeiras, Brenda; Perez, Silvia; Rentería, Fernando; Diez, Graciela; Yantorno, Osvaldo M; Bosch, Alejandra

    2016-01-01

    The epidemiological and clinical management of cystic fibrosis (CF) patients suffering from acute pulmonary exacerbations or chronic lung infections demands continuous updating of medical and microbiological processes associated with the constant evolution of pathogens during host colonization. In order to monitor the dynamics of these processes, it is essential to have expert systems capable of storing and subsequently extracting the information generated from different studies of the patients and microorganisms isolated from them. In this work we have designed and developed an on-line database based on an information system that allows to store, manage and visualize data from clinical studies and microbiological analysis of bacteria obtained from the respiratory tract of patients suffering from cystic fibrosis. The information system, named Cystic Fibrosis Cloud database is available on the http://servoy.infocomsa.com/cfc_database site and is composed of a main database and a web-based interface, which uses Servoy's product architecture based on Java technology. Although the CFC database system can be implemented as a local program for private use in CF centers, it can also be used, updated and shared by different users who can access the stored information in a systematic, practical and safe manner. The implementation of the CFC database could have a significant impact on the monitoring of respiratory infections, the prevention of exacerbations, the detection of emerging organisms, and the adequacy of control strategies for lung infections in CF patients.

  8. DEATH BY VOLUNTARY CESSATION OF THERAPY BY NON-TERMINALLY ILL CYSTIC FIBROSIS PATIENTS - INTERNATIONAL SURVEY OF CLINICIANS

    OpenAIRE

    PISATURO, M.

    2014-01-01

    Background: Little is known about non-terminally ill cystic fibrosis (CF) patients who die by voluntary cessation of therapy. The current study was undertaken to provide an international snapshot of this problem. Methods: An online survey was distributed to the medical directors of the CF Centres affiliated with the US Cystic Fibrosis Foundation and Cystic Fibrosis Australia (with the inclusion of New Zealand); the same letter was sent to every clinician member of the European Cystic Fibrosis...

  9. Respiratory viral infections and interaction with bacteria in children with cystic fibrosis

    NARCIS (Netherlands)

    van Ewijk, E.

    2008-01-01

    Cystic fibrosis (CF) is one of the most common lethal autosomal recessive disorders in the Caucasian population. Mutations of the cystic fibrosis transregulator membrane gene cause the body to produce thick, sticky mucus. In the lungs this results in obstruction of the airways associated with chroni

  10. Modifying Factors of Cystic Fibrosis Disease: Residual Chloride Secrefion, Genefic Background and Epigenetics

    NARCIS (Netherlands)

    I. Bronsveld (Inez)

    2000-01-01

    textabstractCystic fibrosis (CF) is an autosomal recessive disease caused by genetic lesions in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This CFTR gene was cloned in 1989,1-3 and located to the long arm of chromosome 7 (7q3L2). lt encodes the CFTR protein that functions a

  11. β2-Adrenergic receptor agonists activate CFTR in intestinal organoids and subjects with cystic fibrosis

    NARCIS (Netherlands)

    Vijftigschild, Lodewijk A W; Berkers, Gitte; Dekkers, Johanna F; Zomer-van Ommen, Domenique D; Matthes, Elizabeth; Kruisselbrink, Evelien; Vonk, Annelotte; Hensen, Chantal E; Heida-Michel, Sabine; Geerdink, Margot; Janssens, Hettie M; van de Graaf, Eduard A; Bronsveld, Inez; de Winter-de Groot, Karin M; Majoor, Christof J; Heijerman, Harry G M; de Jonge, Hugo R; Hanrahan, John W; van der Ent, Cornelis K; Beekman, Jeffrey M

    2016-01-01

    We hypothesized that people with cystic fibrosis (CF) who express CFTR (cystic fibrosis transmembrane conductance regulator) gene mutations associated with residual function may benefit from G-protein coupled receptor (GPCR)-targeting drugs that can activate and enhance CFTR function.We used intesti

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

    Science.gov (United States)

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

    2014-01-01

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

  13. Cystic Fibrosis Survival Better in Canada Than in U.S.

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_164055.html Cystic Fibrosis Survival Better in Canada Than in U.S. Canadians ... MONDAY, March 13, 2017 (HealthDay News) -- People with cystic fibrosis are living longer than ever, but those in ...

  14. Cystic Fibrosis in a Female Infant with Cardiac, Ocular, and Musculoskeletal Anomalies

    Directory of Open Access Journals (Sweden)

    Azhar Farooqui

    2015-01-01

    Full Text Available Cystic fibrosis (CF remains the most common hereditary disease in the western population. Its concomitant presence with other congenital abnormalities is a rare phenomenon with very little documentation. In this case report we describe a case of cystic fibrosis in a female infant with cardiac, ocular, and musculoskeletal abnormalities. A brief literature review is also provided.

  15. Draft Genome Sequence of Triclosan-Resistant Cystic Fibrosis Isolate Achromobacter xylosoxidans CF304.

    Science.gov (United States)

    Jeukens, Julie; Freschi, Luca; Kukavica-Ibrulj, Irena; Nguyen, Dao; Levesque, Roger C

    2015-07-30

    Achromobacter xylosoxidans is an emerging opportunistic pathogen. Here, we present the genome sequence of cystic fibrosis isolate CF304. Assembly resulted in 29 contigs adding up to 6.3 Mbp. This is the second genome sequence for a cystic fibrosis isolate, and little is known about the genetic basis of pathogenicity in this organism.

  16. Critical Role of Cystic Fibrosis Transmembrane Conductance Regulation(CFTR)in Female Reproduction

    Institute of Scientific and Technical Information of China (English)

    Hsiao Chang CHAN

    2003-01-01

    @@ Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated Cl- channel, mutations of which are responsible for defective Cl- and/or HCO-3 secretions seen in cystic fibrosis (CF), a common lethal genetic disease affecting most exocrine glands/organs, including the lungs, intestine, pancreas and reproductive tracts of both sexes.

  17. Intestinal organoids and personalized medicine in cystic fibrosis : A successful patient-oriented research collaboration

    NARCIS (Netherlands)

    Noordhoek, Jacquelien; Gulmans, Vincent; van der Ent, Kors; Beekman, Jeffrey M.

    2016-01-01

    Purpose of review New therapeutics have been introduced for cystic fibrosis that modulate cystic fibrosis transmembrane conductance regulator (CFTR) function in a mutation-specific fashion. Despite CFTR genotype-based stratification of treatments, treatment efficacy is variable between study partici

  18. Optimal correction of distinct CFTR folding mutants in rectal cystic fibrosis organoids

    NARCIS (Netherlands)

    Dekkers, Johanna F; Gogorza Gondra, Ricardo A; Kruisselbrink, Evelien; Vonk, Annelotte M; Janssens, Hettie M; de Winter-de Groot, Karin M; van der Ent, Cornelis K; Beekman, Jeffrey M

    2016-01-01

    Small-molecule therapies that restore defects in cystic fibrosis transmembrane conductance regulator (CFTR) gating (potentiators) or trafficking (correctors) are being developed for cystic fibrosis (CF) in a mutation-specific fashion. Options for pharmacological correction of CFTR-p.Phe508del (F508d

  19. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis

    NARCIS (Netherlands)

    Dekkers, Johanna F; Berkers, Gitte; Kruisselbrink, Evelien; Vonk, Annelotte; de Jonge, Hugo R; Janssens, Hettie M; Bronsveld, Inez; van de Graaf, Eduard A; Nieuwenhuis, Edward E S; Houwen, Roderick H J; Vleggaar, Frank P; Escher, Johanna C; de Rijke, Yolanda B; Majoor, Christof J; Heijerman, Harry G M; de Winter-de Groot, Karin M; Clevers, Hans; van der Ent, Cornelis K; Beekman, Jeffrey M

    2016-01-01

    Identifying subjects with cystic fibrosis (CF) who may benefit from cystic fibrosis transmembrane conductance regulator (CFTR)-modulating drugs is time-consuming, costly, and especially challenging for individuals with rare uncharacterized CFTR mutations. We studied CFTR function and responses to tw

  20. Reduced Arylsulfatase B Activity in Leukocytes from Cystic Fibrosis Patients

    Science.gov (United States)

    Sharma, Girish; Burke, Jenifer; Bhattacharyya, Sumit; Sharma, Neha; Katyal, Shivani; Park, R. Lucy; Tobacman, Joanne

    2013-01-01

    Summary The enzyme Arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) removes 4-sulfate groups from chondroitin-4-sulfate and dermatan sulfate and is required for the degradation of these sulfated glycosaminoglycans (GAGs). Since these GAGs accumulate in patients with Cystic Fibrosis (CF), we investigated the activity of ARSB in leukocytes of patients with CF, to consider if reduced activity of ARSB might contribute to the pathophysiology of CF. Previous cell-based experiments had demonstrated that when the deficiency of the cystic fibrosis transmembrane regulator (CFTR) was corrected in bronchial epithelial cells, the ARSB activity increased significantly. De-identified, citrated blood samples were collected from 16 children with cystic fibrosis and 31 control subjects, seen in the Pediatric Clinic at Rush University Medical Center. Polymorphonuclear (PMN) and mononuclear cell (MC) populations were separated by density gradient, and blinded determinations of ARSB activity were performed using the exogenous substrate 4-methylumbilliferyl sulfate. Interleukin-6 was measured in the plasma samples by ELISA. ARSB activity was significantly less in the PMN and MC from the CF patients than controls (p<0.0001, unpaired t-test, two-tailed). Interleukin-6 levels in plasma were significantly greater in the CF population (p<0.001). Mean age, age range, and male:female ratio of CF patients and controls were similar, and no association of ARSB activity with age, gender, or CFTR genotype was evident. Since recombinant human ARSB is used successfully for replacement therapy in Mucopolysaccharidosis VI, it may be useful to restore ARSB activity to normal levels and increase degradation of sulfated GAGs in CF patients. PMID:22550062

  1. Gene therapy for the treatment of cystic fibrosis.

    Science.gov (United States)

    Burney, Tabinda J; Davies, Jane C

    2012-01-01

    Gene therapy is being developed as a novel treatment for cystic fibrosis (CF), a condition that has hitherto been widely-researched yet for which no treatment exists that halts the progression of lung disease. Gene therapy involves the transfer of correct copies of cystic fibrosis transmembrane conductance regulator (CFTR) DNA to the epithelial cells in the airways. The cloning of the CFTR gene in 1989 led to proof-of-principle studies of CFTR gene transfer in vitro and in animal models. The earliest clinical trials in CF patients were conducted in 1993 and used viral and non-viral gene transfer agents in both the nasal and bronchial airway epithelium. To date, studies have focused largely on molecular or bioelectric (chloride secretion) outcome measures, many demonstrating evidence of CFTR expression, but few have attempted to achieve clinical efficacy. As CF is a lifelong disease, turnover of the airway epithelium necessitates repeat administration. To date, this has been difficult to achieve with viral gene transfer agents due to host recognition leading to loss of expression. The UK Cystic Fibrosis Gene Therapy Consortium (Imperial College London, University of Edinburgh and University of Oxford) is currently working on a large and ambitious program to establish the clinical benefits of CF gene therapy. Wave 1, which has reached the clinic, uses a non-viral vector. A single-dose safety trial is nearing completion and a multi-dose clinical trial is shortly due to start; this will be powered for clinically-relevant changes. Wave 2, more futuristically, will look at the potential of lentiviruses, which have long-lasting expression. This review will summarize the current status of translational research in CF gene therapy.

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

    Directory of Open Access Journals (Sweden)

    V Moeeni

    2014-04-01

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

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

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke; Erwander, Inger

    2006-01-01

    /CF comprises one CF nurse from each of the centers. The board meets twice a year to plan workshops and courses. SNSG/CF is part of the International Nurse Specialist Group/Cystic Fibrosis (INSG/CF). Results: Within the framework of SNSG/CF a 2-day workshop is held every second year for approximately 40......Aims: SNSG/CF was established to stimulate and improve cooperation between CF nurses from Scandinavian CF centers. Methods: SNSG/CF includes all the CF centers in Norway (Oslo and Bergen), Sweden (Stockholm, Gothenburg, Lund and Uppsala) and Denmark (Copenhagen and Aarhus). The board of SNSG...

  4. Gene therapy for the treatment of cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Burney TJ

    2012-05-01

    Full Text Available Tabinda J Burney1,2, Jane C Davies1,2,31Department of Gene therapy, Imperial College London, 2UK CF Gene Therapy Consortium London, 3Department of Paediatric Respiratory Medicine, Royal Brompton and Harefield NHS Foundation Trust, London, UKAbstract: Gene therapy is being developed as a novel treatment for cystic fibrosis (CF, a condition that has hitherto been widely-researched yet for which no treatment exists that halts the progression of lung disease. Gene therapy involves the transfer of correct copies of cystic fibrosis transmembrane conductance regulator (CFTR DNA to the epithelial cells in the airways. The cloning of the CFTR gene in 1989 led to proof-of-principle studies of CFTR gene transfer in vitro and in animal models. The earliest clinical trials in CF patients were conducted in 1993 and used viral and non-viral gene transfer agents in both the nasal and bronchial airway epithelium. To date, studies have focused largely on molecular or bioelectric (chloride secretion outcome measures, many demonstrating evidence of CFTR expression, but few have attempted to achieve clinical efficacy. As CF is a lifelong disease, turnover of the airway epithelium necessitates repeat administration. To date, this has been difficult to achieve with viral gene transfer agents due to host recognition leading to loss of expression. The UK Cystic Fibrosis Gene Therapy Consortium (Imperial College London, University of Edinburgh and University of Oxford is currently working on a large and ambitious program to establish the clinical benefits of CF gene therapy. Wave 1, which has reached the clinic, uses a non-viral vector. A single-dose safety trial is nearing completion and a multi-dose clinical trial is shortly due to start; this will be powered for clinically-relevant changes. Wave 2, more futuristically, will look at the potential of lentiviruses, which have long-lasting expression. This review will summarize the current status of translational

  5. Gene therapy for the treatment of cystic fibrosis

    OpenAIRE

    2012-01-01

    Tabinda J Burney1,2, Jane C Davies1,2,31Department of Gene therapy, Imperial College London, 2UK CF Gene Therapy Consortium London, 3Department of Paediatric Respiratory Medicine, Royal Brompton and Harefield NHS Foundation Trust, London, UKAbstract: Gene therapy is being developed as a novel treatment for cystic fibrosis (CF), a condition that has hitherto been widely-researched yet for which no treatment exists that halts the progression of lung disease. Gene therapy invol...

  6. Hepatocellular carcinoma complicating cystic fibrosis related liver disease.

    LENUS (Irish Health Repository)

    O'Donnell, D H

    2012-02-01

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

  7. Fluoroquinolones in the treatment of bronchopulmonary disease in cystic fibrosis.

    Science.gov (United States)

    Hurley, Matthew; Smyth, Alan

    2012-12-01

    Fluoroquinolones are commonly used to treat lung infections in patients with cystic fibrosis. These patients are susceptible to lung infection with common bacteria such as Staphylococcus aureus and Haemophilus influenzae, but are also prone to infection by opportunistic bacteria, including Pseudomonas aeruginosa. The good oral bioavailability and broad antimicrobial spectrum of activity, including antipseudomonal properties, make this class of antimicrobial attractive. We review the evidence assessing the use of fluoroquinolones in the context of preventing and eradicating early lung infection and in managing chronic lung infection and pulmonary exacerbations. The safety of fluoroquinolones and the use of newer agents in the class are also discussed.

  8. State of progress in treating cystic fibrosis respiratory disease

    Directory of Open Access Journals (Sweden)

    Flume Patrick A

    2012-08-01

    Full Text Available Abstract Since the discovery of the gene associated with cystic fibrosis (CF, there has been tremendous progress in the care of patients with this disease. New therapies have entered the market and are part of the standard treatment of patients with CF, and have been associated with marked improvement in survival. Now there are even more promising therapies directed at different components of the pathophysiology of this disease. In this review, our current knowledge of the pathophysiology of lung disease in patients with CF is described, along with the current treatment of CF lung disease, and the therapies in development that offer great promise to our patients.

  9. Imaging from cystic fibrosis; Bildgebung bei zystischer Fibrose

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, H. [Frankfurt Univ. (Germany). Funktionsbereich Paediatrische Radiologie; Posselt, H.G. [Frankfurt Univ. (Germany). Zentrum fuer Paediatrische Gastroenterologie und Mukoviszidose

    2008-06-15

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

  10. Developing a handheld record for patients with cystic fibrosis

    Science.gov (United States)

    Narayan, Omendra; Davies, Siobhan; Tibbins, Carly; Rees, JH Martyn; Lenney, Warren; Gilchrist, Francis J

    2015-01-01

    Patient handheld records (PHHRs) promote self-management and empower the holder to take a more active role in the management of their disease. They have been used successfully in improving preventative care for children and have contributed to improved adherence in a number of chronic illnesses. Despite the potential advantages, there are no standard PHHRs for patients with cystic fibrosis (CF). We report the consultation process that led to the development of a CF PHHR, describe the final document, and analyze the feedback from their use at our center. We have made the CF PHHR freely available online. PMID:26316833

  11. Taking stock of gene therapy for cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Alton Eric WFW

    2000-09-01

    Full Text Available Abstract The identification of the cystic fibrosis (CF gene opened the way for gene therapy. In the ten years since then, proof of principle in vitro and then in animal models in vivo has been followed by numerous clinical studies using both viral and non-viral vectors to transfer normal copies of the gene to the lungs and noses of CF patients. A wealth of data have emerged from these studies, reflecting enormous progress and also helping to focus and define key difficulties that remain unresolved. Gene therapy for CF remains the most promising possibility for curative rather than symptomatic therapy.

  12. Health Human Resources Guidelines: Minimum Staffing Standards and Role Descriptions for Canadian Cystic Fibrosis Healthcare Teams.

    Science.gov (United States)

    McIntosh, Ian D

    2016-01-01

    In cystic fibrosis clinics across Canada, the most common barrier that healthcare workers face when providing care to their patients is having too little time. The Health Human Resources Guidelines were developed to define specifically what amounts of time should be allocated for each discipline of cystic fibrosis clinical care and to provide a description of all the roles involved, reinforcing how these work together to provide comprehensive multidisciplinary care. With involvement from all cystic fibrosis clinics in Canada, through the use of a tailored survey, the Health Human Resources Guidelines are an exclusively Canadian document that has been developed for implementation across the country. The guidelines have been incorporated into a national Accreditation Site Visit program for use in evaluating and improving care across the country and have been distributed to all Canadian cystic fibrosis clinics. The guidelines provide hospital administrators with clear benchmarks for allocating personnel resources to the cystic fibrosis clinics hosted within their institutions.

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

    Directory of Open Access Journals (Sweden)

    Kalnins D

    2012-06-01

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

  14. Impact of gene patents and licensing practices on access to genetic testing for cystic fibrosis.

    Science.gov (United States)

    Chandrasekharan, Subhashini; Heaney, Christopher; James, Tamara; Conover, Chris; Cook-Deegan, Robert

    2010-04-01

    Cystic fibrosis is one of the most commonly tested autosomal recessive disorders in the United States. Clinical cystic fibrosis is associated with mutations in the CFTR gene, of which the most common mutation among Caucasians, DeltaF508, was identified in 1989. The University of Michigan, Johns Hopkins University, and the Hospital for Sick Children, where much of the initial research occurred, hold key patents on cystic fibrosis genetic sequences, mutations, and methods for detecting them. Several patents, including the one that covers detection of the DeltaF508 mutation, are jointly held by the University of Michigan and the Hospital for Sick Children in Toronto, with Michigan administering patent licensing in the United States. The University of Michigan broadly licenses the DeltaF508 patent for genetic testing with >60 providers of genetic testing to date. Genetic testing is now used in newborn screening, diagnosis, and for carrier screening. Interviews with key researchers and intellectual property managers, a survey of laboratories' prices for cystic fibrosis genetic testing, a review of literature on cystic fibrosis tests' cost-effectiveness, and a review of the developing market for cystic fibrosis testing provide no evidence that patents have significantly hindered access to genetic tests for cystic fibrosis or prevented financially cost-effective screening. Current licensing practices for cystic fibrosis genetic testing seem to facilitate both academic research and commercial testing. More than 1000 different CFTR mutations have been identified, and research continues to determine their clinical significance. Patents have been nonexclusively licensed for diagnostic use and have been variably licensed for gene transfer and other therapeutic applications. The Cystic Fibrosis Foundation has been engaged in licensing decisions, making cystic fibrosis a model of collaborative and cooperative patenting and licensing practice.

  15. Key findings of the US Cystic Fibrosis Foundation's clinical practice benchmarking project.

    Science.gov (United States)

    Boyle, Michael P; Sabadosa, Kathryn A; Quinton, Hebe B; Marshall, Bruce C; Schechter, Michael S

    2014-04-01

    Benchmarking is the process of using outcome data to identify high-performing centres and determine practices associated with their outstanding performance. The US Cystic Fibrosis Foundation (CFF) Patient Registry contains centre-specific outcomes data for all CFF-certified paediatric and adult cystic fibrosis (CF) care programmes in the USA. The CFF benchmarking project analysed these registry data, adjusting for differences in patient case mix known to influence outcomes, and identified the top-performing US paediatric and adult CF care programmes for pulmonary and nutritional outcomes. Separate multidisciplinary paediatric and adult benchmarking teams each visited 10 CF care programmes, five in the top quintile for pulmonary outcomes and five in the top quintile for nutritional outcomes. Key practice patterns and approaches present in both paediatric and adult programmes with outstanding clinical outcomes were identified and could be summarised as systems, attitudes, practices, patient/family empowerment and projects. These included: (1) the presence of strong leadership and a well-functioning care team working with a systematic approach to providing consistent care; (2) high expectations for outcomes among providers and families; (3) early and aggressive management of clinical declines, avoiding reliance on 'rescues'; and (4) patients/families that were engaged, empowered and well informed on disease management and its rationale. In summary, assessment of practice patterns at CF care centres with top-quintile pulmonary and nutritional outcomes provides insight into characteristic practices that may aid in optimising patient outcomes.

  16. Decoding F508del Misfolding in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Xiaodong Robert Wang

    2014-05-01

    Full Text Available The functional deficiency of the cystic fibrosis transmembrane conductance regulator (CFTR, a plasma membrane chloride channel, leads to the development of cystic fibrosis. The deletion of a phenylalanine at residue 508 (F508del is the most common cause of CFTR misfolding leading to the disease. The F508del misfolding originates in the first nucleotide-binding domain (NBD1, which induces a global conformational change in CFTR through NBD1’s interactions with other domains. Such global misfolding produces a mutant chloride channel that is impaired in exocytic trafficking, peripheral stability, and channel gating. The nature and atomic details of F508del misfolding have been subject to extensive research during the past decade. Current data support a central role for NBD1 in F508del misfolding and rescue. Many cis-acting NBD1 second-site mutations rescue F508del misfolding in the context of full-length CFTR. While some of these mutations appear to specifically counteract the F508del-induced misfolding, others release certain inherent conformational constraints of the human wild-type CFTR. Several small-molecule correctors were recently found to act on key interdomain interfaces of F508del CFTR. Potential rational approaches have been proposed in an attempt to develop highly effective small molecule modulators that improve the cell surface functional expression of F508del CFTR.

  17. The Cystic Fibrosis Transmembrane Regulator (CFTR in the kidney

    Directory of Open Access Journals (Sweden)

    MORALES MARCELO M.

    2000-01-01

    Full Text Available The cystic fibrosis transmembrane regulator (CFTR is a Cl- channel. Mutations of this transporter lead to a defect of chloride secretion by epithelial cells causing the Cystic Fibrosis disease (CF. In spite of the high expression of CFTR in the kidney, patients with CF do not show major renal dysfunction, but it is known that both the urinary excretion of drugs and the renal capacity to concentrate and dilute urine is deficient. CFTR mRNA is expressed in all nephron segments and its protein is involved with chloride secretion in the distal tubule, and the principal cells of the cortical (CCD and medullary (IMCD collecting ducts. Several studies have demonstrated that CFTR does not only transport Cl- but also secretes ATP and, thus, controls other conductances such as Na+ (ENaC and K+ (ROMK2 channels, especially in CCD. In the polycystic kidney the secretion of chloride through CFTR contributes to the cyst enlargement. This review is focused on the role of CFTR in the kidney and the implications of extracellular volume regulators, such as hormones, on its function and expression.

  18. A comparison of bronchial drainage treatments in cystic fibrosis.

    Science.gov (United States)

    Kluft, J; Beker, L; Castagnino, M; Gaiser, J; Chaney, H; Fink, R J

    1996-10-01

    We compared standard chest physical therapy and postural drainage (CPT/PD) with a new airway clearance therapy called high-frequency chest wall oscillation (HFCWO) in a group of stable cystic fibrosis (CF) patients. In this crossover trial, 29 CF patients (15 males, 14 females), aged 7-47 years that met the inclusion criteria were randomly assigned to alternate CPT/PD and HFCWO, on a daily basis, over a 4 day period. Each patient received 2 days of each form of therapy; treatment frequency and the length of treatment were the same for both techniques. Expectorated secretions were collected during each 30 minute therapy session and for 15 minutes following treatment. The wet and dry weights of collected secretions were determined gravimetrically, and the therapy methods were compared. Significantly more sputum was expectorated during HFCWO than during CPT/PD as determined by both the wet (P HFCWO is at least as effective as manual CPT/PD in clearing secretions from the airways in patients with cystic fibrosis.

  19. Developing a handheld record for patients with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Narayan O

    2015-08-01

    Full Text Available Omendra Narayan,1 Siobhan Davies,1 Carly Tibbins,2 JH Martyn Rees,3 Warren Lenney,1,4 Francis J Gilchrist1,4 1Academic Department of Child Health, Royal Stoke University Hospital, Stoke-on-Trent, 2West Midlands Medicines for Children Research Network, Royal Stoke University Hospital, Stoke-on-Trent, 3Department of Paediatrics, Royal Shrewsbury Hospital, Shrewsbury, 4Institute for Science and Technology in Medicine, Keele University, Guy Hilton Research Centre, Stoke-on-Trent, UK Abstract: Patient handheld records (PHHRs promote self-management and empower the holder to take a more active role in the management of their disease. They have been used successfully in improving preventative care for children and have contributed to improved adherence in a number of chronic illnesses. Despite the potential advantages, there are no standard PHHRs for patients with cystic fibrosis (CF. We report the consultation process that led to the development of a CF PHHR, describe the final document, and analyze the feedback from their use at our center. We have made the CF PHHR freely available online.Keywords: cystic fibrosis, pediatrics, patient and public involvement, patient handheld records

  20. Airway acidification initiates host defense abnormalities in cystic fibrosis mice

    Science.gov (United States)

    Shah, Viral S.; Meyerholz, David K.; Tang, Xiao Xiao; Reznikov, Leah; Alaiwa, Mahmoud Abou; Ernst, Sarah E.; Karp, Philip H.; Wohlford-Lenane, Christine L.; Heilmann, Kristopher P.; Leidinger, Mariah R.; Allen, Patrick D.; Zabner, Joseph; McCray, Paul B.; Ostedgaard, Lynda S.; Stoltz, David A.; Randak, Christoph O.; Welsh, Michael J.

    2016-01-01

    Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. In humans and pigs, the loss of CFTR impairs respiratory host defenses, causing airway infection. But CF mice are spared. We found that in all three species, CFTR secreted bicarbonate into airway surface liquid. In humans and pigs lacking CFTR, unchecked H+ secretion by the nongastric H+/K+ adenosine triphosphatase (ATP12A) acidified airway surface liquid, which impaired airway host defenses. In contrast, mouse airways expressed little ATP12A and secreted minimal H+; consequently, airway surface liquid in CF and non-CF mice had similar pH. Inhibiting ATP12A reversed host defense abnormalities in human and pig airways. Conversely, expressing ATP12A in CF mouse airways acidified airway surface liquid, impaired defenses, and increased airway bacteria. These findings help explain why CF mice are protected from infection and nominate ATP12A as a potential therapeutic target for CF. PMID:26823428

  1. Molecular basis of cystic fibrosis in the Republic of Macedonia.

    Science.gov (United States)

    Petreska, L; Koceva, S; Plaseska, D; Chernick, M; Gordova-Muratovska, A; Fustic, S; Nestorov, R; Efremov, G D

    1998-09-01

    Eighty-three cystic fibrosis (CF) patients and their families, belonging to various ethnic groups living in the Republic of Macedonia were studied for molecular defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and for the associated extragenic marker loci XV-2c and KM19. The DNA methodology used included characterization of CFTR mutations in 19 exons (and flanking sequences) of the gene and analysis of distribution of the XV-2c/KM19 haplotypes among normal (N) and CF chromosomes by polymerase chain reaction (PCR) amplification followed by dot blot hybridization, restriction digestion, single-strand conformational polymorphism, constant denaturing gel electrophoresis, denaturing gradient gel electrophoresis, and sequencing. We identified 58.4% (97/166) of the CF chromosomes. Nine different CFTR gene mutations, including three novel ones, were found. Eight known and one new CFTR intragene polymorphisms were also characterized. The haplotype analysis of the XV-2c/TaqI and KM19/PstI polymorphic loci have shown that haplotype C is the most frequently found haplotype among the non-deltaF508 CF chromosomes from Macedonia (36.5%). The results demonstrate the broad heterogeneity of CF origin in this part of the Balkan Peninsula.

  2. Achromobacter xylosoxidans respiratory tract infection in cystic fibrosis patients.

    Science.gov (United States)

    Lambiase, A; Catania, M R; Del Pezzo, M; Rossano, F; Terlizzi, V; Sepe, A; Raia, V

    2011-08-01

    The aims of this study were to evaluate the frequency of Achromobacter xylosoxidans infection in a cohort of cystic fibrosis patients, to investigate antimicrobial sensitivity, to establish possible clonal likeness among strains, and to address the clinical impact of this infection or colonization on the general outcome of these patients. The study was undertaken between January 2004 and December 2008 on 300 patients receiving care at the Regional Cystic Fibrosis Center of the Naples University "Federico II". Sputum samples were checked for bacterial identification. For DNA fingerprinting, pulsed-field gel electrophoresis (PFGE) was carried out. Fifty-three patients (17.6%) had at least one positive culture for A. xylosoxidans; of these, 6/53 (11.3%) patients were defined as chronically infected and all were co-colonized by Pseudomonas aeruginosa. Of the patients, 18.8% persistently carried multidrug-resistant isolates. Macrorestriction analysis showed the presence of seven major clusters. DNA fingerprinting also showed a genetic relationship among strains isolated from the same patients at different times. The results of DNA fingerprinting indicate evidence of bacterial clonal likeness among the enrolled infected patients. We found no significant differences in the forced expiratory volume in 1 s (FEV(1)) and body mass index (BMI) when comparing the case group of A. xylosoxidans chronically infected patients with the control group of P. aeruginosa chronically infected patients.

  3. Two Qatari siblings with cystic fibrosis and apparent mineralocorticoid excess

    Directory of Open Access Journals (Sweden)

    Khalid Zahraldin

    2015-01-01

    Full Text Available Cystic fibrosis (CF and apparent mineralocorticoid excess (AME syndrome are both autosomal recessive disorders that result from mutations of specific identified genes for each condition. CF is caused by defects in the Cystic fibrosis trans membrane conductance regulator (CFTR gene which encodes for a protein that functions as a chloride channel and regulates the flow of other ions across the apical surface of epithelial cells. AME is due to the deficiency of 11β-hydroxysteroid dehydrogenase type 2 enzyme (11βHSD2, which is responsible for the peripheral inactivation of cortisol to cortisone. Cortisol excess stimulates the mineralocoritoid receptors (MR resulting in intense sodium retention, hypokalemia and hypertension. We report on a consanguineous Arab family, in which two sibs inherited both CF and AME. Gene testing for AME revealed previously unreported mutation in the 11βHSD2 gene. This report draws attention to the importance of recognizing the possibility of two recessive disorders in the same child in complex consanguineous families. Moreover, it provides a unique opportunity to highlight the implications of the coexistence of two genetic disorders on patient care and genetic counseling of the family.

  4. Exercise and quality of life in patients with cystic fibrosis: A 12-week intervention study

    DEFF Research Database (Denmark)

    Schmidt, Anne Mette; Jacobsen, Ulla; Bregnballe, Vibeke

    2011-01-01

    , data on QoL, current exercise habits and preferences, anthropometric data, exercise test, and lung function test were collected. Adherence was observed by a heart rate (HR) monitor. A total of 24 patients accepted to be enrolled in the exercise programme and 14 completed the programme. Another 14...... patients declined to be enrolled in the exercise programme but completed the Cystic Fibrosis Questionnaire for Adolescents and Adults (CFQ-R 14+). Four patients did not want to participate at all. The 14 patients completing the exercise programme had a significantly increased VO(2max), but they showed...

  5. Effect of selective phosphodiesterase 4 inhibitor,rolipram, on cytokine and gelatinase B (MMP-9) release in the whole blood from adult patients with cystic fibrosis.

    Institute of Scientific and Technical Information of China (English)

    JouneauSTEPHANE; BelleguicCHANTAL; EpinceALEXANDRAD; BrinchaultORAZIELLA; DesruesBENOIT; CamusCHRISTOPHE; MichelROUSSEY; LagenteVINCENT; CorinneAEMartin-CHOULY

    2004-01-01

    AIM: Inflammation plays a critical role in lung disease progression in cystic fibrosis being able to be associated with the development of tissue remodeling. These processes are mainly due to pro-inflammatory cytokines release and to an imbalance between proteases and antiproteases involving matrix metalloproteinases (MMP). Phosphodiesterase 4 (PDE4) inhibitors, by elevating intracellular cAMP, are known to be potent inhibitors of

  6. A Metagenomic approach to characterize temperate bacteriophage populations from cystic fibrosis and non-cystic fibrosis bronchiectasis patients

    Directory of Open Access Journals (Sweden)

    Mohammad Adnan Tariq

    2015-02-01

    Full Text Available Pseudomonas aeruginosa (Pa, normally a soil commensal, is an important opportunistic pathogen in Cystic Fibrosis (CF and non-Cystic Fibrosis Bronchiectasis (nCFBR. Persistent infection correlates with accelerated decline in lung function and early mortality. The horizontal transfer of DNA by temperate bacteriophages can add gene function and selective advantages to their bacterial host within the constrained environment of the lower lung. In this study, we chemically induce temperate bacteriophages from clonal cultures of Pa and identify their mixed viral communities employing metagenomic approaches. We compared 92 temperate phage metagenomes stratified from these clinical backgrounds (47 CF and 45 nCFBR Pa isolates using MG-RAST and GeneWise2. KEGG analysis shows the complexity of temperate phage accessory gene carriage increases with duration and severity of the disease. Furthermore we identify the presence of Ig-like motifs within phage structural genes linked to bacterial adhesion and carbohydrate binding including Big_2, He_Pig and Fn3. This study provides the first clinical support to the proposed bacteriophage adherence to mucus (BAM model and the evolution of phages interacting at these mucosal surfaces over time.

  7. Use of exercise in the management of cystic fibrosis: short communication about a survey of cystic fibrosis referral centers.

    Science.gov (United States)

    Kaplan, T A; ZeBranek, J D; McKey, R M

    1991-01-01

    A survey of 47 cystic fibrosis referral centers was conducted to study the use of exercise in the management of patients with cystic fibrosis (CF). A questionnaire with 5 brief questions concerning the prescription and application of exercise therapy was sent to the first 47 centers (38.5%) listed in the 1988 CF Foundation Directory, and 46 (97.9%) were returned. While all but one of the respondents recommend exercise at least to selected patients, and while 80.4% of the centers refer patients to summer camp programs, only 43.5% offer exercise stress testing and only 21.7% offer an exercise program for their patients. Most of the respondents who recommend exercise prescribe aerobic exercise, swimming being the most frequently chosen type. Although there is a large discrepancy between those centers that acknowledge the benefits of exercise and those that have arranged for regularly available exercise services, inroads have been made in utilizing this therapeutic tool for patients with CF.

  8. In silico search for modifier genes associated with pancreatic and liver disease in Cystic Fibrosis

    Science.gov (United States)

    Génin, Emmanuelle; Férec, Claude

    2017-01-01

    Cystic Fibrosis is the most common lethal autosomal recessive disorder in the white population, affecting among other organs, the lung, the pancreas and the liver. Whereas Cystic Fibrosis is a monogenic disease, many studies reveal a very complex relationship between genotype and clinical phenotype. Indeed, the broad phenotypic spectrum observed in Cystic Fibrosis is far from being explained by obvious genotype-phenotype correlations and it is admitted that Cystic Fibrosis disease is the result of multiple factors, including effects of the environment as well as modifier genes. Our objective was to highlight new modifier genes with potential implications in the lung, pancreatic and liver outcomes of the disease. For this purpose we performed a system biology approach which combined, database mining, literature mining, gene expression study and network analysis as well as pathway enrichment analysis and protein-protein interactions. We found that IFI16, CCNE2 and IGFBP2 are potential modifiers in the altered lung function in Cystic Fibrosis. We also found that EPHX1, HLA-DQA1, HLA-DQB1, DSP and SLC33A1, GPNMB, NCF2, RASGRP1, LGALS3 and PTPN13, are potential modifiers in pancreas and liver, respectively. Associated pathways indicate that immune system is likely involved and that Ubiquitin C is probably a central node, linking Cystic Fibrosis to liver and pancreatic disease. We highlight here new modifier genes with potential implications in Cystic Fibrosis. Nevertheless, our in silico analysis requires functional analysis to give our results a physiological relevance. PMID:28339466

  9. Dysregulated proinflammatory and fibrogenic phenotype of fibroblasts in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    François Huaux

    Full Text Available Morbi-mortality in cystic fibrosis (CF is mainly related to chronic lung infection and inflammation, uncontrolled tissue rearrangements and fibrosis, and yet the underlying mechanisms remain largely unknown. We evaluated inflammatory and fibrosis responses to bleomycin in F508del homozygous and wild-type mice, and phenotype of fibroblasts explanted from mouse lungs and skin. The effect of vardenafil, a cGMP-specific phosphodiesterase type 5 inhibitor, was tested in vivo and in culture. Responses of proinflammatory and fibrotic markers to bleomycin were enhanced in lungs and skin of CF mice and were prevented by treatment with vardenafil. Purified lung and skin fibroblasts from CF mice proliferated and differentiated into myofibroblasts more prominently and displayed higher sensitivity to growth factors than those recovered from wild-type littermates. Under inflammatory stimulation, mRNA and protein expression of proinflammatory mediators were higher in CF than in wild-type fibroblasts, in which CFTR expression reached similar levels to those observed in other non-epithelial cells, such as macrophages. Increased proinflammatory responses in CF fibroblasts were reduced by half with submicromolar concentrations of vardenafil. Proinflammatory and fibrogenic functions of fibroblasts are upregulated in CF and are reduced by vardenafil. This study provides compelling new support for targeting cGMP signaling pathway in CF pharmacotherapy.

  10. Pseudomembranous colitis in four patients with cystic fibrosis following lung transplantation.

    Science.gov (United States)

    Yates, B; Murphy, D M; Fisher, A J; Gould, F K; Lordan, J L; Dark, J H; Corris, P A

    2007-06-01

    Pseudomembranous colitis is an uncommon complication in patients with cystic fibrosis, despite the use of multiple high-dose antibiotic regimens and the frequency of hospital admissions. Four patients from a total of 137 patients with cystic fibrosis undergoing lung transplantation are described who developed fulminant pseudomembranous colitis. Initial presentation was variable and the mortality rate was 50% despite urgent colectomy. In one case the presenting abdominal distension was thought to be due to meconium ileus equivalent. It is concluded that Clostridium difficile colitis may be a difficult diagnosis in patients with cystic fibrosis and follows a fulminant course after lung transplantation.

  11. Molecular chaperones as targets to circumvent the CFTR defect in cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Rebecca A Chanoux

    2012-07-01

    Full Text Available Cystic Fibrosis (CF is the most common autosomal recessive lethal disorder among Caucasian populations. CF results from mutations and resulting dysfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR. CFTR is a cyclic AMP-dependent chloride channel that is localized to the apical membrane in epithelial cells where it plays a key role in salt and water homeostasis. An intricate network of molecular chaperone proteins regulates CFTR’s proper maturation and trafficking to the apical membrane. Understanding and manipulation of this network may lead to therapeutics for Cystic Fibrosis in cases where mutant CFTR has aberrant trafficking.

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

    Directory of Open Access Journals (Sweden)

    Charles C. Reilly

    2016-03-01

    Full Text Available The electromyogram recorded from the diaphragm (EMGdi and parasternal intercostal muscle using surface electrodes (sEMGpara provides a measure of neural respiratory drive (NRD, the magnitude of which reflects lung disease severity in stable cystic fibrosis. The aim of this study was to explore perception of NRD and breathlessness in both healthy individuals and patients with cystic fibrosis. Given chronic respiratory loading and increased NRD in cystic fibrosis, often in the absence of breathlessness at rest, we hypothesised that patients with cystic fibrosis would be able to tolerate higher levels of NRD for a given level of breathlessness compared to healthy individuals during exercise. 15 cystic fibrosis patients (mean forced expiratory volume in 1 s (FEV1 53.5% predicted and 15 age-matched, healthy controls were studied. Spirometry was measured in all subjects and lung volumes measured in the cystic fibrosis patients. EMGdi and sEMGpara were recorded at rest and during incremental cycle exercise to exhaustion and expressed as a percentage of maximum (% max obtained from maximum respiratory manoeuvres. Borg breathlessness scores were recorded at rest and during each minute of exercise. EMGdi % max and sEMGpara % max and associated Borg breathlessness scores differed significantly between healthy subjects and cystic fibrosis patients at rest and during exercise. The relationship between EMGdi % max and sEMGpara % max and Borg score was shifted to the right in the cystic fibrosis patients, such that at comparable levels of EMGdi % max and sEMGpara % max the cystic fibrosis patients reported significantly lower Borg breathlessness scores compared to the healthy individuals. At Borg score 1 (clinically significant increase in breathlessness from baseline corresponding levels of EMGdi % max (20.2±12% versus 32.15±15%, p=0.02 and sEMGpara % max (18.9±8% versus 29.2±15%, p=0.04 were lower in the healthy individuals compared to the cystic

  13. Reproductive defects in patients of both sexes with cystic fibrosis: a review.

    Science.gov (United States)

    Seale, T W; Flux, M; Rennert, O M

    1985-01-01

    Current knowledge of reproductive duct function in both male and female cystic fibrosis patients is reviewed. Almost all male patients are sterile because of azoospermia. The mechanistic basis of the obstructive defect leading to pre- and post-natal destruction of selected portions of the sperm-conducting network remains unknown. Female cystic fibrosis patients are fertile. Pulmonary status appears to be the most important factor in determining pregnancy outcome. In contrast to earlier concerns about the normality of breast milk, breast milk composition of cystic fibrosis mothers is normal, and they can successfully breast feed their infants.

  14. Anesthesia for Lobectomy in a Pediatric Patient` with Cystic Fibrosis: A Case Report

    Directory of Open Access Journals (Sweden)

    Seyedhejazi Mahin

    2014-07-01

    Full Text Available Cystic Fibrosis is the most common autosomal recessive disease which causes a lot of complications and there are some needed operations in lifelong of such patients. Anesthesia in these patients requires particular attention and a full cooperation of surgeon, anesthetist and pediatrician .We reported a case of lobectomy with lung separation in a 4.5 years old child with cystic fibrosis which was performed with minor complications in the hope that an awareness of such situations may turn up similar cases of study.Keywords: Cystic Fibrosis, Anesthesia, Pulmonic Lobectomy

  15. International Committee on Mental Health in Cystic Fibrosis: Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus statements for screening and treating depression and anxiety.

    Science.gov (United States)

    Quittner, Alexandra L; Abbott, Janice; Georgiopoulos, Anna M; Goldbeck, Lutz; Smith, Beth; Hempstead, Sarah E; Marshall, Bruce; Sabadosa, Kathryn A; Elborn, Stuart

    2016-01-01

    Studies measuring psychological distress in individuals with cystic fibrosis (CF) have found high rates of both depression and anxiety. Psychological symptoms in both individuals with CF and parent caregivers have been associated with decreased lung function, lower body mass index, worse adherence, worse health-related quality of life, more frequent hospitalisations and increased healthcare costs. To identify and treat depression and anxiety in CF, the CF Foundation and the European CF Society invited a panel of experts, including physicians, psychologists, psychiatrists, nurses, social workers, a pharmacist, parents and an individual with CF, to develop consensus recommendations for clinical care. Over 18 months, this 22-member committee was divided into four workgroups: Screening; Psychological Interventions; Pharmacological Treatments and Implementation and Future Research, and used the Population, Intervention, Comparison, Outcome methodology to develop questions for literature search and review. Searches were conducted in PubMed, PsychINFO, ScienceDirect, Google Scholar, Psychiatry online and ABDATA by a methodologist at Dartmouth. The committee reviewed 344 articles, drafted statements and set an 80% acceptance for each recommendation statement as a consensus threshold prior to an anonymous voting process. Fifteen guideline recommendation statements for screening and treatment of depression and anxiety in individuals with CF and parent caregivers were finalised by vote. As these recommendations are implemented in CF centres internationally, the process of dissemination, implementation and resource provision should be closely monitored to assess barriers and concerns, validity and use.

  16. Pseudomonas aeruginosa host-adaptation in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Rau, Martin Holm

    Pseudomonas aeruginosa is an opportunistic pathogen capable of transition from an environmental lifestyle to a host-associated lifestyle, as exemplified in the life-long airway infection of cystic fibrosis (CF) patients. Long-term infection is associated with extensive genetic adaptation of P....... aeruginosa towards the CF airway environment generating variants with markedly altered phenotypes. Gaining insight into this adaptation process has great clinical relevance but simultaneously has the potential to increase our understanding of bacterial adaptation to a host environment. This has been...... to unravel the early adaptive processes possibly securing bacterial persistence. In this early stage, clinical isolates displayed few adaptive events however these included phenotypes often observed in late chronic infection isolates including the conversion to a mucoid phenotype and increased antibiotic...

  17. Cumulative radiation exposure in children with cystic fibrosis.

    LENUS (Irish Health Repository)

    O'Reilly, R

    2010-02-01

    This retrospective study calculated the cumulative radiation dose for children with cystic fibrosis (CF) attending a tertiary CF centre. Information on 77 children with a mean age of 9.5 years, a follow up time of 658 person years and 1757 studies including 1485 chest radiographs, 215 abdominal radiographs and 57 computed tomography (CT) scans, of which 51 were thoracic CT scans, were analysed. The average cumulative radiation dose was 6.2 (0.04-25) mSv per CF patient. Cumulative radiation dose increased with increasing age and number of CT scans and was greater in children who presented with meconium ileus. No correlation was identified between cumulative radiation dose and either lung function or patient microbiology cultures. Radiation carries a risk of malignancy and children are particularly susceptible. Every effort must be made to avoid unnecessary radiation exposure in these patients whose life expectancy is increasing.

  18. Computed tomography dose optimisation in cystic fibrosis: A review.

    LENUS (Irish Health Repository)

    Ferris, Helena

    2016-04-28

    Cystic fibrosis (CF) is the most common autosomal recessive disease of the Caucasian population worldwide, with respiratory disease remaining the most relevant source of morbidity and mortality. Computed tomography (CT) is frequently used for monitoring disease complications and progression. Over the last fifteen years there has been a six-fold increase in the use of CT, which has lead to a growing concern in relation to cumulative radiation exposure. The challenge to the medical profession is to identify dose reduction strategies that meet acceptable image quality, but fulfil the requirements of a diagnostic quality CT. Dose-optimisation, particularly in CT, is essential as it reduces the chances of patients receiving cumulative radiation doses in excess of 100 mSv, a dose deemed significant by the United Nations Scientific Committee on the Effects of Atomic Radiation. This review article explores the current trends in imaging in CF with particular emphasis on new developments in dose optimisation.

  19. The Use of Home Spirometry in Pediatric Cystic Fibrosis Patients

    Science.gov (United States)

    Shakkottai, Aarti; Nasr, Samya Z.

    2017-01-01

    Medication adherence is poor among pediatric cystic fibrosis (CF) patients, with adolescents having one of the lowest adherence rates. We wanted to identify an adherence intervention that would be acceptable to CF adolescents and assess its feasibility. We surveyed 40 adolescents with CF and asked about barriers to and motivators for their own adherence and to generate ideas for potential adherence interventions. Since most of the respondents chose frequent spirometry at home and medication reminders for interventions, we selected 5 subjects, 10 to 14 years of age, with CF to test the feasibility of home spirometry and medication reminders in pediatric CF patients. This article summarizes the results of both the survey and the feasibility pilot study. PMID:28229102

  20. Toll-like receptors as therapeutic targets in cystic fibrosis.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2008-12-01

    Background: Toll-like receptors (TLRs) are pattern recognition receptors that act as a first-line of defence in the innate immune response by recognising and responding to conserved molecular patterns in microbial factors and endogenous danger signals. Cystic fibrosis (CF)-affected airways represent a milieu potentially rich in TLR agonists and the chronic inflammatory phenotype evident in CF airway epithelial cells is probably due in large part to activation of TLRs. Objective\\/methods: To examine the prospects of developing novel therapies for CF by targeting TLRs. We outline the expression and function of TLRs and explore the therapeutic potential of naturally-occurring and synthetic TLR inhibitors for CF. Results\\/conclusion: Modulation of TLRs has therapeutic potential for the inflammatory lung manifestations of CF.

  1. A Roadmap to the Brittle Bones of Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Ashwini P. Gore

    2011-01-01

    Full Text Available Cystic fibrosis (CF is an autosomal recessive disorder which despite advances in medical care continues to be a life-limiting and often fatal disease. With increase in life expectancy of the CF population, bone disease has emerged as a common complication. Unlike the osteoporosis seen in postmenopausal population, bone disease in CF begins at a young age and is associated with significant morbidity due to fractures, kyphosis, increased pain, and decreased lung function. The maintenance of bone health is essential for the CF population during their lives to prevent pain and fractures but also as they approach lung transplantation since severe bone disease can lead to exclusion from lung transplantation. Early recognition, prevention, and treatment are key to maintaining optimal bone health in CF patients and often require a multidisciplinary approach. This article will review the pathophysiology, current clinical practice guidelines, and potential future therapies for treating CF-related bone disease.

  2. Tuberculosis reinfection in a pregnant cystic fibrosis patient

    Directory of Open Access Journals (Sweden)

    Asween Marco

    2015-01-01

    Full Text Available Cystic Fibrosis (CF is a multisystem disease predominantly affecting the airways and predisposing patients to recurrent infections with various multidrug resistant organisms. Mycobacterium tuberculosis (MTB infection is rarely seen, but considered a potential pathogen in CF patients. We report a 26 year old pregnant CF patient on Ivacaftor who was admitted with symptoms suggestive of tuberculosis. Three years prior to the current admission, she had completed four drug anti- MTB therapy for pulmonary tuberculosis and was considered cured as her sputum cultures after six months of treatment were negative. Genotype analysis revealed the current MTB strain to be different from the strain causing the previous infection. After receiving first line anti-tuberculous regimen for nine months, the patient's condition markedly improved culminating in an uneventful pregnancy and delivery. To our knowledge, this is the only reported case of reinfection tuberculosis in a CF patient.

  3. Mucus Distribution Model in a Lung with Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Sara Zarei

    2012-01-01

    Full Text Available Cystic fibrosis (CF is the most common autosomal recessive disease in Caucasians with a reported incidence of 1 in every 3200 live births. Most strikingly, CF is associated with early mortality. Host in flammatory responses result in airway mucus plugging, airway wall edema, and eventual destruction of airway wall support structure. Despite aggressive treatment, the median age of survival is approximately 38 years. This work is the first attempt to parameterize the distributions of mucus in a CF lung as a function of time. By default, the model makes arbitrary choices at each stage of the construction process, whereby the simplest choice is made. The model is sophisticated enough to fit the average CF patients' spirometric data over time and to identify several interesting parameters: probability of colonization, mucus volume growth rate, and scarring rate. Extensions of the model appropriate for describing the dynamics of single patient MRI data are also discussed.

  4. The cystic fibrosis neutrophil: a specialized yet potentially defective cell.

    LENUS (Irish Health Repository)

    Hayes, Elaine

    2012-02-01

    Cystic fibrosis (CF) is one of the commonest genetically inherited diseases in the world. It is characterized by recurrent respiratory tract infections eventually leading to respiratory failure. One of the hallmarks of this disease is a persistent and predominantly neutrophil driven inflammation. Neutrophils provide the first line of defence by killing and digesting phagocytosed bacteria and fungi, yet despite advances in our understanding of the molecular and cellular basis of CF, there remains a paradox of why recruited CF neutrophils fail to eradicate bacterial infections in the lung. This review describes mechanisms involved in neutrophil migration, microbial killing and apoptosis leading to inflammatory resolution. We discuss dysregulated neutrophil activity and consider genetic versus inflammatory neutrophil reprogramming in CF and ultimately pharmacological modulation of the CF neutrophil for therapeutic intervention.

  5. The cystic fibrosis neutrophil: a specialized yet potentially defective cell.

    LENUS (Irish Health Repository)

    Hayes, Elaine

    2011-04-01

    Cystic fibrosis (CF) is one of the commonest genetically inherited diseases in the world. It is characterized by recurrent respiratory tract infections eventually leading to respiratory failure. One of the hallmarks of this disease is a persistent and predominantly neutrophil driven inflammation. Neutrophils provide the first line of defence by killing and digesting phagocytosed bacteria and fungi, yet despite advances in our understanding of the molecular and cellular basis of CF, there remains a paradox of why recruited CF neutrophils fail to eradicate bacterial infections in the lung. This review describes mechanisms involved in neutrophil migration, microbial killing and apoptosis leading to inflammatory resolution. We discuss dysregulated neutrophil activity and consider genetic versus inflammatory neutrophil reprogramming in CF and ultimately pharmacological modulation of the CF neutrophil for therapeutic intervention.

  6. Outbreak of Corynebacterium pseudodiphtheriticum infection in cystic fibrosis patients, France.

    Science.gov (United States)

    Bittar, Fadi; Cassagne, Carole; Bosdure, Emmanuelle; Stremler, Nathalie; Dubus, Jean Christophe; Sarles, Jacques; Reynaud-Gaubert, Martine; Raoult, Didier; Rolain, Jean-Marc

    2010-08-01

    An increasing body of evidence indicates that nondiphtheria corynebacteria may be responsible for respiratory tract infections. We report an outbreak of Corynebacterium pseudodiphtheriticum infection in children with cystic fibrosis (CF). To identify 18 C. pseudodiphtheriticum strains isolated from 13 French children with CF, we used molecular methods (partial rpoB gene sequencing) and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. Clinical symptoms were exhibited by 10 children (76.9%), including cough, rhinitis, and lung exacerbations. The results of MALDI-TOF identification matched perfectly with those obtained from molecular identification. Retrospective analysis of sputum specimens by using specific real-time PCR showed that approximately 20% of children with CF were colonized with these bacteria, whereas children who did not have CF had negative test results. Our study reemphasizes the conclusion that correctly identifying bacteria at the species level facilitates detection of an outbreak of new or emerging infections in humans.

  7. Lifestyle treatments in cystic fibrosis: The NHS should pay.

    Science.gov (United States)

    Ketchell, Robert Ian

    2016-08-01

    With the NHS under increasing financial pressure and healthcare costs soaring year on year, it is perhaps not surprising that assessment agencies focus on cost-effectiveness analysis when assessing new therapies. Such an approach does not however, always take sufficient account of treatment burden, lifestyle and patient choice and therefore new equally effective but perhaps "easier to take" formulations and faster delivery systems for current therapies do not always take precedence in current treatment guidelines. In arguing that the NHS should pay for so-called lifestyle treatments in cystic fibrosis the counterintuitive nature of some of the current decision making is discussed and a more holistic approach to improve NHS efficiency is presented.

  8. Gastrointestinal transit times and motility in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Hedsund, Caroline; Gregersen, Tine; Jønsson, Iben;

    2012-01-01

    OBJECTIVE: Patients with cystic fibrosis (CF) often suffer from gastrointestinal (GI) dysfunction including obstructive symptoms, malabsorption and pain, but the underlying pathophysiology remains obscure. AIM: To compare GI motility and transit times in CF patients and healthy controls. MATERIAL...... AND METHODS: Ten CF patients (five women, median age 23) with pancreatic insufficiency were studied. Total gastrointestinal transit time (GITT) and segmental colonic transit times (SCTT) were assessed by radiopaque markers. Gastric emptying and small intestinal transit were evaluated using the magnet......-based motility tracking system (MTS-1). With each method patients were compared with 16 healthy controls. RESULTS: Basic contraction frequencies of the stomach and small intestine were normal, but the pill reached the cecum after 7 h in only 20% of CF patients while in 88% of controls (p = 0.001). Paradoxically...

  9. Dictamine Stimulates Cystic Fibrosis Transmembrane Conductance Regulator Cl- Transport

    Institute of Scientific and Technical Information of China (English)

    LIU Jun; YANG Hong; LIU Li-dan; WANG Su-mei; XU Li-na; YU Bo; LIN Sen; HOU Shu-guang; ZHOU Na; JIN Ling-ling

    2007-01-01

    Dictamine is a furoquinoline alkaloid isolated from Dictamus dasycarpus Turcz. In the present study, we found that dictamine is able to stimulate the chloride transport activity of wild-type and △F508 mutant CFTR. The activity is cAMP-dependent and can be completely reversed by specific CFTR inhibitor CFTRinh-172. In addition, dictamine can further increase the chloride transport activity when CFTR is maximally activated by the combination of cAMP stimulators forskolin(FSK) and IBMX, suggesting direct interaction of dictamine with CFTR. Dictamine may be useful for probing CFTR channel gating mechanisms and used as a lead compound to develop the pharmacological therapy of CFTR-related diseases such as idiopathic chronic pancreatitis and keratoconjunctivitis sicca and cystic fibrosis.

  10. Mast cells and gastrointestinal dysmotility in the cystic fibrosis mouse.

    Directory of Open Access Journals (Sweden)

    Robert C De Lisle

    Full Text Available BACKGROUND: Cystic fibrosis (CF has many effects on the gastrointestinal tract and a common problem in this disease is poor nutrition. In the CF mouse there is an innate immune response with a large influx of mast cells into the muscularis externa of the small intestine and gastrointestinal dysmotility. The aim of this study was to evaluate the potential role of mast cells in gastrointestinal dysmotility using the CF mouse (Cftr(tm1UNC, Cftr knockout. METHODOLOGY: Wild type (WT and CF mice were treated for 3 weeks with mast cell stabilizing drugs (ketotifen, cromolyn, doxantrazole or were treated acutely with a mast cell activator (compound 48/80. Gastrointestinal transit was measured using gavage of a fluorescent tracer. RESULTS: In CF mice gastric emptying at 20 min post-gavage did not differ from WT, but was significantly less than in WT at 90 min post-gavage. Gastric emptying was significantly increased in WT mice by doxantrazole, but none of the mast cell stabilizers had any significant effect on gastric emptying in CF mice. Mast cell activation significantly enhanced gastric emptying in WT mice but not in CF mice. Small intestinal transit was significantly less in CF mice as compared to WT. Of the mast cell stabilizers, only doxantrazole significantly affected small intestinal transit in WT mice and none had any effect in CF mice. Mast cell activation resulted in a small but significant increase in small intestinal transit in CF mice but not WT mice. CONCLUSIONS: The results indicate that mast cells are not involved in gastrointestinal dysmotility but their activation can stimulate small intestinal transit in cystic fibrosis.

  11. MRI in mucoviscidosis (cystic fibrosis); MRT bei Mukoviszidose

    Energy Technology Data Exchange (ETDEWEB)

    Eichinger, M.; Puderbach, M.; Kauczor, H.-U. [Deutsches Krebsforschungszentrum (DKFZ), Abteilung Radiologie, Heidelberg (Germany); Heussel, C.-P. [Universitaetsklinikum Mainz (Germany). Klinik und Poliklinik fuer Radiologie

    2006-04-15

    Cystic fibrosis (CF) is a multi-systemic disease with major impact on the lungs. Pulmonary manifestation is crucial for the prognosis and life expectancy of patients. Imaging modalities and lung function tests reflect the pulmonary status in these patients. The standard imaging modality for diagnosis and follow-up of pulmonary changes is chest x-ray. The gold standard for the detection of parenchymal lung changes remains high resolution computed tomography (HRCT), but this is not used routinely for CF-patients due to radiation exposure. Magnetic resonance imaging (MRI) used to be of no importance in monitoring cystic fibrosis lung disease, as shown in studies from the 1980s and early 1990s. The continuing improvement of MRI techniques, however, has allowed for an adequate application of this non-radiation method in diagnosing the major pulmonary findings in CF, in addition to the assessment of lung function. (orig.) [German] Die Lunge ist Hauptmanifestationsort der Mukoviszidose (zystischen Fibrose, CF) und entscheidend fuer Prognose und Lebenserwartung der Betroffenen. Bildgebende Verfahren spielen in der Diagnostik und Verlaufsbeurteilung der Lungenveraenderungen sowie dem Monitoring pulmonaler Komplikationen bei zystischer Fibrose eine wichtige Rolle. Obwohl die hochaufloesende Computertomographie (HRCT) als Goldstandard zur Beurteilung morphologischer Lungenveraenderungen bei zystischer Fibrose gilt, ist die Roentgenthoraxaufnahme aufgrund der geringeren Strahlenbelastung bei den meist jungen Patienten das derzeit eingesetzte Standardverfahren zur Diagnostik und Verlaufsbeurteilung. Die Magnetresonanztomographie (MRT) spielte bislang in der Diagnostik und Verlaufsbeobachtung der zystischen Fibrose keine Rolle, da Arbeiten aus den 80er und fruehen 90er Jahren keinen sinnvollen Beitrag der MRT zeigen konnten. Durch die kontinuierliche Verbesserung der Technik ist es seit neuestem erstmals moeglich, die MRT als Alternative fuer die Lungenbildgebung bei zystischer

  12. Fat absorption in cystic fibrosis mice is impeded by defective lipolysis and post-lipolytic events

    NARCIS (Netherlands)

    Bijvelds, MJC; Bronsveld, [No Value; Havinga, R; Sinaasappel, M; de Jonge, HR; Verkade, HJ

    2005-01-01

    Cystic fibrosis (CF) is frequently associated with progressive loss of exocrine pancreas function, leading to incomplete digestion and absorption of dietary fat. Supplementing patients with pancreatic lipase reduces fat excretion, but it does not completely correct fat malabsorption, indicating that

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

    LENUS (Irish Health Repository)

    Keating, Deirdre

    2013-03-01

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

  14. Lumbar disc herniation in three patients with cystic fibrosis: a case series

    Directory of Open Access Journals (Sweden)

    Gruebl Armin

    2011-09-01

    Full Text Available Abstract Introduction To date, lumbar disc herniation has not been reported in the context of cystic fibrosis even though back pain and musculoskeletal problems are very common in patients with cystic fibrosis. Case presentation We report on three patients with cystic fibrosis who experienced lumbar disc herniation in the course of their disease at ages 19 to 21 years (a 22-year-old Caucasian man, a 23-year-old Caucasian man, and a 21-year-old Caucasian woman. Our third patient eventually died because of her deteriorated pulmonary situation, which was influenced by the lumbar disc herniation as it was not possible for her to perform pulmonary drainage techniques properly because of the pain. Conclusions Lumbar disc herniation can lead to a vicious cycle for patients with cystic fibrosis as it may promote pulmonary infections. This report highlights the need to investigate patients correctly.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  16. Iron accumulates in the lavage and explanted lungs of cystic fibrosis patients.

    Science.gov (United States)

    Abstract Oxidative stress participates in the pathophysiology of cystic fibrosis (CF). An underlying disruption in iron homeostasis can frequently be demonstrated in injuries and diseases associated with an oxidative stress. We tested the hypothesis that iron accumulation and ...

  17. Persistent fat malabsorption in cystic fibrosis; lessons from patients and mice

    NARCIS (Netherlands)

    Wouthuyzen-Bakker, M; Bodewes, F A J A; Verkade, H J

    2011-01-01

    Fat malabsorption in pancreatic insufficient cystic fibrosis (CF) patients is classically treated with pancreatic enzyme replacement therapy (PERT). Despite PERT, intestinal fat absorption remains insufficient in most CF patients. Several factors have been suggested to contribute to the persistent f

  18. Vitamin A intake and serum retinol levels in children and adolescents with cystic fibrosis

    NARCIS (Netherlands)

    Woestenenk, JW; Broos, Nancy; Stellato, Rebecca K; Arets, Hubertus G M; van der Ent, Cornelis K.; Houwen, RHJ

    2016-01-01

    BACKGROUND: Pancreatic insufficient cystic fibrosis (CF) patients receive vitamin A supplementation according to CF-specific recommendations to prevent deficiencies. Whether current recommendations are optimal for preventing both deficiency and toxicity is a subject of debate. We assessed the longit

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

    DEFF Research Database (Denmark)

    Fernández-Barat, Laia; Ciofu, Oana; Kragh, Kasper N

    2017-01-01

    BACKGROUND: The influence of suppressive therapy on the different P. aeruginosa phenotypes harbored in the lungs of cystic fibrosis (CF) patients remains unclear. Our aim was to investigate the phenotypic changes (mucoidy, hypermutability, antibiotic resistance, transcriptomic profiles and biofil...

  20. Nocardia farcinica lung infection in a patient with cystic fibrosis: a case report

    Directory of Open Access Journals (Sweden)

    Rolain Jean-Marc

    2010-03-01

    Full Text Available Abstract Introduction Respiratory tract infections are the major causes of morbidity and mortality in patients with cystic fibrosis. Nocardia are rarely implicated in these infections and few reports of the involvement of this species are found in the literature. Case presentation We describe a case of lung infection followed by chronic colonization of trimethoprim and sulfamethoxazole resistant Nocardia farcinica in a patient with cystic fibrosis. The chronic colonization of this uncommon bacterium in patients with cystic fibrosis was proved using a newly developed real-time polymerase chain reaction assay, which indicates that this bacterium, despite treatment, is difficult to eradicate. Conclusion Our case report confirms that this organism can be recovered in persons with cystic fibrosis. Its eradication is necessary especially if the patient is to undergo lung transplantation.

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

    DEFF Research Database (Denmark)

    Amador Hierro, Cristina Isabel; Jelsbak, Lars

    2015-01-01

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

  2. Serum bactericidal effect on Pseudomonas aeruginosa isolates from cystic fibrosis patients.

    OpenAIRE

    Thomassen, M J; Demko, C A

    1981-01-01

    The bactericidal activity against Pseudomonas aeruginosa strains isolated from cystic fibrosis patients was determined in a 10% concentration of normal serum or autologous cystic fibrosis serum. Of the 167 strains tested, 77 (46%) were sensitive (greater than 95% killed) in normal serum. Mucoid strains were more frequently sensitive than nonmucoid strains. Twenty-three sensitive strains tested in ethyleneglycoltetraacetic acid-chelated serum were resistant (less than 10% killed), suggesting o...

  3. Asthma and COPD in cystic fibrosis intron-8 5T carriers. A population-based study

    DEFF Research Database (Denmark)

    Dahl, Morten; Tybjaerg-Hansen, Anne; Lange, Peter;

    2005-01-01

    Carriers of cystic fibrosis intron-8 5T alleles with high exon-9 skipping could have increased annual lung function decline and increased risk for asthma or chronic obstructive pulmonary disease (COPD).......Carriers of cystic fibrosis intron-8 5T alleles with high exon-9 skipping could have increased annual lung function decline and increased risk for asthma or chronic obstructive pulmonary disease (COPD)....

  4. Cystic fibrosis and Crohn’s disease:Successful treatment and long term remission with infliximab

    Institute of Scientific and Technical Information of China (English)

    Francesca; Vincenzi; Barbara; Bizzarri; Alessia; Ghiselli; Nicola; de; Angelis; Fabiola; Fornaroli; Gian; Luigi; de; Angelis

    2010-01-01

    The association of cystic fibrosis and Crohn's disease (CD) is well known, but to date, there are very few cas-es in the literature of patients suffering from mucovisci-dosis who have required treatment with infliximab. We report the case of a 23-year-old patient suffering from cystic fibrosis and severe CD treated successfully with infliximab without any infective complications or wors-ening of the pulmonary disease and with a long term (2 years) complete remission.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Lung infection is the main cause of morbidity and mortality in patients with cystic fibrosis and is mainly dominated by Pseudomonas aeruginosa. The biofilm mode of growth makes eradication of the infection impossible, and it causes a chronic inflammation in the airways. The general mechanisms of ...... of adaptive evolution of the persisting bacteria imposes important therapeutic challenges and requires development of new drug delivery systems able to reach the different niches occupied by the bacteria in the lung of cystic fibrosis patients....

  6. Parents’ Religious Coping Styles in the First Year After Their Child’s Cystic Fibrosis Diagnosis

    OpenAIRE

    Grossoehme, Daniel H.; Ragsdale, Judy; Cotton, Sian; WOOLDRIDGE, JAMIE L.; Grimes, Lisa; Seid, Michael

    2010-01-01

    Parents of children diagnosed with cystic fibrosis described it as “devastating.” Given religion’s importance to many Americans, parents may utilize religious coping. Relatively little is known about parents’ use of religious coping to handle their child’s illness. Interviews with 15 parents about their use of religion in the year following their child’s cystic fibrosis diagnosis were coded for religious coping styles. Sixteen styles were identified. Positive religious coping styles were more...

  7. Nocardia farcinica lung infection in a patient with cystic fibrosis: a case report

    OpenAIRE

    2010-01-01

    Abstract Introduction Respiratory tract infections are the major causes of morbidity and mortality in patients with cystic fibrosis. Nocardia are rarely implicated in these infections and few reports of the involvement of this species are found in the literature. Case presentation We describe a case of lung infection followed by chronic colonization of trimethoprim and sulfamethoxazole resistant Nocardia farcinica in a patient with cystic fibrosis. The chronic colonization of this uncommon ba...

  8. Progress toward generating a ferret model of cystic fibrosis by somatic cell nuclear transfer

    OpenAIRE

    Engelhardt John F; Li Ziyi

    2003-01-01

    Abstract Mammalian cloning by nuclear transfer from somatic cells has created new opportunities to generate animal models of genetic diseases in species other than mice. Although genetic mouse models play a critical role in basic and applied research for numerous diseases, often mouse models do not adequately reproduce the human disease phenotype. Cystic fibrosis (CF) is one such disease. Targeted ablation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in mice does not...

  9. Colonic wall thickness measured by ultrasound: striking differences in patients with cystic fibrosis versus healthy controls.

    OpenAIRE

    1997-01-01

    BACKGROUND: Colonic strictures represent an advanced stage of fibrosing colonopathy in patients with cystic fibrosis. AIMS: To clarify whether ultrasonography can identify patients with an early stage of fibrosing colonopathy and to determine clinical factors that influence bowel wall thickening. PATIENTS: Ninety patients with cystic fibrosis, median age 10 years, and 46 healthy controls, median age 13 years, were investigated. METHODS: Bowel wall thickness was measured by ultrasound in a pro...

  10. Decreased coenzyme Q10 concentration in plasma of children with cystic fibrosis

    NARCIS (Netherlands)

    Oudshoorn, J.H.; Lecluse, A.L.Y.; Berg, R. van den; Vaes, W.H.J.; Laag, J. van der; Houwen, R.H.J.

    2006-01-01

    OBJECTIVES: Coenzyme Q10 (CoQ10) is an effective lipophilic antioxidant and protects against lipid peroxidation by scavenging radicals. Patients with cystic fibrosis generally have fat malabsorption; thus, we hypothesized that overall plasma CoQ10 concentration in pediatric patients with cystic fibr

  11. Optimisation and assessment of airway clearance in children with cystic fibrosis

    NARCIS (Netherlands)

    L.J. van der Giessen (Lianne)

    2009-01-01

    markdownabstract__Abstract__ Cystic Fibrosis (CF) is the most common life-shortening genetic disorder in the white population.1 It affects approximately 1300 individuals in the Netherlands2 and 60.000 individuals worldwide. CF is caused by mutations in the cystic fi brosis transmembrane conductance

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

    Science.gov (United States)

    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 H2-consuming microorganisms, which could increase hydrogen accumulation in the colon and the expulsion of this gas through non-microbial routes.

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

    Science.gov (United States)

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

    2016-01-01

    Abstract Objective: To review the literature addressing the relationship of growth and nutritional parameters with pulmonary function in pediatric patients with cystic fibrosis. Data source: 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. Data synthesis: 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. Conclusions: 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. PMID:27181343

  14. Ivacaftor treatment in patients with cystic fibrosis and the G551D-CFTR mutation

    Directory of Open Access Journals (Sweden)

    Isabelle Sermet-Gaudelus

    2013-03-01

    Full Text Available Cystic fibrosis (CF is an autosomal recessive lethal disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR gene that encodes for CFTR, an epithelial cell-surface expressed protein responsible for the transport of chloride (Cl-. Gating mutations associated with defective conductance can be modulated by CFTR potentiators. Ivacaftor is a CFTR potentiator approved for the treatment of CF patients >6 yrs of age with at least one copy of the G551D-CFTR mutation. Herein, the clinical trial development programme for ivacaftor will be reviewed, including two pivotal studies in adolescents/adults and in children. These studies report sustained improvements in lung function and sweat chloride concentrations, and a reduction in pulmonary exacerbations over a 48-week treatment period. In the era of personalised medicine, ivacaftor offers an effective and well-tolerated treatment for the clinical management of CF patients with the G551D mutation. A long-term, open-label study will report the effects of ivacaftor over a further 48 weeks.

  15. Bone disease in cystic fibrosis: new pathogenic insights opening novel therapies.

    Science.gov (United States)

    Jacquot, J; Delion, M; Gangloff, S; Braux, J; Velard, F

    2016-04-01

    Mutations within the gene encoding for the chloride ion channel cystic fibrosis transmembrane conductance regulator (CFTR) results in cystic fibrosis (CF), the most common lethal autosomal recessive genetic disease that causes a number of long-term health problems, as the bone disease. Osteoporosis and increased vertebral fracture risk associated with CF disease are becoming more important as the life expectancy of patients continues to improve. The etiology of low bone density is multifactorial, most probably a combination of inadequate peak bone mass during puberty and increased bone losses in adults. Body mass index, male sex, advanced pulmonary disease, malnutrition and chronic therapies are established additional risk factors for CF-related bone disease (CFBD). Consistently, recent evidence has confirmed that CFTR plays a major role in the osteoprotegerin (OPG) and COX-2 metabolite prostaglandin E2 (PGE2) production, two key regulators in the bone formation and regeneration. Several others mechanisms were also recognized from animal and cell models contributing to malfunctions of osteoblast (cell that form bone) and indirectly of bone-resorpting osteoclasts. Understanding such mechanisms is crucial for the development of therapies in CFBD. Innovative therapeutic approaches using CFTR modulators such as C18 have recently shown in vitro capacity to enhance PGE2 production and normalized the RANKL-to-OPG ratio in human osteoblasts bearing the mutation F508del-CFTR and therefore potential clinical utility in CFBD. This review focuses on the recently identified pathogenic mechanisms leading to CFBD and potential future therapies for treating CFBD.

  16. Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients.

    Science.gov (United States)

    Cox, Michael J; Allgaier, Martin; Taylor, Byron; Baek, Marshall S; Huang, Yvonne J; Daly, Rebecca A; Karaoz, Ulas; Andersen, Gary L; Brown, Ronald; Fujimura, Kei E; Wu, Brian; Tran, Diem; Koff, Jonathan; Kleinhenz, Mary Ellen; Nielson, Dennis; Brodie, Eoin L; Lynch, Susan V

    2010-06-23

    Bacterial communities in the airways of cystic fibrosis (CF) patients are, as in other ecological niches, influenced by autogenic and allogenic factors. However, our understanding of microbial colonization in younger versus older CF airways and the association with pulmonary function is rudimentary at best. Using a phylogenetic microarray, we examine the airway microbiota in age stratified CF patients ranging from neonates (9 months) to adults (72 years). From a cohort of clinically stable patients, we demonstrate that older CF patients who exhibit poorer pulmonary function possess more uneven, phylogenetically-clustered airway communities, compared to younger patients. Using longitudinal samples collected form a subset of these patients a pattern of initial bacterial community diversification was observed in younger patients compared with a progressive loss of diversity over time in older patients. We describe in detail the distinct bacterial community profiles associated with young and old CF patients with a particular focus on the differences between respective "early" and "late" colonizing organisms. Finally we assess the influence of Cystic Fibrosis Transmembrane Regulator (CFTR) mutation on bacterial abundance and identify genotype-specific communities involving members of the Pseudomonadaceae, Xanthomonadaceae, Moraxellaceae and Enterobacteriaceae amongst others. Data presented here provides insights into the CF airway microbiota, including initial diversification events in younger patients and establishment of specialized communities of pathogens associated with poor pulmonary function in older patient populations.

  17. Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Michael J Cox

    Full Text Available Bacterial communities in the airways of cystic fibrosis (CF patients are, as in other ecological niches, influenced by autogenic and allogenic factors. However, our understanding of microbial colonization in younger versus older CF airways and the association with pulmonary function is rudimentary at best. Using a phylogenetic microarray, we examine the airway microbiota in age stratified CF patients ranging from neonates (9 months to adults (72 years. From a cohort of clinically stable patients, we demonstrate that older CF patients who exhibit poorer pulmonary function possess more uneven, phylogenetically-clustered airway communities, compared to younger patients. Using longitudinal samples collected form a subset of these patients a pattern of initial bacterial community diversification was observed in younger patients compared with a progressive loss of diversity over time in older patients. We describe in detail the distinct bacterial community profiles associated with young and old CF patients with a particular focus on the differences between respective "early" and "late" colonizing organisms. Finally we assess the influence of Cystic Fibrosis Transmembrane Regulator (CFTR mutation on bacterial abundance and identify genotype-specific communities involving members of the Pseudomonadaceae, Xanthomonadaceae, Moraxellaceae and Enterobacteriaceae amongst others. Data presented here provides insights into the CF airway microbiota, including initial diversification events in younger patients and establishment of specialized communities of pathogens associated with poor pulmonary function in older patient populations.

  18. An Approach for Treating the Hepatobiliary Disease of Cystic Fibrosis by Somatic Gene Transfer

    Science.gov (United States)

    Yang, Yiping; Raper, Steven E.; Cohn, Jonathan A.; Engelhardt, John F.; Wilson, James M.

    1993-05-01

    Cystic fibrosis (CF) is an inherited disease of epithelial cell ion transport that is associated with pathology in multiple organ systems, including lung, pancreas, and liver. As treatment of the pulmonary manifestations of CF has improved, management of CF liver disease has become increasingly important in adult patients. This report describes an approach for treating CF liver disease by somatic gene transfer. In situ hybridization and immunocytochemistry analysis of rat liver sections indicated that the endogenous CFTR (cystic fibrosis transmembrane conductance regulator) gene is primarily expressed in the intrahepatic biliary epithelial cells. To specifically target recombinant genes to the biliary epithelium in vivo, recombinant adenoviruses expressing lacZ or human CFTR were infused retrograde into the biliary tract through the common bile duct. Conditions were established for achieving recombinant gene expression in virtually all cells of the intrahepatic bile ducts in vivo. Expression persisted in the smaller bile ducts for the duration of the experiment, which was 21 days. These studies suggest that it may be feasible to prevent CF liver disease by genetically reconstituting CFTR expression in the biliary tract, using an approach that is clinically feasible.

  19. Effects of chest physiotherapy and aerobic exercise training on physical fitness in young children with cystic fibrosis

    OpenAIRE

    2012-01-01

    Abstract Background Cystic fibrosis is a multisystem disease where the main problems are existing in the respiratory system. Aerobic exercise programs are effective in increasing physical fitness and muscle endurance in addition to chest physiotherapy. Objective The aim of this study was to evaluate the effects of chest physiotherapy and aerobic exercise training on physical fitness in young children with cystic fibrosis. Methods Sixteen patients with cystic fibrosis, between the ages 5-13 ye...

  20. Small intestine bacterial overgrowth and fat digestion and absorption in cystic fibrosis patients

    Directory of Open Access Journals (Sweden)

    Aleksandra Lisowska

    2010-12-01

    Full Text Available Background. Available data suggests that small intestine bacterial overgrowth (SIBO may frequently occur in cystic fibrosis (CF subjects. SIBO may result in synthesis of enterotoxic and unabsorbable metabolites which may cause mucosal damage and – additionally – interfere with digestion and absorption. Such a relationship was documented in CF mouse model. Therefore, in the present study we aimed to assess the influence of bacterial overgrowth in small intestine in CF patients on lipid digestion and absorption. Material and methods. The study comprised 60 pancreatic insufficient CF patients, 30 children and 30 adults. All enrolled CF subjects were tested for the presence of SIBO using hydrogen/methane breath test with glucose loading. According to the obtained results CF patients were divided into SIBO positive and negative subgroups. Subsequently, 13C-labelled mixed triglyceride breath test was performed to assess lipid digestion and absorption. Cumulative percentage dose recovery (cPDR was considered to reflect digestion and absorption of lipids. Results. SIBO was detected in 12 (40.0% children and 11 (36.7% adults with CF. The cPDR did not differ between SIBO positive and negative subgroups, neither when assessed separately for children (mean ±SEM: 5.5 ±0.8 vs. 7.4 ±1.0% and adults (4.9 ±0.8 vs. 7.1 ±0.7% nor for the entire studied population. Conclusions. Small intestine bacterial overgrowth does not seem to play a key role in lipid digestion and absorption in cystic fibrosis patients.

  1. Facilitating Positive Psychosocial Adaptation in Children with Cystic Fibrosis by Increasing Family Communication and Problem-Solving Skills. A Research Report to the Cystic Fibrosis Foundation.

    Science.gov (United States)

    Stabler, Brian; And Others

    This study tested the effects of two group-oriented supportive and educational approaches on the parents of children with cystic fibrosis (CF). Thirteen families were randomly assigned either to a group which received information on medical and technical aspects of CF or to a group which received instruction in communication skills in addition to…

  2. L-ornithine derived polyamines in cystic fibrosis airways.

    Directory of Open Access Journals (Sweden)

    Hartmut Grasemann

    Full Text Available Increased arginase activity contributes to airway nitric oxide (NO deficiency in cystic fibrosis (CF. Whether down-stream products of arginase activity contribute to CF lung disease is currently unknown. The objective of this study was to test whether L-ornithine derived polyamines are present in CF airways and contribute to airway pathophysiology. Polyamine concentrations were measured in sputum of patients with CF and in healthy controls, using liquid chromatography-tandem mass spectrometry. The effect of spermine on airway smooth muscle mechanical properties was assessed in bronchial segments of murine airways, using a wire myograph. Sputum polyamine concentrations in stable CF patients were similar to healthy controls for putrescine and spermidine but significantly higher for spermine. Pulmonary exacerbations were associated with an increase in sputum and spermine levels. Treatment for pulmonary exacerbations resulted in decreases in arginase activity, L-ornithine and spermine concentrations in sputum. The changes in sputum spermine with treatment correlated significantly with changes in L-ornithine but not with sputum inflammatory markers. Incubation of mouse bronchi with spermine resulted in an increase in acetylcholine-induced force and significantly reduced nitric oxide-induced bronchial relaxation. The polyamine spermine is increased in CF airways. Spermine contributes to airways obstruction by reducing the NO-mediated smooth muscle relaxation.

  3. Impact of gene editing on the study of cystic fibrosis.

    Science.gov (United States)

    Harrison, Patrick T; Sanz, David J; Hollywood, Jennifer A

    2016-09-01

    Cystic fibrosis (CF) is a chronic and progressive autosomal recessive disorder of secretory epithelial cells, which causes obstructions in the lung airways and pancreatic ducts of 70,000 people worldwide (for recent review see Cutting Nat Rev Genet 16(1):45-56, 2015). The finding that mutations in the CFTR gene cause CF (Kerem et al. Science 245(4922):1073-1080, 1989; Riordan et al. Science 245(4922):1066-1073, 1989; Rommens et al. Science 245(4922):1059-1065, 1989), was hailed as the very happy middle of a story whose end is a cure for a fatal disease (Koshland Science 245(4922):1029, 1989). However, despite two licensed drugs (Ramsey et al. N Engl J Med 365(18):1663-1672, 2011; Wainwright et al. N Engl J Med 373(3):220-231, 2015), and a formal demonstration that repeated administration of CFTR cDNA to patients is safe and effects a modest but significant stabilisation of disease (Alton et al. Lancet Respir Med 3(9):684-691, 2015), we are still a long way from a cure, with many patients taking over 100 tablets per day, and a mean age at death of 28 years. The aim of this review is to discuss the impact on the study of CF of gene-editing techniques as they have developed over the last 30 years, up to and including the possibility of editing as a therapeutic approach.

  4. Nocturnal hypoxemia in children and adolescents with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Regina Terse Trindade Ramos

    2013-12-01

    Full Text Available OBJECTIVE: To determine the prevalence of nocturnal hypoxemia and its association with pulmonary function, nutritional status, sleep macrostructure, and obstructive respiratory events during sleep in a population of clinically stable children and adolescents with cystic fibrosis (CF.METHODS: This was a cross-sectional study involving 67 children and adolescents with CF between 2 and 14 years of age. All of the participants underwent polysomnography, and SpO2 was measured by pulse oximetry. We also evaluated the Shwachman-Kulczycki (S-K scores, spirometry findings, and nutritional status of the patients.RESULTS: The study involved 67 patients. The mean age of the patients was 8 years. The S-K scores differed significantly between the patients with and without nocturnal hypoxemia, which was defined as an SpO2 < 90% for more than 5% of the total sleep time (73.75 ± 6.29 vs. 86.38 ± 8.70; p < 0.01. Nocturnal hypoxemia correlated with the severity of lung disease, FEV1 (rs= −0.42; p = 0.01, FVC (rs= −0.46; p = 0.01, microarousal index (rs= 0.32; p = 0.01, and apnea-hypopnea index (rs = 0.56; p = 0.01.CONCLUSIONS: In this sample of patients with CF and mild-to-moderate lung disease, nocturnal oxygenation correlated with the S-K score, spirometry variables, sleep macrostructure variables, and the apnea-hypopnea index.

  5. Expression of cystic fibrosis transmembrane conductance regulator in rat ovary.

    Science.gov (United States)

    Jin, Lei; Tang, Ruiling

    2008-10-01

    The protein expression of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl(-) channel, in ovarian stimulated premature female rat ovary during a cycle of follicle development and corpus luteum formation was investigated. Animals were injected with 10 U pregnant Mare's serum gonadotropin (PMSG) and subsequently 10 U hCG 48 h later. Time-dependent immunohistochemistry and Western blotting experiments were performed before and 24, 48, 72 h after hCG treatment. The immunohistochemistry revealed that administration of PMSG stimulated the CFTR expression in thecal cell layer and granulosa cell layer of mature follicles 48 h post injection, coincident with the PMSG-induced peak in follicular estradiol. However, the expression of CFTR in the granulose lutein cell layer and thecal lutein cell layer was time-dependently reduced following hCG injection, in accordance with the gradually increased progestogen level during luteum corpus formation. Western blotting analysis demonstrated that rat ovarian tissue expressed the special CFTR band at 170 kD. It is concluded that cAMP-dependent Cl(-) channels are involved in regulation of follicle development and luteum formation.

  6. Body composition and pulmonary function in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Saba eSheikh

    2014-04-01

    Full Text Available Background: Lower body mass index (BMI is associated with worse pulmonary function in cystic fibrosis (CF. Hypothesis: Lean body mass (LBM is more strongly associated with pulmonary function than BMI is.Methods: Anthropometrics, body composition by dual x-ray absorptiometry, and pulmonary function were determined in pancreatic insufficient CF (PI-CF youth. Sex and age-adjusted Z-scores (BMI-Z, LBMI-Z, FMI-Z were generated for CF and controls. 1 Associations of BMI-Z with LBMI-Z and FMI-Z and 2 age-adjusted associations of BMI-Z, LBMI-Z, and FMI-Z with FEV1%-predicted were tested. Results: 208 PI-CF subjects had lower BMI-Z, LBMI-Z, FMI-Z compared to 390 controls. BMI-Z was associated with lower LBMI-Z (pConclusions: In PI-CF youth, deficits in LBM were apparent. At lower BMI percentiles, BMI may not accurately depict LBM in PI-CF. In under-nourished PI-CF youth this preservation of FM in preference to LBM is relevant since LBMI-Z, but not FMI-Z, is positively associated with FEV1%-predicted. LBMI is more strongly associated with lung function compared to BMI, especially in the undernourished child and adolescent with PI-CF.

  7. Proton MRI appearance of cystic fibrosis: Comparison to CT

    Energy Technology Data Exchange (ETDEWEB)

    Puderbach, Michael; Eichinger, Monika; Kauczor, Hans-Ulrich [Department of Radiology (E010), DKFZ, Heidelberg (Germany); Gahr, Julie; Mueller, Frank-Michael [Childrens Hospital, University Heidelberg, Department of Pediatric Pulmonology, Cystic Fibrosis Center and Infectious Diseases, Heidelberg (Germany); Ley, Sebastian [Department of Radiology (E010), DKFZ, Heidelberg (Germany); Childrens Hospital, University Heidelberg, Department of Pediatric Radiology, Heidelberg (Germany); Tuengerthal, Siegfried; Schmaehl, Astrid [Thoraxklinik am Universitaetsklinikum Heidelberg, Department of Radiology, Heidelberg (Germany); Fink, Christian [Department of Radiology (E010), DKFZ, Heidelberg (Germany); University of Munich, Medical Center Grosshadern, Institute of Clinical Radiology, Munich (Germany); Plathow, Christian [Department of Radiology (E010), DKFZ, Heidelberg (Germany); University of Tuebingen, Department of Radiology, Tuebingen (Germany); Wiebel, Matthias [Thoraxklinik am Universitaetsklinikum Heidelberg, Department of Pulmonology, Heidelberg (Germany)

    2007-03-15

    Cystic fibrosis (CF) is the most frequent inherited disorder leading to premature death in the Caucasian population. As life expectancy is limited by pulmonary complications, repeated imaging [chest X-ray, multislice high-resolution computed tomography (MS-HRCT)] is required in the follow-up. Magnetic resonance imaging (MRI) of the lung parenchyma is a promising new diagnostic tool. Its value for imaging lung changes caused by CF compared with CT is demonstrated. MRI performs well when compared with CT, which serves as the gold standard. Its lack in spatial resolution is obvious, but advantages in contrast and functional assessment compensate for this limitation. Thus, MRI is a reasonable alternative for imaging the CF lung and should be introduced as a radiation-free modality for follow-up studies in CF patients. For further evaluation of the impact of MRI, systematic studies comparing MRI and conventional imaging modalities are necessary. Furthermore, the value of the additional functional MRI (fMRI) information has to be studied, and a scoring system for the morphological and functional aspect of MRI has to be established. (orig.)

  8. Nasal Potential Difference in Cystic Fibrosis considering Severe CFTR Mutations

    Directory of Open Access Journals (Sweden)

    Ronny Tah Yen Ng

    2015-01-01

    Full Text Available The gold standard for diagnosing cystic fibrosis (CF is a sweat chloride value above 60 mEq/L. However, this historical and important tool has limitations; other techniques should be studied, including the nasal potential difference (NPD test. CFTR gene sequencing can identify CFTR mutations, but this method is time-consuming and too expensive to be used in all CF centers. The present study compared CF patients with two classes I-III CFTR mutations (10 patients (G1, CF patients with classes IV-VI CFTR mutations (five patients (G2, and 21 healthy subjects (G3. The CF patients and healthy subjects also underwent the NPD test. A statistical analysis was performed using the Mann-Whitney, Kruskal-Wallis, χ2, and Fisher’s exact tests, α=0.05. No differences were observed between the CF patients and healthy controls for the PDMax, Δamiloride, and Δchloride + free + amiloride markers from the NPD test. For the finger value, a difference between G2 and G3 was described. The Wilschanski index values were different between G1 and G3. In conclusion, our data showed that NPD is useful for CF diagnosis when classes I-III CFTR mutations are screened. However, if classes IV-VI are considered, the NPD test showed an overlap in values with healthy subjects.

  9. Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs.

    Science.gov (United States)

    Stoltz, David A; Rokhlina, Tatiana; Ernst, Sarah E; Pezzulo, Alejandro A; Ostedgaard, Lynda S; Karp, Philip H; Samuel, Melissa S; Reznikov, Leah R; Rector, Michael V; Gansemer, Nicholas D; Bouzek, Drake C; Abou Alaiwa, Mahmoud H; Hoegger, Mark J; Ludwig, Paula S; Taft, Peter J; Wallen, Tanner J; Wohlford-Lenane, Christine; McMenimen, James D; Chen, Jeng-Haur; Bogan, Katrina L; Adam, Ryan J; Hornick, Emma E; Nelson, George A; Hoffman, Eric A; Chang, Eugene H; Zabner, Joseph; McCray, Paul B; Prather, Randall S; Meyerholz, David K; Welsh, Michael J

    2013-06-01

    Cystic fibrosis (CF) pigs develop disease with features remarkably similar to those in people with CF, including exocrine pancreatic destruction, focal biliary cirrhosis, micro-gallbladder, vas deferens loss, airway disease, and meconium ileus. Whereas meconium ileus occurs in 15% of babies with CF, the penetrance is 100% in newborn CF pigs. We hypothesized that transgenic expression of porcine CF transmembrane conductance regulator (pCFTR) cDNA under control of the intestinal fatty acid-binding protein (iFABP) promoter would alleviate the meconium ileus. We produced 5 CFTR-/-;TgFABP>pCFTR lines. In 3 lines, intestinal expression of CFTR at least partially restored CFTR-mediated anion transport and improved the intestinal phenotype. In contrast, these pigs still had pancreatic destruction, liver disease, and reduced weight gain, and within weeks of birth, they developed sinus and lung disease, the severity of which varied over time. These data indicate that expressing CFTR in intestine without pancreatic or hepatic correction is sufficient to rescue meconium ileus. Comparing CFTR expression in different lines revealed that approximately 20% of wild-type CFTR mRNA largely prevented meconium ileus. This model may be of value for understanding CF pathophysiology and testing new preventions and therapies.

  10. Sleep-disordered breathing in patients with cystic fibrosis *

    Science.gov (United States)

    Veronezi, Jefferson; Carvalho, Ana Paula; Ricachinewsky, Claudio; Hoffmann, Anneliese; Kobayashi, Danielle Yuka; Piltcher, Otavio Bejzman; Silva, Fernando Antonio Abreu e; Martinez, Denis

    2015-01-01

    Abstract Objective: To test the hypothesis that disease severity in patients with cystic fibrosis (CF) is correlated with an increased risk of sleep apnea. Methods: A total of 34 CF patients underwent clinical and functional evaluation, as well as portable polysomnography, spirometry, and determination of IL-1β levels. Results: Mean apnea-hypopnea index (AHI), SpO2 on room air, and Epworth Sleepiness Scale score were 4.8 ± 2.6, 95.9 ± 1.9%, and 7.6 ± 3.8 points, respectively. Of the 34 patients, 19 were well-nourished, 6 were at nutritional risk, and 9 were malnourished. In the multivariate model to predict the AHI, the following variables remained significant: nutritional status (β = −0.386; p = 0.014); SpO2 (β = −0.453; p = 0.005), and the Epworth Sleepiness Scale score (β = 0.429; p = 0.006). The model explained 51% of the variation in the AHI. Conclusions: The major determinants of sleep apnea were nutritional status, SpO2, and daytime sleepiness. This knowledge not only provides an opportunity to define the clinical risk of having sleep apnea but also creates an avenue for the treatment and prevention of the disease. PMID:26398755

  11. The role for neutrophil extracellular traps in cystic fibrosis autoimmunity

    Science.gov (United States)

    Skopelja, Sladjana; Hamilton, B. JoNell; Jones, Jonathan D.; Yang, Mei-Ling; Mamula, Mark; Ashare, Alix; Gifford, Alex H.; Rigby, William F.C.

    2016-01-01

    While respiratory failure in cystic fibrosis (CF) frequently associates with chronic infection by Pseudomonas aeruginosa, no single factor predicts the extent of lung damage in CF. To elucidate other causes, we studied the autoantibody profile in CF and rheumatoid arthritis (RA) patients, given the similar association of airway inflammation and autoimmunity in RA. Even though we observed that bactericidal permeability-increasing protein (BPI), carbamylated proteins, and citrullinated proteins all localized to the neutrophil extracellular traps (NETs), which are implicated in the development of autoimmunity, our study demonstrates striking autoantibody specificity in CF. Particularly, CF patients developed anti-BPI autoantibodies but hardly any anti-citrullinated protein autoantibodies (ACPA). In contrast, ACPA-positive RA patients exhibited no reactivity with BPI. Interestingly, anti-carbamylated protein autoantibodies (ACarPA) were found in both cohorts but did not cross-react with BPI. Contrary to ACPA and ACarPA, anti-BPI autoantibodies recognized the BPI C-terminus in the absence of posttranslational modifications. In fact, we discovered that P. aeruginosa–mediated NET formation results in BPI cleavage by P. aeruginosa elastase, which suggests a novel mechanism in the development of autoimmunity to BPI. In accordance with this model, autoantibodies associated with presence of P. aeruginosa on sputum culture. Finally, our results provide a role for autoimmunity in CF disease severity, as autoantibody levels associate with diminished lung function. PMID:27777975

  12. Data Mining of Lung Microbiota in Cystic Fibrosis Patients

    Science.gov (United States)

    Xiao, Yan; Wang, Jianwei; Qin, Xuemei

    2016-01-01

    The major therapeutic strategy used to treat exacerbated cystic fibrosis (CF) is antibiotic treatment. As this approach easily generates antibiotic-resistant strains of opportunistic bacteria, optimized antibiotic therapies are required to effectively control chronic and recurrent bacterial infections in CF patients. A promising future for the proper use of antibiotics is the management of lung microbiota. However, the impact of antibiotic treatments on CF microbiota and vice versa is not fully understood. This study analyzed 718 sputum samples from 18 previous studies to identify differences between CF and uninfected lung microbiota and to evaluate the effects of antibiotic treatments on exacerbated CF microbiota. A reference-based OTU (operational taxonomic unit) picking method was used to combine analyses of data generated using different protocols and platforms. Findings show that CF microbiota had greater richness and lower diversity in the community structure than uninfected control (NIC) microbiota. Specifically, CF microbiota showed higher levels of opportunistic bacteria and dramatically lower levels of commensal bacteria. Antibiotic treatment affected exacerbated CF microbiota notably but only transiently during the treatment period. Limited decrease of the dominant opportunistic bacteria and a dramatic decrease of commensal bacteria were observed during the antibiotic treatment for CF exacerbation. Simultaneously, low abundance opportunistic bacteria were thriving after the antibiotic treatment. The inefficiency of the current antibiotic treatment against major opportunistic bacteria and the detrimental effects on commensal bacteria indicate that the current empiric antibiotic treatment on CF exacerbation should be reevaluated and optimized. PMID:27741283

  13. Microstructural alterations of sputum in cystic fibrosis lung disease

    Science.gov (United States)

    Duncan, Gregg A.; Jung, James; Joseph, Andrea; Thaxton, Abigail L.; West, Natalie E.; Boyle, Michael P.; Hanes, Justin

    2016-01-01

    The stasis of mucus secretions in the lungs of cystic fibrosis (CF) patients leads to recurrent infections and pulmonary exacerbations, resulting in decreased survival. Prior studies have assessed the biochemical and biophysical features of airway mucus in individuals with CF. However, these measurements are unable to probe mucus structure on microscopic length scales relevant to key players in the progression of CF-related lung disease, namely, viruses, bacteria, and neutrophils. In this study, we quantitatively determined sputum microstructure based on the diffusion of muco-inert nanoparticle probes in CF sputum and found that a reduction in sputum mesh pore size is characteristic of CF patients with reduced lung function, as indicated by measured FEV1. We also discovered that the effect of ex vivo treatment of CF sputum with rhDNase I (Pulmozyme) on microstructure is dependent upon the time interval between the most recent inhaled rhDNase I treatment and the sample collection. Microstructure of mucus may serve as a marker for the extent of CF lung disease and as a parameter for assessing the effectiveness of mucus-altering agents. PMID:27812540

  14. CFTR Modulators: Shedding Light on Precision Medicine for Cystic Fibrosis

    Science.gov (United States)

    Lopes-Pacheco, Miquéias

    2016-01-01

    Cystic fibrosis (CF) is the most common life-threatening monogenic disease afflicting Caucasian people. It affects the respiratory, gastrointestinal, glandular and reproductive systems. The major cause of morbidity and mortality in CF is the respiratory disorder caused by a vicious cycle of obstruction of the airways, inflammation and infection that leads to epithelial damage, tissue remodeling and end-stage lung disease. Over the past decades, life expectancy of CF patients has increased due to early diagnosis and improved treatments; however, these patients still present limited quality of life. Many attempts have been made to rescue CF transmembrane conductance regulator (CFTR) expression, function and stability, thereby overcoming the molecular basis of CF. Gene and protein variances caused by CFTR mutants lead to different CF phenotypes, which then require different treatments to quell the patients’ debilitating symptoms. In order to seek better approaches to treat CF patients and maximize therapeutic effects, CFTR mutants have been stratified into six groups (although several of these mutations present pleiotropic defects). The research with CFTR modulators (read-through agents, correctors, potentiators, stabilizers and amplifiers) has achieved remarkable progress, and these drugs are translating into pharmaceuticals and personalized treatments for CF patients. This review summarizes the main molecular and clinical features of CF, emphasizes the latest clinical trials using CFTR modulators, sheds light on the molecular mechanisms underlying these new and emerging treatments, and discusses the major breakthroughs and challenges to treating all CF patients. PMID:27656143

  15. Computed tomography dose optimisation in cystic fibrosis:A review

    Institute of Scientific and Technical Information of China (English)

    Helena Ferris; Maria Twomey; Fiachra Moloney; Siobhan B O’Neill; Kevin Murphy; Owen J O’Connor; Michael Maher

    2016-01-01

    Cystic fibrosis(CF)is the most common autosomal recessive disease of the Caucasian population worldwide,with respiratory disease remaining the most relevant source of morbidity and mortality.Computed tomography(CT)is frequently used for monitoring disease complications and progression.Over the last fifteen years there has been a six-fold increase in the use of CT,which has lead to a growing concern in relation to cumulative radiation exposure.The challenge to the medical profession is to identify dose reduction strategies that meet acceptable image quality,but fulfil the requirements of a diagnostic quality CT.Dose-optimisation,particularly in CT,is essential as it reduces the chances of patients receiving cumulative radiation doses in excess of 100 m Sv,a dose deemed significant by the United Nations Scientific Committee on the Effects of Atomic Radiation.This review article explores the current trends in imaging in CF with particular emphasis on new developments in dose optimisation.

  16. Exophiala (Wangiella) dermatitidis and cystic fibrosis - Prevalence and risk factors.

    Science.gov (United States)

    Lebecque, Patrick; Leonard, Anissa; Huang, Daniel; Reychler, Grégory; Boeras, Anca; Leal, Teresinha; Symoens, Françoise

    2010-11-01

    The objective of this prospective study was to assess the prevalence of Exophiala dermatitidis in respiratory secretions of patients with cystic fibrosis (CF) and to identify risk factors for its presence. The results of all cultures performed over a 2-year period in non lung-transplant patients in our CF clinic were included in the study. Samples consisted of sputum (whenever possible) or deep pharyngeal aspirate after a session of physiotherapy. Specimens were inoculated onto Sabouraud gentamicin-chloramphenicol agar (SGCA) medium (Becton-Dickinson) and incubated at 35°C for 2 days and then at ambient temperature (15-25°C) for 3 weeks. The whole study group included 154 patients (mean age ± SD: 18.5 y ± 11.69). E. dermatitidis was isolated from 58 specimens (2.8%) of nine patients (5.8%) out of total of 2065 cultures prepared during the study period. All E. dermatitidis culture-positive patients were pancreatic insufficient and ≥12 y of age. Almost all (8/9) were homozygous for the F508 del mutation. Aspergillus fumigatus colonization and genotype seemed to be predisposing factors. No other significant characteristic was identified in this group, either in terms of predominant bacterial pathogen or treatment. A distinct comparative study performed over 3 months in our laboratory revealed that the use of SGCA yielded identical isolation rates of E. dermatitidis as erythritol-chloramphenicol agar (ECA).

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

    Directory of Open Access Journals (Sweden)

    M.M. Morales

    1999-08-01

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

  18. Cystic fibrosis heterozygote screening in 5,161 pregnant women

    Energy Technology Data Exchange (ETDEWEB)

    Witt, D.R.; Hallam, P.; Blumberg, B.; Fishbach, A. [Kaiser Permanente Medical Care Program of Northern California, San Jose, CA (United States)] [and others

    1996-04-01

    A screening program for cystic fibrosis (CF) heterozygotes was conducted in a large HMO prenatal population, to evaluate the level of interest among eligible patients, the effectiveness of prescreening education, attitudes toward the screening process, psychological effects, and utilization of prenatal diagnosis and its outcomes. The heterozygote identification rate and frequency of specific CFTR mutations were also assessed. Identified carriers were offered genetic counseling and testing of male partners. Prenatal diagnosis was offered if both partners were identified as carriers. A total of 5,161 women underwent carrier testing; 947 others completed survey instruments only. The acceptance rate of screening was high (78%), and pretest education by videotape was generally effective. Adverse psychological effects were not reported. Participants generally found screening to be desirable and useful. Screening identified 142 female heterozygotes, 109 couples in which the male partner was not a carrier, and 7 high-risk couples. The incidence of R117H mutations was much higher than expected. The number of identified carriers was much lower in Hispanics than in Caucasians. We conclude that large-scale prenatal screening for CF heterozygotes in the absence of a family history of CF is an acceptable method for identifying couples at risk for affected fetuses. Sufficient pretest education can be accomplished efficiently, test insensitivity is well accepted, adverse psychological events are not observed, and general patient satisfaction is high. 66 refs., 1 fig., 8 tabs.

  19. Isolation of Pseudomonas cepacia in cystic fibrosis patient

    Directory of Open Access Journals (Sweden)

    Elizabeth de Andrade Marques

    1993-03-01

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

  20. Pharmaceutical intervention in the care of cystic fibrosis patients.

    Science.gov (United States)

    Ramström, H; Erwander, I; Mared, L; Kornfält, R; Seiving, B

    2000-12-01

    In a prospective, randomised, cross-over study including cystic fibrosis patients with indications for HIVAT (home intravenous antibiotic treatment) the prospect of pharmaceutical intervention was investigated. A comparison between the use of disposable infusion devices with antibiotics from the pharmacy and when the patients prepared the drugs themselves was performed. During a first treatment course the patients received either infusion devices during 5 days or reconstituted the drugs themselves during 5 days, or vice versa. During a second treatment course the order was the reversed. Eight patients were included, out of which six completed the original design as a cross-over study, yielding a total of 550 doses of antibiotics. The patients preferred infusion devices from the pharmacy prepared according to GMP (Good Manufacturing Practice) as opposed to reconstituting the antibiotics themselves. Points of view presented included no anxiety over the correct dosage of drugs and less disruption of family and social life. In a practical sense, portable devices are more expensive than the preparation of the drugs by the patients themselves. However, when comparing with in-hospital treatment the direct costs for a hospital stay exceed that of the devices. Another part of the study evaluated the quality of life using a modified form of SEIQoL-DW (Schedule for the Evaluation of Individual Quality of Life - Direct Weighting). Twenty patients took part in the study and the overall quality of life scores increased significantly when patients received infusion devices compared to reconstituting the drugs themselves.

  1. Aztreonam lysine: a novel inhalational antibiotic for cystic fibrosis.

    Science.gov (United States)

    Parkins, Michael D; Elborn, J Stuart

    2010-08-01

    Acquisition of Pseudomonas aeruginosa, the most prevalent organism isolated from cystic fibrosis (CF) airways, is associated with an accelerated clinical deterioration and reduced survival. Strategies to chronically suppress P. aeruginosa infections in individuals with CF have evolved over the last four decades and now largely focus on regular administration of aerosolized antibiotics. Aztreonam lysine (AZLI; Cayston, Gilead Pharmaceuticals [Foster City, CA, USA]), a novel formulation of the monobactam aztreonam suitable for aerosol delivery has recently been developed. AZLI is administered as 75 mg three-times daily for 28 days in 'on/off' cycles using the Altera/eFlow electronic nebulizer (PARI Innovative Manufacturers [Midlothian, VA, USA]). In individuals with CF chronically infected with P. aeruginosa, AZLI improved healthcare-associated quality-of-life scores, pulmonary function and weight, prolonged time to requirement of antibacterial therapy for symptoms of pulmonary exacerbation and reduced P. aeruginosa sputum burdens. These outcomes were durable over 18 months of cycled use. AZLI has been demonstrated to be safe and effective, and expands available chronic maintenance therapies in CF.

  2. Expression of Cystic Fibrosis Transmembrane Conductance Regulator in Rat Ovary

    Institute of Scientific and Technical Information of China (English)

    Lei JIN; Ruiling TANG

    2008-01-01

    Summary: The protein expression of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl- channel, in ovarian stimulated premature female rat ovary during a cycle of follicle development and corpus luteum formation was investigated. Animals were injected with 10 U pregnant Mare's serum gonadotropin (PMSG) and subsequently 10U hCG 48h later. Time-dependent immunohistochemistry and Western blotting experiments were performed before and 24, 48, 72h after hCG treatment. The immnnohistochemistry revealed that administration of PMSG stimulated the CFTR expression in theeal cell layer and granulosa cell layer of mature follicles 48 h post injection, coincident with the PMSG-induced peak in follicular estradiol. However, the expression of CFTR in the granuiose lutein cell layer and theeal lutein cell layer was time-dependently reduced following hCG injection, in accordance with the gradually increased progestogen level during luteum corpus formation. Western blotting analysis demonstrated that rat ovarian tissue expressed the special CFTR band at 170kD. It is concluded that cAMP-dependent Cl- channels are involved in regulation of follicle development and luteum formation.

  3. Prevalence of depression and anxiety in patients with cystic fibrosis and parent caregivers: results of The International Depression Epidemiological Study across nine countries

    NARCIS (Netherlands)

    Quittner, A.L.; Goldbeck, L.; Abbott, J.; Duff, A.; Lambrecht, P.; Sole, A.; Tibosch, M.M.; Bergsten Brucefors, A.; Yuksel, H.; Catastini, P.; Blackwell, L.; Barker, D.

    2014-01-01

    BACKGROUND: Individuals with chronic diseases and parent caregivers are at increased risk for symptoms of depression and anxiety. Prevalence of psychological symptoms was evaluated in adolescents and adults with cystic fibrosis (CF) and parent caregivers across nine countries. METHODS: Patients with

  4. Activated MCTC mast cells infiltrate diseased lung areas in cystic fibrosis and idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Löfdahl Claes-Göran

    2011-10-01

    Full Text Available Abstract Background Although mast cells are regarded as important regulators of inflammation and tissue remodelling, their role in cystic fibrosis (CF and idiopathic pulmonary fibrosis (IPF has remained less studied. This study investigates the densities and phenotypes of mast cell populations in multiple lung compartments from patients with CF, IPF and never smoking controls. Methods Small airways, pulmonary vessels, and lung parenchyma were subjected to detailed immunohistochemical analyses using lungs from patients with CF (20 lung regions; 5 patients, IPF (21 regions; 7 patients and controls (16 regions; 8 subjects. In each compartment the densities and distribution of MCT and MCTC mast cell populations were studied as well as the mast cell expression of IL-6 and TGF-β. Results In the alveolar parenchyma in lungs from patients with CF, MCTC numbers increased in areas showing cellular inflammation or fibrosis compared to controls. Apart from an altered balance between MCTC and MCT cells, mast cell in CF lungs showed elevated expression of IL-6. In CF, a decrease in total mast cell numbers was observed in small airways and pulmonary vessels. In patients with IPF, a significantly elevated MCTC density was present in fibrotic areas of the alveolar parenchyma with increased mast cell expression of TGF-β. The total mast cell density was unchanged in small airways and decreased in pulmonary vessels in IPF. Both the density, as well as the percentage, of MCTC correlated positively with the degree of fibrosis. The increased density of MCTC, as well as MCTC expression of TGF-β, correlated negatively with patient lung function. Conclusions The present study reveals that altered mast cell populations, with increased numbers of MCTC in diseased alveolar parenchyma, represents a significant component of the histopathology in CF and IPF. The mast cell alterations correlated to the degree of tissue remodelling and to lung function parameters. Further

  5. Severe bone demineralisation is associated with higher mortality in children with cystic fibrosis.

    LENUS (Irish Health Repository)

    O'Reilly, R

    2009-02-01

    Decreased bone mineral density (BMD) is an emerging problem for clinicians who care for children with Cystic fibrosis (CF). The aim of this study was to determine prevalence and assess risk factors for reduced BMD in our adolescent population with CF. All bone densitometry scans (n=99) performed on children (n=79) with a mean age 13.6 (10-19.2) years over a 7 year period (2000-2007) were reviewed. Patient records were reviewed for correlating clinical data. Low BMD is frequently present in adults and children with variable reports (36-66%). In our study, BMD expressed as z score of L2-L4 spine was reduced in a total of 50% children with a preponderance of males. Bone demineralization was strongly associated with increasing age (p=0.03), diminished lung function (p=0.027), reduced body mass index (p=0.001) and treatment with oral corticosteroids (p=0.02).

  6. Human amnion epithelial cells induced to express functional cystic fibrosis transmembrane conductance regulator.

    Directory of Open Access Journals (Sweden)

    Sean V Murphy

    Full Text Available Cystic fibrosis, an autosomal recessive disorder caused by a mutation in a gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR, remains a leading cause of childhood respiratory morbidity and mortality. The respiratory consequences of cystic fibrosis include the generation of thick, tenacious mucus that impairs lung clearance, predisposing the individual to repeated and persistent infections, progressive lung damage and shortened lifespan. Currently there is no cure for cystic fibrosis. With this in mind, we investigated the ability of human amnion epithelial cells (hAECs to express functional CFTR. We found that hAECs formed 3-dimensional structures and expressed the CFTR gene and protein after culture in Small Airway Growth Medium (SAGM. We also observed a polarized CFTR distribution on the membrane of hAECs cultured in SAGM, similar to that observed in polarized airway cells in vivo. Further, hAECs induced to express CFTR possessed functional iodide/chloride (I(-/Cl(- ion channels that were inhibited by the CFTR-inhibitor CFTR-172, indicating the presence of functional CFTR ion channels. These data suggest that hAECs may be a promising source for the development of a cellular therapy for cystic fibrosis.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Hannah K Bayes

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

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

    Science.gov (United States)

    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.

  10. Determinants of Serum Glycerophospholipid Fatty Acids in Cystic Fibrosis

    Science.gov (United States)

    Drzymała-Czyż, Sławomira; Krzyżanowska, Patrycja; Koletzko, Berthold; Nowak, Jan; Miśkiewicz-Chotnicka, Anna; Moczko, Jerzy A.; Lisowska, Aleksandra; Walkowiak, Jarosław

    2017-01-01

    The etiology of altered blood fatty acid (FA) composition in cystic fibrosis (CF) is understood only partially. We aimed to investigate the determinants of serum glycerophospholipids’ FAs in CF with regard to the highest number of FAs and in the largest cohort to date. The study comprised 172 CF patients and 30 healthy subjects (HS). We assessed Fas’ profile (gas chromatography/mass spectrometry), CF transmembrane conductance regulator (CFTR) genotype, spirometry, fecal elastase-1, body height and weight Z-scores, liver disease, diabetes and colonization by Pseudomonas aeruginosa. The amounts of saturated FAs (C14:0, C16:0) and monounsaturated FAs (C16:1n-7, C18:1n-9, C20:1n-9, C20:3n-9) were significantly higher in CF patients than in HS. C18:3n-6, C20:3n-6 and C22:4n-6 levels were also higher in CF, but C18:2n-6, C20:2n-6 and C20:4n-6, as well as C22:6n-3, were lower. In a multiple regression analysis, levels of seven FAs were predicted by various sets of factors that included age, genotype, forced expiratory volume in one second, pancreatic status and diabetes. FA composition abnormalities are highly prevalent in CF patients. They seem to be caused by both metabolic disturbances and independent clinical risk factors. Further research into the influence of CFTR mutations on fat metabolism and desaturases’ activity is warranted. PMID:28106773

  11. Body Composition and Pulmonary Function in Cystic Fibrosis

    Science.gov (United States)

    Sheikh, Saba; Zemel, Babette S.; Stallings, Virginia A.; Rubenstein, Ronald C.; Kelly, Andrea

    2014-01-01

    Background: Lower body mass index (BMI) is associated with worse pulmonary function in cystic fibrosis (CF). Hypothesis: lean body mass (LBM) is more strongly associated with pulmonary function than BMI is. Methods: Anthropometrics, body composition by dual x-ray absorptiometry, and pulmonary function were determined in pancreatic insufficient CF (PI-CF) youth. Sex and age-adjusted Z-scores (BMI-Z, LBMI-Z, FMI-Z) were generated for CF and controls. (1) Associations of BMI-Z with LBMI-Z and FMI-Z and (2) age-adjusted associations of BMI-Z, LBMI-Z, and FMI-Z with FEV1%-predicted were tested. Results: Two hundred eight PI-CF subjects had lower BMI-Z, LBMI-Z, and FMI-Z compared to 390 controls. BMI-Z was associated with lower LBMI-Z (p < 0.0001) in PI-CF. In females, LBMI-Z and BMI-Z were positively associated with FEV1%-predicted; this relationship did not persist for FMI-Z after adjustment for LBMI-Z. In males, only LBMI-Z and BMI-Z were associated with FEV1%-predicted. Conclusion: In PI-CF youth, deficits in LBM were apparent. At lower BMI percentiles, BMI may not accurately depict LBM in PI-CF. In under-nourished PI-CF youth, this preservation of FM in preference to LBM is relevant since LBMI-Z, but not FMI-Z, is positively associated with FEV1%-predicted. Lean body mass index is more strongly associated with lung function compared to BMI, especially in the under-nourished child and adolescent with PI-CF. PMID:24783186

  12. Autoantibodies in serum and sputum from patients with cystic fibrosis.

    Science.gov (United States)

    Schiøtz, P O; Egeskjold, E M; Høiby, N; Permin, H

    1979-10-01

    Sera from 89 patients with cystic fibrosis (CF) and 88 control persons were examined for the occurrence of rheumatoid factors (RF) of the IgG, IgA and IgM classes by an indirect immunofluorescence method and by the latex fixation slide test. The prevalence of RF-IgG was significantly higher (88%) (p less than 0.0005) among the CF patients than among the control persons (7%), while no difference was found between the two groups with regard to RF of the IgA or IgM classes. Fifty-five of the CF patients had chronic Pseudomonas aeruginosa infection in their lungs and two or more precipitins against these bacteria in their sera determined by crossed immunoelectrophoresis. These CF patients did not differ from the 34 CF patients without chronic P. aeruginosa infection, neither with regard to prevalence nor titer of RFs, but there was a positive correlation between the number of P. aeruginosa precipitins in the 55 chronically infected CF patients and their titers of IgG-RF. Nineteen CF patients were examined also for RFs, antinuclear antibodies (ANA) and anti-DNA antibodies in their sputum sol phase and corresponding sera. RFs were demonstrated in the sputum sol phase from 6 of the patients by the latex fixation test, whereas their sera were negative in this test, possibly indicating a local production of RF. Positive reactions for ANA and anti-DNA antibodies were found in 7 and 10 of the sputa respectively, and in higher titers than in the corresponding sera, also suggesting a local production. Titers of autoantibodies in sputum were low and no difference was found between patients with chronic P. aeruginosa infection and patients without P. aeruginosa infection. The possible role of autoantibodies in the patogenesis of pulmonary tissue damage in CF patients is discussed.

  13. Vitamin K status in young children with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Patrycja Krzyżanowska

    2011-09-01

    Full Text Available   Introduction. Cystic fibrosis (CF patients are at risk of developing vitamin K deficiency. However, there is no clinical data clearly describing vitamin K status in the youngest age group. Therefore, in the present study we aimed to assess body resources of vitamin K in children aged up to 3 years and to correlate vitamin K status with selected clinical factors. Material and methods. The study comprised 52 CF patients receiving and not receiving vitamin K supplementation. In all subjects, the concentration of the undercarboxylated prothrombin (PIVKA-II, as a marker of vitamin K deficiency, was determined. Results. PIVKA-II concentrations were pathological in 24 (46.2% CF children, in remaining 28 (53.8% patients vitamin K status was found to be normal. No statistical differences in clinical parameters (Z-score for body height and weight, number of hospitalizations and sweat chloride concentrations neither in distribution of Pseudomonas aeruginosa colonization nor in pancreatic status between selected subgroups with normal and abnormal PIVKA-II concentrations were documented. Normal vitamin K status was more frequent in patients receiving proper vitamin K supplementation (p < 0.0078. However, vitamin K deficiency appeared in 5 out of 21 patients receiving at least 2.5 mg vitamin K/week. In logistic regression model, no clinical parameter was proven to be a risk factor for vitamin K deficiency. Conclusion. Vitamin K deficiency is frequent in CF infants and toddlers, and may also appear in those receiving recommended supplementation. There is no strong relationship between clinical expression of the disease and vitamin K status.  

  14. Correction of a Cystic Fibrosis Splicing Mutation by Antisense Oligonucleotides.

    Science.gov (United States)

    Igreja, Susana; Clarke, Luka A; Botelho, Hugo M; Marques, Luís; Amaral, Margarida D

    2016-02-01

    Cystic fibrosis (CF), the most common life-threatening genetic disease in Caucasians, is caused by ∼2,000 different mutations in the CF transmembrane conductance regulator (CFTR) gene. A significant fraction of these (∼13%) affect pre-mRNA splicing for which novel therapies have been somewhat neglected. We have previously described the effect of the CFTR splicing mutation c.2657+5G>A in IVS16, showing that it originates transcripts lacking exon 16 as well as wild-type transcripts. Here, we tested an RNA-based antisense oligonucleotide (AON) strategy to correct the aberrant splicing caused by this mutation. Two AONs (AON1/2) complementary to the pre-mRNA IVS16 mutant region were designed and their effect on splicing was assessed at the RNA and protein levels, on intracellular protein localization and function. To this end, we used the 2657+5G>A mutant CFTR minigene stably expressed in HEK293 Flp-In cells that express a single copy of the transgene. RNA data from AON1-treated mutant cells show that exon 16 inclusion was almost completely restored (to 95%), also resulting in increased levels of correctly localized CFTR protein at the plasma membrane (PM) and with increased function. A novel two-color CFTR splicing reporter minigene developed here allowed the quantitative monitoring of splicing by automated microscopy localization of CFTR at the PM. The AON strategy is thus a promising therapeutic approach for the specific correction of alternative splicing.

  15. Antibiotic therapy and fat digestion and absorption in cystic fibrosis.

    Science.gov (United States)

    Lisowska, Aleksandra; Pogorzelski, Andrzej; Oracz, Grzegorz; Skorupa, Wojciech; Cofta, Szczepan; Szydłowski, Jarosław; Socha, Jerzy; Walkowiak, Jarosław

    2011-01-01

    Antibiotic therapy in the cystic fibrosis (CF) mouse model has been shown to result in reduced bacterial load of the intestine and significant body mass gain. The effect was suggested to be linked to the improvement of intestinal digestion and absorption. Therefore, we aimed to assess the influence of routinely applied antibiotic therapy in CF patients on fat assimilation. Twenty-four CF patients aged 6 to 30 years entered the study. Inclusion criteria comprised confirmed exocrine pancreatic insufficiency and bronchopulmonary exacerbation demanding antibiotic therapy. Exclusion criteria comprised: antibiotic therapy six weeks prior to the test, liver cirrhosis, diabetes mellitus, oxygen dependency, the use of systemic corticosteroids. In all enrolled CF subjects, (13)C-labelled mixed triglyceride breath test ((13)C MTG-BT) was performed to assess lipid digestion and absorption, before and after antibiotic therapy. Sixteen subjects were treated intravenously with ceftazidime and amikacin, eight patients orally with ciprofloxacin. Cumulative percentage dose recovery (CPDR) was considered to reflect digestion and absorption of lipids. The values are expressed as means (medians). The values of CPDR before and after antibiotic therapy did not differ in the whole studied group [4.6(3.3) % vs. 5.7(5.3) %, p = 0.100] as well as in the subgroup receiving them intravenously [4.6(3.2) % vs. 5.7(5.3) %, p = 0.327] or in that with oral drug administration [4.6(3.4) % vs. 5.7(5.4) %, p = 0.167]. In conclusion, antibiotic therapy applied routinely in the course of pulmonary exacerbation in CF patients does not seem to result in an improvement of fat digestion and absorption.

  16. Hallmarks of therapeutic management of the cystic fibrosis functional landscape.

    Science.gov (United States)

    Amaral, Margarida D; Balch, William E

    2015-11-01

    The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein does not operate in isolation, rather in a dynamic network of interacting components that impact its synthesis, folding, stability, intracellular location and function, referred to herein as the 'CFTR Functional Landscape (CFFL)'. For the prominent F508del mutation, many of these interactors are deeply connected to a protein fold management system, the proteostasis network (PN). However, CF encompasses an additional 2000 CFTR variants distributed along its entire coding sequence (referred to as CFTR2), and each variant contributes a differential liability to PN management of CFTR and to a protein 'social network' (SN) that directs the probability of the (patho)physiologic events that impact ion transport in each cell, tissue and patient in health and disease. Recognition of the importance of the PN and SN in driving the unique patient CFFL leading to disease highlights the importance of precision medicine in therapeutic management of disease progression. We take the view herein that it is not CFTR, rather the PN/SN, and their impact on the CFFL, that are the key physiologic forces driving onset and clinical progression of CF. We posit that a deep understanding of each patients PN/SN gained by merging genomic, proteomic (mass spectrometry (MS)), and high-content microscopy (HCM) technologies in the context of novel network learning algorithms will lead to a paradigm shift in CF clinical management. This should allow for generation of new classes of patient specific PN/SN directed therapeutics for personalized management of the CFFL in the clinic.

  17. Diffusion weighted imaging in cystic fibrosis disease: beyond morphological imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ciet, Pierluigi [Erasmus Medical Center, Department of Radiology, Rotterdam (Netherlands); Erasmus Medical Center - Sophia Children' s Hospital, Department of Paediatrics, Respiratory Medicine and Allergology, P.O. Box 2060, Rotterdam, Zuid-Holland (Netherlands); Ca' Foncello - General Hospital, Department of Radiology, Treviso (Italy); Serra, Goffredo; Catalano, Carlo [University of Rome ' ' Sapienza' ' , Department of Radiology, Rome (Italy); Andrinopoulou, Eleni Rosalina [Erasmus Medical Center, Department of Biostatistics, Rotterdam (Netherlands); Bertolo, Silvia; Morana, Giovanni [Ca' Foncello - General Hospital, Department of Radiology, Treviso (Italy); Ros, Mirco [Ca' Foncello Hospital, Department of Pediatrics, Treviso (Italy); Colagrande, Stefano [University of Florence - Azienda Ospedaliero-Universitaria Careggi, Department of Experimental and Clinical Biomedical Sciences, Radiodiagnostic Unit n. 2, Florence (Italy); Tiddens, Harm A.W.M. [Erasmus Medical Center, Department of Radiology, Rotterdam (Netherlands); Erasmus Medical Center - Sophia Children' s Hospital, Department of Paediatrics, Respiratory Medicine and Allergology, P.O. Box 2060, Rotterdam, Zuid-Holland (Netherlands)

    2016-11-15

    To explore the feasibility of diffusion-weighted imaging (DWI) to assess inflammatory lung changes in patients with Cystic Fibrosis (CF) CF patients referred for their annual check-up had spirometry, chest-CT and MRI on the same day. MRI was performed in a 1.5 T scanner with BLADE and EPI-DWI sequences (b = 0-600 s/mm{sup 2}). End-inspiratory and end-expiratory scans were acquired in multi-row scanners. DWI was scored with an established semi-quantitative scoring system. DWI score was correlated to CT sub-scores for bronchiectasis (CF-CT{sub BE}), mucus (CF-CT{sub mucus}), total score (CF-CT{sub total-score}), FEV{sub 1}, and BMI. T-test was used to assess differences between patients with and without DWI-hotspots. Thirty-three CF patients were enrolled (mean 21 years, range 6-51, 19 female). 4 % (SD 2.6, range 1.5-12.9) of total CF-CT alterations presented DWI-hotspots. DWI-hotspots coincided with mucus plugging (60 %), consolidation (30 %) and bronchiectasis (10 %). DWI{sub total-score} correlated (all p < 0.0001) positively to CF-CT{sub BE} (r = 0.757), CF-CT{sub mucus} (r = 0.759) and CF-CT{sub total-score} (r = 0.79); and negatively to FEV{sub 1} (r = 0.688). FEV{sub 1} was significantly higher (p < 0.0001) in patients without DWI-hotspots. DWI-hotspots strongly correlated with radiological and clinical parameters of lung disease severity. Future validation studies are needed to establish the exact nature of DWI-hotspots in CF patients. (orig.)

  18. Culture enriched molecular profiling of the cystic fibrosis airway microbiome.

    Science.gov (United States)

    Sibley, Christopher D; Grinwis, Margot E; Field, Tyler R; Eshaghurshan, Christina S; Faria, Monica M; Dowd, Scot E; Parkins, Michael D; Rabin, Harvey R; Surette, Michael G

    2011-01-01

    The microbiome of the respiratory tract, including the nasopharyngeal and oropharyngeal microbiota, is a dynamic community of microorganisms that is highly diverse. The cystic fibrosis (CF) airway microbiome refers to the polymicrobial communities present in the lower airways of CF patients. It is comprised of chronic opportunistic pathogens (such as Pseudomonas aeruginosa) and a variety of organisms derived mostly from the normal microbiota of the upper respiratory tract. The complexity of these communities has been inferred primarily from culture independent molecular profiling. As with most microbial communities it is generally assumed that most of the organisms present are not readily cultured. Our culture collection generated using more extensive cultivation approaches, reveals a more complex microbial community than that obtained by conventional CF culture methods. To directly evaluate the cultivability of the airway microbiome, we examined six samples in depth using culture-enriched molecular profiling which combines culture-based methods with the molecular profiling methods of terminal restriction fragment length polymorphisms and 16S rRNA gene sequencing. We demonstrate that combining culture-dependent and culture-independent approaches enhances the sensitivity of either approach alone. Our techniques were able to cultivate 43 of the 48 families detected by deep sequencing; the five families recovered solely by culture-independent approaches were all present at very low abundance (<0.002% total reads). 46% of the molecular signatures detected by culture from the six patients were only identified in an anaerobic environment, suggesting that a large proportion of the cultured airway community is composed of obligate anaerobes. Most significantly, using 20 growth conditions per specimen, half of which included anaerobic cultivation and extended incubation times we demonstrate that the majority of bacteria present can be cultured.

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

    Directory of Open Access Journals (Sweden)

    Edith T Zemanick

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

  20. Culture enriched molecular profiling of the cystic fibrosis airway microbiome.

    Directory of Open Access Journals (Sweden)

    Christopher D Sibley

    Full Text Available The microbiome of the respiratory tract, including the nasopharyngeal and oropharyngeal microbiota, is a dynamic community of microorganisms that is highly diverse. The cystic fibrosis (CF airway microbiome refers to the polymicrobial communities present in the lower airways of CF patients. It is comprised of chronic opportunistic pathogens (such as Pseudomonas aeruginosa and a variety of organisms derived mostly from the normal microbiota of the upper respiratory tract. The complexity of these communities has been inferred primarily from culture independent molecular profiling. As with most microbial communities it is generally assumed that most of the organisms present are not readily cultured. Our culture collection generated using more extensive cultivation approaches, reveals a more complex microbial community than that obtained by conventional CF culture methods. To directly evaluate the cultivability of the airway microbiome, we examined six samples in depth using culture-enriched molecular profiling which combines culture-based methods with the molecular profiling methods of terminal restriction fragment length polymorphisms and 16S rRNA gene sequencing. We demonstrate that combining culture-dependent and culture-independent approaches enhances the sensitivity of either approach alone. Our techniques were able to cultivate 43 of the 48 families detected by deep sequencing; the five families recovered solely by culture-independent approaches were all present at very low abundance (<0.002% total reads. 46% of the molecular signatures detected by culture from the six patients were only identified in an anaerobic environment, suggesting that a large proportion of the cultured airway community is composed of obligate anaerobes. Most significantly, using 20 growth conditions per specimen, half of which included anaerobic cultivation and extended incubation times we demonstrate that the majority of bacteria present can be cultured.

  1. Parallel improvement of sodium and chloride transport defects by miglustat (n-butyldeoxynojyrimicin) in cystic fibrosis epithelial cells

    NARCIS (Netherlands)

    S. Noël (Sabrina); M. Wilke (Martina); A.G. Bot (Alice); H.R. de Jonge (Hugo); F. Becq (Frédéric)

    2008-01-01

    textabstractCystic fibrosis, an autosomal recessive disease frequently diagnosed in the Caucasian population, is characterized by deficient Cl-transport due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. A second major hallmark of the disease is Na+hyperabsorpti

  2. Fifteen-year follow-up of pulmonary function in individuals heterozygous for the cystic fibrosis phenylalanine-508 deletion

    DEFF Research Database (Denmark)

    Dahl, Morten; Nordestgaard, B G; Lange, P;

    2001-01-01

    In a cross-sectional study, we previously showed that cystic fibrosis phenylalanine-508 deletion (DeltaF508) heterozygosity may be overrepresented among individuals with asthma.......In a cross-sectional study, we previously showed that cystic fibrosis phenylalanine-508 deletion (DeltaF508) heterozygosity may be overrepresented among individuals with asthma....

  3. Predictive value of chest CT in patients with cystic fibrosis: A single-center 10-year experience

    NARCIS (Netherlands)

    F. Cademartiri (Filippo); G. Luccichenti; A.A. Palumbo; E. Maffei (Erica); G. Pisi (Giovanna); M. Zompatori; G.P. Krestin (Gabriel)

    2008-01-01

    textabstractOBJECTIVE. The objective of our study was to assess the accuracy of one of the most used scoring systems, the Bhalla scoring system, in the detection of lung impairment in patients with cystic fibrosis and in the prediction of cystic fibrosis progression. MATERIALS AND METHODS. From the

  4. Is the raised volume rapid thoracic compression technique ready for use in clinical trials in infants with cystic fibrosis?

    NARCIS (Netherlands)

    Matecki, Stefan; Kent, Lisa; de Boeck, Kris; Le Bourgeois, Muriel; Zielen, Stefan; Braggion, Cesare; Arets, H. G M; Bradley, Judy; Davis, Stephanie; Sermet, Isabelle; Reix, Philippe

    2016-01-01

    The European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN) has established a Standardization Committee to undertake a rigorous evaluation of promising outcome measures with regard to use in multicentre clinical trials in cystic fibrosis (CF). The aim of this article is to present a revie

  5. Ten years' of experience in patient education of families with a child/adolescent suffering from cystic fibrosis

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke

    2007-01-01

    Aims: The patient education programme for families with children or adolescents with cystic fibrosis (the CF school) was established ten years ago to enable patients to make choices in their lives as CF patients. The CF school provides patients with knowledge about cystic fibrosis (CF), teaches...

  6. Nutrición, fibrosis quística y aparato digestivo Nutrition, cystic fibrosis and the digestive tract

    Directory of Open Access Journals (Sweden)

    Gabriel Olveira

    2008-05-01

    empleo no está avalado en evidencias científicas sólidas. Los preparados más empleados suelen ser poliméricos e hipercalóricos. Las indicaciones de soporte nutricional enteral por sonda (especialmente gastrostomía o parenteral son similares a las empleadas en otras patologías. El control dietético y nutricional debe incluirse en un programa multidisciplinar que permita mejorar la capacidad funcional, la calidad de vida y reducir, al menos teóricamente, la morbi-mortalidad asociada a la malnutrición en estos pacientes.The prevalence of hyponutrition in cystic fibrosis is high although it may vary according to the different studies. Detection of hyponutrition should be done by combining different methods, depending on their availability. However, the simplest and most validated criterion is to measure at each visit the weight (and height in children in order to calculate the body mass index and categorizing hyponutrition according to absolute criteria: in adults < 18.5 kg/m², and in children as percentiles of the body mass index. Worsening of the nutritional status is directly related with the decrease in lung function parameters and it has been proposed as a morbidity (and even mortality predictive factor in people with cystic fibrosis, independently of the level of pulmonary dysfunction. Exocrine pancreatic insufficiency is present is approximately 70-90% of the patients with cystic fibrosis and the genotype-phenotype correlation is high. Most of the patients with exocrine pancreatic insufficiency tolerate a high-fat diet provided that they are treated with pancreatic enzymes at appropriate doses. The prevalence of diabetes increases with age, reaching up 40% of the cases in patients older than 30 years. Clinical liver involvement is less prevalent (it approximately affects 1/3 of the patients. Other intestinal complications such as meconial ileus, gastroesophageal reflux, obstruction of the distal intestine, or fibrosing colon disease may also condition

  7. Child With Cystic Fibrosis And Pyopneumothorax For Emergency Thoracotomy For Decortication

    Directory of Open Access Journals (Sweden)

    Rakesh Garg

    2008-01-01

    Full Text Available We describe a child of cystic fibrosis for emergency thoracotomy. A 7 year female diagnosed as cystic fibrosis, pyopneumothorax with pneumonia was posted for emergency left thoracotomy. On examination, child had decreased air entry on left side of chest and bilateral crepts. Anaesthesia was induced with fentanyl, propofol, vecuronium and sevoflurane in oxygen/air. Airway was secured with tracheal tube. Central venous line and caudal epidural catheter was placed. There were multiple episodes of desaturation and airway pressures were high. Child was shifted to ICU with tube in situ and put on ventilator and gradually weaned. Epidural infusion was initiated. Child had an uneventful recovery. Patient with cystic fibrosis for emergency thoracotomy requires proper choice of anaesthetic techniques along with perioperative pain relief.

  8. Mechanisms of lipid malabsorption in Cystic Fibrosis: the impact of essential fatty acids deficiency

    Directory of Open Access Journals (Sweden)

    Peretti N

    2005-05-01

    Full Text Available Abstract Transport mechanisms, whereby alimentary lipids are digested and packaged into small emulsion particles that enter intestinal cells to be translocated to the plasma in the form of chylomicrons, are impaired in cystic fibrosis. The purpose of this paper is to focus on defects that are related to intraluminal and intracellular events in this life-limiting genetic disorder. Specific evidence is presented to highlight the relationship between fat malabsorption and essential fatty acid deficiency commonly found in patients with cystic fibrosis that are often related to the genotype. Given the interdependency of pulmonary disease, pancreatic insufficiency and nutritional status, greater attention should be paid to the optimal correction of fat malabsorption and essential fatty acid deficiency in order to improve the quality of life and extend the life span of patients with cystic fibrosis.

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

    Science.gov (United States)

    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.

  10. Limited premature termination codon suppression by read-through agents in cystic fibrosis intestinal organoids.

    Science.gov (United States)

    Zomer-van Ommen, D D; Vijftigschild, L A W; Kruisselbrink, E; Vonk, A M; Dekkers, J F; Janssens, H M; de Winter-de Groot, K M; van der Ent, C K; Beekman, J M

    2016-03-01

    Premature termination codon read-through drugs offer opportunities for treatment of multiple rare genetic diseases including cystic fibrosis. We here analyzed the read-through efficacy of PTC124 and G418 using human cystic fibrosis intestinal organoids (E60X/4015delATTT, E60X/F508del, G542X/F508del, R1162X/F508del, W1282X/F508del and F508del/F508del). G418-mediated read-through induced only limited CFTR function, but functional restoration of CFTR by PTC124 could not be confirmed. These studies suggest that better read-through agents are needed for robust treatment of nonsense mutations in cystic fibrosis.

  11. Diminished concentrations of insulin-like growth factor I in cystic fibrosis

    DEFF Research Database (Denmark)

    Laursen, Erik; Juul, A; Lanng, S;

    1995-01-01

    Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data...... on IGF-I in cystic fibrosis are sparse and conflicting. From 1990-3, 235 of our 240 patients (114 males, 121 females, median age 16.2 years, ranged 0.1-44.0 years) had IGF-I measured once by radioimmunoassay. IGF-I was significantly reduced compared with a healthy Scandinavian control population: mean...... = 0.28, p cystic fibrosis and play a part in their abnormal growth pattern....

  12. Sepsis Caused by Achromobacter Xylosoxidans in a Child with Cystic Fibrosis and Severe Lung Disease.

    Science.gov (United States)

    Stobbelaar, Kim; Van Hoorenbeeck, Kim; Lequesne, Monique; De Dooy, Jozef; Ho, Erwin; Vlieghe, Erika; Ieven, Margaretha; Verhulst, Stijn

    2016-08-08

    BACKGROUND Achromobacter xylosoxidans is an aerobic, motile, Gram-negative, opportunistic pathogen that can be responsible for various severe nosocomial and community-acquired infections. It has been found in immunocompromised patients and patients with several other underlying conditions, but the clinical role of this microorganism in cystic fibrosis is unclear. CASE REPORT We describe a case of septic shock caused by A. xylosoxidans in a 10-year-old child with cystic fibrosis and severe lung disease. CONCLUSIONS As the prevalence of A. xylosoxidans in cystic fibrosis patients is rising and patient-to-patient transmission is highly probable, further studies are warranted to determine its role and to document the appropriate treatment strategy for eradication and long-term treatment of this organism.

  13. Parenting adolescents with cystic fibrosis: an interpretive description of the adolescent point of view

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke; Schiøtz, Peter Oluf; Lomborg, Kirsten

    2011-01-01

    , we conducted a secondaryanalysis of the interview data. Results: The adolescents wanted their parents educated about the adolescent experience. They wanted their parents to learn a pedagogical parenting style, to learn to trust the adolescents, and to learn to gradually transfer responsibility......Background: Decreases in disease-related physiological and quality of life parameters are often seen in adolescents with cystic fibrosis. The aim of this study was to identify the types of parental support that adolescents with cystic fibrosis find helpful in terms of preventing these decreases...... for the adolescents’ medical treatment. Conclusion: Parenting an adolescent with cystic fibrosis is a challenge, and the adolescents felt that their parents need to learn skills to help the adolescents better manage their disease. These findings indicate that health professionals may need to educate parents about...

  14. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR

    DEFF Research Database (Denmark)

    Wainwright, Claire E; Elborn, J Stuart; Ramsey, Bonnie W

    2015-01-01

    BACKGROUND: 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. METHODS: 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...... homozygous for the Phe508del CFTR mutation. (Funded by Vertex Pharmaceuticals and others; TRAFFIC and TRANSPORT ClinicalTrials.gov numbers, NCT01807923 and NCT01807949.)....

  15. [Autosomal-recessive renal cystic disease and congenital hepatic fibrosis: clinico-anatomic case].

    Science.gov (United States)

    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. An "ex vivo model" contributing to the diagnosis and evaluation of new drugs in cystic fibrosis.

    Science.gov (United States)

    Di Lullo, A M; Scorza, M; Amato, F; Comegna, M; Raia, V; Maiuri, L; Ilardi, G; Cantone, E; Castaldo, G; Iengo, M

    2016-11-29

    Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. About 2000 mutations have been described so far. We setup an ex vivo model of human nasal epithelial cells (HNECs) to study CF patients testing the effect of novel mutations and molecular therapies. We performed the sampling (by brushing), followed by culture and analysis of HNECs using a series of molecular techniques. We performed 50 brushings from CF patients and controls. Using cultured cells, we: i) demonstrated the widely heterogeneous CFTR expression in patients and in controls; ii) defined the splicing effect of a CFTR mutation; iii) assessed the CFTR gating activity in patients bearing different mutations; iv) demonstrated that butyrate significantly enhances CFTR expression. Based on our data, we can conclude: 1) HNEC brushing is performed without anaesthesia and is well tolerated in all CF patients (children and adults); 2) HNECs can be preserved for up to 48 hours before culture allowings multicenter studies; 3) HNECs culture can be considered a suitable model to study the molecular effects of new CFTR gene mutations and/or uncertain meaning specific mutations of carriers; 4) an ex vivo model of HNECs may be used to evaluate, before human use, the effect of new drugs on patients' cells bearing specific CFTR mutations; 5) the methodology is adequate for a quantitative measurement, by fluorescence, of the CFTR gating activity of the HNECs from patients with different genotypes identifying: a) CF patients bearing two severe mutations with an activity < 10% (compared to controls - 100%); b) CF patients bearing at least a mild mutation with an activity of 10-20%; c) CF carriers (heterozygous subjects) with an activity between 40-70%.

  17. Higher Mobility Scores in Patients with Cystic Fibrosis Are Associated with Better Lung Function

    Directory of Open Access Journals (Sweden)

    Aneesha Thobani

    2015-01-01

    Full Text Available Objective. The purpose of this study was to determine whether mobility and physical activity were associated with lung function in adults with cystic fibrosis (CF. Design. This was a prospective cohort observational study in an urban, academic, specialized care center. Participants were ambulatory, nonhospitalized adults with CF. Main Outcome Measures. Mobility was assessed monthly by the Life-Space Assessment (LSA questionnaire and quarterly by pedometer. Lung function was assessed by spirometry. Results. Twenty-seven subjects participated. Subjects recorded mean pedometer steps of 20,213 ± 11,331 over three days and FEV1% predicted of 77.48% ± 22.60% over one year. The LSA score at enrollment was correlated with initial pedometer steps (r=0.42 and P=0.03, and mean LSA score over one year was correlated with mean number of steps (r=0.51 and P=0.007. LSA mobility and pedometer scores were correlated with FEV1% predicted at enrollment and throughout the study. Conclusions. Mobility and physical activity measured by LSA questionnaire and pedometer are positively associated with lung function in adults with CF. This study confirms the importance of mobility and physical activity and supports the utility of a simple office-based questionnaire as a measure of mobility in adults with CF.

  18. Improving performance in the detection and management of cystic fibrosis-related diabetes in the Mountain West Cystic Fibrosis Consortium

    Science.gov (United States)

    Liou, Theodore G; Jensen, Judith L; Allen, Sarah E; Brayshaw, Sara J; Brown, Mark A; Chatfield, Barbara; Koenig, Joni; McDonald, Catherine; Packer, Kristyn A; Peet, Kimberly; Radford, Peggy; Reineke, Linda M; Otsuka, Kim; Wagener, Jeffrey S; Young, David; Marshall, Bruce C

    2016-01-01

    Objective Cystic fibrosis (CF)-related diabetes (CFRD) is associated with increased morbidity and mortality. Improved detection and management may improve outcomes; however, actual practice falls short of published guidelines. We studied efforts to improve CFRD screening and management in the Mountain West CF Consortium (MWCFC). Research design and methods This is a prospective observational cohort study evaluating quality improvement by accredited CF centers in Arizona, Colorado, New Mexico, and Utah performed between 2002 and 2008. After Institutional Review Board (IRB) approval, centers evaluated adherence with CF Foundation guidelines for CFRD. Each center developed and implemented quality improvement plans to improve both screening and management. Centers were reassessed 1 year later. Results Initially, each CF center had low adherence with screening recommendations (26.5% of eligible patients) that did not improve during the study. However, patients with confirmed CFRD markedly increased (141 (12% of MWCFC patients) to 224 (17%), p<0.001), and with improved adherence to management guidelines, patients with CFRD had increased weight (56.8–58.9 kg, p<0.001), body mass index (21.1–21.4, p=0.003), and weight-for-age z-score (−1.42 to –0.84, p<0.001). Quality improvement methods were specific to the practice settings of each center but shared the common goal of adhering to CFRD care guidelines. 1 year after implementation, no center significantly differed from any other in level of adherence to guidelines. Conclusions Improving adherence with CFRD care guidelines requires substantial effort and may be incompletely successful, particularly for CFRD screening, but the effort may significantly improve patient monitoring and clinically relevant outcomes such as weight. PMID:27158517

  19. Transfer of the Cystic Fibrosis Transmembrane Conductance Regulator to Human Cystic Fibrosis Cells Mediated by Extracellular Vesicles.

    Science.gov (United States)

    Vituret, Cyrielle; Gallay, Kathy; Confort, Marie-Pierre; Ftaich, Najate; Matei, Constantin I; Archer, Fabienne; Ronfort, Corinne; Mornex, Jean-François; Chanson, Marc; Di Pietro, Attilio; Boulanger, Pierre; Hong, Saw See

    2016-02-01

    Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in a deficiency in chloride channel activity. In this study, extracellular vesicles (EVs), microvesicles, and exosomes were used as vehicles to deliver exogenous CFTR glycoprotein and its encoding mRNA (mRNA(GFP-CFTR)) to CF cells to correct the CFTR chloride channel function. We isolated microvesicles and exosomes from the culture medium of CFTR-positive Calu-3 cells, or from A549 cells transduced with an adenoviral vector overexpressing a GFP-tagged CFTR (GFP-CFTR). Both microvesicles and exosomes had the capacity to package and deliver the GFP-CFTR glycoprotein and mRNA(GFP-CFTR) to target cells in a dose-dependent manner. Homologous versus heterologous EV-to-cell transfer was studied, and it appeared that the cellular uptake of EVs was significantly more efficient in homologous transfer. The incubation of CF15 cells, a nasal epithelial cell line homozygous for the ΔF508 CFTR mutation, with microvesicles or exosomes loaded with GFP-CFTR resulted in the correction of the CFTR function in CF cells in a dose-dependent manner. A time-course analysis of EV-transduced CF cells suggested that CFTR transferred as mature glycoprotein was responsible for the CFTR-associated channel activity detected at early times posttransduction, whereas GFP-CFTR translated from exogenous mRNA(GFP-CFTR) was responsible for the CFTR function at later times. Collectively, this study showed the potential application of microvesicles and exosomes as vectors for CFTR transfer and functional correction of the genetic defect in human CF cells.

  20. Metagenomic analysis of respiratory tract DNA viral communities in cystic fibrosis and non-cystic fibrosis individuals.

    Directory of Open Access Journals (Sweden)

    Dana Willner

    Full Text Available The human respiratory tract is constantly exposed to a wide variety of viruses, microbes and inorganic particulates from environmental air, water and food. Physical characteristics of inhaled particles and airway mucosal immunity determine which viruses and microbes will persist in the airways. Here we present the first metagenomic study of DNA viral communities in the airways of diseased and non-diseased individuals. We obtained sequences from sputum DNA viral communities in 5 individuals with cystic fibrosis (CF and 5 individuals without the disease. Overall, diversity of viruses in the airways was low, with an average richness of 175 distinct viral genotypes. The majority of viral diversity was uncharacterized. CF phage communities were highly similar to each other, whereas Non-CF individuals had more distinct phage communities, which may reflect organisms in inhaled air. CF eukaryotic viral communities were dominated by a few viruses, including human herpesviruses and retroviruses. Functional metagenomics showed that all Non-CF viromes were similar, and that CF viromes were enriched in aromatic amino acid metabolism. The CF metagenomes occupied two different metabolic states, probably reflecting different disease states. There was one outlying CF virome which was characterized by an over-representation of Guanosine-5'-triphosphate,3'-diphosphate pyrophosphatase, an enzyme involved in the bacterial stringent response. Unique environments like the CF airway can drive functional adaptations, leading to shifts in metabolic profiles. These results have important clinical implications for CF, indicating that therapeutic measures may be more effective if used to change the respiratory environment, as opposed to shifting the taxonomic composition of resident microbiota.

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

    Directory of Open Access Journals (Sweden)

    Katharina Staufer

    2014-08-01

    Full Text Available 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.

  2. Avidity of anti-P aeruginosa antibodies during chronic infection in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Ciofu, O; Petersen, T D; Jensen, P;

    1999-01-01

    BACKGROUND: In order to study the impact on the lung function of patients with cystic fibrosis of the avidity of antipseudomonal antibodies, the avidity of antibodies against the chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) and against the 60-65 kDa heat shock protein of P...... function the avidity of a beta ab was higher than in patients with poor lung function (p = 0.018). No significant difference in the avidity of the anti-GroEL antibodies was observed between the two groups of patients. CONCLUSION: In patients with cystic fibrosis a high avidity of a beta ab could contribute...

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

    Science.gov (United States)

    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

  4. Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype

    Directory of Open Access Journals (Sweden)

    De Lisle Robert C

    2010-09-01

    Full Text Available Abstract Background Cystic fibrosis (CF is caused by mutations in the CFTR gene that impair the function of CFTR, a cAMP-regulated anion channel. In the small intestine loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have small intestinal bacterial overgrowth, an altered innate immune response, and impaired intestinal transit. We investigated whether lubiprostone, which can activate the CLC2 Cl- channel, would improve the intestinal phenotype in CF mice. Methods Cftrtm1UNC (CF and wildtype (WT littermate mice on the C57BL/6J background were used. Lubiprostone (10 μg/kg-day was administered by gavage for two weeks. Mucus accumulation was estimated from crypt lumen widths in periodic acid-Schiff base, Alcian blue stained sections. Luminal bacterial load was measured by qPCR for the bacterial 16S gene. Gastric emptying and small intestinal transit in fasted mice were assessed using gavaged rhodamine dextran. Gene expression was evaluated by Affymetrix Mouse430 2.0 microarray and qRT-PCR. Results Crypt width in control CF mice was 700% that of WT mice (P P = 0.001. Lubiprostone increased bacterial load in WT mice to 490% of WT control levels (P = 0.008. Conversely, lubiprostone decreased bacterial overgrowth in CF mice by 60% (P = 0.005. Lubiprostone increased gastric emptying at 20 min postgavage in both WT (P P P = 0.024 but not in CF mice (P = 0.377. Among other innate immune markers, expression of mast cell genes was elevated 4-to 40-fold in the CF intestine as compared to WT, and lubiprostone treatment of CF mice decreased expression to WT control levels. Conclusions These results indicate that lubiprostone has some benefits for the CF intestinal phenotype, especially on bacterial overgrowth and the innate immune response. The unexpected observation of increased mucus accumulation in the crypts of lubiprostone-treated CF mice

  5. Pathogen and autoantigen homologous regions within the cystic fibrosis transmembrane conductance regulator (CFTR) protein suggest an autoimmune treatable component of cystic fibrosis.

    Science.gov (United States)

    Carter, Chris J

    2011-07-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel provides the glutathione and hypochlorous acid necessary for bactericidal/viricidal actions. CFTR mutations block these effects, diminishing pathogen defence and allowing extracellular pathogen accumulation, where antibody encounter is likely. KEGG pathway analysis of the CFTR interactome shows that CFTR is involved in pathogen entry pathways and immune defence as well as in pathways relevant to comorbid conditions (diabetes, cardiomyopathies and sexual organ development). Pseudomonas aeruginosa and Staphylococcus aureus infections decrease the lifespan of cystic fibrosis patients and Stenotrophomonas maltophilia colonization is increased. Autoantibodies, targeting myeloperoxidase, the bactericidal/permeability-increasing protein and calgranulin may further compromise pathogen defence. Short consensus sequences, within immunogenic extracellular regions of the CFTR protein, are homologous to proteins expressed by P. aeruginosa, S. aureus and S. maltophilia, and to several autoantigens, with a universal overlap between autoantigen/pathogen/CFTR consensi. Antibodies to pathogens are thus likely responsible for the creation of these autoantibodies, which, with pathogen antibodies, may target the CFTR protein acting as antagonists, further compromising its function. This creates a feedforward cycle, diminishing the function of the CFTR protein and increasing the probability of pathogen accumulation and antibody production at every turn. Interruption of this cycle by antibody adsorption or immunosuppressant therapy may be beneficial in cystic fibrosis.

  6. Diminished concentrations of insulin-like growth factor I in cystic fibrosis

    DEFF Research Database (Denmark)

    Laursen, Erik; Juul, A; Lanng, S

    1995-01-01

    Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data on ...

  7. Inflammatory and growth factor response to continuous and intermittent exercise in youth with cystic fibrosis

    NARCIS (Netherlands)

    Thanh Nguyen, [No Value; Obeid, Joyce; Ploeger, Hilde E.; Takken, Tim; Pedder, Linda; Timmons, Brian W.

    2012-01-01

    Background: Children with cystic fibrosis (CF) tend to suffer from chronic systemic inflammation and may have impaired growth associated with muscle catabolism. Therefore, investigating which type of exercise can elicit an anabolic response with minimal inflammation is of clinical value. Methods: Tw

  8. Effect of antibiotic treatment on fat absorption in mice with cystic fibrosis

    NARCIS (Netherlands)

    Wouthuyzen-Bakker, Marjan; Bijvelds, Marcel J. C.; de Jonge, Hugo R.; De Lisle, Robert C.; Burgerhof, Johannes G. M.; Verkade, Henkjan J.

    2012-01-01

    INTRODUCTION: Improving fat absorption remains a challenge in cystic fibrosis (CF). Antibiotics (AB) treatment has been shown to improve body weight in CF mice. The mechanism may include improvement in fat absorption. We aimed to determine the effect of AB on fat absorption in two CF mouse models. R

  9. Guidelines for the management of pregnancy in women with cystic fibrosis

    NARCIS (Netherlands)

    Edenborough, F P; Borgo, G; Knoop, C; Lannefors, L; Mackenzie, W E; Madge, S; Morton, A M; Oxley, H C; Touw, D J; Benham, M; Johannesson, M

    2008-01-01

    Women with cystic fibrosis (CF) now regularly survive into their reproductive years in good health and wish to have a baby. Many pregnancies have been reported in the literature and it is clear that whilst the outcome for the baby is generally good and some mothers do very well, others find either t

  10. Nebulized hypertonic saline decreases IL-8 in sputum of patients with cystic fibrosis.

    LENUS (Irish Health Repository)

    Reeves, Emer P

    2011-06-01

    Inflammation within the cystic fibrosis (CF) lung is mediated by inflammatory chemokines, such as IL-8. IL-8 is protected from proteolytic degradation in the airways by binding to glycosaminoglycans, while remaining active. Evidence that increased hypertonicity of airway secretions induced by hypertonic saline treatment alters levels of IL-8 is lacking.

  11. Cost-effectiveness of newborn screening for cystic fibrosis determined with real-life data

    NARCIS (Netherlands)

    Ploeg, C.P.B. van der; Akker-van Marle, M.E. van den; Vernooij-van Langen, A.M.M.; Elvers, L.H.; Gille, J.J.P.; Verkerk, P.H.; Dankert-Roelse, J.E.; Loeber, J.G.; Triepels, R.H.; Pal, S.M. van der; Dompeling, E.; Pals, G.; Gulmans, V.A.M.; Oey-Spauwen, M.J.W.; Wijnands, Y.H.H.M.; Castricum, L.M.; Arets, H.G.M.; Ent, C.K. van der; Tiddens, H.A.W.M.; Rijke, Y.B. de; Yntema, J.B.

    2015-01-01

    BACKGROUND: Previous cost-effectiveness studies using data from the literature showed that newborn screening for cystic fibrosis (NBSCF) is a good economic option with positive health effects and longer survival. METHODS: We used primary data to compare cost-effectiveness of four screening strategie

  12. Cost-effectiveness of newborn screening for cystic fibrosis determined with real-life data

    NARCIS (Netherlands)

    van der Ploeg, C. P B; van den Akker-van Marle, M. E.; Vernooij-van Langen, A. M M; Elvers, L. H.; Gille, J. J P; Verkerk, P. H.; Dankert-Roelse, J. E.; Dankert-Roelse, J. E.; Vernooij-van Langen, A. M M; Loeber, J. G.; Elvers, L. H.; Triepels, R. H.; Gille, J. J P; Van der Ploeg, C. P B; van der Pal, S. M.; Dompeling, E.; Pals, G.; van den Akker van Marle, M. E.; Gulmans, V. A M; Oey-Spauwen, M. J W; Wijnands, Y. H H M; Castricum, L. M.; Arets, H. G M; van der Ent, C. K.; Tiddens, H. A W M; de Rijke, Y. B.; Yntema, J. B.

    2015-01-01

    Background: Previous cost-effectiveness studies using data from the literature showed that newborn screening for cystic fibrosis (NBSCF) is a good economic option with positive health effects and longer survival. Methods: We used primary data to compare cost-effectiveness of four screening strategie

  13. Atypical presentation of cystic fibrosis: Obese adolescent with hypertension and pseudo-Bartter’s syndrome

    Directory of Open Access Journals (Sweden)

    Sovtić Aleksandar

    2012-01-01

    Full Text Available Introduction. Infants with cystic fibrosis may fail to thrive despite recommended caloric intake because of electrolyte disurbances caused by salt depletion resulting in hypochloremic metabolic alkalosis or pseudo-Bartter's syndrome. In most patients reported symptoms began in infancy, but it may be an initial presentation of disease in a previously healthy adolescent. Case report. A 15-year-old boy was admitted for evaluation of recurrent episodes of malaise associated with dehydration and acute renal insufficiency. Laboratory analysis showed hypochloremic metabolic alkalosis with hyponatremia and hypokalemia. On admission the boy was obese, with body weight of 95.5 kg (> P97, height 174 cm (> P75, and body mass index of 31.2 kg/m2 (> P95. Physical examination was inconclusive. Blood pressure holter monitoring proved significant systolic hypertension. Routine urinalysis, protein and electrolyte levels in urine were normal. Plasma renin and aldosteron were normal. Sweat chloride concentration was 63 mmol/L. Genetic testing confirmed the diagnosis of cystic fibrosis. Conclusion. To our knowledge, this is the first reported case of atypical presentation of cystic fibrosis in an adolescent presented with pseudo-Bartter's syndrome and signs of obesity and hypertension. We suggest that every patient with hypochloremic metabolic alkalosis should be evaluated for cystic fibrosis.

  14. Serum retinol levels and pulmonary function in children and adolescents with cystic fibrosis

    NARCIS (Netherlands)

    Woestenenk, J. W.; Broos, N.; Stellato, R. K.; Arets, H. G M; van der Ent, C. K.; Houwen, R. H J; Arets, HGM

    2015-01-01

    Background: It has been suggested that higher serum retinol levels could have protective effects on pulmonary function (PF) in patients with cystic fibrosis (CF). However, serum retinol levels will be transiently decreased during pulmonary exacerbation. Therefore, the extent of chronic pulmonary inf

  15. Monitoring Cystic Fibrosis Lung Disease : Chest imaging and patient-related outcome measures

    NARCIS (Netherlands)

    L.A. Tepper (Leonie)

    2014-01-01

    markdownabstract__Abstract__ Cystic Fibrosis (CF) is a severe, life-shortening genetic disease with a wide spectrum of clinical manifestations, affecting 70,000 patients in the EU and USA. The most prevalent clinical manifestation is structural lung disease. Structural lung disease is the main caus

  16. Composition of mineralizing incisor enamel in cystic fibrosis transmembrane conductance regulator-deficient mice

    NARCIS (Netherlands)

    Bronckers, A.L.J.J.; Lyaruu, D.M.; Guo, J.; Bijvelds, M.J.C.; Bervoets, T.J.M.; Zandieh-Doulabi, B.; Medina, J.F.; Li, Z.; Zhang, Y.; DenBesten, P.K.

    2015-01-01

    Formation of crystals in the enamel space releases protons that need to be buffered to sustain mineral accretion. We hypothesized that apical cystic fibrosis transmembrane conductance regulator (CFTR) in maturation ameloblasts transduces chloride into forming enamel as a critical step to secrete bic

  17. Simultaneous liver-pancreas transplantation for cystic fibrosis-related liver disease : A multicenter experience

    NARCIS (Netherlands)

    Bandsma, R. H. J.; Bozic, M. A.; Fridell, J. A.; Crull, M. H.; Molleston, J.; Avitzur, Y.; Mozer-Glassberg, Y.; Gonzalez-Peralta, R. P.; Hodik, M.; Fecteau, A.; de Angelis, M.; Durie, P.; Ng, V. L.

    2014-01-01

    Background: Diabetes is associated with increased morbidity and mortality in patients with cystic fibrosis (CF). While liver transplantation is well established for CF-related liver disease (CFLD), the role of simultaneous liver pancreas transplantation is less understood. Methods: We polled 81 pedi

  18. Biomarkers in exhaled breath condensate indicate presence and severity of cystic fibrosis in children.

    NARCIS (Netherlands)

    Robroeks, C.M.; Rosias, P.P.; Vliet, D van; Jobsis, Q.; Yntema, J.L.; Brackel, H.J.; Damoiseaux, J.G.; Hartog, GM den; Wodzig, W.K.; Dompeling, E.

    2008-01-01

    Chronic airway inflammation is present in cystic fibrosis (CF). Non-invasive inflammometry may be useful in disease management. The aim of the present cross-sectional study was to investigate: (i) the ability of fractional exhaled nitric oxide and inflammatory markers (IM) [exhaled breath condensate

  19. In Vitro Activities against Cystic Fibrosis Pathogens of Synthetic Host Defence Propeptides Processed by Neutrophil Elastase.

    LENUS (Irish Health Repository)

    Desgranges, Stephane

    2011-02-22

    The antimicrobial and haemolytic activities of a host defence peptide can be controlled by modification as a propeptide of reduced net charge which can be processed by neutrophil elastase, a serine protease involved in chronic airway inflammation and infections associated with cystic fibrosis.

  20. The genome of Burkholderia cenocepacia J2315, an epidemic pathogen of cystic fibrosis patients

    DEFF Research Database (Denmark)

    Holden, Matthew T G; Seth-Smith, Helena M B; Crossman, Lisa C;

    2009-01-01

    Bacterial infections of the lungs of cystic fibrosis (CF) patients cause major complications in the treatment of this common genetic disease. Burkholderia cenocepacia infection is particularly problematic since this organism has high levels of antibiotic resistance, making it difficult to eradica...

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

    DEFF Research Database (Denmark)

    Jalal, S; Ciofu, O; Høiby, Niels;

    2000-01-01

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

  2. Serial lung function and responsiveness in cystic fibrosis during early childhood

    DEFF Research Database (Denmark)

    Nielsen, Kim G; Pressler, Tacjana; Klug, Bent;

    2004-01-01

    to bronchodilators and cold air in 30 children (mean [range] age 5.7 [2 to 8] years) with cystic fibrosis (CF). Spirometry was done at school age. Mean sRaw was consistently abnormal: the mean z score (SD) was 2.52 (2.02) (p

  3. Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis : a European consensus

    NARCIS (Netherlands)

    Döring, G; Conway, S P; Heijerman, H G; Hodson, M E; Høiby, N; Smyth, A; Touw, D J

    2000-01-01

    Cystic fibrosis (CF) is the most common lethal hereditary disorder with autosomal recessive heredity in caucasians. The majority of CF patients suffer from chronic respiratory infection with the opportunistic bacterial pathogen Pseudomonas aeruginosa. No consensus among clinicians has been reached s

  4. Chronic pulmonary infection with Stenotrophomonas maltophilia and lung function in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Dalbøge, C S; Hansen, C R; Pressler, T;

    2011-01-01

    Background The clinical consequences of chronic Stenotrophomonas maltophilia infection in cystic fibrosis (CF) patient are still unclear. Method All patients treated in the Copenhagen CF centre (N=278) from 1 January 2008 to 31 December 2009 were included. Each patient chronically infected with S...

  5. Polymorphisms Associated with Expression of BPIFA1/BPIFB1 and Lung Disease Severity in Cystic Fibrosis

    NARCIS (Netherlands)

    Saferali, Aabida; Obeidat, Ma'en; Berube, Jean-Christophe; Lamontagne, Maxime; Bosse, Yohan; Laviolette, Michel; Hao, Ke; Nickle, David C.; Timens, Wim; Sin, Don D.; Postma, Dirkje S.; Strug, Lisa J.; Gallins, Paul J.; Pare, Peter D.; Bingle, Colin D.; Sandford, Andrew J.

    2015-01-01

    BPI fold containing family A, member 1 (BPIFA1) and BPIFB1 are putative innate immune molecules expressed in the upper airways. Because of their hypothesized roles in airway defense, these molecules may contribute to lung disease severity in cystic fibrosis (CF). We interrogated BPIFA1/BPIFB1 single

  6. Family Stress with Chronic Childhood Illness: Cystic Fibrosis, Neuromuscular Disease, and Renal Disease.

    Science.gov (United States)

    Holroyd, Jean; Guthrie, Donald

    1986-01-01

    Parents of children with neuromuscular disease, cystic fibrosis, and renal disease were compared with parents of control subjects matched by age to the clinical cases. The three clinical groups exhibited different patterns of stressful response, consistent with the nature of their illnesses and the requirements for care imposed on the families.…

  7. Cystic fibrosis liver disease and the enterohepatic circulation of bile acids

    NARCIS (Netherlands)

    Bodewes, Frank

    2014-01-01

    Cystic fibrosis (CF) is one of the most frequently occurring life threatening congenital diseases. This progressive disease manifests itself in several organ systems. The disease is caused by a mutation in the CFTR protein. The studies in the thesis focused on the development and treatment of CF in

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  9. The evolution and adaptation of clinical Pseudomonas aeruginosa isolates from early cystic fibrosis infections

    DEFF Research Database (Denmark)

    Lindegaard, Mikkel

    Pseudomonas aeruginosa is a major cause of morbidity and mortality in cystic fibrosis (CF) patients. P. aeruginosa infects the CF airways and establishes chronic infections that can last for a lifetime during which P.aeruginosa evolves in order to adapt to the environment.In this PhD thesis, we...

  10. Serum-surfactant SP-D correlates inversely to lung function in cystic fibrosis

    DEFF Research Database (Denmark)

    Olesen, Hanne Vebert; Holmskov, Uffe; Schiøtz, Peter Oluf;

    2010-01-01

    BACKGROUND: Cystic fibrosis (CF) affects the lungs causing infections and inflammation. Surfactant protein D (SP-D) is an innate defense lectin primarily secreted in the lungs. We investigated the influence of the SP-D Met11Thr polymorphism on CF lung function; and serum SP-D as a marker for CF...

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

    DEFF Research Database (Denmark)

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

    1997-01-01

    The efficacy and safety of anti-inflammatory treatment with inhaled glucocorticosteroids in patients with cystic fibrosis (CF) and complicating chronic Pseudomonas aeruginosa (P.a.) lung infection was studied in a placebo-controlled, parallel, double-blind single center trial. Active treatment...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    Biofilms are thought to play a key role in the occurrence of lung infections by Pseudomonas aeruginosa in patients with cystic fibrosis (CF). In this study, 20 nonmucoid P. aeruginosa isolates collected during different periods of chronic infection from eight CF patients were assessed with respect...

  14. Improved quality of life after lung transplantation in individuals with cystic fibrosis

    NARCIS (Netherlands)

    Vermeulen, KM; van der Bij, W; Erasmus, ME; Duiverman, EJ; Koeter, GH; TenVergert, EM

    2004-01-01

    The aim of the present study was to assess the effect of lung transplantation (LgTX) on health-related quality of life (HRQL) in a group of patients with cystic fibrosis (CF), compared to patients with other diagnoses (non-CF). HRQL was assessed before transplantation in a group of 32 CIF patients a

  15. No hearing loss after repeated courses of tobramycin in cystic fibrosis patients

    NARCIS (Netherlands)

    Scheenstra, Renske J; Heijerman, Harry G M; Zuur, Charlotte L; Touw, Daan J; Rijntjes, Evert

    2010-01-01

    CONCLUSION: Our results indicate that repeated treatment courses with tobramycin 10 mg/kg (twice daily for 3 weeks) may be safely applied in cystic fibrosis (CF) patients with respect to ototoxicity. The risk of hearing loss in this patient group is less than expected, which could be explained by ei

  16. The microorganisms in chronically infected end-stage and non-end-stage cystic fibrosis patients

    DEFF Research Database (Denmark)

    Rudkjøbing, Vibeke Børsholt; Thomsen, Trine Rolighed; Alhede, Morten;

    2012-01-01

    Patients suffering from cystic fibrosis (CF) develop chronic lung infections because of highly viscous mucus, where bacteria can form biofilms. In this study, we investigated the microorganisms present in the lungs of end-stage and non-end-stage patients using standard culturing techniques and mo...

  17. Bordetella bronchiseptica in a paediatric cystic fibrosis patient: possible transmission from a household cat

    Science.gov (United States)

    Bordetella bronchiseptica was isolated from the sputum of a cystic fibrosis patient recently exposed to a kitten with an acute respiratory disease. Genetic characterization of the isolate and comparison with other isolates of human or feline origin strongly implicate the kitten as the source of infe...

  18. Description and validation of a scoring system for tomosynthesis in pulmonary cystic fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Vult von Steyern, Kristina; Bjoerkman-Burtscher, Isabella M.; Bozovic, Gracijela; Wiklund, Marie; Geijer, Mats [Skaane University Hospital, Lund University, Centre for Medical Imaging and Physiology, Lund (Sweden); Hoeglund, Peter [Skaane University Hospital, Competence Centre for Clinical Research, Lund (Sweden)

    2012-12-15

    To design and validate a scoring system for tomosynthesis (digital tomography) in pulmonary cystic fibrosis. A scoring system dedicated to tomosynthesis in pulmonary cystic fibrosis was designed. Three radiologists independently scored 88 pairs of radiographs and tomosynthesis examinations of the chest in 60 patients with cystic fibrosis and 7 oncology patients. Radiographs were scored according to the Brasfield scoring system and tomosynthesis examinations were scored using the new scoring system. Observer agreements for the tomosynthesis score were almost perfect for the total score with square-weighted kappa >0.90, and generally substantial to almost perfect for subscores. Correlation between the tomosynthesis score and the Brasfield score was good for the three observers (Kendall's rank correlation tau 0.68, 0.77 and 0.78). Tomosynthesis was generally scored higher as a percentage of the maximum score. Observer agreements for the total score for Brasfield score were almost perfect (square-weighted kappa 0.80, 0.81 and 0.85). The tomosynthesis scoring system seems robust and correlates well with the Brasfield score. Compared with radiography, tomosynthesis is more sensitive to cystic fibrosis changes, especially bronchiectasis and mucus plugging, and the new tomosynthesis scoring system offers the possibility of more detailed and accurate scoring of disease severity. (orig.)

  19. Associations between Academic Achievement and Psychosocial Variables in Adolescents with Cystic Fibrosis

    Science.gov (United States)

    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…

  20. Exploring Cystic Fibrosis Using Bioinformatics Tools: A Module Designed for the Freshman Biology Course

    Science.gov (United States)

    Zhang, Xiaorong

    2011-01-01

    We incorporated a bioinformatics component into the freshman biology course that allows students to explore cystic fibrosis (CF), a common genetic disorder, using bioinformatics tools and skills. Students learn about CF through searching genetic databases, analyzing genetic sequences, and observing the three-dimensional structures of proteins…

  1. "No Time to Play": Perceptions toward Physical Activity in Youth with Cystic Fibrosis

    Science.gov (United States)

    Moola, Fiona; Faulkner, Guy E. J.; Schneiderman, Jane E.

    2012-01-01

    Although physical activity may reduce lung function decline in youth with cystic fibrosis (CF), most patients are inactive. Little is known about why youth with CF are inactive or how to facilitate physical activity. This study explored perceptions toward physical activity in 14 youth with CF at a Canadian Hospital. Qualitative interviews were…

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

    LENUS (Irish Health Repository)

    Linnane, Barry

    2015-10-01

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

  3. Costs, effects, and savings of screening for cystic fibrosis gene carriers

    NARCIS (Netherlands)

    Wildhagen, MF; Hilderink, HBM; Verzijl, JG; Verheij, JBGM; Kooij, L; Tijmstra, T; ten Kate, LP; Habbema, JDF

    1998-01-01

    Study objective-Evaluating the costs, effects, and savings of several strategies for cystic fibrosis (CF) gene carrier screening. Design-A general model for evaluating prenatal, preconceptional, school, and neonatal carrier screening was constructed. For prenatal and preconceptional screening, two s

  4. Personal experiences of cystic fibrosis (CF) carrier couples prospectively identified in CF families

    NARCIS (Netherlands)

    Henneman, L; Kooij, L; Bouman, K; ten Kate, LP

    2002-01-01

    This qualitative study explores the experiences of cystic fibrosis (CF) carrier couples, prospectively identified in CF families, and the impact of the resulting genetic risk on reproductive behavior. Of the 12 couples identified until 1997, seven couples participated in semistructured interviews an

  5. June 2014 critical care case of the month: acute exacerbation in cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Yun S

    2014-06-01

    Full Text Available No abstract available. Article truncated after 150 words. History of Present Illness: A 28 year-old woman with a history of cystic fibrosis, presented with worsening shortness of breath and cough associated with productive secretions. She was diagnosed with cystic fibrosis when she was 14 months old, and has a history of multiple inpatient admissions for acute pulmonary exacerbation of cystic fibrosis. Her most recent hospitalization was a month prior to this admission, and sputum culture demonstrated methicillin-resistant Staphylococcus aureus, multidrug-resistant Pseudomonas aeruginosa, and Achromobacter xylosoxidans. She was treated with linezolide, meropenum, colistin, and azithromycin with significant symptom improvement, then, discharged home with ciprofloxacin, linezolide and zosyn. However, she developed worsening respiratory distress again and came back to hospital. In the emergency department she required 10 L/min of oxygen to maintain an SpO2 above 90 %. PMH: cystic fibrosis, seizure, kidney stone, portacath placement, gastrostomy tube placement. Medications: azithromycin 500 mg 3 times, dornase alpha 1 mg/ml nebulizer twice ...

  6. Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease.

    Science.gov (United States)

    Hartl, Dominik; Latzin, Philipp; Hordijk, Peter; Marcos, Veronica; Rudolph, Carsten; Woischnik, Markus; Krauss-Etschmann, Susanne; Koller, Barbara; Reinhardt, Dietrich; Roscher, Adelbert A; Roos, Dirk; Griese, Matthias

    2007-12-01

    Interleukin-8 (IL-8) activates neutrophils via the chemokine receptors CXCR1 and CXCR2. However, the airways of individuals with cystic fibrosis are frequently colonized by bacterial pathogens, despite the presence of large numbers of neutrophils and IL-8. Here we show that IL-8 promotes bacterial killing by neutrophils through CXCR1 but not CXCR2. Unopposed proteolytic activity in the airways of individuals with cystic fibrosis cleaved CXCR1 on neutrophils and disabled their bacterial-killing capacity. These effects were protease concentration-dependent and also occurred to a lesser extent in individuals with chronic obstructive pulmonary disease. Receptor cleavage induced the release of glycosylated CXCR1 fragments that were capable of stimulating IL-8 production in bronchial epithelial cells via Toll-like receptor 2. In vivo inhibition of proteases by inhalation of alpha1-antitrypsin restored CXCR1 expression and improved bacterial killing in individuals with cystic fibrosis. The cleavage of CXCR1, the functional consequences of its cleavage, and the identification of soluble CXCR1 fragments that behave as bioactive components represent a new pathophysiologic mechanism in cystic fibrosis and other chronic lung diseases.

  7. Care for Amish and Mennonite children with cystic fibrosis: a case series

    Directory of Open Access Journals (Sweden)

    Anbar Ran D

    2009-01-01

    Full Text Available Abstract Background Published articles have described a lack of willingness to allow preventative measures, as well as other types of modern therapies, as an obstacle to providing medical care for Amish and Mennonite populations. Methods We present data regarding the 12 Amish and Mennonite patients at the SUNY Upstate Medical University Pediatric Cystic Fibrosis Center and three representative case reports. Results Families of patients from these communities receiving care at our Center have accepted preventive therapy, acute medical interventions including home intravenous antibiotic administration, and some immunizations for their children with cystic fibrosis, which have improved the health of our patients. Some have even participated in clinical research trials. Health care education for both the child and family is warranted and extensive. Significant Cystic Fibrosis Center personnel time and fundraising are needed in order to address medical bills incurred by uninsured Amish and Mennonite patients. Conclusion Amish and Mennonite families seeking care for cystic fibrosis may choose to utilize modern medical therapies for their children, with resultant significant improvement in outcome.

  8. Increase of Serum gamma-Glutamyltransferase Associated With Development of Cirrhotic Cystic Fibrosis Liver Disease

    NARCIS (Netherlands)

    Bodewes, Frank A. J. A.; van der Doef, Hubert P. J.; Houwen, Roderick H. J.; Verkade, Henkjan J.

    2015-01-01

    Background:Identification of patients at risk for developing cirrhotic cystic fibrosis liver disease (CCFLD) is essential for targeting potentially preventive treatment. We studied the evolution of serum liver enzymes and thrombocyte counts as predictors of CCFLD development.Methods:For this study,

  9. Pharmacoeconomic review of recombinant human DNase in the management of cystic fibrosis

    NARCIS (Netherlands)

    Zijlstra, Gerrit; Boersma, Cornelis; Frijlink, Henderik W.; Postma, Maarten J.

    2004-01-01

    For the treatment of patients with cystic fibrosis, recombinant human deoxyribonuclease I is widely used. Deoxyribonuclease I has a positive effect on lung function and the number of hospitalizations. Deoxyribonuclease I is currently administered by nebulization, which is an inefficient administrati

  10. Severe liver dysfunction in an infant with cystic fibrosis masquerading as metabolic liver disease

    Directory of Open Access Journals (Sweden)

    K P Srikanth

    2016-01-01

    Full Text Available We present a rare presentation of cystic fibrosis with neonatal cholestasis. Histological features of mucoviscidosis were present in liver involving the biliary tract, intestinal mucosa, pancreas, and lung. Besides, there was a rare association with autosomal dominant type of polycystic renal disease.

  11. EFFECT OF A HOME EXERCISE TRAINING-PROGRAM IN PATIENTS WITH CYSTIC-FIBROSIS

    NARCIS (Netherlands)

    DEJONG, W; GREVINK, RG; ROORDA, RJ; KAPTEIN, AA; VANDERSCHANS, CP

    1994-01-01

    Physical training in patients with pulmonary diseases, including cystic fibrosis (CF), may improve exercise tolerance in these patients. Most training programs are performed in a clinical setting. Little information is available concerning the effect of home exercise training programs in CF patients

  12. Mixed-morphotype broth microdilution susceptibility testing of Pseudomonas aeruginosa from cystic fibrosis patients.

    OpenAIRE

    1993-01-01

    Multiple morphotypes of Pseudomonas aeruginosa isolated from 50 respiratory specimens of cystic fibrosis patients were tested for correlation of broth microdilution susceptibility results of a mixed-morphotype inoculum with a predicted antibiogram of the individual isolates. The overall correlation was 96.0%, with only 1.6% very major or major errors.

  13. Preconceptional cystic fibrosis carrier screening: attitudes and intentions of the target population.

    NARCIS (Netherlands)

    Poppelaars, F.; Henneman, L.; Ader, H.J.; Cornel, M.C.; Hermens, R.P.M.G.; Wal, G. van der; Kate, L. ten

    2004-01-01

    The aim of this study was to assess the attitudes and intentions of individuals planning a pregnancy with regard to preconceptional cystic fibrosis (CF) carrier screening and to determine factors associated with a positive and negative/neutral intention to have the test. A survey, based on a questio

  14. Molecular epidemiology of chronic Pseudomonas aeruginosa airway infections in cystic fibrosis

    DEFF Research Database (Denmark)

    Cramer, Nina; Wiehlmann, Lutz; Ciofu, Oana

    2012-01-01

    The molecular epidemiology of the chronic airway infections with Pseudomonas aeruginosa in individuals with cystic fibrosis (CF) was investigated by cross-sectional analysis of bacterial isolates from 51 CF centers and by longitudinal analysis of serial isolates which had been collected at the CF...

  15. Nontuberculous Mycobacterial Disease Is Not a Contraindication to Lung Transplantation in Patients With Cystic Fibrosis

    DEFF Research Database (Denmark)

    Qvist, Tavs; Pressler, Tanja; Thomsen, V O;

    2013-01-01

    Whether nontuberculous mycobacterial (NTM) disease is a contraindication to lung transplantation remains controversial. We conducted a nationwide study to evaluate the clinical importance of NTM infection among lung transplant patients with cystic fibrosis (CF) in Denmark and to determine if NTM...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    The present study was undertaken to investigate the appearance and location of Pseudomonas aeruginosa in the cystic fibrosis (CF) lung and in sputum. Samples include preserved tissues of CF patients who died due to chronic P. aeruginosa lung infection prior to the advent of intensive antibiotic...

  17. Epidemiology of nontuberculous mycobacteria among patients with cystic fibrosis in Scandinavia

    DEFF Research Database (Denmark)

    Qvist, Tavs; Gilljam, Marita; Jönsson, Bodil;

    2015-01-01

    BACKGROUND: Nontuberculous mycobacteria (NTM) are an emerging threat to cystic fibrosis (CF) patients but their epidemiology is not well described. METHODS: In this retrospective observational study we identified all Scandinavian CF patients with a positive NTM culture from airway secretions from...

  18. Effect of screening for cystic-fibrosis on the influence of genetic-counseling

    NARCIS (Netherlands)

    Dankert-Roelse, J E; te Meerman, G J; Knol, K; ten Kate, L P

    1987-01-01

    We studied the influence of genetic counseling for cystic fibrosis on family planning, using neonatal screening, family size at time of diagnosis, and maternal age as possible determinants for reproductive behaviour. The expected number of children born to mothers of equal age and parity in the same

  19. Loss of Social Behaviours in Populations of Pseudomonas aeruginosa Infecting Lungs of Patients with Cystic Fibrosis

    DEFF Research Database (Denmark)

    Jiricny, Natalie; Molin, Søren; Foster, Kevin

    2014-01-01

    Pseudomonas aeruginosa, is an opportunistic, bacterial pathogen causing persistent and frequently fatal infections of the lung in patients with cystic fibrosis. Isolates from chronic infections differ from laboratory and environmental strains in a range of traits and this is widely interpreted as...

  20. Radiologic imaging in cystic fibrosis: cumulative effective dose and changing trends over 2 decades.

    LENUS (Irish Health Repository)

    O'Connell, Oisin J

    2012-06-01

    With the increasing life expectancy for patients with cystic fibrosis (CF), and a known predisposition to certain cancers, cumulative radiation exposure from radiologic imaging is of increasing significance. This study explores the estimated cumulative effective radiation dose over a 17-year period from radiologic procedures and changing trends of imaging modalities over this period.

  1. Very mild disease phenotype of congenic CftrTgH(neoim)Hgu cystic fibrosis mice

    NARCIS (Netherlands)

    B. Tóth (Balázs); M. Wilke (Martina); F. Stanke (Frauke); M. Dorsch (Martina); S. Jansen (Silke); D. Wedekind (Dirk); N. Charizopoulou (Nikoletta); A.G. Bot (Alice); M. Burmester (Marion); S. Leonhard-Marek (Sabine); H.R. de Jonge (Hugo); H.J. Hedrich; G. Breves (Gerhard); B. Tümmler (Burkhard)

    2008-01-01

    textabstractBackground: A major boost to cystic fibrosis disease research was given by the generation of various mouse models using gene targeting in embryonal stem cells. Moreover, the introduction of the same mutation on different inbred strains generating congenic strains facilitated the search f

  2. The Streptococcus milleri population of a cystic fibrosis clinic reveals patient specificity and intraspecies diversity.

    Science.gov (United States)

    Sibley, Christopher D; Sibley, Kristen A; Leong, Tara A; Grinwis, Margot E; Parkins, Michael D; Rabin, Harvey R; Surette, Michael G

    2010-07-01

    The genetic relatedness of Streptococcus milleri group isolates from the airways of cystic fibrosis patients was determined by using pulsed-field gel electrophoresis. This study reveals no evidence for patient-to-patient transmission in our patient population; however, within individual patients, complex inter- and intraspecies diversity and dynamics can be observed.

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

    Science.gov (United States)

    Coutinho, Henrique Douglas M; Falcão-Silva, Vivyanne S; Gonçalves, Gregório Fernandes

    2008-11-07

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

  4. Draft genome sequence of Acinetobacter pittii ST643 shared by cystic fibrosis patients

    Science.gov (United States)

    Rocha, Géssica A; Ferreira, Alex G; Lima, Danielle F; Leão, Robson S; Carvalho-Assef, Ana Paula D; Folescu, Tânia W; Albano, Rodolpho M; Marques, Elizabeth A

    2016-01-01

    Acinetobacter pittii has emerged as an important hospital pathogen that is associated with outbreaks and drug resistance. In cystic fibrosis (CF) patients, the detection of Acinetobacter spp. is rare; however, we isolated the A. pittii sequence type ST643 in several Brazilian CF patients treated in the same centre. The current study describes the draft genome of A. pittii ST643. PMID:27653362

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

    DEFF Research Database (Denmark)

    Jensen, P Ø; Moser, C; Kharazmi, A;

    2006-01-01

    Chronic Pseudomonas aeruginosa lung infection is the major reason for premature death in patients with cystic fibrosis (CF). Infected patients experience a progressive deterioration of the lung tissue caused by a persistent accumulation of PMNs. We investigated if the pulmonary accumulation of PMNs...

  6. 21 CFR 866.5900 - Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation detection system.

    Science.gov (United States)

    2010-04-01

    ... regulator (CFTR) gene mutation detection system. 866.5900 Section 866.5900 Food and Drugs FOOD AND DRUG... DEVICES Immunological Test Systems § 866.5900 Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation detection system. (a) Identification. The CFTR gene mutation detection system is a...

  7. Assessment of Airway Microbiota and Inflammation in Cystic Fibrosis Using Multiple Sampling Methods

    OpenAIRE

    Edith T Zemanick; Brandie D Wagner; Robertson, Charles E.; Stevens, Mark J.; Szefler, Stanley J; Accurso, Frank J.; Sagel, Scott D; Harris, J. Kirk

    2015-01-01

    Rationale: Oropharyngeal (OP) swabs and induced sputum (IS) are used for airway bacteria surveillance in nonexpectorating children with cystic fibrosis (CF). Molecular analyses of these airway samples detect complex microbial communities. However, the optimal noninvasive sampling approach for microbiota analyses and the clinical relevance of microbiota, particularly its relationship to airway inflammation, is not well characterized.

  8. Extended gene analysis can increase specificity of neonatal screening for cystic fibrosis

    NARCIS (Netherlands)

    Merelle, Marieke E.; Scheffer, Hans; de Jong, Debora; Dankert-Roelse, Jeannette E.

    2006-01-01

    Aim: To assess whether carriers and patients can be accurately identified by extended gene analysis for cystic fibrosis (CF) in dried blood spots. Methods: A blinded analysis was performed in 10-mm(2) blood spots on Guthrie cards, punched as if to remove material for the IRT test, from 10 CF patient

  9. Antimicrobial susceptibility of Haemophilus influenzae in the respiratory tracts of patients with cystic fibrosis

    NARCIS (Netherlands)

    Moller, LVM; Regelink, AG; Grasselier, H; van Alphen, L

    1998-01-01

    We analyzed the antimicrobial susceptibilities of Haemophilus influenzae isolates from 157 sputum specimens prospectively collected from 39 cystic fibrosis (CF) patients during a 2-year study, These isolates were characterized by random amplified polymorphic DNA analysis and major outer membrane pro

  10. Parenting adolescents with cystic fibrosis: the adolescents’ and young adults’ perspectives

    Directory of Open Access Journals (Sweden)

    Bregnballe V

    2011-11-01

    Full Text Available Vibeke Bregnballe1, Peter Oluf Schiøtz1, Kirsten Lomborg21Department of Pediatrics, Aarhus University Hospital; 2Department of Nursing Science, Institute of Public Health, Aarhus University, Aarhus, DenmarkBackground: When suffering from cystic fibrosis (CF, a number of problems may arise during adolescence; for example, poor adherence. The problems may be attributed to the adolescent being insufficiently prepared for adult life. Research on different ways of parenting adolescents with CF and the influence of different parenting styles on the adolescents' adherence to treatment is still limited.Aim: The aim of this study was to identify the types of parental support that adolescents and young adults with CF want and find helpful in terms of preparing them for adult life.Methods: Sixteen Danish adolescents with CF, aged 14–25, participated in the study. Two focus group interviews were carried out, one for 14–18-year-olds and one for 19–25-year-olds. Individual interviews were conducted, with three subjects. Using interpretive description strategy, a secondary analysis of the interview data was conducted.Results: The adolescents and young adults wanted their parents educated about the adolescent experience. They wanted their parents to learn a pedagogical parenting style, to learn to trust them, and to learn to gradually transfer responsibility for their medical treatment. Additionally, the adolescents noted that meeting other parents may be beneficial for the parents.Conclusion: The findings of this study suggest that adolescents and young adults with CF want their parents to be educated about how to handle adolescents with CF and thereby sufficiently prepare them for adult life.Keywords: chronic illness, parenting style, qualitative research, patient preferences, interpretive description

  11. Prenatal diagnosis of meconium ileus and meconium peritonitis: Indications for cystic fibrosis testing

    Directory of Open Access Journals (Sweden)

    Egić Amira

    2011-01-01

    Full Text Available Introduction. More recently, the regions of increased abdominal echogenicity such as echogenic bowel, meconium ileus and meconium peritonitis have been associated with an increased prevalence of a variety of unfavourable outcomes including chromosomal abnormalities, cytomegalovirus infection, intestinal obstruction, anorectal malformations and cystic fibrosis. Earlier prenatal examinations of these severe autosomal recessive diseases had been suggested only to families with history of cystic fibrosis. Recently, systemic examination has been introduced by ultrasound with bowel hyperechogenicity where the fetus is the index case for genetic disease. Risk for cystic fibrosis with this ultrasonography findings ranges from 0-33%. Outline of Cases. Two patients are presented, aged 24 and 29 years, both primigravide. The first one had ultrasonography finding of meconium peritonitis revealed at the 37th week of gestation and the other meconium ileus revealed on ultrasonography at the 29th week of gestation. Both patients had prenatal testing of foetal blood obtained by cordocenthesis, both had normal kariotype and were negative for cytomegalovirus infection. Parental DNA testing for the 2nd patient showed that parents were not carriers for the 29 most frequent mutations. Both neonates had intestinal obstruction, underwent surgery and early postoperative course was normal. Hystopathological finding suggested a possibility of cystic fibrosis for the 1st patient, but parents did not want to be tested and for the 2nd one congenital bowel stenosis as a cause of intestinal obstruction. Conclusion. Ultrasonographic echogenic bowel is an indication for invasive procedures for foetal blood testing for chromosomal abnormalities, congenital infections and parental testing for cystic fibrosis. Only if parental heterozygosity is proven foetus should be tested.

  12. Coincidence of Cystic Fibrosis in Mother and her Child Related to Infertility

    Directory of Open Access Journals (Sweden)

    Alireza Nikzad Jamnani

    2010-01-01

    Full Text Available Cystic fibrosis (CF, the most common life-shortening, hereditary disease in whites, manifestsitself principally in childhood. Patients presenting with CF as adults appear to be different whencompared to patients diagnosed with CF during childhood. Often these patients have been previouslydiagnosed with asthma, chronic bronchitis or emphysema.We present a case of a woman diagnosed with CF at age 37 years. We noticed her finger clubbingduring her son’s hospital admission for CF decompensation. Taking a thorough history, shecomplained of chronic productive cough and was treated for hyper reactive airway disease for manyyears. A Computed Tomography scan was performed which showed bronchiectasis, atelectasis andthe presence of a honey comb pattern in her lung fields. Two sweat tests were performed, both ofwhich were strongly positive. Her CF diagnosis was confirmed.The clinical course of patients receiving a diagnosis of CF in adulthood is largely unknown, butfrequently they have milder disease and a more favorable prognosis. The proportion and number ofpatients with CF diagnosed in adulthood has increased. A large number of these patients present withsubtle symptoms or single-organ disease. Since the majority have pulmonary disease CF should beincluded in the differential diagnosis of chronic respiratory symptoms in adults.

  13. Effects of High Frequency Chest Compression on Respiratory System Mechanics in Normal Subjects and Cystic Fibrosis Patients

    Directory of Open Access Journals (Sweden)

    Richard L Jones

    1995-01-01

    Full Text Available OBJECTIVE: To investigate the short term effects of high frequency chest compression (HFCC on several indices of respiratory system mechanics in normal subjects and patients with cystic fibrosis (CF.

  14. Effects of flutter and PEP mask physiotherapy on symptoms and lung function in children with cystic fibrosis

    NARCIS (Netherlands)

    C.M. van Winden; A. Visser (Adriaan); P.J. Sterk (Peter); S. Beckers; J.C. de Jongste (Johan); W.C.J. Hop (Wim)

    1998-01-01

    textabstractRecently, the flutter was introduced as a new device to improve sputum expectoration. Preliminary data suggested a significant improvement in expectoration and lung function during flutter treatment in patients with cystic fibrosis (CF). The aim of the prese

  15. Development of low-dose protocols for thin-section CT assessment of cystic fibrosis in pediatric patients.

    LENUS (Irish Health Repository)

    O'Connor, Owen J

    2010-12-01

    To develop low-dose thin-section computed tomographic (CT) protocols for assessment of cystic fibrosis (CF) in pediatric patients and determine the clinical usefulness thereof compared with chest radiography.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

    Ulrich, Martina; Beer, Isabelle; Braitmaier, Peter;

    2010-01-01

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

  18. Phenotypic characterization and differentiation potential of cells from human placenta: new approaches of stem cell theraphy for cystic fibrosis

    OpenAIRE

    Paracchini, Valentina

    2011-01-01

    Cystic fibrosis (CF) is the most frequent severe autosomal recessive disorder in the European population. The gene is located on the long arm of chromosome 7 and encodes for CFTR protein (Cystic Fibrosis Transmembrane Conductance Regulator). Despite the disease involves different organs, the most clinically relevant symptoms are found in the lung. Recently, given the monogenic nature of CF, different gene therapy strategies have been developed, but the results show that the correction of the ...

  19. Invariant Natural Killer T (iNKT Cells Prevent Autoimmunity, but Induce Pulmonary Inflammation in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Nanna Siegmann

    2014-06-01

    Full Text Available Background/Aims: Inflammation is a major and critical component of the lung pathology in the hereditary disease cystic fibrosis. The molecular mechanisms of chronic inflammation in cystic fibrosis require definition. Methods: We used several genetic mouse models to test a role of iNKT cells and ceramide in pulmonary inflammation of cystic fibrosis mice. Inflammation was determined by the pulmonary cytokine profil and the abundance of inflammatory cells in the lung. Results: Here we provide a new concept how inflammation in the lung of individuals with cystic fibrosis is initiated. We show that in cystic fibrosis mice the mutation in the Cftr gene provokes a significant up-regulation of iNKT cells in the lung. Accumulation of iNKT cells serves to control autoimmune disease, which is triggered by a ceramide-mediated induction of cell death in CF organs. Autoimmunity becomes in particular overt in cystic fibrosis mice lacking iNKT cells and although suppression of the autoimmune response by iNKT cells is beneficial, IL-17+ iNKT cells attract macrophages and neutrophils to CF lungs resulting in chronic inflammation. Genetic deletion of iNKT cells in cystic fibrosis mice prevents inflammation in CF lungs. Conclusion: Our data demonstrate an important function of iNKT cells in the chronic inflammation affecting cystic fibrosis lungs. iNKT cells suppress the auto-immune response induced by ceramide-mediated death of epithelial cells in CF lungs, but also induce a chronic pulmonary inflammation.

  20. Patients' knowledge of cystic fibrosis: genetic determinism and implications for treatment.

    Science.gov (United States)

    Chapman, Elizabeth; Bilton, Diana

    2004-10-01

    This paper uses the self-regulation model of illness perceptions (Leventhal et al. , 1984) to consider the implications of different ways of thinking about the causes of illness. The relationship between anxiety/depression and knowledge or denial of illness is also considered. These issues are explored using adherence to treatment in cystic fibrosis (CF) as an example. Twenty-six CF patients took part in semistructured interviews and completed a standardized anxiety and depression scale (HAD, Zigmond and Snaith, 1983). Interview data were analyzed using Interpretative Phenomenological Analysis (Chapman and Smith, 2002). HAD data were analyzed using SPSS. The respondents displayed widely differing levels of knowledge of their condition. Some deterministic comments were also reported. Findings are discussed in relation to the information that physicians might provide to patients and families in the light of increasing knowledge about genetics in society and the genotyping of individuals with genetic conditions specifically. Any important gaps in patient knowledge could usefully be discussed at transition from pediatric to adult care and issues relating to control and genetic determinism discussed with the patients individually.

  1. Isolation and characterization of microparticles in sputum from cystic fibrosis patients

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    Martínez Maria C

    2010-07-01

    Full Text Available Abstract Background Microparticles (MPs are membrane vesicles released during cell activation and apoptosis. MPs have different biological effects depending on the cell from they originate. Cystic fibrosis (CF lung disease is characterized by massive neutrophil granulocyte influx in the airways, their activation and eventually apoptosis. We investigated on the presence and phenotype of MPs in the sputum, a rich non-invasive source of inflammation biomarkers, of acute and stable CF adult patients. Methods Spontaneous sputum, obtained from 21 CF patients (10 acute and 11 stable and 7 patients with primary ciliary dyskinesia (PCD, was liquefied with Sputasol. MPs were counted, visualized by electron microscopy, and identified in the supernatants of treated sputum by cytofluorimetry and immunolabelling for leukocyte (CD11a, granulocyte (CD66b, and monocyte-macrophage (CD11b antigens. Results Electron microscopy revealed that sputum MPs were in the 100-500 nm range and did not contain bacteria, confirming microbiological tests. CF sputa contained higher number of MPs in comparison with PCD sputa. Levels of CD11a+-and CD66b+-, but not CD11b+-MPs were significantly higher in CF than in PCD, without differences between acute and stable patients. Conclusions In summary, MPs are detectable in sputa obtained from CF patients and are predominantly of granulocyte origin. This novel isolation method for MPs from sputum opens a new opportunity for the study of lung pathology in CF.

  2. Exogenous and endogenous determinants of vitamin K status in cystic fibrosis.

    Science.gov (United States)

    Krzyżanowska, Patrycja; Pogorzelski, Andrzej; Skorupa, Wojciech; Moczko, Jerzy; Grebowiec, Philip; Walkowiak, Jarosław

    2015-07-10

    Cystic fibrosis (CF) patients are at high risk for vitamin K deficiency. The effects of vitamin K supplementation are very ambiguous. Therefore, we aimed to define the determinants of vitamin K deficiency in a large cohort of supplemented - 146 (86.9%) and non-supplemented - 22 (13.1%) CF patients. Vitamin K status was assessed using prothrombin inducted by vitamin K absence (PIVKA-II) and undercarboxylated osteocalcin (u-OC). The pathological PIVKA-II concentration (≥ 2 ng/ml) and abnormal percentage of osteocalcin (≥ 20%) were found in 72 (42.8%) and 60 (35.7%) subjects, respectively. We found that liver involvement, diabetes, and glucocorticoid therapy were potential risk factors for vitamin K deficiency. Pathological concentrations of PIVKA-II occurred more frequently in patients with pancreatic insufficiency and those who have two severe mutations in both alleles of the CFTR gene. Pathological percentage of u-OC was found more frequently in adult CF patients and those not receiving vitamin K. However, it seems that there are no good predictive factors of vitamin K deficiency in CF patients in everyday clinical care. Early vitamin K supplementation in CF patients seems to be warranted. It is impossible to clearly determine the supplementation dose. Therefore, constant monitoring of vitamin K status seems to be justified.

  3. Mucociliary clearance techniques for treating non-cystic fibrosis bronchiectasis: Is there evidence?

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    Snijders, D; Fernandez Dominguez, B; Calgaro, S; Bertozzi, I; Escribano Montaner, A; Perilongo, G; Barbato, A

    2015-06-01

    Non-cystic fibrosis bronchiectasis (nCFb) is an acquired condition of variable etiology. An impaired mucociliary clearance seems to be one of the mechanisms behind nCFb, and treatment involves antibiotics, mucoactive agents, and airway clearance techniques (ACTs). Traditional ACTs have four components: postural drainage, percussion, vibration of the chest wall, and coughing. Reviewing the international medical literature on the use of ACTs for patients with nCFb from 1989 to the present day, we retrieved 93 articles, of which 35 met our selection criteria for this analysis. We reviewed active cycle of breathing techniques (ACBT), forced expiration techniques (FET), autogenic drainage, postural drainage, oscillating positive expiratory pressure (OPep), high frequency chest wall oscillation (HFCWO), and exercise or pulmonary rehabilitation. Overall, ACTs appear to be safe for individuals (adults and children) with stable bronchiectasis; where there may be improvements in sputum expectoration, selected measures of lung function, and health-related quality of life. Unfortunately, there is a lack of RCTs in nCFb patients, especially in children. Moreover, none of the studies describes long-term effects of ACTs. It should be noted that a single intervention might not reflect the longer-term outcome and there is no evidence to recommend or contest any type of ACTs in nCFb management. Multicenter RCTs are necessary to evaluate the different techniques of ACTs especially in children with nCFb.

  4. GENETIC MARKERS OF LOW BONE MINERAL DENSITY IN PATIENTS WITH CYSTIC FIBROSIS.

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    Tatjana Jakovska

    2015-03-01

    Full Text Available Introduction: failure to maintain bone mass density is a major problem in patients with cystic fibrosis (CF. CF is due to mutations in the CFTR gene and other genes may contribute to modifying the disease. Genetic and environmental factors may play a role in determining the variability of bone mass. Aim of the study: to analyse the association between polymorphic variants of genes considered to be risk factors of bone metabolism disturbances and decreased bone mineral density (BMD in children and adults with CF in R. Macedonia. Materials and methods: the study included 80 clinically stable CF patients (age range 5-36y, who regularly attended the CF center at the Pediatric Clinic in Skopje, Macedonia. Three candidate genes likely associated with BMD variability were studied: the vitamin D receptor (VDR gene, the estrogen receptor alpha (ESR1 and the type I alpha I collagen (COLIA1 gene. A complete bone and CF evaluation was obtained for all patients: 55 had normal BMD (group 1, 17 were osteopenic (group 2 and 8 were osteoporotic (group 3. Results: Low bone mineral density (Z score < -1SD was found in 31.25% patients and in 10% of them BMD was below -2SD. Patients with low BMD had worse BMI, FEV1 and more severe symptoms of CF. No significant correlation was found between COLIA1 and VDR polymorphisms and BMD. Conclusion: There was no evidence that the genes under study may modulate bone phenotype in CF.

  5. Reactive-oxygen-species-mediated P. aeruginosa killing is functional in human cystic fibrosis macrophages.

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    Noemi Cifani

    Full Text Available Pseudomonas aeruginosa is the most common pathogen for chronic lung infection in cystic fibrosis (CF patients. About 80% of adult CF patients have chronic P. aeruginosa infection, which accounts for much of the morbidity and most of the mortality. Both bacterial genetic adaptations and defective innate immune responses contribute to the bacteria persistence. It is well accepted that CF transmembrane conductance regulator (CFTR dysfunction impairs the airways-epithelium-mediated lung defence; however, other innate immune cells also appear to be affected, such as neutrophils and macrophages, which thus contribute to this infectious pathology in the CF lung. In macrophages, the absence of CFTR has been linked to defective P. aeruginosa killing, increased pro-inflammatory cytokine secretion, and reduced reactive oxygen species (ROS production. To learn more about macrophage dysfunction in CF patients, we investigated the generation of the oxidative burst and its impact on bacterial killing in CF macrophages isolated from peripheral blood or lung parenchyma of CF patients, after P. aeruginosa infection. Our data demonstrate that CF macrophages show an oxidative response of similar intensity to that of non-CF macrophages. Intracellular ROS are recognized as one of the earliest microbicidal mechanisms against engulfed pathogens that are activated by macrophages. Accordingly, NADPH inhibition resulted in a significant increase in the intracellular bacteria survival in CF and non-CF macrophages, both as monocyte-derived macrophages and as lung macrophages. These data strongly suggest that the contribution of ROS to P. aeruginosa killing is not affected by CFTR mutations.

  6. TLR5 as an anti-inflammatory target and modifier gene in cystic fibrosis.

    Science.gov (United States)

    Blohmke, Christoph J; Park, Julie; Hirschfeld, Aaron F; Victor, Rachel E; Schneiderman, Julia; Stefanowicz, Dorota; Chilvers, Mark A; Durie, Peter R; Corey, Mary; Zielenski, Julian; Dorfman, Ruslan; Sandford, Andrew J; Daley, Denise; Turvey, Stuart E

    2010-12-15

    New treatments are needed to improve the health of people with cystic fibrosis (CF). Reducing lung-damaging inflammation is likely to be beneficial, but specific anti-inflammatory targets have not been identified. By combining cellular immunology with a population-based genetic modifier study, we examined TLR5 as an anti-inflammatory target and modifier gene in CF. Using two pairs of human CF and control airway epithelial cells, we demonstrated that the TLR5-flagellin interaction is a major mediator of inflammation following exposure to Pseudomonas aeruginosa. To validate TLR5 as an anti-inflammatory target, we analyzed the disease modifying effects of the TLR5 c.1174C>T single nucleotide polymorphism (rs5744168) in a large cohort of CF patients (n = 2219). rs5744168 encodes a premature stop codon and the T allele is associated with a 45.5-76.3% reduction in flagellin responsiveness (p impact of TLR5 on nutritional status, this translational research provides evidence that genetic variation in TLR5 resulting in reduced flagellin responsiveness is associated with improved health indicators in adults with CF.

  7. McKay agar enables routine quantification of the 'Streptococcus milleri' group in cystic fibrosis patients.

    Science.gov (United States)

    Sibley, Christopher D; Grinwis, Margot E; Field, Tyler R; Parkins, Michael D; Norgaard, Jens C; Gregson, Daniel B; Rabin, Harvey R; Surette, Michael G

    2010-05-01

    The 'Streptococcus milleri' group (SMG) has recently been recognized as a contributor to bronchopulmonary disease in cystic fibrosis (CF). Routine detection and quantification is limited by current CF microbiology protocols. McKay agar was developed previously for the semi-selective isolation of this group. Here, McKay agar was validated against a panel of clinical SMG isolates, which revealed improved SMG recovery compared with Columbia blood agar. The effectiveness of this medium was evaluated by appending it to the standard CF sputum microbiology protocols in a clinical laboratory for a 6-month period. All unique colony types were isolated and identified by 16S rRNA gene sequencing. Whilst a wide variety of organisms were isolated, members of the SMG were the most prevalent bacteria cultured, and McKay agar allowed routine quantification of the SMG from 10(3) to >10(8) c.f.u. ml(-1) directly from sputum. All members of the SMG were detected [Streptococcus anginosus (40.7 %), Streptococcus intermedius (34.3 %) and Streptococcus constellatus (25 %)] with an overall prevalence rate of 40.6 % in our adult CF population. Without exception, samples where SMG isolates were cultured at 10(7) c.f.u. ml(-1) or greater were associated with pulmonary exacerbations. This study demonstrates that McKay agar can be used routinely to quantify the SMG from complex clinical samples.

  8. From registry to quality management: the German Cystic Fibrosis Quality Assessment project 1995 2006.

    Science.gov (United States)

    Stern, M; Wiedemann, B; Wenzlaff, P

    2008-01-01

    Since 1995, the German Cystic Fibrosis Quality Assessment project has collected demographic data and outcome parameters. It aims to develop tools for quality management. The basic data of 6,835 patients has been collected annually by 93 centres. Weight for height and body mass index (BMI) indicated nutritional status, and forced expiratory volume in one second (FEV(1)) served as the central respiratory parameter. Data on mortality and survival were calculated. The mean age of all patients has increased from 13.9 yrs in 1995 to 17.7 yrs in 2005, and the percentage of adult patients has increased from 28.4 to 43.4%. Benchmarking diagrams and centre reports indicated considerable differences between the centres. The achievement of basic aims at the age of 6, 12 and 18 yrs indicated a positive development in 1995 to 2005. In 2005, median age at death was 23.7 yrs and the median cumulative survival was 37.4 yrs. Mortality correlated with a BMI auditing; benchmarking; and in-house training.

  9. Attitudes of cystic fibrosis patients and parents toward carrier screening and related reproductive issues.

    Science.gov (United States)

    Janssens, Sandra; Chokoshvilli, Davit; Binst, Carmen; Mahieu, Inge; Henneman, Lidewij; De Paepe, Anne; Borry, Pascal

    2016-04-01

    Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder affecting ~1 in 2500-4000 Caucasians. As most CF patients have no family history of the disorder, carrier screening for CF has the potential to prospectively identify couples at risk of conceiving an affected child. At-risk couples may consequently choose to act on the provided information and take steps to avoid the birth of a child with CF. Although carrier screening is widely believed to enhance reproductive autonomy of prospective parents, the practice also raises important ethical questions. A written questionnaire was administered to adult patients and parents of children with CF with the aim to explore participants' attitudes toward CF carrier screening and related reproductive issues. The study population was recruited from a CF patient registry in Belgium and comprised 111 participants (64 parents, 47 patients aged 16 or older). We found that more than 80% of all participants were in favor of preconception carrier screening for CF. However, some were concerned over potential negative consequences of population-wide CF carrier screening. Regarding future reproductive intentions, 43% of the participants indicated a desire to have children. Among these, preimplantation genetic diagnosis was found to be the most preferred reproductive option, closely followed by spontaneous pregnancy and prenatal diagnosis. Although the findings of our study suggest that patients and parents of children with CF support a population-based carrier screening program for CF, they also highlight some issues deserving particular attention when implementing such a program.

  10. 'It is not in my world': an exploration of attitudes and influences associated with cystic fibrosis carrier screening.

    Science.gov (United States)

    McClaren, Belinda J; Delatycki, Martin B; Collins, Veronica; Metcalfe, Sylvia A; Aitken, MaryAnne

    2008-04-01

    Carrier screening for cystic fibrosis has been recommended for pregnant women and their partners, individuals and couples prior to conception, and for people with a family history. Many pilot programmes offering cystic fibrosis carrier screening, most commonly in the prenatal setting, have shown that uptake and acceptability are high. This article explores perspectives of the Victorian community regarding carrier screening for cystic fibrosis prior to offering screening. In particular whether or not such carrier screening should be offered, the best time for offering carrier screening, the information required for making a decision about carrier screening, and how this information can best be provided. A qualitative approach was taken to enable exploration of the views of stakeholders. Four focus groups and 32 interviews were conducted with a total of 68 participants. Participants were in agreement that cystic fibrosis carrier screening should be made available to everyone. However, potential consumers viewed cystic fibrosis carrier screening as 'not in my world' and were unlikely to request such screening unless it was offered by a health professional, or they had a family history. The best time for carrier screening was seen to be an individual preference and an information brochure was perceived to be useful when considering carrier screening. Lack of knowledge around the irrelevance of family history is a barrier to cystic fibrosis carrier screening. This study highlights the importance of community consultation, with stakeholders, prior to implementation of carrier screening programmes.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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    Bates Jason HT

    2004-07-01

    Full Text Available Abstract Background Cystic Fibrosis is a pleiotropic disease in humans with primary morbidity and mortality associated with a lung disease phenotype. However, knockout in the mouse of cftr, the gene whose mutant alleles are responsible for cystic fibrosis, has previously failed to produce a readily, quantifiable lung phenotype. Results Using measurements of pulmonary mechanics, a definitive lung phenotype was demonstrated in the cftr-/- mouse. Lungs showed decreased compliance and increased airway resistance in young animals as compared to cftr+/+ littermates. These changes were noted in animals less than 60 days old, prior to any long term inflammatory effects that might occur, and are consistent with structural differences in the cftr-/- lungs. Surprisingly, the cftr+/- animals exhibited a lung phenotype distinct from either the homozygous normal or knockout genotypes. The heterozygous mice showed increased lung compliance and decreased airway resistance when compared to either homozygous phenotype, suggesting a heterozygous advantage that might explain the high frequency of this mutation in certain populations. Conclusions In the mouse the gene dosage of cftr results in distinct differences in pulmonary mechanics of the adult. Distinct phenotypes were demonstrated in each genotype, cftr-/-, cftr +/-, and cftr+/+. These results are consistent with a developmental role for CFTR in the lung.

  13. High-attenuation mucus plugs on MDCT in a child with cystic fibrosis: potential cause and differential diagnosis

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    Morozov, Andrey; Brown, Shanaree [Indiana University Medical School, Indianapolis, IN (United States); Applegate, Kimberly E. [Riley Hospital for Children, Department of Radiology, Indiana University Medical Center, Indianapolis, IN (United States); Howenstine, Michelle [Riley Hospital for Children, Department of Pulmonology, Indiana University Medical Center, Indianapolis, IN (United States)

    2007-06-15

    High-attenuation mucus plugging is a rare finding in both adults and children. When it occurs, the field of differential diagnoses is typically quite small and includes acute hemorrhage, aspiration of radiodense material, and allergic bronchopulmonary aspergillosis (ABPA). The last of these three diagnoses is the most difficult to make, although ABPA is more commonly seen in children with cystic fibrosis (CF) or asthma. ABPA is radiographically characterized by recurrent mucus plugging, atelectasis, and central bronchiectasis. Thus far, high-attenuation mucus plugs have only been reported in adults. We report a rare case of a child with CF who had high-attenuation mucus plugs and atelectasis that raised the possibility of ABPA. We discuss the differential diagnoses of this finding and the role of multidetector CT in these children. (orig.)

  14. Primary care summary of the British Thoracic Society Guideline on the management of non-cystic fibrosis bronchiectasis.

    Science.gov (United States)

    Hill, Adam T; Pasteur, Mark; Cornford, Charles; Welham, Sally; Bilton, Diana

    2011-06-01

    The British Thoracic Society (BTS) has recently published a guideline for the management of non-cystic fibrosis (non-CF) bronchiectasis in children and adults. This paper summarises the key recommendations applicable to the primary care setting. The key points are: • Think of the diagnosis of bronchiectasis in adults and children who present with a chronic productive cough or unexplained haemoptysis, and in children with asthma which responds poorly to treatment; • High resolution computed tomography (HRCT) scanning is needed to confirm the diagnosis • Sputum culture should be obtained at the start of an exacerbation prior to initiating treatment with antibiotics; Treatment should be started whilst awaiting the sputum result and should be continued for 14 days; • Patients with bronchiectasis have significant morbidity. Management in primary care is aimed at improving morbidity, and includes; patient education, treatment and monitoring, as well as appropriate referral to secondary care including assessment for long term antibiotics.

  15. "Bronchial Artery Delivery of Viral Vectors for Gene delivery in Cystic Fibrosis; Superior to Airway Delivery?"

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    Coutelle Charles C

    2002-04-01

    Full Text Available Abstract Background Attempts at gene therapy for the pulmonary manifestations of Cystic Fibrosis have relied mainly on airway delivery. However the efficiency of gene transfer and expression in the airway epithelia has not reached therapeutic levels. Access to epithelial cells is not homogenous for a number of reasons and the submucosal glands cannot be reached via the airways. Presentation We propose to inject gene delivery vectors directly into bronchial arteries combined with pre-delivery of vascular endothelial growth factor to increase vascular endothelial permeability and post-delivery flow reduction by balloon occlusion. Thus it may be possible to reach mucous secreting cells of the bronchial luminal epithelium and the submucosal glands in an increased and homogenous fashion. Testing This combination of techniques to the best of our knowledge has not previously been investigated, and may enable us to overcome some of the current limitations to gene therapy for Cystic Fibrosis.

  16. Targeted Correction and Restored Function of the CFTR Gene in Cystic Fibrosis Induced Pluripotent Stem Cells

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    Ana M. Crane

    2015-04-01

    Full Text Available Recently developed reprogramming and genome editing technologies make possible the derivation of corrected patient-specific pluripotent stem cell sources—potentially useful for the development of new therapeutic approaches. Starting with skin fibroblasts from patients diagnosed with cystic fibrosis, we derived and characterized induced pluripotent stem cell (iPSC lines. We then utilized zinc-finger nucleases (ZFNs, designed to target the endogenous CFTR gene, to mediate correction of the inherited genetic mutation in these patient-derived lines via homology-directed repair (HDR. We observed an exquisitely sensitive, homology-dependent preference for targeting one CFTR allele versus the other. The corrected cystic fibrosis iPSCs, when induced to differentiate in vitro, expressed the corrected CFTR gene; importantly, CFTR correction resulted in restored expression of the mature CFTR glycoprotein and restoration of CFTR chloride channel function in iPSC-derived epithelial cells.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    The paranasal sinuses can be a focus for colonisation of the cystic fibrosis (CF) lungs with pathogens. In the sinuses, bacteria can adapt to the lung environment and enhance their antibiotic resistance, with biofilm formation thought to be the most important adaptive mechanism, causing recalcitr...... biofilms in intermittently lung-colonised patients encourage us to intensify the attempt to eradicate pathogenic bacteria from the CF sinuses in an early stage using combined antibiotic therapy in the prolonged exposure of the sinus-mucosal surface.......The paranasal sinuses can be a focus for colonisation of the cystic fibrosis (CF) lungs with pathogens. In the sinuses, bacteria can adapt to the lung environment and enhance their antibiotic resistance, with biofilm formation thought to be the most important adaptive mechanism, causing...

  18. Epidemiology and genetics of cystic fibrosis in Asia: In preparation for the next-generation treatments.

    Science.gov (United States)

    Singh, Meenu; Rebordosa, Cristina; Bernholz, Juliane; Sharma, Neeraj

    2015-11-01

    Cystic fibrosis (CF) in the Asian population is less frequently reported due to under-diagnosis and lack of centralized CF patient registries. Clinical studies on CF cases from Asia have documented a severe course of the disease. The spectrum of the cystic fibrosis transmembrane conductance regulator (CFTR) variants in this population is quite heterogeneous. In total, 166 variants have been reported on approximately 3700 Asian CF chromosomes. The frequency of F508del among Asians is low compared with Caucasians. Recent in vitro studies have shown promise of small molecule correction and potentiation of 45 different CFTR variants. Of these variants, 16 (including G551D and F508del) have also been observed among Asian CF individuals. We suggest undertaking molecular studies extensively to annotate CFTR variants that will help Asian CF individuals to benefit from the precision medicine gaining momentum in the Western countries.

  19. Interest of Colchicine for the Treatment of Cystic Fibrosis Patients. Preliminary Report

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    I. Sermet-Gaudelus

    1999-01-01

    Full Text Available Cystic fibrosis (CF lung disease is characterized by persistent inflammation. Antiinflammatory drugs, such as corticosteroids and ibuprofene, have proved to slow the decline of pulmonary function although their use is limited because of frequent adverse events. We hypothesized that colchicine could be an alternative treatment because of its antiinflammatory properties and upregulatory effect on cystic fibrosis transmembrane regulator (CFTR closely related proteins. We herein present results obtained in an open study of eight CF children treated with colchicine for at least 6 months. Clinical status was better in all patients and respiratory function tests significantly improved in five. Median duration of antibiotherapy decreased significantly. These preliminary results support our hypothesis of a beneficial effect of colchicine in CF patients and stress the need for a controlled therapeutic trial.

  20. Aspergillus species and other molds in respiratory samples from patients with cystic fibrosis:

    DEFF Research Database (Denmark)

    Mortensen, Klaus Leth; Jensen, Rasmus Hare; Johansen, Helle Krogh

    2011-01-01

    Respiratory tract colonization by molds in patients with cystic fibrosis (CF) were analyzed, with particular focus on the frequency, genotype, and underlying mechanism of azole resistance among Aspergillus fumigatus isolates. Clinical and demographic data were also analyzed. A total of 3,336 resp......Respiratory tract colonization by molds in patients with cystic fibrosis (CF) were analyzed, with particular focus on the frequency, genotype, and underlying mechanism of azole resistance among Aspergillus fumigatus isolates. Clinical and demographic data were also analyzed. A total of 3......,336 respiratory samples from 287 CF patients were collected during two 6-month periods in 2007 and 2009. Azole resistance was detected using an itraconazole screening agar (4 mg/liter) and the EUCAST method. cyp51A gene sequencing and microsatellite genotyping were performed for isolates from patients harboring...