Sample records for cystic fibrosis lungs

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

    PubMed

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

    2015-08-01

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

  2. Pediatric heart-lung transplantation for cystic fibrosis.

    PubMed

    Maynard, L C

    1994-01-01

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

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

    PubMed

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

    2017-05-17

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

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

    PubMed

    Blue, Elizabeth; Louie, Tin L; Chong, Jessica X; Hebbring, Scott J; Barnes, Kathleen C; Rafaels, Nicholas M; Knowles, Michael R; Gibson, Ronald L; Bamshad, Michael J; Emond, Mary J

    2018-04-01

    Cystic fibrosis, like primary ciliary dyskinesia, is an autosomal recessive disorder characterized by abnormal mucociliary clearance and obstructive lung disease. We hypothesized that genes underlying the development or function of cilia may modify lung disease severity in persons with cystic fibrosis. To test this hypothesis, we compared variants in 93 candidate genes in both upper and lower tertiles of lung function in a large cohort of children and adults with cystic fibrosis with those of a population control dataset. Variants within candidate genes were tested for association using the SKAT-O test, comparing cystic fibrosis cases defined by poor (n = 127) or preserved (n = 127) lung function with population controls (n = 3,269 or 3,148, respectively). Associated variants were then tested for association with related phenotypes in independent datasets. Variants in DNAH14 and DNAAF3 were associated with poor lung function in cystic fibrosis, whereas variants in DNAH14 and DNAH6 were associated with preserved lung function in cystic fibrosis. Associations between DNAH14 and lung function were replicated in disease-related phenotypes characterized by obstructive lung disease in adults. Genetic variants within DNAH6, DNAH14, and DNAAF3 are associated with variation in lung function among persons with cystic fibrosis.

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

    PubMed

    Lee, T; Southern, K W

    2007-04-18

    Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic lung infection resulting in inflammation and progressive lung damage that results in a reduced life expectancy. To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes, and to assess any adverse effects. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. Date of most recent search: February 2007 Randomised controlled trials comparing topical CFTR gene delivery to the lung, using either viral or non-viral delivery systems, with placebo or an alternative delivery system in people with confirmed cystic fibrosis. The authors independently extracted data and assessed study quality. Authors of included studies were contacted and asked for any available additional data. Meta-analysis was limited due to differing study designs. Three randomised controlled trials met the inclusion criteria for this review, involving a total of 155 participants. Thirteen studies were excluded. The included studies differed in terms of CFTR gene replacement agent and study design, which limited the meta-analysis. Although the first Moss study reported a significant improvement in respiratory function (FEV(1)) 30 days after participants had received their first dose of gene therapy agent, this finding was not confirmed in their larger second study or in our meta-analysis.In participants who received the CFTR gene transfer agents in the Alton study, "influenza-like" symptoms were found (relative risk 7.00 (95% confidence interval (CI) 1.10 to 44.61)). There were no other significant increases in adverse events in any of the studies. Alton

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

    PubMed

    Lee, Tim W R; Southern, Kevin W

    2013-11-26

    Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic lung infection resulting in inflammation and progressive lung damage that results in a reduced life expectancy. To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes, and to assess any adverse effects. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.Date of most recent search: 22 August 2013.An additional search of the National Institutes for Health (NIH) Genetic Modification Clinical Research Information System (GeMCRIS) was also performed for the years 1992 to 2013.Date of most recent search: 04 September 2013. Randomised controlled trials comparing topical CFTR gene delivery to the lung, using either viral or non-viral delivery systems, with placebo or an alternative delivery system in people with confirmed cystic fibrosis. The authors independently extracted data and assessed study quality. Authors of included studies were contacted and asked for any available additional data. Meta-analysis was limited due to differing study designs. Three randomised controlled trials met the inclusion criteria for this review, involving a total of 155 participants. Fourteen studies were excluded. The included studies differed in terms of CFTR gene replacement agent and study design, which limited the meta-analysis.Although the first Moss study reported a significant improvement in respiratory function (forced expiratory volume at one second) 30 days after participants had received their first dose of gene therapy agent, this finding was not confirmed in their larger second study or in our meta-analysis.In participants

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

    PubMed

    Lee, Tim W R; Southern, Kevin W

    2012-10-17

    Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic lung infection resulting in inflammation and progressive lung damage that results in a reduced life expectancy. To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes, and to assess any adverse effects. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.Date of most recent search: 19 July 2012.An additional search of the National Institutes for Health (NIH) Genetic Modification Clinical Research Information System (GeMCRIS) was also performed for the years 1992 to 2012.Date of most recent search: 25 July 2012. Randomised controlled trials comparing topical CFTR gene delivery to the lung, using either viral or non-viral delivery systems, with placebo or an alternative delivery system in people with confirmed cystic fibrosis. The authors independently extracted data and assessed study quality. Authors of included studies were contacted and asked for any available additional data. Meta-analysis was limited due to differing study designs. Three randomised controlled trials met the inclusion criteria for this review, involving a total of 155 participants. Fourteen studies were excluded. The included studies differed in terms of CFTR gene replacement agent and study design, which limited the meta-analysis.Although the first Moss study reported a significant improvement in respiratory function (forced expiratory volume at one second) 30 days after participants had received their first dose of gene therapy agent, this finding was not confirmed in their larger second study or in our meta-analysis.In participants who

  8. Lung transplantation for cystic fibrosis.

    PubMed

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

    2004-04-01

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

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

    PubMed

    Lobo, Leonard J; Noone, Peadar G

    2014-01-01

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

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

    PubMed

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

    2018-04-26

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

  11. Lung transplantation in patients with cystic fibrosis.

    PubMed

    Morton, Judith; Glanville, Allan R

    2009-10-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Bush, Andrew; Sly, Peter D

    2015-11-01

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

  14. Cystic fibrosis.

    PubMed

    Elborn, J Stuart

    2016-11-19

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

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

    PubMed

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

    2005-10-01

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

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

    PubMed

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

    2018-06-18

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2017-06-15

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

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

    PubMed Central

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

    2007-01-01

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

  1. Pediatric and adult lung transplantation for cystic fibrosis.

    PubMed

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

    1998-02-01

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

  2. Cystic fibrosis lung transplantation.

    PubMed

    Braun, Andrew T; Merlo, Christian A

    2011-11-01

    This review summarizes recently published investigations on issues pertaining to cystic fibrosis (CF) lung transplantation. We specifically focus on indications and candidate selection as well as infectious and noninfectious issues specific to CF lung transplant recipients. Recent studies have focused on candidate adequacy in high-risk CF patients. We review the current literature on individuals who develop respiratory failure requiring mechanical ventilation and those patients with a pretransplant diagnosis of pulmonary hypertension. Furthermore, the management of peri-operative infectious issues is reviewed including recurrent infections with multidrug-resistant bacterial, mycobacterial, and fungal organisms. Other CF-specific issues addressed include common comorbidities such as CF-related diabetes, gastroesophageal reflux, CF liver disease, and bone metabolism. Lung transplantation is a limited, but potentially life-saving therapeutic option for patients with CF. Optimal candidate selection and awareness of CF-specific issues in the pretransplant and posttransplant setting may lead to better long-term outcomes. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

  3. Best practices in the treatment of early cystic fibrosis lung disease.

    PubMed

    Proesmans, Marijke

    2017-02-01

    For many years, management of cystic fibrosis (CF) lung disease was focused on symptomatic treatment of chronic lung infection, which is characterized by cough and sputum production, leading to progressive lung damage. With increasing survival and better knowledge of the pathogenesis of CF lung disease, it has become clear that treatment has to start very early because lung damage occurs in young patients, often before obvious symptoms appear. The arrival of new cystic fibrosis transmembrane conductance-regulator (CFTR)-correcting therapies will bring more opportunities to prevent the disease, apart from only treating chronic lung infection. In this review, a summary of the current knowledge of early CF lung disease is provided, based on animal model studies, as well as on data obtained from well structured follow-up programs after newborn screening (NBS). The most important clinical guidelines for treating young CF patients are also summarized.

  4. Longitudinal cystic fibrosis care.

    PubMed

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

    2013-01-01

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

  5. Correlation between sinus and lung cultures in lung transplant patients with cystic fibrosis.

    PubMed

    Choi, Kevin J; Cheng, Tracy Z; Honeybrook, Adam L; Gray, Alice L; Snyder, Laurie D; Palmer, Scott M; Abi Hachem, Ralph; Jang, David W

    2018-03-01

    Lung transplantation has revolutionized the treatment of end-stage pulmonary disease due to cystic fibrosis. However, infection of the transplanted lungs can lead to serious complications, including graft failure and death. Although many of these patients have concurrent sinusitis, it is unclear whether bacteria from the sinuses can infect the allograft. This is a single-institution retrospective study of all patients who underwent lung transplantation for cystic fibrosis from 2005 to 2015 at Duke University Hospital. Pre- and posttransplant nasal and pulmonary cultures obtained via nasal endoscopy and bronchoalveolar lavage (BAL), respectively, were analyzed. A total of 141 patients underwent 144 lung transplants. Sinus cultures were available for 76 patients (12 pretransplant, 42 posttransplant, 22 both pre- and posttransplant). Pretransplant BAL cultures were available for 139 patients, and posttransplant BAL cultures were available for all patients. Pseudomonas aeruginosa (PsA) and methicillin-resistant Staphylococcus aureus (MRSA) were the most common organisms cultured. There was a significant correlation between pretransplant sinus and posttransplant BAL cultures for PsA (p = 0.003), MRSA (p = 0.013), and Burkholderia cepacia (p = 0.001). There was a high correlation between pretransplant sinus cultures and posttransplant BAL cultures for PsA, MRSA, and Burkholderia sp. This suggests that the paranasal sinuses may act as a reservoir for allograft colonization in patients with cystic fibrosis. Further studies are needed to determine whether treatment of sinusitis affects allograft colonization and transplant outcomes. © 2017 ARS-AAOA, LLC.

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

    PubMed

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

    2016-04-01

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

  7. Microbial colonization and lung function in adolescents with cystic fibrosis.

    PubMed

    Hector, Andreas; Kirn, Tobias; Ralhan, Anjali; Graepler-Mainka, Ute; Berenbrinker, Sina; Riethmueller, Joachim; Hogardt, Michael; Wagner, Marlies; Pfleger, Andreas; Autenrieth, Ingo; Kappler, Matthias; Griese, Matthias; Eber, Ernst; Martus, Peter; Hartl, Dominik

    2016-05-01

    With intensified antibiotic therapy and longer survival, patients with cystic fibrosis (CF) are colonized with a more complex pattern of bacteria and fungi. However, the clinical relevance of these emerging pathogens for lung function remains poorly defined. The aim of this study was to assess the association of bacterial and fungal colonization patterns with lung function in adolescent patients with CF. Microbial colonization patterns and lung function parameters were assessed in 770 adolescent European (German/Austrian) CF patients in a retrospective study (median follow-up time: 10years). Colonization with Pseudomonas aeruginosa and MRSA were most strongly associated with loss of lung function, while mainly colonization with Haemophilus influenzae was associated with preserved lung function. Aspergillus fumigatus was the only species that was associated with an increased risk for infection with P. aeruginosa. Microbial interaction analysis revealed three distinct microbial clusters within the longitudinal course of CF lung disease. Collectively, this study identified potentially protective and harmful microbial colonization patterns in adolescent CF patients. Further studies in different patient cohorts are required to evaluate these microbial patterns and to assess their clinical relevance. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    1994-02-01

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

  10. Effects of Aspergillus fumigatus colonization on lung function in cystic fibrosis.

    PubMed

    Speirs, Jennifer J; van der Ent, Cornelis K; Beekman, Jeffrey M

    2012-11-01

    Aspergillus fumigatus is frequently isolated from cystic fibrosis (CF) patients and is notorious for its role in the debilitating condition of allergic bronchopulmonary aspergillosis (ABPA). Although CF patients suffer from perpetual microorganism-related lung disease, it is unclear whether A. fumigatus colonization has a role in causing accelerated lung function decline and whether intervention is necessary. A. fumigatus morbidity appears to be related to cystic fibrosis transmembrane conductance regulator-dependant function of the innate immune system. A. fumigatus-colonized patients have a lower lung capacity, more frequent hospitalizations and more prominent radiological abnormalities than noncolonized patients. Treatment with antifungal agents can be of value but has several drawbacks and a direct effect on lung function is yet to be shown. A. fumigatus appears to have an important role in CF lung disease, not exclusive to the context of ABPA. However, a causal relationship still needs to be confirmed. Study observations and trends indicate a need to further elucidate the mechanisms of A. fumigatus interactions with the host innate immune system and its role in CF lung morbidity.

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2018-04-01

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

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

    PubMed Central

    Hirche, T. O.; Knoop, C.; Hebestreit, H.; Shimmin, D.; Solé, A.; Elborn, J. S.; Ellemunter, H.; Aurora, P.; Hogardt, M.; Wagner, T. O. F.; ECORN-CF Study Group

    2014-01-01

    There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation. PMID:24800072

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

    NASA Astrophysics Data System (ADS)

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

    1996-01-01

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

  15. Lung Transplantation for Cystic Fibrosis

    PubMed Central

    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 and transplantation on the patient's quality of life. Although recent population-based analyses of the US lung allocation system for the CF population have raised controversies about the survival benefits of transplantation, studies from the United Kingdom and Canada have suggested a definite survival advantage for those receiving transplants. In response to these and other controversies, leaders in transplantation and CF met together in Lansdowne, Virginia, to consider the state of the art in lung transplantation for CF in an international context, focusing on advances in surgical technique, measurement of outcomes, use of prognostic criteria, variations in local control over listing, and prioritization among the United States, Canada, the United Kingdom, and The Netherlands, patient adherence before and after transplantation and other issues in the broader context of lung transplantation. Finally, the conference members carefully considered how efforts to improve outcomes for lung transplantation for CF lung disease might best be studied. This Roundtable seeks to communicate the substance of our discussions. PMID:20008865

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

    PubMed

    Cano Megías, Marta; González Albarrán, Olga

    2015-01-01

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

  17. Lung Infections Associated with Cystic Fibrosis

    PubMed Central

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

    2002-01-01

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

  18. Diabetes in cystic fibrosis.

    PubMed

    Bridges, Nicola

    2013-05-01

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

  19. Burkholderia cepacia, cystic fibrosis and outcomes following lung transplantation: experiences from a single center in Brazil.

    PubMed

    de Souza Carraro, Danila; Carraro, Rafael Medeiros; Campos, Silvia Vidal; Iuamoto, Leandro Ryuchi; Braga, Karina Andrighetti de Oliveira; Oliveira, Lea Campos de; Sabino, Ester Cerdeira; Rossi, Flavia; Pêgo-Fernandes, Paulo Manuel

    2018-03-12

    To evaluate the impact of Burkholderia cepacia complex colonization in cystic fibrosis patients undergoing lung transplantation. We prospectively analyzed clinical data and respiratory tract samples (sputum and bronchoalveolar lavage) collected from suppurative lung disease patients between January 2008 and November 2013. We also subtyped different Burkholderia cepacia complex genotypes via DNA sequencing using primers against the recA gene in samples collected between January 2012 and November 2013. From 2008 to 2013, 34 lung transplants were performed on cystic fibrosis patients at our center. Burkholderia cepacia complex was detected in 13 of the 34 (38.2%) patients. Seven of the 13 (53%) strains were subjected to genotype analysis, from which three strains of B. metallica and four strains of B. cenocepacia were identified. The mortality rate was 1/13 (7.6%), and this death was not related to B. cepacia infection. The results of our study suggest that colonization by B. cepacia complex and even B. cenocepacia in patients with cystic fibrosis should not be considered an absolute contraindication to lung transplantation in Brazilian centers.

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

    PubMed

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

    2016-06-17

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

  1. Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice.

    PubMed

    Crosby, Jeff R; Zhao, Chenguang; Jiang, Chong; Bai, Dong; Katz, Melanie; Greenlee, Sarah; Kawabe, Hiroshi; McCaleb, Michael; Rotin, Daniela; Guo, Shuling; Monia, Brett P

    2017-11-01

    Epithelial sodium channel (ENaC, Scnn1) hyperactivity in the lung leads to airway surface dehydration and mucus accumulation in cystic fibrosis (CF) patients and in mice with CF-like lung disease. We identified several potent ENaC specific antisense oligonucleotides (ASOs) and tested them by inhalation in mouse models of CF-like lung disease. The inhaled ASOs distributed into lung airway epithelial cells and decreased ENaC expression by inducing RNase H1-dependent degradation of the targeted Scnn1a mRNA. Aerosol delivered ENaC ASO down-regulated mucus marker expression and ameliorated goblet cell metaplasia, inflammation, and airway hyper-responsiveness. Lack of systemic activity of ASOs delivered via the aerosol route ensures the safety of this approach. Our results demonstrate that antisense inhibition of ENaC in airway epithelial cells could be an effective and safe approach for the prevention and reversal of lung symptoms in CF and potentially other inflammatory diseases of the lung. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  2. The Epidemiology and Management of Lung Diseases in Sickle Cell Disease: Lessons Learned from Acute and Chronic Lung Disease in Cystic Fibrosis.

    PubMed

    Willen, Shaina M; DeBaun, Michael R

    2018-06-01

    Although sickle cell disease and cystic fibrosis are two of the most common monogenic diseases presenting in childhood worldwide, cystic fibrosis and sickle cell disease enjoy vastly different funding and collaborative research efforts. Pulmonary complications in cystic fibrosis have well established guidelines and multidisciplinary involvement focusing on comorbidities, routine monitoring, infectious complications, nutrition, and treatment recommendations. These guidelines can provide a framework on which to build knowledge of lung disease in sickle cell disease. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    PubMed

    Frayman, Katherine B; Armstrong, David S; Carzino, Rosemary; Ferkol, Thomas W; Grimwood, Keith; Storch, Gregory A; Teo, Shu Mei; Wylie, Kristine M; Ranganathan, Sarath C

    2017-12-01

    In infants and young children with cystic fibrosis, lower airway infection and inflammation are associated with adverse respiratory outcomes. However, the role of lower airway microbiota in the pathogenesis of early cystic fibrosis lung disease remains uncertain. To assess the development of the lower airway microbiota over time in infants and young children with cystic fibrosis, and to explore its association with airway inflammation and pulmonary function at age 6 years. Serial, semi-annual bronchoscopies and bronchoalveolar lavage (BAL) procedures were performed in infants newly diagnosed with cystic fibrosis following newborn screening. Quantitative microbiological cultures and inflammatory marker (interleukin 8 and neutrophil elastase) measurements were undertaken contemporaneously. 16S ribosomal RNA gene sequencing was conducted on stored BAL samples. Spirometry results recorded at 6 years of age were extracted from medical records. Ninety-five BAL samples provided 16S ribosomal RNA gene data. These were collected from 48 subjects aged 1.2-78.3 months, including longitudinal samples from 27 subjects and 13 before age 6 months. The lower airway microbiota varied, but diversity decreased with advancing age. Detection of recognised cystic fibrosis bacterial pathogens was associated with reduced microbial diversity and greater lower airway inflammation. There was no association between the lower airway microbiota and pulmonary function at age 6 years. In infants with cystic fibrosis, the lower airway microbiota is dynamic. Dominance of the microbiota by recognised cystic fibrosis bacterial pathogens is associated with increased lower airway inflammation, however early microbial diversity is not associated with pulmonary function at 6 years of age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

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

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

    PubMed

    Pillarisetti, Naveen; Linnane, Barry; Ranganathan, Sarath

    2010-08-01

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

  6. Lung Abscess: An Early Complication of Lung Transplantation in a Patient with Cystic Fibrosis.

    PubMed

    Markelić, I; Jakopović, M; Klepetko, W; Džubur, F; Hećimović, A; Makek, M J; Samaržija, M; Dugac, A V

    2017-01-01

    A 22-year-old woman with cystic fibrosis (CF) developed lung abscess, as a rare complication caused by multidrug-resistant (MDR) Acinetobacter baumannii infection, after lung transplantation (LT). After 6 months of long-term antibiotic therapy, the abscess was successfully eliminated. In reviewed published literature, no previous report was found describing this kind of complication caused by MDR A. baumannii in post-LT patient with CF. In our experience, lung abscess in LT recipients with CF can be successfully treated with prolonged antibiotic therapy.

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

    PubMed

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

    2016-11-01

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

  8. Heart-lung transplantation for cystic fibrosis and subsequent domino heart transplantation.

    PubMed

    Yacoub, M H; Banner, N R; Khaghani, A; Fitzgerald, M; Madden, B; Tsang, V; Radley-Smith, R; Hodson, M

    1990-01-01

    Between September 1984 and October 1988, 27 patients underwent combined heart-lung transplantation for treatment of end-stage respiratory disease caused by cystic fibrosis. The actuarial patient survival was 78% at 1 year and 72% at 2 years. Bacterial respiratory infections were common in the early postoperative period and necessitated vigorous medical therapy. The dose of cyclosporine required in these patients was higher than in conventional transplant recipients, and this contributed to an increased cost of postoperative care. Lung function was greatly improved after transplantation, and long-term survivors achieved an excellent quality of life. Lymphoproliferative disorders developed in two patients; these disorders regressed after a reduction in immunosuppression. Two patients required retransplantation: one because of obliterative bronchiolitis and the other because of recurrent respiratory infections associated with a moderate tracheal stenosis and severe deterioration in lung function. A modification of the technique used for heart-lung transplantation allowed 20 hearts from cystic fibrosis patients to be used for subsequent heart transplantation. Immediate heart function was satisfactory in all cases. The actuarial survival of the recipients of these domino heart transplants was 75% at 1 year. No coronary artery disease was present in the 12 patients who have undergone coronary angiography at 1 year.

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

    PubMed

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

    2012-12-01

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

  10. Nutritional state and lung disease in cystic fibrosis.

    PubMed

    Bakker, W

    1992-10-01

    The life expectancy of patients with cystic fibrosis (CF) is largely dependent on the severity and progress of the pulmonary involvement associated with the disease. Many data support the view that malnutrition and deterioration of lung function are closely interrelated and interdependent, with each affecting the other, leading to a spiral decline in both. The occurrence of malnutrition appears to be associated with poor lung function and poor survival, and conversely prevention of malnutrition appears to be associated with better lung function and improved survival. Nutritional intervention may lead to an improvement in body weight, lung function and exercise tolerance, provided that the intervention is combined with exercise training in order to increase both respiratory and other muscle mass. These improvements can be preserved when patients have the stamina to continue with a high-energy, high-fat diet and daily exercise training at home.

  11. Interactions Between Secondhand Smoke and Genes That Affect Cystic Fibrosis Lung Disease

    PubMed Central

    Collaco, J. Michael; Vanscoy, Lori; Bremer, Lindsay; McDougal, Kathryn; Blackman, Scott M.; Bowers, Amanda; Naughton, Kathleen; Jennings, Jacky; Ellen, Jonathan; Cutting, Garry R.

    2011-01-01

    Context Disease variation can be substantial even in conditions with a single gene etiology such as cystic fibrosis (CF). Simultaneously studying the effects of genes and environment may provide insight into the causes of variation. Objective To determine whether secondhand smoke exposure is associated with lung function and other outcomes in individuals with CF, whether socioeconomic status affects the relationship between secondhand smoke exposure and lung disease severity, and whether specific gene-environment interactions influence the effect of secondhand smoke exposure on lung function. Design, Setting, and Participants Retrospective assessment of lung function, stratified by environmental and genetic factors. Data were collected by the US Cystic Fibrosis Twin and Sibling Study with missing data supplemented by the Cystic Fibrosis Foundation Data Registry. All participants were diagnosed with CF, were recruited between October 2000 and October 2006, and were primarily from the United States. Main Outcome Measures Disease-specific cross-sectional and longitudinal measures of lung function. Results Of 812 participants with data on secondhand smoke in the home, 188 (23.2%) were exposed. Of 780 participants with data on active maternal smoking during gestation, 129 (16.5%) were exposed. Secondhand smoke exposure in the home was associated with significantly lower cross-sectional (9.8 percentile point decrease; P<.001) and longitudinal lung function (6.1 percentile point decrease; P=.007) compared with those not exposed. Regression analysis demonstrated that socioeconomic status did not confound the adverse effect of secondhand smoke exposure on lung function. Interaction between gene variants and secondhand smoke exposure resulted in significant percentile point decreases in lung function, namely in CFTR non-ΔF508 homozygotes (12.8 percentile point decrease; P=.001), TGFβ1-509 TT homozygotes (22.7 percentile point decrease; P=.006), and TGFβ1 codon 10 CC

  12. Chronic Mycobacterium abscessus infection and lung function decline in cystic fibrosis.

    PubMed

    Esther, Charles R; Esserman, Denise A; Gilligan, Peter; Kerr, Alan; Noone, Peadar G

    2010-03-01

    Although nontuberculous mycobacteria (NTM) are recognized pathogens in cystic fibrosis (CF), associations with clinical outcomes remain unclear. Microbiological data was obtained from 1216 CF patients over 8years (481+/-55patients/year). Relationships to clinical outcomes were examined in the subset (n=271, 203+/-23 patients/year) with longitudinal data. Five hundred thirty-six of 4862 (11%) acid-fast bacilli (AFB) cultures grew NTM, with Mycobacterium abscessus (n=298, 55.6%) and Mycobacterium avium complex (n=190, 35.4%) most common. Associated bacterial cultures grew Stenotrophomonas or Aspergillus species more often when NTM were isolated (18.2% vs. 8.4% and 13.9% vs. 7.2%, respectively, p<0.01). After controlling for confounders, patients with chronic M. abscessus infection had greater rates of lung function decline than those with no NTM infection (-2.52 vs. -1.64% predicted FEV(1)/year, p<0.05). NTM infection is common in CF and associated with particular pathogens. Chronic M. abscessus infection is associated with increased lung function decline. Copyright (c) 2009 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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

    ClinicalTrials.gov

    2017-10-12

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

  14. Cystic fibrosis - resources

    MedlinePlus

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

  15. Fatal disseminated Rasamsonia infection in cystic fibrosis post-lung transplantation.

    PubMed

    Hong, Gina; White, Marissa; Lechtzin, Noah; West, Natalie E; Avery, Robin; Miller, Heather; Lee, Richard; Lovari, Robert J; Massire, Christian; Blyn, Lawrence B; Liang, Xinglun; Sutton, Deanna A; Fu, Jianmin; Wickes, Brian L; Wiederhold, Nathan P; Zhang, Sean X

    2017-03-01

    Disseminated fungal infections are a known serious complication in individuals with cystic fibrosis (CF) following orthotopic lung transplantation. Aspergillus fumigatus and Scedosporium species are among the more common causes of invasive fungal infection in this population. However, it is also important for clinicians to be aware of other emerging fungal species which may require markedly different antifungal therapies. We describe the first laboratory-documented case of a fatal disseminated fungal infection caused by Rasamsonia aegroticola in a 21-year-old female CF patient status post-bilateral lung transplantation, which was only identified post-mortem. Molecular analysis revealed the presence of the identical Rasamsonia strains in the patient's respiratory cultures preceding transplantation. We propose that the patient's disseminated fungal disease and death occurred as a result of recrudescence of Rasamsonia infection from her native respiratory system in the setting of profound immunosuppression post-operatively. Since Rasamsonia species have been increasingly recovered from the respiratory tract of CF patients, we further review the literature on these fungi and discuss their association with invasive fungal infections in the CF lung transplant host. Our report suggests Rasamsonia species may be important fungal pathogens that may have fatal consequences in immunosuppressed CF patients after solid organ transplantation. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  16. Critical evaluation of lung scintigraphy in cystic fibrosis: study of 113 patients

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

    Piepsz, A.; Wetzburger, C.; Spehl, M.

    1980-10-01

    A long-term study has been performed on 285 lung perfusion scintigrams obtained from 113 patients with cystic fibrosis. Transverse and longitudinal comparisons with clinical and radiological scores, as well as retrospective analysis of the deceased patients, were the methods used in order to evaluate the importance of the scintigraphic images. It appears that lung scintigraphy is the best index of the regional lung impairment, and contributes, as does a chest radiograph, to the early detection of lung lesions, the two methods being complementary.

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

    PubMed

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

    2014-11-15

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

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

    PubMed

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

    2016-07-01

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

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

    PubMed

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

    2013-12-15

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

  20. Update on host-pathogen interactions in cystic fibrosis lung disease.

    PubMed

    Hector, Andreas; Frey, Nina; Hartl, Dominik

    2016-12-01

    Bacterial and fungal infections are hallmarks of cystic fibrosis (CF) lung disease. In the era of long-term inhaled antibiotics and increasing CF patient survival, new "emerging" pathogens are detected in CF airways, yet their pathophysiological disease relevance remains largely controversial and incompletely defined. As a response to chronic microbial triggers, innate immune cells, particularly neutrophils, are continuously recruited into CF airways where they combat pathogens but also cause tissue injury through release of oxidants and proteases. The coordinated interplay between host immune cell activation and pathogens is essential for the outcome of CF lung disease. Here, we provide a concise overview and update on host-pathogen interactions in CF lung disease.

  1. [Lung transplantation in cystic fibrosis].

    PubMed

    Borro Maté, J M; Calvo Medina, V; Morant Guillén, P; Morales Marín, P; Vicente Guillén, R; Tarrazona Hervas, V; Ramos Briones, F; Lozano Ruiz, C; Ferrer Calvete, F

    1996-11-01

    Since 1990 we have performed 40 lung transplants in the Hospital "La Fe" in Valencia. Nine of them have been performed in cystic fibrosis patients, which is the subject of this paper. The mean age of the patients was 19.8 years, with the youngest patient being 14 years of age. In regards to patient selection, it is important to mention that one had a previous lobectomy, another one a thoracic deformity due to long term atelectasis and one needed intubation for hemoptysis within the 7 days before the lung transplant. Prophylaxis with imipenem and cyprofloxicin, aerosolized colistin and amphotericin B, prompt weaning and intensive respiratory physiotherapy were important for controlling postoperative infection. With 15.3 months as the mean follow-up (range 36-3), 3 year survival was 87.5%. Pulmonary infection, which was the most frequent complication, had a good response to adequate antibiotic treatment. The main postoperative problem pertained to the bronchial suture with 2 partial dehiscences, 2 stenoses and one bronchopleural fistula by Aspergillus, all of which were resolved with conservative procedures without surgery. Middle and long term evolution in these patients shows an excellent quality of life with spirometric and ergometric tests within the normal range.

  2. Aspergillus infections in cystic fibrosis.

    PubMed

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

    2016-07-05

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

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

    PubMed

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

    2015-10-26

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

  4. [Nocardia farcinica lung infection in a patient with cystic fibrosis and a lung transplant].

    PubMed

    Chacón, C F; Vicente, R; Ramos, F; Porta, J; Lopez Maldonado, A; Ansotegui, E

    2015-03-01

    Patients with cystic fibrosis have a higher risk of developing chronic respiratory infectious diseases. The Nocardia farcinica lung infection is rare in this group of patients, and there are limited publications about this topic. Its diagnosis is complex, due to the clinical and the radiology signs being non-specific. Identification of the agent responsible in the sputum culture is occasionally negative. It is a slow growing organism and for this reason treatment is delayed, which can lead to an increase in complications, hospitable stays, and mortality. A case is reported on a 26 year-old woman with cystic fibrosis and chronic lung colonization by Nocardia farcinica and Aspergillus fumigatus, on long-term treatment with ciprofloxacin, trimethoprim-sulfamethoxazole, and posaconazole, who was admitted to ICU after bilateral lung transplantation. The initial post-operative progress was satisfactory. After discharge, the patient showed a gradual respiratory insufficiency with new chest X-ray showing diffuse infiltrates. Initially, the agent was not seen in the sputum culture. Prompt and aggressive measures were taken, due to the high clinical suspicion of a Nocardia farcinica lung infection. Treatment with a combination of amikacin and meropenem, and later combined with linezolid, led to the disappearance of the lung infiltrates and a clinical improvement. In our case, we confirm the rapid introduction of Nocardia farcinica in the new lungs. The complex identification and the delay in treatment increased the morbimortality. There is a special need for its eradication in patients with lung transplant, due to the strong immunosuppressive treatment. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    PubMed

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

    2016-09-01

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

  6. Future directions in early cystic fibrosis lung disease research: an NHLBI workshop report.

    PubMed

    Ramsey, Bonnie W; Banks-Schlegel, Susan; Accurso, Frank J; Boucher, Richard C; Cutting, Garry R; Engelhardt, John F; Guggino, William B; Karp, Christopher L; Knowles, Michael R; Kolls, Jay K; LiPuma, John J; Lynch, Susan; McCray, Paul B; Rubenstein, Ronald C; Singh, Pradeep K; Sorscher, Eric; Welsh, Michael

    2012-04-15

    Since the 1989 discovery that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), there has been substantial progress toward understanding the molecular basis for CF lung disease, leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation are poorly understood. Universal newborn screening for CF in the United States represents an unprecedented opportunity for investigating CF clinical manifestations very early in life. Recently developed animal models with pulmonary phenotypic manifestations also provide a window into the early consequences of this genetic disorder. For these reasons, the National Heart, Lung, and Blood Institute (NHLBI) convened a working group of extramural experts, entitled "Future Research Directions in Early CF Lung Disease" on September 21-22, 2010, to identify future research directions of great promise in CF. The priority areas identified included (1) exploring pathogenic mechanisms of early CF lung disease; (2) leveraging newborn screening to elucidate the natural history of early lung disease; (3) developing a spectrum of biomarkers of early lung disease that reflects CF pathophysiology, clinical outcome, and response to treatment; (4) exploring the role of genetics/genomics (e.g., modifier genes, gene-environmental interactions, and epigenetics) in early CF pathogenesis; (5) defining early microbiological events in CF lung disease; and (6) elucidating the initial airway inflammatory, remodeling, and repair mechanisms in CF lung disease.

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2017-11-01

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

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

    PubMed

    Ramsey, Kathryn A; Foong, Rachel E; Grdosic, Jasmine; Harper, Alana; Skoric, Billy; Clem, Charles; Davis, Miriam; Turkovic, Lidija; Stick, Stephen M; Davis, Stephanie D; Ranganathan, Sarath C; Hall, Graham L

    2017-09-01

    The lung clearance index is a measure of ventilation distribution derived from the multiple-breath washout technique. The lung clearance index is increased in the presence of lower respiratory tract inflammation and infection in infants with cystic fibrosis; however, the associations during the preschool years are unknown. We assessed the ability of the lung clearance index to detect the presence and extent of lower respiratory tract inflammation and infection in preschool children with cystic fibrosis. Ventilation distribution outcomes were assessed at 82 visits with 58 children with cystic fibrosis and at 38 visits with 31 healthy children aged 3-6 years. Children with cystic fibrosis also underwent bronchoalveolar lavage fluid collection for detection of lower respiratory tract inflammation and infection. Associations between multiple-breath washout indices and the presence and extent of airway inflammation and infection were assessed using linear mixed effects models. Lung clearance index was elevated in children with cystic fibrosis (mean [SD], 8.00 [1.45]) compared with healthy control subjects (6.67 [0.56]). In cystic fibrosis, the lung clearance index was elevated in individuals with lower respiratory tract infections (difference compared with uninfected [95% confidence interval], 0.62 [0.06, 1.18]) and correlated with the extent of airway inflammation. These data suggest that the lung clearance index may be a useful surveillance tool for monitoring the presence and extent of lower airway inflammation and infection in preschool children with cystic fibrosis.

  10. Managing central venous obstruction in cystic fibrosis recipients--lung transplant considerations.

    PubMed

    Otani, Shinji; Westall, Glen P; Levvey, Bronwyn J; Marasco, Silvana; Lyon, Stuart; Snell, Gregory I

    2015-03-01

    The superior vena cava (SVC) syndrome in cystic fibrosis (CF) patients is rare, but presents unique challenges in the peri-transplant period. We reviewed our experience of SVC syndrome in CF recipients undergoing lung transplantation. This is a retrospective case series from a single center chart-review. SVC obstruction is defined by clinically significant stenosis or obstruction of the SVC as detected by contrast studies. We identified SVC obstruction in seven post-transplant cases and one pre-transplant case. All eight patients had previous or current history of indwelling central venous catheters. Three recipients experienced operative complications. Five of the seven recipients suffered at least one episode of post-operative SVC obstruction or bleeding despite prophylactic anticoagulation. At a median follow-up of 29 months, six of the seven patients transplanted are well. Strategies are available to minimize the risks of intra/peri-operative acute life-threatening SVC obstruction in CF patients. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  11. Management of the Upper Airway in Cystic Fibrosis

    PubMed Central

    Illing, Elisa A.; Woodworth, Bradford A.

    2015-01-01

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

  12. Challenges in pulmonary fibrosis · 3: Cystic lung disease

    PubMed Central

    Cosgrove, Gregory P; Frankel, Stephen K; Brown, Kevin K

    2007-01-01

    Cystic lung disease is a frequently encountered problem caused by a diverse group of diseases. Distinguishing true cystic lung disease from other entities, such as cavitary lung disease and emphysema, is important given the differing prognostic implications. In this paper the features of the cystic lung diseases are reviewed and contrasted with their mimics, and the clinical and radiographic features of both diffuse (pulmonary Langerhans' cell histiocytosis and lymphangioleiomyomatosis) and focal or multifocal cystic lung disease are discussed. PMID:17726170

  13. Distribution and function of the peptide transporter PEPT2 in normal and cystic fibrosis human lung.

    PubMed

    Groneberg, D A; Eynott, P R; Döring, F; Dinh, Q Thai; Oates, T; Barnes, P J; Chung, K F; Daniel, H; Fischer, A

    2002-01-01

    Aerosol administration of peptide based drugs has an important role in the treatment of various pulmonary and systemic diseases. The characterisation of pulmonary peptide transport pathways can lead to new strategies in aerosol drug treatment. Immunohistochemistry and ex vivo uptake studies were established to assess the distribution and activity of the beta-lactam transporting high affinity proton coupled peptide transporter PEPT2 in normal and cystic fibrosis human airway tissue. PEPT2 immunoreactivity in normal human airways was localised to cells of the tracheal and bronchial epithelium and the endothelium of small vessels. In peripheral lung immunoreactivity was restricted to type II pneumocytes. In sections of cystic fibrosis lung a similar pattern of distribution was obtained with signals localised to endothelial cells, airway epithelium, and type II pneumocytes. Functional ex vivo uptake studies with fresh lung specimens led to an uptake of the fluorophore conjugated dipeptide derivative D-Ala-L-Lys-AMCA into bronchial epithelial cells and type II pneumocytes. This uptake was competitively inhibited by dipeptides and cephalosporins but not ACE inhibitors, indicating a substrate specificity as described for PEPT2. These findings provide evidence for the expression and function of the peptide transporter PEPT2 in the normal and cystic fibrosis human respiratory tract and suggest that PEPT2 is likely to play a role in the transport of pulmonary peptides and peptidomimetics.

  14. Distribution and function of the peptide transporter PEPT2 in normal and cystic fibrosis human lung

    PubMed Central

    Groneberg, D; Eynott, P; Doring, F; Thai, D; Oates, T; Barnes, P; Chung, K; Daniel, H; Fischer, A

    2002-01-01

    Background: Aerosol administration of peptide based drugs has an important role in the treatment of various pulmonary and systemic diseases. The characterisation of pulmonary peptide transport pathways can lead to new strategies in aerosol drug treatment. Methods: Immunohistochemistry and ex vivo uptake studies were established to assess the distribution and activity of the ß-lactam transporting high affinity proton coupled peptide transporter PEPT2 in normal and cystic fibrosis human airway tissue. Results: PEPT2 immunoreactivity in normal human airways was localised to cells of the tracheal and bronchial epithelium and the endothelium of small vessels. In peripheral lung immunoreactivity was restricted to type II pneumocytes. In sections of cystic fibrosis lung a similar pattern of distribution was obtained with signals localised to endothelial cells, airway epithelium, and type II pneumocytes. Functional ex vivo uptake studies with fresh lung specimens led to an uptake of the fluorophore conjugated dipeptide derivative D-Ala-L-Lys-AMCA into bronchial epithelial cells and type II pneumocytes. This uptake was competitively inhibited by dipeptides and cephalosporins but not ACE inhibitors, indicating a substrate specificity as described for PEPT2. Conclusions: These findings provide evidence for the expression and function of the peptide transporter PEPT2 in the normal and cystic fibrosis human respiratory tract and suggest that PEPT2 is likely to play a role in the transport of pulmonary peptides and peptidomimetics. PMID:11809991

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

    PubMed Central

    Keiser, Nicholas W.; Engelhardt, John F.

    2013-01-01

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

  16. The airway microbiota in early cystic fibrosis lung disease.

    PubMed

    Frayman, Katherine B; Armstrong, David S; Grimwood, Keith; Ranganathan, Sarath C

    2017-11-01

    Infection plays a critical role in the pathogenesis of cystic fibrosis (CF) lung disease. Over the past two decades, the application of molecular and extended culture-based techniques to microbial analysis has changed our understanding of the lungs in both health and disease. CF lung disease is a polymicrobial disorder, with obligate and facultative anaerobes recovered alongside traditional pathogens in varying proportions, with some differences observed to correlate with disease stage. While healthy lungs are not sterile, differences between the lower airway microbiota of individuals with CF and disease-controls are already apparent in childhood. Understanding the evolution of the CF airway microbiota, and its relationship with clinical treatments and outcome at each disease stage, will improve our understanding of the pathogenesis of CF lung disease and potentially inform clinical management. This review summarizes current knowledge of the early development of the respiratory microbiota in healthy children and then discusses what is known about the airway microbiota in individuals with CF, including how it evolves over time and where future research priorities lie. © 2017 Wiley Periodicals, Inc.

  17. Cystic fibrosis: a mucosal immunodeficiency syndrome

    PubMed Central

    Cohen, Taylor Sitarik; Prince, Alice

    2013-01-01

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

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

    PubMed

    Eising, Jacobien B; van der Ent, Cornelis K; Teske, Arco J; Vanderschuren, Maaike M; Uiterwaal, Cuno S P M; Meijboom, Folkert J

    2018-02-02

    As life expectancy increases in patients with cystic fibrosis, it is important to pay attention to extra-pulmonary comorbidities. Several studies have shown signs of myocardial dysfunction in adult patients, but little is known about onset and development of these changes over time. In this prospective study, cardiac function in children with cystic fibrosis was compared to that of healthy children. 33 children, aged 3-12years, with cystic fibrosis were recruited from the Wilhelmina Children's hospital and 33 age-matched healthy children were selected from the WHISTLER study, a population-based cohort study. Measurements of lung function, arterial stiffness, and echocardiography (conventional measures and myocardial deformation imaging) were performed. There were no differences in anthropometrics, lung function and blood pressure between the two groups. The cystic fibrosis children had a higher arterial stiffness compared to the healthy children (pulse wave velocity respectively 5.76±0.57m/s versus 5.43±0.61m/s, p-value 0.049). Using conventional echocardiographic parameters for right ventricular function, Tricuspid Annular Plane Systolic Excursion) and Tissue Doppler Imaging, cystic fibrosis children had a reduced right ventricular systolic function when compared to the healthy children. After adjustment for lung function, global strains of both right and left ventricles were significantly lower in the cystic fibrosis group than in healthy children (linear regression coefficient 1.45% left ventricle, p-value 0.022 and 4.42% right ventricle, p-value <0.01). Systolic strain rate of basal segment of the left ventricle, the mid segment of the right ventricle and the apical septum were significantly lower in the cystic fibrosis children than in healthy controls. Our study suggests that already at a very young age, children with cystic fibrosis show an increased arterial stiffness and some signs of diminished both right and left ventricular function. Copyright © 2018

  19. Reduced survival in adult cystic fibrosis despite attenuated lung function decline.

    PubMed

    Keating, Claire; Poor, Armeen D; Liu, Xinhua; Chiuzan, Codruta; Backenroth, Daniel; Zhang, Yuan; DiMango, Emily

    2017-01-01

    There is limited data on disease progression and survival in adult diagnosis cystic fibrosis (CF). This study evaluates change of lung function over time and rates of death/lung transplant in adult diagnosis CF. The CF Foundation Patient Registry was reviewed for patients diagnosed 1993-2003. Rate of FEV1 decline was calculated up to 2010 for age groups 6-11, 12-17, and 18 and above. Kaplan Meier method was used for 10 and 15year survival rate calculations for patients diagnosed as adults. Cox Proportional hazards models using predictors affecting disease progression and survival without transplant were run. Between 1993 and 2003, 11,884 patients were diagnosed with CF, of which 2848 were ages 6 and older. Annual rate of change of FEV1% predicted over 5years differed by diagnosis age group: -1.42% per year for ages 6-11, -2.04% for ages 12-17 and -1.13% for ages 18-65 (p<0.0001). Pseudomonas aeruginosa infection was associated with faster rates of lung function decline in all age groups. Survival without transplant for CF patients diagnosed at ≥18years were 76% and 65% by 10 and 15years, respectively. Of adults with FEV1 of >70% predicted at diagnosis, 95% were alive without transplant at 10years, whereas of those with FEV1<40% predicted at diagnosis, 31% were alive without transplant at 10years. Lung function declines at a slower rate in adult diagnosis CF. However, particularly in those with low lung function at diagnosis, rates of death or transplant in adult diagnosis CF after 10 and 15years is not negligible. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  20. Respiratory pathogens mediate the association between lung function and temperature in cystic fibrosis.

    PubMed

    Collaco, Joseph M; Raraigh, Karen S; Appel, Lawrence J; Cutting, Garry R

    2016-11-01

    Mean annual ambient temperature is a replicated environmental modifier of cystic fibrosis (CF) lung disease with warmer temperatures being associated with lower lung function. The mechanism of this relationship is not completely understood. However, Pseudomonas aeruginosa, a pathogen that infects the lungs of CF individuals and decreases lung function, also has a higher prevalence in individuals living in warmer climates. We therefore investigated the extent to which respiratory pathogens mediated the association between temperature and lung function. Thirteen respiratory pathogens observed on CF respiratory cultures were assessed in multistep fashion using clustered linear and logistic regression to determine if any mediated the association between temperature and lung function. Analysis was performed in the CF Twin-Sibling Study (n=1730; primary population); key findings were then evaluated in the U.S. CF Foundation Data Registry (n=15,174; replication population). In the primary population, three respiratory pathogens (P. aeruginosa, mucoid P. aeruginosa, and methicillin-resistant Staphylococcus aureus) mediated the association between temperature and lung function. P. aeruginosa accounted for 19% of the association (p=0.003), mucoid P. aeruginosa for 31% (p=0.001), and MRSA for 13% (p=0.023). The same three pathogens mediated association in the replication population (7%, p<0.001; 7%, p=0.002; and 4%, (p=0.002), respectively). Three important respiratory pathogens in CF mediate the association between lower lung function and warmer temperatures. These findings have implications for understanding regional variations in clinical outcomes, and interpreting results of epidemiologic studies and clinical trials that encompass regions with different ambient temperatures. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  1. Progression of structural lung disease on CT scans in children with cystic fibrosis related diabetes.

    PubMed

    Widger, John; Ranganathan, Sarath; Robinson, Philip J

    2013-05-01

    Diabetes has a deleterious effect on clinical status in children with Cystic Fibrosis (CF). We hypothesized that children with CF Related Diabetes (CFRD) or Impaired Glucose Tolerance (IGT) would have more rapidly progressive lung disease based on chest computed tomography (CT) than those with normal glucose tolerance (NGT). In a retrospective study we compared lung structure changes over time, as assessed by CT, in 34 CF children with CFRD, IGT or NGT. We then compared CT findings with changes in lung function. Percentage forced expiratory volume in 1s (%FEV1) remained stable over time with a mean (±SD) yearly change of -0.5% (±3.9), -0.4% (±2.3) and -0.85% (±2.8) (p=0.92) for the CFRD, IGT and NGT groups respectively. However, there was a mean (95%CI) increase in % CT score of 3.86%/year (1.77-5.95%), 1.59%/year (0.6-2.58%) and 1.09%/year (0.07-2.11%) (p=0.023). In patients with CFRD, there was a more rapid progression of structural lung disease, compared to those who had NGT that was not reflected by change in lung function. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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

    PubMed

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

    2014-08-23

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

  3. Pediatric lung transplantation and end of life care in cystic fibrosis: Barriers and successful strategies.

    PubMed

    Dellon, Elisabeth; Goldfarb, Samuel B; Hayes, Don; Sawicki, Gregory S; Wolfe, Joanne; Boyer, Debra

    2017-11-01

    Pediatric lung transplantation has advanced over the years, providing a potential life-prolonging therapy to patients with cystic fibrosis. Despite this, many challenges in lung transplantation remain and result in worse outcomes than other solid organ transplants. As CF lung disease progresses, children and their caregivers are often simultaneously preparing for lung transplantation and end of life. In this article, we will discuss the current barriers to success in pediatric CF lung transplantation as well as approaches to end of life care in this population. © 2017 Wiley Periodicals, Inc.

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

    PubMed

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

    2016-12-01

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

  5. Preferential reduction of quadriceps over respiratory muscle strength and bulk after lung transplantation for cystic fibrosis.

    PubMed

    Pinet, C; Scillia, P; Cassart, M; Lamotte, M; Knoop, C; Mélot, C; Estenne, M

    2004-09-01

    In the absence of complications, recipients of lung transplants for cystic fibrosis have normal pulmonary function but the impact of the procedure on the strength and bulk of respiratory and limb muscles has not been studied. Twelve stable patients who had undergone lung transplantation for cystic fibrosis 48 months earlier (range 8-95) and 12 normal subjects matched for age, height, and sex were studied. The following parameters were measured: standard lung function, peak oxygen uptake by cycle ergometry, diaphragm surface area by computed tomographic (CT) scanning, diaphragm and abdominal muscle thickness by ultrasonography, twitch transdiaphragmatic and gastric pressures, quadriceps isokinetic strength, and quadriceps cross section by CT scanning, and lean body mass. Diaphragm mass was computed from diaphragm surface area and thickness. Twitch transdiaphragmatic and gastric pressures, diaphragm mass, and abdominal muscle thickness were similar in the two groups but quadriceps strength and cross section were decreased by nearly 30% in the patients. Patients had preserved quadriceps strength per unit cross section but reduced quadriceps cross section per unit lean body mass. The cumulative dose of corticosteroids was an independent predictor of quadriceps atrophy. Peak oxygen uptake showed positive correlations with quadriceps strength and cross section in the two groups, but peak oxygen uptake per unit quadriceps strength or cross section was reduced in the patient group. The diaphragm and abdominal muscles have preserved strength and bulk in patients transplanted for cystic fibrosis but the quadriceps is weak due to muscle atrophy. This atrophy is caused in part by corticosteroid therapy and correlates with the reduction in exercise capacity.

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

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

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

    Cystic fibrosis is a common genetic disorder characterized by a severe lung inflammation and fibrosis leading to the patient's death. Enhanced angiogenesis in cystic fibrosis (CF) tissue has been suggested, probably caused by the process of inflammation, as similarly described in asthma and chronic bronchitis. The present study demonstrates an intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells. Microarray experiments showed that CF airway epithelial cells expressed several angiogenic factors such as VEGF-A, VEGF-C, bFGF, and PLGF at higher levels than control cells. These data were confirmed by real-time quantitative PCR and, at the protein level, by ELISA. Conditionedmore » media of these cystic fibrosis cells were able to induce proliferation, migration and sprouting of cultured primary endothelial cells. This report describes for the first time that cystic fibrosis epithelial cells have an intrinsic angiogenic activity. Since excess of angiogenesis is correlated with more severe pulmonary disease, our results could lead to the development of new therapeutic applications.« less

  7. Predictors of deterioration of lung function in Polish children with cystic fibrosis.

    PubMed

    Olszowiec-Chlebna, Małgorzata; Koniarek-Maniecka, Agnieszka; Stelmach, Włodzimierz; Smejda, Katarzyna; Jerzyńska, Joanna; Majak, Paweł; Białas, Monika; Stelmach, Iwona

    2016-04-01

    Severity of lung disease varies in patients with the same CFTR genotype. It suggests that other factors affect the severity of cystic fibrosis (CF). The aim of the study was to identify risk factors that determine lung function decline in Polish cystic fibrosis children. The follow-up time was no less than 5 years of respiratory status observation based on the forced expiratory volume in 1 s value (FEV1). The socio-economic data, perinatal interview, presence of meconium ileus (MI), time of CF diagnosis, initiation of tobramycin inhalation solution (TIS), pancreatic function, sensitization to Aspergillus fumigatus, presence of impaired glucose tolerance (IGT) or diabetes mellitus, chronic bacterial colonization and number of exacerbations and hospitalizations were assessed. The mean age of 61 included children was 13.3 ±7.6 years. Delta F508 homozygosity was detected in 45.9%, 44.3% were delta F508 heterozygous, and 9.8% had other genotypes. FEV1 decline was observed among 20% of patients; the rest of the patients presented stable values of FEV1 during at least 5 years of observation. The most significant predictors related to the decline of FEV1 were presentation of MI (p = 0.0344), IGT (p = 0.0227), number of exacerbations (p = 0.0288), and early Pseudomonas aeruginosa (PA) chronic colonization (p = 0.0165) followed by late TIS initiation after the first detection of PA (p=0.0071). Neither time of diagnosis nor type of CFTR mutation was statistically significant as a predictor of lung deterioration. The presence of MI, IGT, chronic PA colonization, and number of exacerbations are risk factors for lung function deterioration.

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

    PubMed

    McCuaig, Sarah; Martin, James G

    2013-04-01

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

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

    PubMed

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

    2017-07-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  12. Cystic fibrosis.

    PubMed

    O'Sullivan, Brian P; Freedman, Steven D

    2009-05-30

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

  13. Fungi in the cystic fibrosis lung: bystanders or pathogens?

    PubMed

    Chotirmall, Sanjay H; McElvaney, Noel G

    2014-07-01

    Improvement to the life expectancy of people with cystic fibrosis (PWCF) brings about novel challenges including the need for evaluation of the role of fungi in the cystic fibrosis (CF) lung. To determine if such organisms represent bystanders or pathogens affecting clinical outcomes we review the existing knowledge from a clinical, biochemical, inflammatory and immunological perspective. The prevalence and importance of fungi in the CF airway has likely been underestimated with the most frequently isolated filamentous fungi being Aspergillus fumigatus and Scedosporium apiospermum and the major yeast Candida albicans. Developing non-culture based microbiological methods for fungal detection has improved both our classification and understanding of their clinical consequences including localized, allergic and systemic infections. Cross-kingdom interaction between bacteria and fungi are discussed as is the role of biofilms further affecting clinical outcome. A combination of host and pathogen-derived factors determines if a particular fungus represents a commensal, colonizer or pathogen in the setting of CF. The underlying immune state, disease severity and treatment burden represent key host variables whilst fungal type, form, chronicity and virulence including the ability to evade immune recognition determines the pathogenic potential of a specific fungus at a particular point in time. Further research in this emerging field is warranted to fully elucidate the spectrum of disease conferred by the presence of fungi in the CF airway and the indications for therapeutic interventions. Copyright © 2014. Published by Elsevier Ltd.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2017-10-05

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

  17. Immune response, diagnosis and treatment of allergic bronchopulmonary aspergillosis in cystic fibrosis lung disease.

    PubMed

    Eickmeier, Olaf; Rieber, Nikolaus; Eckrich, Jonas; Hector, Andreas; Graeppler-Mainka, Ute; Hartl, Dominik

    2013-01-01

    Patients with cystic fibrosis (CF) suffer from chronic infective lung disease, which determines morbidity and mortality. While bacteria, such as Pseudomonas aeruginosa, are well-known to contribute to pulmonary pathology, the relevance of fungi in CF airways remains poorly understood. The best studied fungus in CF is Aspergillus fumigatus, which frequently colonizes CF airways and causes a disease condition termed allergic bronchopulmonary aspergillosis. This review aims to provide an update on the immunological mechanisms, diagnostic approaches and therapeutic strategies for allergic bronchopulmonary aspergillosis and other Aspergillus fumigatusmediated phenotypes in CF lung disease.

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

    PubMed

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

    2016-07-01

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

  19. Oral calorie supplements for cystic fibrosis.

    PubMed

    Smyth, Rosalind L; Rayner, Oli

    2017-05-04

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

  20. Chronic Stenotrophomonas maltophilia infection and mortality or lung transplantation in cystic fibrosis patients.

    PubMed

    Waters, Valerie; Atenafu, Eshetu G; Lu, Annie; Yau, Yvonne; Tullis, Elizabeth; Ratjen, Felix

    2013-09-01

    Chronic Stenotrophomonas maltophilia infection is an independent risk factor for severe pulmonary exacerbations in cystic fibrosis (CF) patients. The goal of this study was to determine the effect of chronic S. maltophilia infection on mortality and the need for lung transplantation in a longitudinal study of children and adults with CF. This was a cohort study of CF patients from the Hospital for Sick Children and St Michael's Hospital (Toronto, Canada) from 1997 to 2008. A Cox Regression model was used to estimate the hazard ratio (HR) to time of death or lung transplantation adjusting for age, gender, genotype, pancreatic status, CF related diabetes (CFRD), forced expiratory volume in 1 s (FEV1), body mass index, number of pulmonary exacerbations, Pseudomonas aeruginosa, Burkholderia cepacia complex, Aspergillus and chronic S. maltophilia infection. A total of 687 patients were followed over the 12 year study period; 95 patients underwent a lung transplantation (of which 26 died) and an additional 49 patients died (total 144 events). In a Cox Regression model adjusting for baseline FEV1, baseline infection with B. cepacia complex (HR 1.72, 95% CI 1.09-2.71) and baseline chronic S. maltophilia infection (HR 2.80, 95% CI 1.65-4.76) were significantly associated with death or lung transplant. However, in a time-varying model, infection with B. cepacia complex and chronic S. maltophilia infection were no longer significant. Baseline chronic S. maltophilia infection is associated with an almost three-fold increased risk of death or lung transplant in CF patients. It is still unclear, however, whether chronic S. maltophilia infection is simply a marker of severity of disease and ultimate mortality or whether it is causally related to disease progression. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  1. Multicenter, open-label study of recombinant human DNase in cystic fibrosis patients with moderate lung disease. DNase International Study Group.

    PubMed

    Harms, H K; Matouk, E; Tournier, G; von der Hardt, H; Weller, P H; Romano, L; Heijerman, H G; FitzGerald, M X; Richard, D; Strandvik, B; Kolbe, J; Kraemer, R; Michalsen, H

    1998-09-01

    Cystic fibrosis is characterized by the accumulation of thick viscous purulent secretions. Recombinant human deoxyribonuclease I (rhDNase) breaks down extracellular DNA, which contributes to the increased viscosity of sputum. A multinational, open-label study was conducted in 974 cystic fibrosis patients with moderate lung disease [forced vital capacity (FVC) 40-70% of predicted values] to examine the safety and efficacy of aerosolized rhDNase, 2.5 mg, once daily over a period of at least 12 weeks. Patients were assessed under conditions reflecting routine clinical practice. During rhDNase therapy, at least one respiratory tract infection (RTI) requiring intravenous antibiotics was experienced by 29.5% of patients. Forced expiratory volume in 1 second (FEV1) and FVC were significantly improved from baseline by a mean of 10.5% and 7.2%, respectively. Voice alteration and pharyngitis were the most frequent rhDNase-related adverse events, but only 2% of all patients discontinued treatment due to adverse events. The results obtained were similar to a subanalysis of data from the first 3 months of a placebo-controlled U.S. study. The patients in the present study had a similar frequency of RTIs and improvement in pulmonary function, and reported fewer rhDNase-related and cystic fibrosis-related adverse events than patients in the U.S. study. We conclude that administration of rhDNase is safe, well tolerated, and effective under conditions reflecting routine clinical practice in patients with cystic fibrosis and moderate lung disease.

  2. Reemergence of Lower-Airway Microbiota in Lung Transplant Patients with Cystic Fibrosis.

    PubMed

    Syed, Saad A; Whelan, Fiona J; Waddell, Barbara; Rabin, Harvey R; Parkins, Michael D; Surette, Michael G

    2016-12-01

    Chronic lung infections are a hallmark of cystic fibrosis; they are responsible for progressive airway destruction and ultimately lead to respiratory death or the requirement for life-saving bilateral lung transplant. Furthermore, recurrent isolation of airway pathogens such as Pseudomonas aeruginosa in the allograft after transplant is associated with adverse outcomes, including bronchiolitis obliterans syndrome and acute infections. Little information exists on the impact of bilateral lung transplant on the lower-airway microbiota. To compare, at a microbiome and single-pathogen level (P. aeruginosa), the bacterial communities in pre- and post-transplant samples. We retrospectively accessed our biobank of sputum samples and sputum-derived bacterial pathogens for patients who had matched samples, including those who were clinically stable before transplant, those who had a pulmonary exacerbation before transplant, and those who had pulmonary exacerbation after transplant. We used 16S ribosomal RNA gene sequencing to characterize the lower-airway microbiome of 14 adult transplant patients with cystic fibrosis. Genotyping and phenotyping of P. aeruginosa isolates from 12 of these patients with matched isolates was performed. Although α-diversity (richness and evenness) of patient microbiomes was similar before and after transplant, β- diversity (core microbiome composition) measures stratified patients evenly into two groups with more similar and more dissimilar communities. P. aeruginosa strains isolated before transplant were found to reemerge in 11 of 12 patients; however, phenotypic variation was observed. These findings indicate that recolonization by P. aeruginosa after transplant is almost always strain specific, suggesting a within-host source. The polymicrobial colonization of the airways after transplant does not always reflect the pretransplant sputum microbiota.

  3. Predictive 5-Year Survivorship Model of Cystic Fibrosis

    PubMed Central

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

    2007-01-01

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

  4. Lung transplantation for cystic fibrosis.

    PubMed

    Mendeloff, E N

    1998-07-01

    Cystic fibrosis (CF) is an inherited disease in which the fundamental physiological defect is failure of cAMP regulation of chloride transport. More than 90% of patients with CF will die of chronic, suppurative, obstructive lung disease, with the median survival in the United States currently being 29 years of age. Currently, although other therapies are being aggressively investigated, bilateral lung transplantation offers the only hope for short-term and mid-term survival in patients with CF and end-stage pulmonary disease. Since 1989, 103 bilateral sequential lung transplants (BLT) for CF have been performed at our institution (46 pediatric, 48 adult, 9 redo) at a mean age of 21+/-10 years. Cardiopulmonary bypass was used in all but one pediatric (age <18) transplantation, and in 15% of adults. The hospital mortality rate was 4.9%, with 80% of early deaths related to infection. Bronchial anastomotic complications occurred with equal frequency in the pediatric and the adult populations (7.3%). One- and 3-year actuarial survival rates are 84% and 61%, respectively (no significant difference between pediatric and adult age groups; average follow-up 2.1+/-1.6 years). Mean forced expiratory volume in 1 second increased from 25%+/-9% pretransplantation to 79%+/-35% 1 year posttransplantation. Acute rejection occurred 1.7 times per patient-year, with the majority of these episodes taking place the first 6 months posttransplantation. Need for treatment of lower respiratory infections occurred 1.2 times per patient in the first year after transplantation. Actuarial freedom from bronchiolitis obliterans was 63% at 2 years and 43% at 3 years. Redo transplantation was performed only in the pediatric population, and was associated with an early mortality of 33%. Eight living donor transplants (4 primary transplants, 4 redo transplants) were performed with an early survival of 87.5%. Patients with end-stage CF can undergo BLT with morbidity and mortality comparable with that

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

    PubMed

    Kaskavage, Jillian; Sklansky, Daniel

    2012-07-01

    Adolescents with well-controlled cystic fibrosis, including good lung function and appropriate growth, commonly participate in competitive athletic activities. We present the case of an adolescent male with cystic fibrosis, hyponatremia, dehydration, and rhabdomyolysis after participating in football practice on a summer morning. The patient presented with severe myalgia and serum sodium of 129 mmol/L, chloride 90 mmol/L, and creatine phosphokinase 1146 U/L. Aggressive hydration with intravenous 0.9% saline resulted in clinical improvement with no renal or muscular sequelae. Health care providers need to educate patients with cystic fibrosis about maintaining adequate hydration and sodium repletion during exercise. Research is needed regarding the appropriate amount and composition of oral rehydration fluids in exercising individuals with cystic fibrosis, as the physiology encountered in these patients provides a unique challenge to maintaining electrolyte balance and stimulation of thirst.

  6. Hyperglycemia impedes lung bacterial clearance in a murine model of cystic fibrosis-related diabetes

    PubMed Central

    Hunt, William R.; Zughaier, Susu M.; Guentert, Dana E.; Shenep, Melissa A.; Koval, Michael; McCarty, Nael A.

    2013-01-01

    Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity associated with cystic fibrosis (CF), impacting more than half of patients over age 30. CFRD is clinically significant, portending accelerated decline in lung function, more frequent pulmonary exacerbations, and increased mortality. Despite the profound morbidity associated with CFRD, little is known about the underlying CFRD-related pulmonary pathology. Our aim was to develop a murine model of CFRD to explore the hypothesis that elevated glucose in CFRD is associated with reduced lung bacterial clearance. A diabetic phenotype was induced in gut-corrected CF transmembrane conductance regulator (CFTR) knockout mice (CFKO) and their CFTR-expressing wild-type littermates (WT) utilizing streptozotocin. Mice were subsequently challenged with an intratracheal inoculation of Pseudomonas aeruginosa (PAO1) (75 μl of 1–5 × 106 cfu/ml) for 18 h. Bronchoalveolar lavage fluid was collected for glucose concentration and cell counts. A portion of the lung was homogenized and cultured as a measure of the remaining viable PAO1 inoculum. Diabetic mice had increased airway glucose compared with nondiabetic mice. The ability to clear bacteria from the lung was significantly reduced in diabetic WT mice and control CFKO mice. Critically, bacterial clearance by diabetic CFKO mice was significantly more diminished compared with nondiabetic CFKO mice, despite an even more robust recruitment of neutrophils to the airways. This finding that CFRD mice boast an exaggerated, but less effective, inflammatory cell response to intratracheal PAO1 challenge presents a novel and useful murine model to help identify therapeutic strategies that promote bacterial clearance in CFRD. PMID:24097557

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

    PubMed Central

    Kalnins, Daina; Wilschanski, Michael

    2012-01-01

    Poor clinical outcomes in cystic fibrosis are often associated with undernutrition. Normal growth and development should be achieved in cystic fibrosis, and nutritional counseling is paramount at all ages. Prevention and early detection of growth failure is the key to successful nutritional intervention. The advance in nutritional management is certainly one factor that has contributed to the improved survival in recent decades. This review outlines the major nutritional parameters in the management of the patient with cystic fibrosis, including recent advances in pancreatic enzyme replacement therapy and fat-soluble vitamin therapy. There are sections on complicated clinical situations which directly affect nutrition, for example, before and after lung transplantation, cystic fibrosis-related diabetes, and bone health. PMID:22787388

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

    PubMed

    Talbot, Nick P; Flight, William G

    2016-08-01

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

  9. Heritability of Lung Disease Severity in Cystic Fibrosis

    PubMed Central

    Vanscoy, Lori L.; Blackman, Scott M.; Collaco, Joseph M.; Bowers, Amanda; Lai, Teresa; Naughton, Kathleen; Algire, Marilyn; McWilliams, Rita; Beck, Suzanne; Hoover-Fong, Julie; Hamosh, Ada; Cutler, Dave; Cutting, Garry R.

    2007-01-01

    Rationale: Obstructive lung disease, the major cause of mortality in cystic fibrosis (CF), is poorly correlated with mutations in the disease-causing gene, indicating that other factors determine severity of lung disease. Objectives: To quantify the contribution of modifier genes to variation in CF lung disease severity. Methods: Pulmonary function data from patients with CF living with their affected twin or sibling were converted into reference values based on both healthy and CF populations. The best measure of FEV1 within the last year was used for cross-sectional analysis. FEV1 measures collected over at least 4 years were used for longitudinal analysis. Genetic contribution to disease variation (i.e., heritability) was estimated in two ways: by comparing similarity of lung function in monozygous (MZ) twins (∼ 100% gene sharing) with that of dizygous (DZ) twins/siblings (∼ 50% gene sharing), and by comparing similarity of lung function measures for related siblings to similarity for all study subjects. Measurements and Main Results: Forty-seven MZ twin pairs, 10 DZ twin pairs, and 231 sibling pairs (of a total of 526 patients) with CF were studied. Correlations for all measures of lung function for MZ twins (0.82–0.91, p < 0.0001) were higher than for DZ twins and siblings (0.50–0.64, p < 0.001). Heritability estimates from both methods were consistent for each measure of lung function and ranged from 0.54 to 1.0. Heritability estimates generally increased after adjustment for differences in nutritional status (measured as body mass index z-score). Conclusions: Our heritability estimates indicate substantial genetic control of variation in CF lung disease severity, independent of CFTR genotype. PMID:17332481

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

    PubMed

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

    2017-01-01

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

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

    PubMed

    Elphick, Heather E; Southern, Kevin W

    2014-11-28

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

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

    PubMed

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

    2018-04-16

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

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

    PubMed

    Elphick, Heather E; Southern, Kevin W

    2012-06-13

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

  14. Cystic Fibrosis and Pregnancy

    MedlinePlus

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

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

    NASA Astrophysics Data System (ADS)

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

    1990-12-01

    Respiratory distress and progressive lung destruction in cystic fibrosis can be attributed to bacterial persistence and the accumulation of viscous purulent secretions in the airways. More than 30 yr ago it was suggested that the large amounts of DNA in purulent secretions contribute to its viscosity and that bovine pancreatic DNase I could reduce the viscosity. To evaluate the potential clinical utility of recombinant human DNase I (rhDNase) in the treatment of cystic fibrosis, we have cloned, sequenced, and expressed rhDNase. Catalytic amounts of rhDNase greatly reduce the viscosity of purulent cystic fibrosis sputum, transforming it within minutes from a nonflowing viscous gel to a flowing liquid. The reduction in viscosity is associated with a decrease in size of DNA in the sputum. Inhalation of a rhDNase aerosol may be a simple direct approach that will help individuals with cystic fibrosis and other patients with pneumonia or bronchitis to clear their airways of purulent secretions.

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

    PubMed

    Shak, S; Capon, D J; Hellmiss, R; Marsters, S A; Baker, C L

    1990-12-01

    Respiratory distress and progressive lung destruction in cystic fibrosis can be attributed to bacterial persistence and the accumulation of viscous purulent secretions in the airways. More than 30 yr ago it was suggested that the large amounts of DNA in purulent secretions contribute to its viscosity and that bovine pancreatic DNase I could reduce the viscosity. To evaluate the potential clinical utility of recombinant human DNase I (rhDNase) in the treatment of cystic fibrosis, we have cloned, sequenced, and expressed rhDNase. Catalytic amounts of rhDNase greatly reduce the viscosity of purulent cystic fibrosis sputum, transforming it within minutes from a nonflowing viscous gel to a flowing liquid. The reduction in viscosity is associated with a decrease in size of DNA in the sputum. Inhalation of a rhDNase aerosol may be a simple direct approach that will help individuals with cystic fibrosis and other patients with pneumonia or bronchitis to clear their airways of purulent secretions.

  17. Advanced glycation end products are elevated in cystic fibrosis-related diabetes and correlate with worse lung function.

    PubMed

    Hunt, William R; Helfman, Beth R; McCarty, Nael A; Hansen, Jason M

    2016-09-01

    The onset of cystic fibrosis-related diabetes (CFRD) exacerbates lung function decline and increases mortality. One pathway that may worsen the lung dysfunction associated with CFRD is that of the receptor for advanced glycation end products (RAGE) and its ligands. Human plasma was obtained from age-matched healthy, CF and CFRD patients. Plasma RAGE ligands (i.e. advanced glycation end products, S100A12, and high-mobility group protein B1) and soluble RAGE (sRAGE) levels were measured. CFRD patients had elevated plasma levels of AGEs and S100A12. Soluble RAGE, a RAGE ligand decoy receptor, was not significantly different between groups. Plasma AGE levels and S100A12 levels had significantly negative correlations with FEV1. AGEs are significantly elevated in CFRD and correlate negatively with FEV1. CFRD patients did not have significant increases in the decoy sRAGE, suggesting there may be heightened binding and activation of RAGE in CFRD exacerbating activation of proinflammatory pathways. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  18. Pharmacological considerations for azole antifungal drug management in cystic fibrosis lung transplant patients.

    PubMed

    Billaud, Eliane M; Guillemain, Romain; Berge, Maud; Amrein, Catherine; Lefeuvre, Sandrine; Louët, Agnès Lillo-Le; Boussaud, Véronique; Chevalier, Patrick

    2010-11-01

    This paper aims to present our experience in the pharmacological approach of the management of azole antifungal drugs in cystic fibrosis lung transplant patients. Cystic fibrosis (CF) lung transplantation is associated with multi-factorial care management, because of immunosuppressive requirements, risk of infections, frequency of gastro-oesophageal reflux disease, hepatic alterations and CF pharmacokinetics (PK) specificities that result in important PK variability. CF is associated with frequent colonization of the airways by filamentous fungi, especially by Aspergillus species. Today the antifungal therapeutic arsenal offers several possibilities for long-term oral therapy including azole drugs (itraconazole, voriconazole and posaconazole). Therefore, nephrotoxic amphotericin B should be avoided. The liver is important in the pharmacological profile of azole drugs, due to metabolic elimination, hepatotoxicity and PK drug-drug interaction (DDI) involving CYP3A4 metabolic inhibition. Targets for such DDI are numerous, but immunosuppressive drugs are of major concern, justifying combined therapeutic drug monitoring (TDM) of both azoles (inhibitors) and immunosuppressants (targets) on an individualized patient basis to adjust the coprescription quantitatively. The risk of long under-dosed periods, frequently addressed in this population, could justify, on a PK basis, the need for combination with an exclusive parenteral antifungal while waiting for azole relevant drug level. High PK variability, the risk of low exposure, therapeutic issues and DDI management in this complex underlying disease justify close monitoring with systematic combined TDM of azole and immunosuppressants, in case of coprescription.

  19. Impact of lung disease on respiratory impedance in young children with cystic fibrosis.

    PubMed

    Ramsey, Kathryn A; Ranganathan, Sarath C; Gangell, Catherine L; Turkovic, Lidija; Park, Judy; Skoric, Billy; Stick, Stephen M; Sly, Peter D; Hall, Graham L

    2015-12-01

    This study aimed to evaluate the ability of the forced oscillation technique (FOT) to detect underlying lung disease in preschool children with cystic fibrosis (CF) diagnosed following newborn screening.184 children (aged 3-6 years) with CF underwent lung function testing on 422 occasions using the FOT to assess respiratory resistance and reactance at the time of their annual bronchoalveolar lavage collection and chest computed tomography scan. We examined associations between FOT outcomes and the presence and progression of respiratory inflammation, infection and structural lung disease.Children with CF who had pronounced respiratory disease, including free neutrophil elastase activity, infection with pro-inflammatory pathogens and structural lung abnormalities had similar FOT outcomes to those children without detectable lung disease. In addition, the progression of lung disease over 1 year was not associated with worsening FOT outcomes.We conclude that the forced oscillation technique is relatively insensitive to detect underlying lung disease in preschool children with CF. However, FOT may still be of value in improving our understanding of the physiological changes associated with early CF lung disease. Copyright ©ERS 2015.

  20. Long-term success of combined kidney-lung transplantation in a patient with cystic fibrosis.

    PubMed

    Borro, José M; Rama, Pablo; Rey, Teresa; Fernández-Rivera, Constantino

    2013-06-01

    Advanced kidney disease is usually considered an absolute contraindication for lung transplantation due to the difficult management of these patients in the post-operative period. Combined lung-kidney transplantation, however, could offer an opportunity for selected patients with renal and pulmonary dysfunction. This study summarizes the long-term success of a double transplantation in a 38-year-old male patient with cystic fibrosis who presented respiratory and kidney failure. After a complicated post-operative period, the patient currently lives completely independently 46 months after the operation and he enjoys excellent pulmonary and renal function. Copyright © 2012 SEPAR. Published by Elsevier España, S.L. All rights reserved.

  1. Does current reporting of lung function by the UK cystic fibrosis registry allow a fair comparison of adult centres?

    PubMed

    Nightingale, Julia Anne; Osmond, Clive

    2017-09-01

    Outcome data for UK cystic fibrosis centres are publicly available in an annual report, which ranks centres by median FEV 1 % predicted. We wished to assess whether there are differences in lung function outcomes between adult centres that might imply differing standards of care. UK Registry data from 4761 subjects at 34 anonymised adult centres were used to calculate mean FEV 1 % and rate of change of lung function for 2007-13. These measures were used to rank centres and compare outcomes. There are minor differences between centres for mean FEV 1 % for some years of the study and for rate of change of lung function over the study period. However, rankings are critically dependent on the outcome measure chosen and centre variation becomes negligible once patient population characteristics are taken into account. We have demonstrated that the ranking of centres is biased and any apparent difference in respiratory outcomes is unlikely to be related to differing standards of care between centres. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

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

    1996-03-01

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

  3. Volumetric dynamic oxygen-enhanced MRI (OE-MRI): comparison with CT Brody score and lung function in cystic fibrosis patients.

    PubMed

    Martini, K; Gygax, C M; Benden, C; Morgan, A R; Parker, G J M; Frauenfelder, T

    2018-04-13

    To demonstrate, in patients with cystic fibrosis (CF), the correlation between three-dimensional dynamic oxygen-enhanced magnetic resonance imaging (OE-MRI) measurements and computed tomography Brody score (CF-CT) and lung function testing (LFT). Twenty-one patients (median age, 25 years; female, n = 8) with a range of CF lung disease and five healthy volunteers (median age, 31 years; female, n = 2) underwent OE-MRI performed on a 1.5-T MRI scanner. Coronal volumes were acquired while patients alternately breathed room air and 100% oxygen. Pre-oxygen T 1 was measured. Dynamic series of T 1 -weighted volumes were then obtained while breathing oxygen. T 1 -parameter maps were generated and the following OE-MRI parameters were measured: oxygen uptake (ΔPO 2max ), wash-in time and wash-out time. High-resolution CT and LFT were performed. The relationship between CF-CT, LFT and OE-MRI parameters were evaluated using Pearson correlation for the whole lung and regionally. Mean CF-CT was 24.1±17.1. Mean ΔPO 2max and mean wash-in as well as skewness of wash-out showed significant correlation with CF-CT (ΔPO 2max : r = -0.741, p < 0.001; mean wash-in: r = 0.501, p = 0.017; skewness of wash-out: r = 0.597, p = 0.001). There was significant correlation for the whole lung and regionally between LFT parameters and OE-MR (ΔPO 2max : r = 0.718, p < 0.001; wash-in: r = -0.576, p = 0.003; wash-out skewness: r = -0.552, p = 0.004). Functional lung imaging using OE-MRI has the capability to assess the severity of CF lung disease and shows a significant correlation with LFT and CF-CT. • Oxygen-enhanced MRI might play a future role in evaluation and follow-up of cystic fibrosis. • Heterogeneity of parameter maps reflects localised functional impairment in cystic fibrosis. • Avoidance of cumulative radiation burden in CF is feasible using OE-MRI.

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

    PubMed

    Elphick, Heather E; Southern, Kevin W

    2016-11-08

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

  5. Molecular Diagnosis of Cystic Fibrosis.

    PubMed

    Deignan, Joshua L; Grody, Wayne W

    2016-01-01

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

  6. Cystic Fibrosis Gene Therapy in the UK and Elsewhere

    PubMed Central

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

    2015-01-01

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

  7. Cystic Fibrosis Transmembrane Conductance Regulator Controls Lung Proteasomal Degradation and Nuclear Factor-κB Activity in Conditions of Oxidative Stress

    PubMed Central

    Boncoeur, Emilie; Roque, Telma; Bonvin, Elise; Saint-Criq, Vinciane; Bonora, Monique; Clement, Annick; Tabary, Olivier; Henrion-Caude, Alexandra; Jacquot, Jacky

    2008-01-01

    Cystic fibrosis is a lethal inherited disorder caused by mutations in a single gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, resulting in progressive oxidative lung damage. In this study, we evaluated the role of CFTR in the control of ubiquitin-proteasome activity and nuclear factor (NF)-κB/IκB-α signaling after lung oxidative stress. After a 64-hour exposure to hyperoxia-mediated oxidative stress, CFTR-deficient (cftr−/−) mice exhibited significantly elevated lung proteasomal activity compared with wild-type (cftr+/+) animals. This was accompanied by reduced lung caspase-3 activity and defective degradation of NF-κB inhibitor IκB-α. In vitro, human CFTR-deficient lung cells exposed to oxidative stress exhibited increased proteasomal activity and decreased NF-κB-dependent transcriptional activity compared with CFTR-sufficient lung cells. Inhibition of the CFTR Cl− channel by CFTRinh-172 in the normal bronchial immortalized cell line 16HBE14o− increased proteasomal degradation after exposure to oxidative stress. Caspase-3 inhibition by Z-DQMD in CFTR-sufficient lung cells mimicked the response profile of increased proteasomal degradation and reduced NF-κB activity observed in CFTR-deficient lung cells exposed to oxidative stress. Taken together, these results suggest that functional CFTR Cl− channel activity is crucial for regulation of lung proteasomal degradation and NF-κB activity in conditions of oxidative stress. PMID:18372427

  8. Dornase alfa for cystic fibrosis.

    PubMed

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

    2016-04-04

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

  9. Postnatal airway growth in cystic fibrosis piglets.

    PubMed

    Adam, Ryan J; Abou Alaiwa, Mahmoud H; Bouzek, Drake C; Cook, Daniel P; Gansemer, Nicholas D; Taft, Peter J; Powers, Linda S; Stroik, Mallory R; Hoegger, Mark J; McMenimen, James D; Hoffman, Eric A; Zabner, Joseph; Welsh, Michael J; Meyerholz, David K; Stoltz, David A

    2017-09-01

    Mutations in the gene encoding the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) anion channel cause CF. The leading cause of death in the CF population is lung disease. Increasing evidence suggests that in utero airway development is CFTR-dependent and that developmental abnormalities may contribute to CF lung disease. However, relatively little is known about postnatal CF airway growth, largely because such studies are limited in humans. Therefore, we examined airway growth and lung volume in a porcine model of CF. We hypothesized that CF pigs would have abnormal postnatal airway growth. To test this hypothesis, we performed CT-based airway and lung volume measurements in 3-wk-old non-CF and CF pigs. We found that 3-wk-old CF pigs had tracheas of reduced caliber and irregular shape. Their bronchial lumens were reduced in size proximally but not distally, were irregularly shaped, and had reduced distensibility. Our data suggest that lack of CFTR results in aberrant postnatal airway growth and development, which could contribute to CF lung disease pathogenesis. NEW & NOTEWORTHY This CT scan-based study of airway morphometry in the cystic fibrosis (CF) postnatal period is unique, as analogous studies in humans are greatly limited for ethical and technical reasons. Findings such as reduced airway lumen area and irregular caliber suggest that airway growth and development are CF transmembrane conductance regulator-dependent and that airway growth defects may contribute to CF lung disease pathogenesis. Copyright © 2017 the American Physiological Society.

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

    PubMed Central

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

    2016-01-01

    Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with pre-existing inflammatory lung disease such as cystic fibrosis (CF). Pulmonary disease caused by NTM has emerged as a major threat to the health of individuals with CF but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened an expert panel of specialists to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM pulmonary disease in individuals with CF. Nineteen experts were invited to participate in the recommendation development process. Population, Intervention, Comparison, Outcome (PICO) methodology and systematic literature reviews were employed to inform draft recommendations. An anonymous voting process was used by the committee to reach consensus. All committee members were asked to rate each statement on a scale of: 0, completely disagree, to 9, completely agree; with 80% or more of scores between 7 and 9 being considered ‘good’ agreement. Additionally, the committee solicited feedback from the CF communities in the USA and Europe and considered the feedback in the development of the final recommendation statements. Three rounds of voting were conducted to achieve 80% consensus for each recommendation statement. Through this process, we have generated a series of pragmatic, evidence-based recommendations for the screening, investigation, diagnosis and treatment of NTM infection in individuals with CF as an initial step in optimising management for this challenging condition. PMID:26666259

  11. Survival in Patients with Advanced Non-cystic Fibrosis Bronchiectasis Versus Cystic Fibrosis on the Waitlist for Lung Transplantation.

    PubMed

    Hayes, Don; Kopp, Benjamin T; Tobias, Joseph D; Woodley, Frederick W; Mansour, Heidi M; Tumin, Dmitry; Kirkby, Stephen E

    2015-12-01

    Survival in non-cystic fibrosis (CF) bronchiectasis is not well studied. The United Network for Organ Sharing database was queried from 1987 to 2013 to compare survival in adult patients with non-CF bronchiectasis to patients with CF listed for lung transplantation (LTx). Each subject was tracked from waitlist entry date until death or censoring to determine survival differences between the two groups. Of 2112 listed lung transplant candidates with bronchiectasis (180 non-CF, 1932 CF), 1617 were used for univariate Cox and Kaplan-Meier survival function analysis, 1173 for multivariate Cox models, and 182 for matched-pairs analysis based on propensity scores. Compared to CF, patients with non-CF bronchiectasis had a significantly lower mortality by univariate Cox analysis (HR 0.565; 95 % CI 0.424, 0.754; p < 0.001). Adjusting for potential confounders, multivariate Cox models identified a significant reduction in risk for death associated with non-CF bronchiectasis who were lung transplant candidates (HR 0.684; 95 % CI 0.475, 0.985; p = 0.041). Results were consistent in multivariate models adjusting for pulmonary hypertension and forced expiratory volume in one second. Non-CF bronchiectasis with advanced lung disease was associated with significantly lower mortality hazard compared to CF bronchiectasis on the waitlist for LTx. Separate referral and listing criteria for LTx in non-CF and CF populations should be considered.

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

    PubMed

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

    2018-05-04

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

  13. Short-term effects of physiotherapy on ventilation inhomogeneity in cystic fibrosis patients with a wide range of lung disease severity.

    PubMed

    Pfleger, A; Steinbacher, M; Schwantzer, G; Weinhandl, E; Wagner, M; Eber, E

    2015-09-01

    Lung clearance index (LCI) is increasingly used as a study endpoint for therapeutic interventions in cystic fibrosis (CF) patients. We set out to assess the effect of chest physiotherapy on ventilation inhomogeneity in clinically stable patients with CF lung disease of varying severity. In 29 CF patients (7.3-43.7 years) N2MBW (nitrogen multiple breath washout), plethysmography, and spirometry measurements were conducted, followed by 30 min of supervised PEP mask chest physiotherapy and repeated measurements 30 min after therapy. We observed a mean change in LCI after physiotherapy from 15.00 to 14.80 (range, -4.84 to 3.37; p=0.578). In seven patients, LCI decreased, and in ten patients, LCI increased by ≥1. For the whole group, statistically significant improvements were seen in Reff, FEV1, FVC, and MEF50. By opening up previously poorly ventilated lung regions, physiotherapy may either increase or decrease ventilation inhomogeneity; the short-term effect of physiotherapy on LCI appears to be unpredictable. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  14. Voice Disorder in Cystic Fibrosis Patients

    PubMed Central

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

    2014-01-01

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

  15. Vitamin A supplementation for cystic fibrosis.

    PubMed

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

    2014-05-14

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

  16. Defective innate immunity and hyperinflammation in newborn cystic fibrosis transmembrane conductance regulator-knockout ferret lungs.

    PubMed

    Keiser, Nicholas W; Birket, Susan E; Evans, Idil A; Tyler, Scott R; Crooke, Adrianne K; Sun, Xingshen; Zhou, Weihong; Nellis, Joseph R; Stroebele, Elizabeth K; Chu, Kengyeh K; Tearney, Guillermo J; Stevens, Mark J; Harris, J Kirk; Rowe, Steven M; Engelhardt, John F

    2015-06-01

    Mucociliary clearance (MCC) and submucosal glands are major components of airway innate immunity that have impaired function in cystic fibrosis (CF). Although both of these defense systems develop postnatally in the ferret, the lungs of newborn ferrets remain sterile in the presence of a functioning cystic fibrosis transmembrane conductance regulator gene. We evaluated several components of airway innate immunity and inflammation in the early CF ferret lung. At birth, the rates of MCC did not differ between CF and non-CF animals, but the height of the airway surface liquid was significantly reduced in CF newborn ferrets. CF ferrets had impaired MCC after 7 days of age, despite normal rates of ciliogenesis. Only non-CF ferrets eradicated Pseudomonas directly introduced into the lung after birth, whereas both genotypes could eradicate Staphylococcus. CF bronchoalveolar lavage fluid (BALF) had significantly lower antimicrobial activity selectively against Pseudomonas than non-CF BALF, which was insensitive to changes in pH and bicarbonate. Liquid chromatography-tandem mass spectrometry and cytokine analysis of BALF from sterile Caesarean-sectioned and nonsterile naturally born animals demonstrated CF-associated disturbances in IL-8, TNF-α, and IL-β, and pathways that control immunity and inflammation, including the complement system, macrophage functions, mammalian target of rapamycin signaling, and eukaryotic initiation factor 2 signaling. Interestingly, during the birth transition, IL-8 was selectively induced in CF BALF, despite no genotypic difference in bacterial load shortly after birth. These results suggest that newborn CF ferrets have defects in both innate immunity and inflammatory signaling that may be important in the early onset and progression of lung disease in these animals.

  17. Defective Innate Immunity and Hyperinflammation in Newborn Cystic Fibrosis Transmembrane Conductance Regulator–Knockout Ferret Lungs

    PubMed Central

    Keiser, Nicholas W.; Birket, Susan E.; Evans, Idil A.; Tyler, Scott R.; Crooke, Adrianne K.; Sun, Xingshen; Zhou, Weihong; Nellis, Joseph R.; Stroebele, Elizabeth K.; Chu, Kengyeh K.; Tearney, Guillermo J.; Stevens, Mark J.; Harris, J. Kirk; Rowe, Steven M.

    2015-01-01

    Mucociliary clearance (MCC) and submucosal glands are major components of airway innate immunity that have impaired function in cystic fibrosis (CF). Although both of these defense systems develop postnatally in the ferret, the lungs of newborn ferrets remain sterile in the presence of a functioning cystic fibrosis transmembrane conductance regulator gene. We evaluated several components of airway innate immunity and inflammation in the early CF ferret lung. At birth, the rates of MCC did not differ between CF and non-CF animals, but the height of the airway surface liquid was significantly reduced in CF newborn ferrets. CF ferrets had impaired MCC after 7 days of age, despite normal rates of ciliogenesis. Only non-CF ferrets eradicated Pseudomonas directly introduced into the lung after birth, whereas both genotypes could eradicate Staphylococcus. CF bronchoalveolar lavage fluid (BALF) had significantly lower antimicrobial activity selectively against Pseudomonas than non-CF BALF, which was insensitive to changes in pH and bicarbonate. Liquid chromatography–tandem mass spectrometry and cytokine analysis of BALF from sterile Caesarean-sectioned and nonsterile naturally born animals demonstrated CF-associated disturbances in IL-8, TNF-α, and IL-β, and pathways that control immunity and inflammation, including the complement system, macrophage functions, mammalian target of rapamycin signaling, and eukaryotic initiation factor 2 signaling. Interestingly, during the birth transition, IL-8 was selectively induced in CF BALF, despite no genotypic difference in bacterial load shortly after birth. These results suggest that newborn CF ferrets have defects in both innate immunity and inflammatory signaling that may be important in the early onset and progression of lung disease in these animals. PMID:25317669

  18. Effects of sinus surgery in patients with cystic fibrosis after lung transplantation: a 10-year experience.

    PubMed

    Holzmann, David; Speich, Rudolf; Kaufmann, Thomas; Laube, Irene; Russi, Erich W; Simmen, Daniel; Weder, Walter; Boehler, Annette

    2004-01-15

    Chronic infectious rhinosinusitis with Pseudomonas aeruginosa is common in cystic fibrosis and may result in allograft infection after lung transplantation. Sinus surgery followed by nasal care may reduce these adverse effects. Sinus surgery was performed in 37 patients with cystic fibrosis after transplantation. Bacteriology of sinus aspirates (n=771) and bronchoalveolar lavage (BAL) (n=256) was correlated with clinical data. Sinus surgery was successful in 54% and partially successful in 27% of patients. A significant correlation between negative sinus aspirates and negative BAL and between positive sinus aspirates and positive BAL (P<0.0001) was found. Successful sinus management led to a lower incidence of tracheobronchitis and pneumonia (P=0.009) and a trend toward a lower incidence of bronchiolitis obliterans syndrome (P=0.23). Sinus surgery followed by daily nasal douching may control posttransplant lower airway colonization and infection. In the long term, this concept may lead to less bronchiolitis obliterans syndrome by decreasing bronchiolar inflammation.

  19. Timing of dornase alfa inhalation for cystic fibrosis.

    PubMed

    Dentice, Ruth; Elkins, Mark

    2016-07-26

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

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

    PubMed

    Onady, Gary M; Stolfi, Adrienne

    2016-04-18

    The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/liter (125 mg/deciliter); or oral glucose tolerance tests greater than 11.11 mmol/liter (200 mg/deciliter) at two hours; or symptomatic diabetes for random glucose levels greater than 11.11 mmol/liter (200 mg/deciliter); or glycated hemoglobin levels of at least 6.5%. To establish the effectiveness of insulin and oral agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 18 February 2016. Randomized controlled trials comparing all methods of diabetes therapy in people with diagnosed cystic fibrosis-related diabetes. Two authors independently extracted data and assessed the risk of bias in the included studies. The searches identified 22 trials (34 references). Four trials (200 participants) are included: one short-term single-center trial (n = 7) comparing insulin with oral repaglinide and no medication in people with cystic fibrosis-related diabetes and normal fasting glucose; one long-term multicenter trial (n = 100, 74 of whom had cystic fibrosis-related diabetes) comparing insulin with oral repaglinide and placebo; one long-term multicenter trial (n = 73) comparing insulin with oral repaglinide; and one 12-week single-center trial (n = 20) comparing the long-acting insulin glargine to short-term neutral protamine Hagedorn

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

    PubMed

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

    2015-07-01

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

  2. Diagnosis of biofilm infections in cystic fibrosis patients.

    PubMed

    Høiby, Niels; Bjarnsholt, Thomas; Moser, Claus; Jensen, Peter Østrup; Kolpen, Mette; Qvist, Tavs; Aanaes, Kasper; Pressler, Tanja; Skov, Marianne; Ciofu, Oana

    2017-04-01

    Chronic Pseudomonas aeruginosa biofilm lung infection in cystic fibrosis patients is the best described biofilm infection in medicine. The initial focus can be the paranasal sinuses and then follows repeated colonization and infection of the lungs by aspiration. The matrix of the biofilms is dominated by alginate and the pathogenesis of tissue damage is immune complex-mediated chronic inflammation dominated by polymorphonuclear leukocytes and their products (DNA, oxygen radicals and proteases). The P. aeruginosa biofilm infection can be diagnosed by microscopy of lung tissue, sputum and mucus from the paranasal sinuses, where aggregates of the bacteria are found surrounded by the abundant alginate matrix. Specific PNA-FISH probes can be used to identify P. aeruginosa and other pathogens in situ in the biofilms. Growth of mucoid colonies from the locations mentioned above is also diagnostic for biofilm infection. Rise of specific anti-P. aeruginosa antibodies is likewise diagnostic, IgG in serum in case of lung infection, sIgA in saliva or nasal secretions in case of paranasal sinus infection. Similar approaches have been developed to diagnose chronic biofilm infections in cystic fibrosis caused by other pathogens e.g., Stenotrophomonas, Burkholderia multivorans, Achromobacter xylosoxidans and Mycobacterium abscessus complex. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  3. Vanishing bronchus intermedius syndrome in a pediatric patient with cystic fibrosis after lung transplantation.

    PubMed

    Hayes, Don; Mansour, Heidi M

    2012-12-01

    Airway complications occur frequently after lung transplantation. Bronchial stenosis is the most frequently encountered complication with the most severe form of that being the vanishing bronchus intermedius syndrome (VBIS). This rare disorder has never been reported in the pediatric population. This is the first report of VBIS in a pediatric patient, specifically a 16-yr-old male patient with cystic fibrosis whose course was complicated by a lower airway infection with Aspergillus fumigatus. The VBIS responded to bronchoscopic balloon dilation and placement of an airway stent. © 2012 John Wiley & Sons A/S.

  4. Gastrointestinal Manifestations of Cystic Fibrosis

    PubMed Central

    2016-01-01

    Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis. PMID:27330503

  5. Abnormal Ion Permeation through Cystic Fibrosis Respiratory Epithelium

    NASA Astrophysics Data System (ADS)

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

    1983-09-01

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

  6. Aspergillus fumigatus colonization in cystic fibrosis: implications for lung function?

    PubMed

    de Vrankrijker, A M M; van der Ent, C K; van Berkhout, F T; Stellato, R K; Willems, R J L; Bonten, M J M; Wolfs, T F W

    2011-09-01

    Aspergillus fumigatus is commonly found in the respiratory secretions of patients with cystic fibrosis (CF). Although allergic bronchopulmonary aspergillosis (ABPA) is associated with deterioration of lung function, the effects of A. fumigatus colonization on lung function in the absence of ABPA are not clear. This study was performed in 259 adults and children with CF, without ABPA. A. fumigatus colonization was defined as positivity of >50% of respiratory cultures in a given year. A cross-sectional analysis was performed to study clinical characteristics associated with A. fumigatus colonization. A retrospective cohort analysis was performed to study the effect of A. fumigatus colonization on lung function observed between 2002 and 2007. Longitudinal data were analysed with a linear mixed model. Sixty-one of 259 patients were at least intermittently colonized with A. fumigatus. An association was found between A. fumigatus colonization and increased age and use of inhaled antibiotics. In the longitudinal analysis, 163 patients were grouped according to duration of colonization. After adjustment for confounders, there was no significant difference in lung function between patients colonized for 0 or 1 year and patients with 2-3 or more than 3 years of colonization (p 0.40 and p 0.64) throughout the study. There was no significant difference in lung function decline between groups. Although colonization with A. fumigatus is more commonly found in patients with more severe lung disease and increased treatment burden, it is not independently associated with lower lung function or more severe lung function decline over a 5-year period. © 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.

  7. Inhaled mannitol improves lung function in cystic fibrosis.

    PubMed

    Jaques, Anna; Daviskas, Evangelia; Turton, James A; McKay, Karen; Cooper, Peter; Stirling, Robert G; Robertson, Colin F; Bye, Peter T P; LeSouëf, Peter N; Shadbolt, Bruce; Anderson, Sandra D; Charlton, Brett

    2008-06-01

    The airways in patients with cystic fibrosis (CF) are characterized by the accumulation of tenacious, dehydrated mucus that is a precursor for chronic infection, inflammation, and tissue destruction. The clearance of mucus is an integral component of daily therapy. Inhaled mannitol is an osmotic agent that increases the water content of the airway surface liquid, and improves the clearance of mucus with the potential to improve lung function and respiratory health. To this end, this study examined the efficacy and safety of therapy with inhaled mannitol over a 2-week period. This was a randomized, double-blind, placebo-controlled, crossover study. Thirty-nine subjects with mild-to-moderate CF lung disease inhaled 420 mg of mannitol or placebo twice daily for 2 weeks. Following a 2-week washout period, subjects were entered in the reciprocal treatment arm. Lung function, respiratory symptoms, quality of life, and safety were assessed. Mannitol treatment increased FEV(1) from baseline by a mean of 7.0% (95% confidence interval [CI], 3.3 to 10.7) compared to placebo 0.3% (95% CI, - 3.4 to 4.0; p < 0.001). The absolute improvement with mannitol therapy was 121 mL (95% CI, 56.3 to 185.7), which was significantly more than that with placebo (0 mL; 95% CI, - 64.7 to 64.7). The forced expiratory flow in the middle half of the FVC increased by 15.5% (95% CI, - 6.5 to 24.6) compared to that with placebo (increase, 0.7%; 95% CI, - 8.3 to 9.7; p < 0.02). The safety profile of mannitol was adequate, and no serious adverse events related to treatment were observed. Inhaled mannitol treatment over a period of 2 weeks significantly improved lung function in patients with CF. Mannitol therapy was safe and well tolerated. (ClinicalTrials.gov) Identifier: NCT00455130.

  8. Genetics Home Reference: cystic fibrosis

    MedlinePlus

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

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

    PubMed

    Johansen, Helle Krogh; Gøtzsche, Peter C

    2015-08-23

    Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. This is an update of a previously published review. To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30 March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013). Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis. The authors independently selected trials, assessed them and extracted data. Six trials were identified. Two trials were excluded since they were not randomised and one old, small trial because it was not possible to assess whether is was randomised. The three included trials comprised 483, 476 and 37 patients, respectively. No data have been published from one of the large trials, but the company stated in a press release that the trial failed to confirm the results from an earlier study and that further clinical development was suspended. In the other large trial, relative risk for chronic infection was 0.91 (95% confidence interval 0.55 to 1.49), and in the small trial, the risk was also close to one. In the large trial, one patient was reported to have died in the observation period. In that trial, 227 adverse events (4 severe) were registered in the vaccine group and 91 (1 severe) in the control group. In this large trial of a vaccine developed against flagella antigens, antibody titres against the epitopes contained in the vaccine were higher in the vaccine group compared to the placebo group (P < 0.0001). Vaccines

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

    PubMed

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

    2016-01-01

    The epidemiological and clinical management of cystic fibrosis (CF) patients suffering from acute pulmonary exacerbations or chronic lung infections demands continuous updating of medical and microbiological processes associated with the constant evolution of pathogens during host colonization. In order to monitor the dynamics of these processes, it is essential to have expert systems capable of storing and subsequently extracting the information generated from different studies of the patients and microorganisms isolated from them. In this work we have designed and developed an on-line database based on an information system that allows to store, manage and visualize data from clinical studies and microbiological analysis of bacteria obtained from the respiratory tract of patients suffering from cystic fibrosis. The information system, named Cystic Fibrosis Cloud database is available on the http://servoy.infocomsa.com/cfc_database site and is composed of a main database and a web-based interface, which uses Servoy's product architecture based on Java technology. Although the CFC database system can be implemented as a local program for private use in CF centers, it can also be used, updated and shared by different users who can access the stored information in a systematic, practical and safe manner. The implementation of the CFC database could have a significant impact on the monitoring of respiratory infections, the prevention of exacerbations, the detection of emerging organisms, and the adequacy of control strategies for lung infections in CF patients. Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Cystic Fibrosis Transmembrane Conductance Regulator Potentiation as a Therapeutic Strategy for Pulmonary Edema: A Proof-of-Concept Study in Pigs.

    PubMed

    Li, Xiaopeng; Vargas Buonfiglio, Luis G; Adam, Ryan J; Stoltz, David A; Zabner, Joseph; Comellas, Alejandro P

    2017-12-01

    To determine the feasibility of using a cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770/Kalydeco, Vertex Pharmaceuticals, Boston, MA), as a therapeutic strategy for treating pulmonary edema. Prospective laboratory animal investigation. Animal research laboratory. Newborn and 3 days to 1 week old pigs. Hydrostatic pulmonary edema was induced in pigs by acute volume overload. Ivacaftor was nebulized into the lung immediately after volume overload. Grams of water per grams of dry lung tissue were determined in the lungs harvested 1 hour after volume overload. Ivacaftor significantly improved alveolar liquid clearance in isolated pig lung lobes ex vivo and reduced edema in a volume overload in vivo pig model of hydrostatic pulmonary edema. To model hydrostatic pressure-induced edema in vitro, we developed a method of applied pressure to the basolateral surface of alveolar epithelia. Elevated hydrostatic pressure resulted in decreased cystic fibrosis transmembrane conductance regulator activity and liquid absorption, an effect which was partially reversed by cystic fibrosis transmembrane conductance regulator potentiation with ivacaftor. Cystic fibrosis transmembrane conductance regulator potentiation by ivacaftor is a novel therapeutic approach for pulmonary edema.

  12. Combined double lung-liver transplantation for cystic fibrosis without cardio-pulmonary by-pass.

    PubMed

    Corno, V; Dezza, M C; Lucianetti, A; Codazzi, D; Carrara, B; Pinelli, D; Parigi, P C; Guizzetti, M; Strazzabosco, M; Melzi, M L; Gaffuri, G; Sonzogni, V; Rossi, A; Fagiuoli, S; Colledan, M

    2007-10-01

    Sequential bilateral single lung-liver transplantation (SBSL-LTx) is a therapeutic option for patients with end stage lung and liver disease (ESLLD) due to cystic fibrosis (CF). A few cases have been reported, all of them were performed with the use of cardio-pulmonary by-pass (CPB). We performed SBSL-LTx in three young men affected by CF. All the recipients had respiratory failure and portal hypertension with hypersplenism. Along with lung transplants, two patients received a whole liver graft and one an extended right graft from an in situ split liver. During transplantation neither CPB nor veno-venous by-pass (VVB) were employed. Immunosuppression was based on basiliximab, tacrolimus, steroids and azathioprine. The three recipients are alive with a median follow-up of 670 days (range 244-1,533). Combined SBSL-LTx is a complex but effective procedure for the treatment of ESLLD due to CF, not necessarily requiring the use of CPB or VVB.

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

    MedlinePlus

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

  14. Vitamin A supplementation for cystic fibrosis.

    PubMed

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

    2012-08-15

    People with cystic fibrosis and pancreatic insufficiency are at risk of fat soluble vitamin deficiency as these vitamins (A, D, E and K) are co-absorbed with fat. Thus, some cystic fibrosis centres routinely administer these vitamins as supplements but the centres vary in their approach of addressing the possible development of deficiencies in these vitamins. Vitamin A deficiency causes predominantly eye and skin problems while supplementation of vitamin A to excessive levels may cause harm to the respiratory and skeletal systems in children. Thus a systematic review on vitamin A supplementation in people with cystic fibrosis would help guide clinical practice. To determine if vitamin A supplementation in children and adults with CF: 1. reduces the frequency of vitamin A deficiency disorders; 2. improves general and respiratory health; 3. increases the frequency of vitamin A toxicity. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 23 May 2012. All randomised or quasi-randomised controlled trials comparing all preparations of oral vitamin A used as a supplement compared to either no supplementation (or placebo) at any dose and for any duration, in children or adults with cystic fibrosis (defined by sweat tests or genetic testing) with and without pancreatic insufficiency. No relevant studies for inclusion were identified in the search. No studies were included in this review. As there were no randomised or quasi-randomised controlled trials identified, we cannot draw any conclusions on the benefits (or otherwise) of regular administration of vitamin A in people with cystic fibrosis. Until further data are available, country or region specific guidelines on the use of vitamin A in

  15. Lung transplantation for cystic fibrosis: results, indications, complications, and controversies.

    PubMed

    Lynch, Joseph P; Sayah, David M; Belperio, John A; Weigt, S Sam

    2015-04-01

    Survival in patients with cystic fibrosis (CF) has improved dramatically over the past 30 to 40 years, with mean survival now approximately 40 years. Nonetheless, progressive respiratory insufficiency remains the major cause of mortality in CF patients, and lung transplantation (LT) is eventually required. Timing of listing for LT is critical, because up to 25 to 41% of CF patients have died while awaiting LT. Globally, approximately 16.4% of lung transplants are performed in adults with CF. Survival rates for LT recipients with CF are superior to other indications, yet LT is associated with substantial morbidity and mortality (∼50% at 5-year survival rates). Myriad complications of LT include allograft failure (acute or chronic), opportunistic infections, and complications of chronic immunosuppressive medications (including malignancy). Determining which patients are candidates for LT is difficult, and survival benefit remains uncertain. In this review, we discuss when LT should be considered, criteria for identifying candidates, contraindications to LT, results post-LT, and specific complications that may be associated with LT. Infectious complications that may complicate CF (particularly Burkholderia cepacia spp., opportunistic fungi, and nontuberculous mycobacteria) are discussed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  16. Lung Transplantation for Cystic Fibrosis: Results, Indications, Complications, and Controversies

    PubMed Central

    Lynch, Joseph P.; Sayah, David M.; Belperio, John A.; Weigt, S. Sam

    2016-01-01

    Survival in patients with cystic fibrosis (CF) has improved dramatically over the past 30 to 40 years, with mean survival now approximately 40 years. Nonetheless, progressive respiratory insufficiency remains the major cause of mortality in CF patients, and lung transplantation (LT) is eventually required. Timing of listing for LT is critical, because up to 25 to 41% of CF patients have died while awaiting LT. Globally, approximately 16.4% of lung transplants are performed in adults with CF. Survival rates for LT recipients with CF are superior to other indications, yet LT is associated with substantial morbidity and mortality (~50% at 5-year survival rates). Myriad complications of LT include allograft failure (acute or chronic), opportunistic infections, and complications of chronic immunosuppressive medications (including malignancy). Determining which patients are candidates for LT is difficult, and survival benefit remains uncertain. In this review, we discuss when LT should be considered, criteria for identifying candidates, contraindications to LT, results post-LT, and specific complications that may be associated with LT. Infectious complications that may complicate CF (particularly Burkholderia cepacia spp., opportunistic fungi, and nontuberculous mycobacteria) are discussed. PMID:25826595

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

    PubMed

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

    2014-06-18

    cover interventions with generic approaches, as well as interventions developed specifically to target disease-specific symptoms and problems in people with cystic fibrosis. These include cognitive behavioural interventions to improve adherence to nutrition or psychosocial adjustment, cognitive interventions to improve adherence or those associated with decision making in lung transplantation, a community-based support intervention and other interventions, such as self-hypnosis, respiratory muscle biofeedback, music therapy, dance and movement therapy, and a tele-medicine intervention to support patients awaiting transplantation.A substantial proportion of outcomes relate to adherence, changes in physical status or other specific treatment concerns during the chronic phase of the disease.There is some evidence that behavioural interventions targeting nutrition and growth in children (4 to 12 years) with cystic fibrosis are effective in the short term. Evidence was found that providing a structured decision-making tool for patients considering lung transplantation improves patients' knowledge of and expectations about the transplant, and reduces decisional conflict in the short term. One study about training in biofeedback-assisted breathing demonstrated some evidence that it improved some lung function measurements. Currently there is insufficient evidence for interventions aimed at other aspects of the disease process. Currently, insufficient evidence exists on psychological interventions or approaches to support people with cystic fibrosis and their caregivers, although some of the studies were promising. Due to the heterogeneity between studies, more of each type of intervention are needed to support preliminary evidence. Multicentre studies, with consequent funding implications, are needed to increase the sample size of these studies and enhance the statistical power and precision to detect important findings. In addition, multicentre studies could improve the

  18. NonTuberculous Mycobacteria infection and lung transplantation in cystic fibrosis: a worldwide survey of clinical practice.

    PubMed

    Tissot, Adrien; Thomas, Matthew F; Corris, Paul A; Brodlie, Malcolm

    2018-05-22

    In people with cystic fibrosis infection with NonTuberculous Mycobacteria is of increasing prevalence. Mycobacterium abscessus complex is of particular concern and has been associated with adverse clinical outcomes. Optimal treatment usually requires multiple antibiotics for over 12 months. When considering lung transplantation for patients with NonTuberculous Mycobacteria potential benefits must be balanced against the risks of uncontrolled infection post-transplant and significant side-effects associated with treatment. In this survey we assessed current international practice with regard to assessing and listing patients for lung transplantation. We designed a questionnaire enquiring about local practice regarding screening for NonTuberculous Mycobacteria infection, specific contra-indications to transplantation, management and segregation of patients pre- and post-transplant. The survey was sent via e-mail to 37 paediatric and adult lung transplant centres across Europe, North America and Australia. We gathered complete questionnaires from 21 centres (57% response rate). Few centres (29%) have a clear written policy regarding NonTuberculous Mycobacteria. Sixteen (76%) centres require molecular identification of NonTuberculous Mycobacteria species. Only four centres would consider infection with M. abscessus complex in itself a contra-indication for listing, however 76% regard it as a relative contra-indication. Eighty-six percent require treatment pre-transplantation. Finally, only 61% of centres had a clear policy regarding segration of patients pre-transplant and 48% post-transplant. The issue of NonTuberculous Mycobacteria infection in people with cystic fibrosis requiring lung transplantation is well-recognized however current international recommendations are not detailed and there is variation in practice between centres. There is an urgent requirement for high quality clinical data to inform decision-making.

  19. Successful prevention of scedosporiosis after lung transplantation in a cystic fibrosis patient by combined local and systemic triazole therapy☆

    PubMed Central

    Hartmann, Carolin; Müller, Carsten; Weißbrodt, Hartmut; Suerbaum, Sebastian; Tintelnot, Kathrin; Stolle, Stefan; Hansen, Gesine; Sedlacek, Ludwig

    2013-01-01

    A persistent colonization with Scedosporium apiospermum (S. apiospermum) often results in disseminated infection with a high mortality rate in immunosuppressed patients. We present the first case of successful prevention of scedosporiosis in an adolescent female cystic fibrosis patient post double lung transplant, with a combination of local and systemic voriconazole therapy and surgical intervention. PMID:24432232

  20. Chloride impermeability in cystic fibrosis

    NASA Astrophysics Data System (ADS)

    Quinton, Paul M.

    1983-02-01

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

  1. Effects of sinus surgery on lung transplantation outcomes in cystic fibrosis.

    PubMed

    Leung, Man-Kit; Rachakonda, Leelanand; Weill, David; Hwang, Peter H

    2008-01-01

    In cystic fibrosis (CF) patients who are candidates for lung transplant, pretransplant sinus surgery has been advocated to avoid bacterial seeding of the transplanted lungs. This study reviews the 17-year experience of pretransplant sinus surgery among CF patients at a major transplant center. Retrospective chart review was performed in all CF patients who underwent heart-lung or lung transplantation at Stanford Medical Center between 1988 and 2005. Postoperative culture data from bronchoalveolar lavage (BAL) and sinus aspirates were evaluated, in addition to survival data. Eighty-seven CF transplant recipients underwent pretransplant sinus surgery; 87% (n=59/68) of patients showed recolonization of the lung grafts with Pseudomonas on BAL cultures. The median postoperative time to recolonization was 19 days. Bacterial floras cultured from sinuses were similar in type and prevalence as the floras cultured from BAL. When compared with published series of comparable cohorts in which pretransplant sinus surgery was not performed, there was no statistically significant difference in the prevalence of Pseudomonas recolonization. Times to recolonization also were similar. Survival rates in our cohort were similar to national survival rates for CF lung transplant recipients. Despite pretransplant sinus surgery, recolonization of lung grafts occurs commonly and rapidly with a spectrum of flora that mimics the sinus flora. Survival rates of CF patients who undergo prophylactic sinus surgery are similar to those from centers where prophylactic sinus surgery is not performed routinely. Pretransplant sinus surgery does not appear to prevent lung graft recolonization and is not associated with overall survival benefit.

  2. Sleep quality and daytime function in adults with cystic fibrosis and severe lung disease.

    PubMed

    Dancey, D R; Tullis, E D; Heslegrave, R; Thornley, K; Hanly, P J

    2002-03-01

    It was hypothesized that adult cystic fibrosis (CF) patients with severe lung disease have impaired daytime function related to nocturnal hypoxaemia and sleep disruption. Nineteen CF patients (forced expiratory volume in one second 28+/-7% predicted) and 10 healthy subjects completed sleep diaries, overnight polysomnography (PSG), and assessment of daytime sleepiness and neurocognitive function. CF patients tended to report more awakenings (0.7+/-0.5 versus 0.3+/-0.2 x h(-1), p=0.08), and PSG revealed reduced sleep efficiency (71+/-25 versus 93+/-4%, p=0.004) and a higher frequency of awakenings (4.2+/-2.7 versus 2.4+/-1.4 x h(-1), p=0.06). Mean arterial oxygen saturation during sleep was lower in CF patients (84.4+/-6.8 versus 94.3+/-1.5%, p<0.0001) and was associated with reduced sleep efficiency (regression coefficient (r)=0.57, p=0.014). CF patients had short sleep latency on the multiple sleep latency test (6.7+/-3 min). The CF group reported lower levels of activation and happiness and greater levels of fatigue (p<0.01), which correlated with indices of sleep loss, such as sleep efficiency (r=0.47, p=10.05). Objective neurocognitive performance was also impaired in CF patients, reflected by lower throughput for simple addition/subtraction, serial reaction and colour-word conflict. The authors concluded that adult cystic fibrosis patients with severe lung disease have impaired neurocognitive function and daytime sleepiness, which is partly related to chronic sleep loss and nocturnal hypoxaemia.

  3. Cystic Fibrosis (CF) Respiratory Screen: Sputum

    MedlinePlus

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

  4. Airway mucosal bioelectric potential difference in cystic fibrosis after lung transplantation.

    PubMed

    Wood, A; Higenbottam, T; Jackson, M; Scott, J; Stewart, S; Wallwork, J

    1989-12-01

    Bioelectrical potential difference (PD) across the respiratory mucosa is raised in cystic fibrosis (CF). We have recorded airway potentials from seven patients with CF who had undergone heart-lung transplantation and from eight patients without CF who had had transplants for cardiovascular disease; comparison of these populations controls for the effects of denervation and immunosuppressive treatment. Six patients without CF who had not had transplants formed an additional control. PD was recorded during routine fiberoptic bronchoscopy, using a Ringer's-perfused exploring bridge connected across a high impedance amplifier to an intravenous reference bridge. Bronchial lavage and sputum culture revealed no evidence of infection. Bronchial PD was similar in all three groups of patients at equivalent sites. However, nasal PD was raised in the CF group (mean value, 44 mV +/- 3.9 SE) compared with the patients who had transplants for cardiovascular disease (mean, 18 mV +/- 1.1 SE), and the control patients (mean, 15 mV +/- 1.2 SE). We conclude that the epithelial defects that result in raised airway potentials in CF do not recur in the transplanted lung.

  5. Comparative biology of cystic fibrosis animal models.

    PubMed

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

    2011-01-01

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

  6. Doxycycline improves clinical outcomes during cystic fibrosis exacerbations.

    PubMed

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

    2017-04-01

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

  7. Molecular diagnosis of cystic fibrosis.

    PubMed

    Shrimpton, Antony E

    2002-05-01

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

  8. Cystic fibrosis screening in assisted reproduction.

    PubMed

    Gazvani, Rafet; Lewis-Jones, Iwan

    2006-06-01

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

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

    PubMed

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

    2016-01-01

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

  10. Vitamin D supplementation for cystic fibrosis.

    PubMed

    Ferguson, Janet H; Chang, Anne B

    2014-05-14

    -blind randomised cross-over study; only nine children who completed both vitamin D and placebo groups after six-months supplementation and a three-month washout period are included; pancreatic sufficiency or disease status of participants are not defined. The studies are not directly comparable due to differences in supplementation, outcome reporting and possibly participant characteristics (e.g. severity of lung disease, growth and nutrition, pancreatic sufficiency).The only outcome for which we could combine data from more than two studies was 25-hydroxyvitamin D levels; patients receiving vitamin D supplementation had significantly higher levels, mean difference 7.24 ng/ml (95% confidence interval 5.01 to 9.46). However, ironically one study reported 1,25(OH)2D with levels significantly favouring the placebo group, mean difference -30.30 pmol/ml (95% confidence interval -59.89 to -0.71). Bone mineral density was measured in two studies; both described no significant change between groups. There were no adverse events in any study.The remaining three studies are published as abstracts only and did not provide data for analysis. These abstracts include: a report of pre-intervention data in a study comparing daily calcitriol (0.25 or 0.5 micrograms) with placebo in pancreatic insufficient children and young adults; an interim report of a double-blind randomised control study comparing 5000 IU vitamin D daily for 12 weeks during winter in 67 adult cystic fibrosis patients; and a comparison of the effect of three months of vitamin D supplementation (dose not specified) with placebo on bone mineral density in 42 children with cystic fibrosis and low bone mineral density.Risk of bias was highly variable between all studies. Only one study had a low risk of bias for the five main criteria (random sequence generation, allocation, blinding, attrition and reporting). The rest of the studies had unclear or high risks of bias. Two studies had a low risk of bias for blinding and another two

  11. Supine posture changes lung volumes and increases ventilation heterogeneity in cystic fibrosis.

    PubMed

    Smith, Laurie J; Macleod, Kenneth A; Collier, Guilhem J; Horn, Felix C; Sheridan, Helen; Aldag, Ina; Taylor, Chris J; Cunningham, Steve; Wild, Jim M; Horsley, Alex

    2017-01-01

    Lung Clearance Index (LCI) is recognised as an early marker of cystic fibrosis (CF) lung disease. The effect of posture on LCI however is important when considering longitudinal measurements from infancy and when comparing LCI to imaging studies. 35 children with CF and 28 healthy controls (HC) were assessed. Multiple breath washout (MBW) was performed both sitting and supine in triplicate and analysed for LCI, Scond, Sacin, and lung volumes. These values were also corrected for the Fowler dead-space to create 'alveolar' indices. From sitting to supine there was a significant increase in LCI and a significant decrease in FRC for both CF and HC (p<0.01). LCI, when adjusted to estimate 'alveolar' LCI (LCIalv), increased the magnitude of change with posture for both LCIalv and FRCalv in both groups, with a greater effect of change in lung volume in HC compared with children with CF. The % change in LCIalv for all subjects correlated significantly with lung volume % changes, most notably tidal volume/functional residual capacity (Vtalv/FRCalv (r = 0.54,p<0.001)). There is a significant increase in LCI from sitting to supine, which we believe to be in part due to changes in lung volume and also increasing ventilation heterogeneity related to posture. This may have implications in longitudinal measurements from infancy to older childhood and for studies comparing supine imaging methods to LCI.

  12. Inhaled mannitol for cystic fibrosis.

    PubMed

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

    2015-10-09

    -term cross-over study supplied additional results. The fourth study compared mannitol to dornase alfa alone and to mannitol plus dornase alfa. There was generally a low risk of bias in relation to randomisation and blinding; evidence from the parallel studies was judged to be of low to moderate quality and from the cross-over studies was judged to be of low to very low quality. While the published papers did not provide all the data required for our analysis, additional unpublished data were provided by the drug's manufacturer and the author of one of the studies. There was an initial test to see if participants tolerated mannitol, with only those who could tolerate the drug being randomised to the studies; therefore the study results are not applicable to the cystic fibrosis population as a whole.For the comparison of mannitol and control, we found no consistent differences in health-related quality of life in any of the domains, except for burden of treatment, which was less for mannitol up to four months in the two pooled studies of a similar design; this difference was not maintained at six months. Up to and including six months, lung function in terms of forced expiratory volume at one second (millilitres) and per cent predicted were significantly improved in all three studies comparing mannitol to control. Beneficial results were observed in these studies in adults and in both concomitant dornase alfa users and non users. A significant reduction was shown in the incidence of pulmonary exacerbations in favour of mannitol at six months; however, the estimate of this effect was imprecise so it is unclear whether the effect is clinically meaningful. Cough, haemoptysis, bronchospasm, pharyngolaryngeal pain and post-tussive vomiting were the most commonly reported side effects on both treatments. Mannitol was not associated with any increase in isolation of bacteria over a six-month period.In the 12-week cross-over study (28 participants), no significant differences were

  13. Cystic Fibrosis: Microbiology and Host Response.

    PubMed

    Zemanick, Edith T; Hoffman, Lucas R

    2016-08-01

    The earliest descriptions of lung disease in people with cystic fibrosis (CF) showed the involvement of 3 interacting pathophysiologic elements in CF airways: mucus obstruction, inflammation, and infection. Over the past 7 decades, our understanding of CF respiratory microbiology and inflammation has evolved with the introduction of new treatments, increased longevity, and increasingly sophisticated laboratory techniques. This article reviews the current understanding of infection and inflammation and their roles in CF lung disease. It also discusses how this constantly evolving information is used to inform current therapeutic strategies, measures and predictors of disease severity, and research priorities. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. CYSTIC FIBROSIS: MICROBIOLOGY AND HOST RESPONSE

    PubMed Central

    Zemanick, Edith T.

    2016-01-01

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

  15. Lung Transplantation in Cystic Fibrosis and the Impact of Extracorporeal Circulation.

    PubMed

    Jauregui, Alberto; Deu, Maria; Romero, Laura; Roman, Antonio; Moreno, Antonio; Armengol, Manuel; Solé, Juan

    2018-03-10

    Lung disease is the major cause of death among cystic fibrosis (CF) patients, affecting 80% of the population. The impact of extracorporeal circulation (ECC) during transplantation has not been fully clarified. This study aimed to evaluate the outcomes of lung transplantation for CF in a single center, and to assess the impact of ECC on survival. We performed a retrospective observational study of all trasplanted CF patients in a single center between 1992 and 2011. During this period, 64 lung transplantations for CF were performed. Five- and 10-year survival of trasplanted patients was 56.7% and 41.3%, respectively. Pre-transplantation supplemental oxygen requirements and non-invasive mechanical ventilation (NIMV) do not seem to affect survival (P=.44 and P=.63, respectively). Five- and 10-year survival among patients who did not undergo ECC during transplantation was 75.69% and 49.06%, respectively, while in those did undergo ECC during the procedure, 5- and 10-year survival was 34.14% and 29.87%, respectively (P=.001). PaCO 2 is an independent risk factor for the need for ECC. The survival rates of CF patients undergoing lung transplantation in our hospital are similar to those described in international registries. Survival is lower among patients receiving ECC during the procedure. PaCO 2 is a risk factor for the need for ECC during lung transplantation. Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Changing epidemiology of non-cystic fibrosis bronchiectasis.

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  19. Consequences of Expiratory Flow Limitation at Rest in Subjects with Cystic Fibrosis.

    PubMed

    Vilozni, Daphna; Lavie, Moran; Ofek, Miryam; Sarouk, Ifat; Bar-Aluma, Bat-El; Dagan, Adi; Ashkenazi, Moshe; Segel, Michael J; Efrati, Ori

    2016-06-01

    Expiratory flow limitation at resting tidal volume (EFLTV) presents a severe mechanical constraint in chronic lung diseases and has not yet been studied longitudinally in cystic fibrosis. To study the effect of EFLTV as it emerged from simple spirometry on lung function and clinical status in cystic fibrosis. Best year spirometry that included tidal flow/volume curves and the related clinical data were retrospectively collected over 12 ± 3.0 yr/person from 108 subjects with cystic fibrosis. The year in which forced expiratory flow, midexpiratory phase (FEF25-75%, L/s) was equal to tidal peak expiratory flow (L/s) was defined as EFLTV-onset year. EFLTV occurred in 55 (51%) subjects, at age 23 ± 6 years. At EFLTV onset, tidal peak expiratory flow and FEF25-75% values were 1.44 ± 0.23 L/s and FEV1 was 62 ± 10% predicted. Within the following 2 years, FEV1 dropped to 48 ± 11% predicted, and 35 (63%) of the subjects reported shortness of breath at rest. Hospital days increased from 5.3 ± 24.6 to 24.12 ± 9.0 d/yr (P = 0.0001). Of the 55 subjects, 29 (53%) received transplant or died, with survival time being 6.9 ± 3.9 years. EFLTV onset may be an important pathophysiological event that could influence the natural history of lung function decline in subjects with cystic fibrosis. This may lead to a significant deterioration in lung function in the following 2 years alongside an increase in the number of hospitalization days. The monitoring of FEV1 alone does not offer as good a threshold signal, because values are only moderately reduced. Therefore, identifying EFLTV appearance is potentially a signal for therapeutic intervention. Further studies are warranted to confirm our findings.

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

    PubMed

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

    2016-09-01

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

  1. Intestinal bile acid malabsorption in cystic fibrosis.

    PubMed

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

    1993-08-01

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

  2. Intestinal bile acid malabsorption in cystic fibrosis.

    PubMed Central

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

    1993-01-01

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

  3. Pregnancy and cystic fibrosis: Approach to contemporary management

    PubMed Central

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

    2014-01-01

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

  4. Detection of early subclinical lung disease in children with cystic fibrosis by lung ventilation imaging with hyperpolarised gas MRI.

    PubMed

    Marshall, Helen; Horsley, Alex; Taylor, Chris J; Smith, Laurie; Hughes, David; Horn, Felix C; Swift, Andrew J; Parra-Robles, Juan; Hughes, Paul J; Norquay, Graham; Stewart, Neil J; Collier, Guilhem J; Teare, Dawn; Cunningham, Steve; Aldag, Ina; Wild, Jim M

    2017-08-01

    Hyperpolarised 3 He ventilation-MRI, anatomical lung MRI, lung clearance index (LCI), low-dose CT and spirometry were performed on 19 children (6-16 years) with clinically stable mild cystic fibrosis (CF) (FEV 1 >-1.96), and 10 controls. All controls had normal spirometry, MRI and LCI. Ventilation-MRI was the most sensitive method of detecting abnormalities, present in 89% of patients with CF, compared with CT abnormalities in 68%, LCI 47% and conventional MRI 22%. Ventilation defects were present in the absence of CT abnormalities and in patients with normal physiology, including LCI. Ventilation-MRI is thus feasible in young children, highly sensitive and provides additional information about lung structure-function relationships. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  5. Year to year change in FEV1 in patients with cystic fibrosis and different mutation classes.

    PubMed

    De Boeck, K; Zolin, A

    2017-03-01

    In patients with cystic fibrosis, most treatments addressing the underlying basic defect are mutation or mutation class specific. These treatments are disease modifying if they lower the year to year change in lung function. We therefore calculated the current loss of lung function, measured by year to year change in forced expired volume in 1s in 11,417 patients included in the European Cystic Fibrosis Society Patient Registry. Whereas patients with at least one mutation of class IV or V have on average a lower year to year change, we did not find a difference between patients with a stop codon mutation, homozygous for F508del or at least one class III mutation. These data are useful background information to discuss the impact of different disease modifying treatments. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  6. Singing for children and adults with cystic fibrosis.

    PubMed

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

    2010-05-12

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

  7. Direct sampling of cystic fibrosis lungs indicates that DNA-based analyses of upper-airway specimens can misrepresent lung microbiota.

    PubMed

    Goddard, Amanda F; Staudinger, Benjamin J; Dowd, Scot E; Joshi-Datar, Amruta; Wolcott, Randall D; Aitken, Moira L; Fligner, Corinne L; Singh, Pradeep K

    2012-08-21

    Recent work using culture-independent methods suggests that the lungs of cystic fibrosis (CF) patients harbor a vast array of bacteria not conventionally implicated in CF lung disease. However, sampling lung secretions in living subjects requires that expectorated specimens or collection devices pass through the oropharynx. Thus, contamination could confound results. Here, we compared culture-independent analyses of throat and sputum specimens to samples directly obtained from the lungs at the time of transplantation. We found that CF lungs with advanced disease contained relatively homogenous populations of typical CF pathogens. In contrast, upper-airway specimens from the same subjects contained higher levels of microbial diversity and organisms not typically considered CF pathogens. Furthermore, sputum exhibited day-to-day variation in the abundance of nontypical organisms, even in the absence of clinical changes. These findings suggest that oropharyngeal contamination could limit the accuracy of DNA-based measurements on upper-airway specimens. This work highlights the importance of sampling procedures for microbiome studies and suggests that methods that account for contamination are needed when DNA-based methods are used on clinical specimens.

  8. A Novel Lung Disease Phenotype Adjusted for Mortality Attrition for Cystic Fibrosis Genetic Modifier Studies

    PubMed Central

    Taylor, Chelsea; Commander, Clayton W.; Collaco, Joseph M.; Strug, Lisa J.; Li, Weili; Wright, Fred A.; Webel, Aaron D.; Pace, Rhonda G.; Stonebraker, Jaclyn R.; Naughton, Kathleen; Dorfman, Ruslan; Sandford, Andrew; Blackman, Scott M.; Berthiaume, Yves; Paré, Peter; Drumm, Mitchell L.; Zielenski, Julian; Durie, Peter; Cutting, Garry R.; Knowles, Michael R.; Corey, Mary

    2011-01-01

    SUMMARY Genetic studies of lung disease in Cystic Fibrosis are hampered by the lack of a severity measure that accounts for chronic disease progression and mortality attrition. Further, combining analyses across studies requires common phenotypes that are robust to study design and patient ascertainment. Using data from the North American Cystic Fibrosis Modifier Consortium (Canadian Consortium for CF Genetic Studies, Johns Hopkins University CF Twin and Sibling Study, and University of North Carolina/Case Western Reserve University Gene Modifier Study), the authors calculated age-specific CF percentile values of FEV1 which were adjusted for CF age-specific mortality data. The phenotype was computed for 2061 patients representing the Canadian CF population, 1137 extreme phenotype patients in the UNC/Case Western study, and 1323 patients from multiple CF sib families in the CF Twin and Sibling Study. Despite differences in ascertainment and median age, our phenotype score was distributed in all three samples in a manner consistent with ascertainment differences, reflecting the lung disease severity of each individual in the underlying population. The new phenotype score was highly correlated with the previously recommended complex phenotype, but the new phenotype is more robust for shorter follow-up and for extreme ages. A disease progression and mortality adjusted phenotype reduces the need for stratification or additional covariates, increasing statistical power and avoiding possible distortions. This approach will facilitate large scale genetic and environmental epidemiological studies which will provide targeted therapeutic pathways for the clinical benefit of patients with CF. PMID:21462361

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

    PubMed

    Kessler, L; Abély, M

    2016-12-01

    The exocrine pancreatic insufficiency affects more than 80% of cystic fibrosis (CF) infants. Pancreatic insufficiency is diagnosed by low levels of fecal elastase. An optimal caloric intake, a pancreatic enzyme treatment are the keys to maintain a good nutritional status. The fat soluble vitamins supplementation will be associated with pancreatic enzymes treatment and will be adapted to plasma levels. Iron and oligo-element deficiency such as zinc is common. The pancreatic enzymes function is not optimal in the proximal bowel: the intraluminal intestinal pH is low because of the absence of bicarbonate release by the pancreas. The use of proton pump inhibitors may improve the functionality of pancreatic enzymes treatment. New therapies such as ivacaftor in patients with a G551D mutation allows a weight gain in particular by restoring intestinal pH similar to controls. Lengthening of the life expectancy of patients with CF is accompanied by the emergence new aspects of the disease, especially diabetes, favored by pancreatic cystic fibrosis resulting in an anatomical destruction of pancreatic islets. Currently, diabetes affects a third of the patients after 20 years, and half after 30 years. Cystic fibrosis-related diabetes is a major factor of morbidity-mortality in all stages of the disease and is characterized by a preclinical phase of glucose intolerance particularly long reaching up to 10 years. Its pathophysiology combines a lack of insulin secretion, an insulin resistance secondary to chronic infection, and a decrease in the production of the GIP and GLP-1. The insulin secretion depending on the channel chlorine (Cystic Fibrosis Transmembrane conductance Regulator [CFTR]) activity at the membrane surface of insulin cell is reduced prior to the occurrence of pancreatic histological lesions. At the stage of diabetes, obtaining a normoglycemia by insulin treatment began very early allows to slow the decline of lung function and nutritional status. Given the silent

  10. Infection, inflammation, and lung function decline in infants with cystic fibrosis.

    PubMed

    Pillarisetti, Naveen; Williamson, Elizabeth; Linnane, Barry; Skoric, Billy; Robertson, Colin F; Robinson, Phil; Massie, John; Hall, Graham L; Sly, Peter; Stick, Stephen; Ranganathan, Sarath

    2011-07-01

    Better understanding of evolution of lung function in infants with cystic fibrosis (CF) and its association with pulmonary inflammation and infection is crucial in informing both early intervention studies aimed at limiting lung damage and the role of lung function as outcomes in such studies. To describe longitudinal change in lung function in infants with CF and its association with pulmonary infection and inflammation. Infants diagnosed after newborn screening or clinical presentation were recruited prospectively. FVC, forced expiratory volume in 0.5 seconds (FEV(0.5)), and forced expiratory flows at 75% of exhaled vital capacity (FEF(75)) were measured using the raised-volume technique, and z-scores were calculated from published reference equations. Pulmonary infection and inflammation were measured in bronchoalveolar lavage within 48 hours of lung function testing. Thirty-seven infants had at least two successful repeat lung function measurements. Mean (SD) z-scores for FVC were -0.8 (1.0), -0.9 (1.1), and -1.7 (1.2) when measured at the first visit, 1-year visit, or 2-year visit, respectively. Mean (SD) z-scores for FEV(0.5) were -1.4 (1.2), -2.4 (1.1), and -4.3 (1.6), respectively. In those infants in whom free neutrophil elastase was detected, FVC z-scores were 0.81 lower (P=0.003), and FEV(0.5) z-scores 0.96 lower (P=0.001), respectively. Significantly greater decline in FEV(0.5) z-scores occurred in those infected with Staphylococcus aureus (P=0.018) or Pseudomonas aeruginosa (P=0.021). In infants with CF, pulmonary inflammation is associated with lower lung function, whereas pulmonary infection is associated with a greater rate of decline in lung function. Strategies targeting pulmonary inflammation and infection are required to prevent early decline in lung function in infants with CF.

  11. Microbiome in the pathogenesis of cystic fibrosis and lung transplant-related disease.

    PubMed

    Cribbs, Sushma K; Beck, James M

    2017-01-01

    Significant advances in culture-independent methods have expanded our knowledge about the diversity of the lung microbial environment. Complex microorganisms and microbial communities can now be identified in the distal airways in a variety of respiratory diseases, including cystic fibrosis (CF) and the posttransplantation lung. Although there are significant methodologic concerns about sampling the lung microbiome, several studies have now shown that the microbiome of the lower respiratory tract is distinct from the upper airway. CF is a disease characterized by chronic airway infections that lead to significant morbidity and mortality. Traditional culture-dependent methods have identified a select group of pathogens that cause exacerbations in CF, but studies using bacterial 16S rRNA gene-based microarrays have shown that the CF microbiome is an intricate and dynamic bacterial ecosystem, which influences both host immune health and disease pathogenesis. These microbial communities can shift with external influences, including antibiotic exposure. In addition, there have been a number of studies suggesting a link between the gut microbiome and respiratory health in CF. Compared with CF, there is significantly less knowledge about the microbiome of the transplanted lung. Risk factors for bronchiolitis obliterans syndrome, one of the leading causes of death, include microbial infections. Lung transplant patients have a unique lung microbiome that is different than the pretransplanted microbiome and changes with time. Understanding the host-pathogen interactions in these diseases may suggest targeted therapies and improve long-term survival in these patients. Published by Elsevier Inc.

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

    PubMed

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

    2013-06-05

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

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

    PubMed

    Moss, Richard B

    2015-04-01

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

  14. Outcome of heart-lung and bilateral sequential lung transplantation for cystic fibrosis: a UK national study.

    PubMed

    Ganesh, J S; Rogers, C A; Bonser, R S; Banner, N R

    2005-06-01

    Cystic fibrosis (CF) patients requiring transplantation for respiratory failure may undergo either heart-lung (HLT) or bilateral sequential lung (BSLT) transplantation. The choice of operation varies between surgeons, centres and countries. The current authors investigated whether operation type influenced outcome in adult CF patients transplanted in the UK between July 1995 and June 2002. Propensity scores for receipt of BSLT versus HLT were derived using logistic regression. Cox regression was used to compare survival. In total, 88 BSLTs and 93 HLTs were identified. Patient characteristics were similar overall, but HLT recipients were more likely to be on long-term oxygen therapy and to have had prior resuscitation. There were 72 deaths (29 BSLT and 43 HLT) within 4 yrs. There was a trend towards higher unadjusted survival following BSLT, but, after adjustment, no difference was found (hazard ratio = 0.77; 95% confidence interval 0.29-2.06). Time to the first rejection episode and infection rates were also similar. A total of 82% of hearts from HLT recipients were used as domino heart transplants. In conclusion, after adjusting for comorbidity, donor factors and ischaemia time, it was found that heart-lung and bilateral sequential lung transplantation achieved a similar outcome. The use of domino heart transplantation ameliorated the impact of heart-lung transplantation on total organ availability.

  15. Patient factors associated with lung transplant referral and waitlist for patients with cystic fibrosis and pulmonary fibrosis.

    PubMed

    Liu, Yuan; Vela, Monica; Rudakevych, Tanya; Wigfield, Christopher; Garrity, Edward; Saunders, Milda R

    2017-03-01

    Since 2005, the Lung Allocation Score (LAS) has prioritized patient benefit and post-transplant survival, reducing waitlist to transplant time to <200 days and decreasing mortality on the waitlist. A current challenge is the wait for the waitlist-the time between the patient's transplant-eligible diagnosis and waitlist registration. We investigated whether sociodemographic (age, sex, race, insurance, marital status, median household income) and clinical (forced expiratory volume in 1 second [FEV 1 ] percent of predicted, body mass index, depression/anxiety, alcohol/substance misuse, absolute/relative contraindications) factors influenced referral and waitlist registration. We conducted a retrospective cohort study through chart review of hospitalized patients on the University of Chicago general medicine service from 2006 to 2014 who met transplant-eligible criteria and ICD-9 billing codes for cystic fibrosis (CF) and pulmonary fibrosis (PF). We analyzed the times from transplant eligibility to referral, work-up and waitlisting using Kaplan-Meier curves and log-rank tests. Overall, the referral rate for transplant-eligible patients was 64%. Of those referred, approximately 36% reach the lung transplant waitlist. Referred CF patients were significantly more likely to reach the transplant waitlist than PF patients (CF 60% vs PF 22%, p < 0.05). In addition, CF patients had a shorter wait from transplant eligibility to waitlist than PF patients (329 vs 2,369 days, respectively [25th percentile], p < 0.05). Patients with PF and CF both faced delays from eligibility to referral and waitlist. Quality improvement efforts are needed to better identify and refer appropriate patients for lung transplant evaluation. Targeted interventions may facilitate more efficient evaluation completion and waitlist appearance. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

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

    PubMed

    Durieu, Isabelle

    2015-10-01

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

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

    PubMed Central

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

    2007-01-01

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

  18. Chloride and potassium channels in cystic fibrosis airway epithelia

    NASA Astrophysics Data System (ADS)

    Welsh, Michael J.; Liedtke, Carole M.

    1986-07-01

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

  19. Data Mining of Lung Microbiota in Cystic Fibrosis Patients.

    PubMed

    Li, Jianguo; Hao, Chunyan; Ren, Lili; 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.

  20. Data Mining of Lung Microbiota in Cystic Fibrosis Patients

    PubMed Central

    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

  1. Enteral tube feeding for cystic fibrosis.

    PubMed

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

    2008-04-16

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

  2. Oral anti-pseudomonal antibiotics for cystic fibrosis.

    PubMed

    Remmington, Tracey; Jahnke, Nikki; Harkensee, Christian

    2016-07-14

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

  3. GI complications after lung transplantation in patients with cystic fibrosis.

    PubMed

    Gilljam, Marita; Chaparro, Cecilia; Tullis, Elizabeth; Chan, Charles; Keshavjee, Shaf; Hutcheon, Michael

    2003-01-01

    Lung transplantation is now available for patients with cystic fibrosis (CF) and end-stage lung disease. While pulmonary graft function is often considered the major priority following transplantation, the nonpulmonary complications of this systemic disease also continue. We examined the GI complications in a cohort of patients who underwent transplantation. This was a retrospective study of all patients with CF who underwent transplantation between March 1988 and December 1998 in Toronto. Medical records were reviewed, and a short questionnaire was mailed to patients who were alive as of December 1998. There were 80 bilateral lung transplants performed in 75 patients. The questionnaire was distributed to 43 patients, of whom 27 patients (63%) responded. Pancreatic insufficiency requiring enzyme intake was evident in 72 of 75 patients (96%) at the time of surgery. Of three pancreatic-sufficient patients (4%), pancreatic insufficiency was diagnosed in two patients later. Biliary cirrhosis was diagnosed in three patients prior to transplantation. Distal intestinal obstruction syndrome (DIOS) was recorded for 15 patients (20%). Ten patients had a single episode, of which eight episodes occurred early in the postoperative period. Five patients had recurrent episodes. All were medically treated, except for two patients who underwent surgery. Other complications included cholecystitis (n = 3), mucocele of the appendix (n = 1), peptic ulcer disease (n = 3), and colonic carcinoma (n = 1). GI complications after lung transplantation are common in patients with CF, and attention should be paid to the risk for DIOS in the early postoperative period. Prevention and early medical treatment are important in order to avoid acute surgery. Close collaboration with the CF clinic, in order to diagnose and treat CF-related complications, is recommended.

  4. Multiple Antibiotic–Resistant Pseudomonas aeruginosa and Lung Function Decline in Patients with Cystic Fibrosis

    PubMed Central

    Ren, Clement L; Konstan, Michael W.; Yegin, Ashley; Rasouliyan, Lawrence; Trzaskoma, Benjamin; Morgan, Wayne J.; Regelmann, Warren

    2014-01-01

    Background The goal of this study was to determine the association of multiple antibiotic– resistant Pseudomonas aeruginosa (MARPA) acquisition with lung function decline in patients with cystic fibrosis (CF). Methods Using data from Epidemiologic Study of Cystic Fibrosis (ESCF), we identified patients with spirometry data and MARPA, defined as PA (1) resistant to gentamicin and either tobramycin or amikacin and (2) resistant to ≥1 antipseudomonal beta lactam. MARPA had to be detected in a respiratory culture after ≥ 2 years of PA-positive but MARPA-negative respiratory cultures. Multivariable piecewise linear regression was performed to model the annual rate of decline in forced expiratory volume in 1 second (FEV1) % predicted 2 calendar years before and after the index year of MARPA detection, adjusting for patient characteristics and CF therapies. Results In total, 4,349 patients with chronic PA and adequate PFT data were identified; 1,111 subsequently developed MARPA, while 3,238 patients were PA positive but MARPA negative. Compared with patients who did not acquire MARPA, MARPA-positive patients had lower FEV1 and received more oral (p<0.013) and inhaled p<0.001) antibiotic therapy. Mean FEV1 decline did not change significantly after MARPA detection (−2.22 % predicted/year before detection and −2.43 after, p=0.45). There was no relationship between persistent infection or FEV1 quartile and FEV1 decline. Conclusions Newly detected MARPA was not associated with a significant change in the rate of FEV1 decline. These results suggest that MARPA is more likely to be a marker of more severe disease and more intensive therapy, and less likely to be contributing independently to more rapid lung function decline. PMID:22445849

  5. Acute Scedosporium apiospermum Endobronchial Infection in Cystic Fibrosis.

    PubMed

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

    2016-06-01

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

  6. Multicentre standardisation of chest MRI as radiation-free outcome measure of lung disease in young children with cystic fibrosis.

    PubMed

    Wielpütz, Mark O; von Stackelberg, Oyunbileg; Stahl, Mirjam; Jobst, Bertram J; Eichinger, Monika; Puderbach, Michael U; Nährlich, Lutz; Barth, Sandra; Schneider, Christian; Kopp, Matthias V; Ricklefs, Isabell; Buchholz, Michael; Tümmler, Burkhard; Dopfer, Christian; Vogel-Claussen, Jens; Kauczor, Hans-Ulrich; Mall, Marcus A

    2018-05-24

    A recent single-centre study demonstrated that MRI is sensitive to detect early abnormalities in the lung and response to therapy in infants and preschool children with cystic fibrosis (CF) supporting MRI as an outcome measure of early CF lung disease. However, the feasibility of multicentre standardisation remains unknown. To determine the feasibility of multicentre standardisation of chest MRI in infants and preschool children with CF. A standardised chest 1.5 T MRI protocol was implemented across four specialised CF centres. Following training and initiation visits, 42 infants and preschool children (mean age 3.2 ± 1.5 years, range 0-6 years) with clinically stable CF underwent MRI and chest X-ray (CXR). Image quality and lung abnormalities were assessed using a standardised questionnaire and an established CF MRI and CXR score. MRI was successfully performed with diagnostic quality in all patients (100%). Incomplete lung coverage was observed in 6% and artefacts also in 6% of sequence acquisitions, but these were compensated by remaining sequences in all patients. The range of the MRI score in CF patients was similar across centres with a mean global MRI score of 13.3 ± 5.8. Cross-validation of the MRI against the CXR score revealed a moderate correlation (r = 0.43-0.50, p < 0.01). Our results demonstrate that multicentre standardisation of chest MRI is feasible and support its use as radiation-free outcome measure of lung disease in infants and preschool children with CF. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  7. The role of multispecies social interactions in shaping Pseudomonas aeruginosa pathogenicity in the cystic fibrosis lung.

    PubMed

    O'Brien, Siobhán; Fothergill, Joanne L

    2017-08-15

    Pseudomonas aeruginosa is a major pathogen in the lungs of cystic fibrosis (CF) patients. However, it is now recognised that a diverse microbial community exists in the airways comprising aerobic and anaerobic bacteria as well as fungi and viruses. This rich soup of microorganisms provides ample opportunity for interspecies interactions, particularly when considering secreted compounds. Here, we discuss how P. aeruginosa-secreted products can have community-wide effects, with the potential to ultimately shape microbial community dynamics within the lung. We focus on three well-studied traits associated with worsening clinical outcome in CF: phenazines, siderophores and biofilm formation, and discuss how secretions can shape interactions between P. aeruginosa and other commonly encountered members of the lung microbiome: Staphylococcus aureus, the Burkholderia cepacia complex, Candida albicans and Aspergillus fumigatus. These interactions may shape the evolutionary trajectory of P. aeruginosa while providing new opportunities for therapeutic exploitation of the CF lung microbiome. © FEMS 2017.

  8. The role of multispecies social interactions in shaping Pseudomonas aeruginosa pathogenicity in the cystic fibrosis lung

    PubMed Central

    Fothergill, Joanne L.

    2017-01-01

    Abstract Pseudomonas aeruginosa is a major pathogen in the lungs of cystic fibrosis (CF) patients. However, it is now recognised that a diverse microbial community exists in the airways comprising aerobic and anaerobic bacteria as well as fungi and viruses. This rich soup of microorganisms provides ample opportunity for interspecies interactions, particularly when considering secreted compounds. Here, we discuss how P. aeruginosa-secreted products can have community-wide effects, with the potential to ultimately shape microbial community dynamics within the lung. We focus on three well-studied traits associated with worsening clinical outcome in CF: phenazines, siderophores and biofilm formation, and discuss how secretions can shape interactions between P. aeruginosa and other commonly encountered members of the lung microbiome: Staphylococcus aureus, the Burkholderia cepacia complex, Candida albicans and Aspergillus fumigatus. These interactions may shape the evolutionary trajectory of P. aeruginosa while providing new opportunities for therapeutic exploitation of the CF lung microbiome. PMID:28859314

  9. [Genetic counseling in cystic fibrosis].

    PubMed

    Julia, S; Bieth, E

    2000-08-01

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

  10. Aspergillus fumigatus in the cystic fibrosis lung: pros and cons of azole therapy

    PubMed Central

    Burgel, Pierre-Régis; Paugam, André; Hubert, Dominique; Martin, Clémence

    2016-01-01

    Aspergillus fumigatus is the main fungus cultured in the airways of patients with cystic fibrosis (CF). Allergic bronchopulmonary aspergillosis occurs in ~10% of CF patients and is clearly associated with airway damage and lung function decline. The effects of A. fumigatus colonization in the absence of allergic bronchopulmonary aspergillosis are less well established. Retrospective clinical studies found associations of A. fumigatus-positive cultures with computed tomography scan abnormalities, greater risk of CF exacerbations and hospitalizations, and/or lung function decline. These findings were somewhat variable among studies and provided only circumstantial evidence for a role of A. fumigatus colonization in CF lung disease progression. The availability of a growing number of oral antifungal triazole drugs, together with the results of nonrandomized case series suggesting positive effects of azole therapies, makes it tempting to treat CF patients with these antifungal drugs. However, the only randomized controlled trial that has used itraconazole in CF patients showed no significant benefit. Because triazoles may have significant adverse effects and drug interactions, and because their prolonged use has been associated with the emergence of azole-resistant A. fumigatus isolates, it remains unclear whether or not CF patients benefit from azole therapy. PMID:27703383

  11. Aspergillus fumigatus in the cystic fibrosis lung: pros and cons of azole therapy.

    PubMed

    Burgel, Pierre-Régis; Paugam, André; Hubert, Dominique; Martin, Clémence

    2016-01-01

    Aspergillus fumigatus is the main fungus cultured in the airways of patients with cystic fibrosis (CF). Allergic bronchopulmonary aspergillosis occurs in ~10% of CF patients and is clearly associated with airway damage and lung function decline. The effects of A. fumigatus colonization in the absence of allergic bronchopulmonary aspergillosis are less well established. Retrospective clinical studies found associations of A. fumigatus -positive cultures with computed tomography scan abnormalities, greater risk of CF exacerbations and hospitalizations, and/or lung function decline. These findings were somewhat variable among studies and provided only circumstantial evidence for a role of A. fumigatus colonization in CF lung disease progression. The availability of a growing number of oral antifungal triazole drugs, together with the results of nonrandomized case series suggesting positive effects of azole therapies, makes it tempting to treat CF patients with these antifungal drugs. However, the only randomized controlled trial that has used itraconazole in CF patients showed no significant benefit. Because triazoles may have significant adverse effects and drug interactions, and because their prolonged use has been associated with the emergence of azole-resistant A. fumigatus isolates, it remains unclear whether or not CF patients benefit from azole therapy.

  12. Initiating transitional care for adolescents with cystic fibrosis at the age of 12 is both feasible and promising.

    PubMed

    Skov, M; Teilmann, G; Damgaard, I N; Nielsen, K G; Hertz, P G; Holgersen, M G; Presfeldt, M; Dalager, A M S; Brask, M; Boisen, K A

    2018-05-05

    Adolescence is a vulnerable period in cystic fibrosis, associated with declining lung function. This study described, implemented and evaluated a transition programme for adolescents. We conducted a single centre, non-randomised and non-controlled prospective programme at the cystic fibrosis centre at Copenhagen University Hospital Rigshospitalet from 2010-2011, assessing patients aged 12 to 18 at baseline and after 12 months. Changes implemented included staff training on communication, a more youth friendly feel to the outpatient clinic, the introduction of youth consultations partly alone with the adolescent, and a parents' evening focusing on cystic fibrosis in adolescence. Lung function and body mass index (BMI) were measured monthly and adolescents were assessed for their readiness for transition and quality of life at baseline and 12 months. We found that 40 (98%) of the eligible patients participated and youth consultations were successfully implemented with no dropouts. The readiness checklist score increased significantly over the one-year study period, indicating increased readiness for transfer and self-care. Overall quality of life, lung function and BMI remained stable during the study period. A well structured transition programme for cystic fibrosis patients as young as 12 years of age proved to be both feasible and sustainable. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  13. True survival benefit of lung transplantation for cystic fibrosis patients: the Zurich experience.

    PubMed

    Hofer, Markus; Benden, Christian; Inci, Ilhan; Schmid, Christoph; Irani, Sarosh; Speich, Rudolf; Weder, Walter; Boehler, Annette

    2009-04-01

    Lung transplantation is the ultimate therapy for end-stage cystic fibrosis (CF) lung disease; however, the debate continues as to whether lung transplantation improves survival. We report post-transplant outcome in CF at our institution by comparing 5-year post-transplant survival with a calculated 5-year survival without lung transplantation, using a predictive 5-year survivorship model, and describe pre-transplant parameters influencing transplant outcome. CF patients undergoing lung transplantation at our center were included (1992 to 2007). Survival rates were calculated and compared, and univariate and multivariate Cox regression analyses were used for statistical assessment. Eighty transplants were performed in CF patients, 11 (13.8%) of whom were children. Mean age at transplant was 26.2 years (95% confidence interval: 24.4 to 28.0). The Liou raw score at transplant was -20 (95% confidence interval: -16 to -24), resulting in an estimated 5-year survival without transplantation of 33 +/- 14%, compared with a 5-year post-transplant survival of 68.2 +/- 5.6%. Further improvement was noted in the recent transplant era (since 2000), with a 5-year survival of 72.7 +/- 7.3%. Univariate analysis revealed that later year of transplant and diagnosis of diabetes influenced survival positively. Pediatric age had no negative impact. In the multivariate analysis, only diabetes influenced survival, in a positive manner. Lung transplantation performed at centers having experience with the procedure can offer a true survival benefit to patients with end-stage CF lung disease.

  14. Immediate effects of lumacaftor/ivacaftor administration on lung function in patients with severe cystic fibrosis lung disease.

    PubMed

    Popowicz, Natalia; Wood, Jamie; Tai, Anna; Morey, Sue; Mulrennan, Siobhain

    2017-05-01

    Safety-data for lumacaftor/ivacaftor (LUM/IVA) combination therapy in patients with severe lung disease (percent predicted forced expiratory volume in 1s [ppFEV 1 ] <40) remain limited. We report immediate post-dose respiratory-related adverse events in 12 patients with severe cystic fibrosis (CF) lung disease (median [IQR] ppFEV 1 : 34 [31-36]) prescribed LUM/IVA. All patients experienced a decline in ppFEV 1 from baseline at 2-hours (median [IQR] relative change: -19 [-21 to -11]%, p<0.001) that persisted at 24-hours but recovered in most patients at 1-month. No pre- and post-differences in bronchodilator response were observed. Ten (83.3%) patients reported non-severe respiratory-related adverse events within 24-hours of LUM/IVA initiation. At 1-month, eight (67%) patients had persistent symptoms and six (50%) were treated for a pulmonary exacerbation. Our results highlight that LUM/IVA respiratory-related adverse events are common in patients with a ppFEV 1 <40. We recommend close assessment of adverse events. Further studies are required to evaluate the efficacy of LUM/IVA in patients with severe lung disease. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  15. Inhaled mannitol for cystic fibrosis.

    PubMed

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

    2018-02-09

    available. The remaining studies had much smaller sample sizes (ranging from 22 to 95) and data could not be pooled due to differences in design, interventions and population.Pooled evidence from the two large parallel studies was judged to be of low to moderate quality and from the smaller studies was judged to be of low to very low quality. In all studies, there was an initial test to see if participants tolerated mannitol, with only those who could tolerate the drug being randomised; therefore, the study results are not applicable to the cystic fibrosis population as a whole.While the published papers did not provide all the data required for our analysis, additional unpublished data were provided by the drug's manufacturer and the author of one of the studies.Pooling the large parallel studies comparing mannitol to control, up to and including six months, lung function (forced expiratory volume at one second) measured in both mL and % predicted was significantly improved in the mannitol group compared to the control group (moderate-quality evidence). Beneficial results were observed in these studies in adults and in both concomitant dornase alfa users and non-users in these studies. In the smaller studies, statistically significant improvements in lung function were also observed in the mannitol groups compared to the non-respirable mannitol groups; however, we judged this evidence to be of low to very low quality.For the comparisons of mannitol and control, we found no consistent differences in health-related quality of life in any of the domains except for burden of treatment, which was less for mannitol up to four months in the two pooled studies of a similar design; this difference was not maintained at six months. It should be noted that the tool used to measure health-related quality of life was not designed to assess mucolytics and pooling of the age-appropriate tools (as done in some of the included studies) may not be valid so results were judged to be low to

  16. [News in cystic fibrosis].

    PubMed

    Delaisi, B

    2013-08-01

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

  17. Lung function in infants with cystic fibrosis diagnosed by newborn screening.

    PubMed

    Linnane, Barry M; Hall, Graham L; Nolan, Gary; Brennan, Siobhan; Stick, Stephen M; Sly, Peter D; Robertson, Colin F; Robinson, Philip J; Franklin, Peter J; Turner, Stephen W; Ranganathan, Sarath C

    2008-12-15

    Progressive lung damage in cystic fibrosis (CF) starts in infancy, and early detection may aid preventative strategies. To measure lung function in infants with CF diagnosed by newborn screening and describe its association with pulmonary infection and inflammation. Infants with CF (n = 68, 6 weeks to 30 months of age) and healthy infants without CF (n = 49) were studied. Forced vital capacity, FEV(0.5), and forced expiratory flows at 75% of exhaled vital capacity (FEF(75)) were measured using the raised-volume rapid thoracoabdominal compression technique. Forty-eight hours later, infants with CF had bronchoalveolar lavage (BAL) for assessment of pulmonary infection and inflammation. In the CF group, the deficit in FEV(0.5) z score increased by -0.77 (95% confidence interval, -1.14 to -0.41; P < 0.001) with each year of age. The mean FEV(0.5) z score did not differ between infants with CF and healthy control subjects less than 6 months of age (-0.06 and 0.02, respectively; P = 0.87). However, the mean FEV(0.5) z score was lower by 1.15 in infants with CF who were older than 6 months of age compared with healthy infants (P < 0.001). FVC and FEF(75) followed a similar pattern. Pulmonary infection and inflammation in BAL samples did not explain the lung function results. Lung function, measured by forced expiration, is normal in infants with CF at the time of diagnosis by newborn screening but is diminished in older infants. These findings suggest that in CF the optimal timing of therapeutic interventions aimed at preserving lung function may be within the first 6 months of life.

  18. Association of sweat chloride concentration at time of diagnosis and CFTR genotype with mortality and cystic fibrosis phenotype.

    PubMed

    McKone, Edward F; Velentgas, Priscilla; Swenson, Anna J; Goss, Christopher H

    2015-09-01

    The extent to which sweat chloride concentration predicts survival and clinical phenotype independently of CFTR genotype in cystic fibrosis is not well understood. We analyzed the US Cystic Fibrosis Foundation Patient Registry data using Cox regression to examine the relationship between sweat chloride concentration (<60, 60-<80, ≥80mmol/L), CFTR genotype (high and lower risk for lung function decline), and survival and mixed linear regression to examine the relationship between sweat chloride, CFTR genotype, and measures of lung function and growth. When included in the same model, CFTR genotype, but not sweat chloride, was independently associated with survival and with lung function, height, and BMI. Among patients with unclassified CFTR genotype, sweat chloride was an independent predictor of survival (<60 HR 0.53 [0.37, 0.77], 60-<80 0.51 [0.42, 0.63]). Sweat chloride concentration may be a useful predictor of mortality and clinical phenotype when CFTR genotype functional class is unclassified. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  19. Self-reported exercise and longitudinal outcomes in cystic fibrosis: a retrospective cohort study.

    PubMed

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

    2014-10-06

    Cystic fibrosis (CF) is characterized by recurrent respiratory infections and progressive lung disease. Whereas exercise may contribute to preserving lung function, its benefit is difficult to ascertain given the selection bias of healthier patients being more predisposed to exercise. Our objective was to examine the role of self-reported exercise with longitudinal lung function and body mass index (BMI) measures in CF. A total of 1038 subjects with CF were recruited through the U.S. CF Twin-Sibling Study. Questionnaires were used to determine exercise habits. Questionnaires, chart review, and U.S. CF Foundation Patient Registry data were used to track outcomes. Within the study sample 75% of subjects self-reported regular exercise. Exercise was associated with an older age of diagnosis (p = 0.002), older age at the time of ascertainment (p < 0.001), and higher baseline FEV1 (p = 0.001), but not CFTR genotype (p = 0.64) or exocrine pancreatic function (p = 0.19). In adjusted mixed models, exercise was associated with both a reduced decline in FEV1 (p < 0.001) and BMI Z-score (p = 0.001) for adults, but not children aged 10-17 years old. In our retrospective study, self-reported exercise was associated with improved longitudinal nutritional and pulmonary outcomes in cystic fibrosis for adults. Although prospective studies are needed to confirm these associations, programs to promote regular exercise among individuals with cystic fibrosis would be beneficial.

  20. Lung phenotype of juvenile and adult cystic fibrosis transmembrane conductance regulator-knockout ferrets.

    PubMed

    Sun, Xingshen; Olivier, Alicia K; Liang, Bo; Yi, Yaling; Sui, Hongshu; Evans, Turan I A; Zhang, Yulong; Zhou, Weihong; Tyler, Scott R; Fisher, John T; Keiser, Nicholas W; Liu, Xiaoming; Yan, Ziying; Song, Yi; Goeken, J Adam; Kinyon, Joann M; Fligg, Danielle; Wang, Xiaoyan; Xie, Weiliang; Lynch, Thomas J; Kaminsky, Paul M; Stewart, Zoe A; Pope, R Marshall; Frana, Timothy; Meyerholz, David K; Parekh, Kalpaj; Engelhardt, John F

    2014-03-01

    Chronic bacterial lung infections in cystic fibrosis (CF) are caused by defects in the CF transmembrane conductance regulator chloride channel. Previously, we described that newborn CF transmembrane conductance regulator-knockout ferrets rapidly develop lung infections within the first week of life. Here, we report a more slowly progressing lung bacterial colonization phenotype observed in juvenile to adult CF ferrets reared on a layered antibiotic regimen. Even on antibiotics, CF ferrets were still very susceptible to bacterial lung infection. The severity of lung histopathology ranged from mild to severe, and variably included mucus obstruction of the airways and submucosal glands, air trapping, atelectasis, bronchopneumonia, and interstitial pneumonia. In all CF lungs, significant numbers of bacteria were detected and impaired tracheal mucociliary clearance was observed. Although Streptococcus, Staphylococcus, and Enterococcus were observed most frequently in the lungs of CF animals, each animal displayed a predominant bacterial species that accounted for over 50% of the culturable bacteria, with no one bacterial taxon predominating in all animals. Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry fingerprinting was used to quantify lung bacteria in 10 CF animals and demonstrated Streptococcus, Staphylococcus, Enterococcus, or Escherichia as the most abundant genera. Interestingly, there was significant overlap in the types of bacteria observed in the lung and intestine of a given CF animal, including bacterial taxa unique to the lung and gut of each CF animal analyzed. These findings demonstrate that CF ferrets develop lung disease during the juvenile and adult stages that is similar to patients with CF, and suggest that enteric bacterial flora may seed the lung of CF ferrets.

  1. Lung Phenotype of Juvenile and Adult Cystic Fibrosis Transmembrane Conductance Regulator–Knockout Ferrets

    PubMed Central

    Sun, Xingshen; Olivier, Alicia K.; Liang, Bo; Yi, Yaling; Sui, Hongshu; Evans, Turan I. A.; Zhang, Yulong; Zhou, Weihong; Tyler, Scott R.; Fisher, John T.; Keiser, Nicholas W.; Liu, Xiaoming; Yan, Ziying; Song, Yi; Goeken, J. Adam; Kinyon, Joann M.; Fligg, Danielle; Wang, Xiaoyan; Xie, Weiliang; Lynch, Thomas J.; Kaminsky, Paul M.; Stewart, Zoe A.; Pope, R. Marshall; Frana, Timothy; Meyerholz, David K.; Parekh, Kalpaj

    2014-01-01

    Chronic bacterial lung infections in cystic fibrosis (CF) are caused by defects in the CF transmembrane conductance regulator chloride channel. Previously, we described that newborn CF transmembrane conductance regulator–knockout ferrets rapidly develop lung infections within the first week of life. Here, we report a more slowly progressing lung bacterial colonization phenotype observed in juvenile to adult CF ferrets reared on a layered antibiotic regimen. Even on antibiotics, CF ferrets were still very susceptible to bacterial lung infection. The severity of lung histopathology ranged from mild to severe, and variably included mucus obstruction of the airways and submucosal glands, air trapping, atelectasis, bronchopneumonia, and interstitial pneumonia. In all CF lungs, significant numbers of bacteria were detected and impaired tracheal mucociliary clearance was observed. Although Streptococcus, Staphylococcus, and Enterococcus were observed most frequently in the lungs of CF animals, each animal displayed a predominant bacterial species that accounted for over 50% of the culturable bacteria, with no one bacterial taxon predominating in all animals. Matrix-assisted laser desorption–ionization time-of-flight mass spectrometry fingerprinting was used to quantify lung bacteria in 10 CF animals and demonstrated Streptococcus, Staphylococcus, Enterococcus, or Escherichia as the most abundant genera. Interestingly, there was significant overlap in the types of bacteria observed in the lung and intestine of a given CF animal, including bacterial taxa unique to the lung and gut of each CF animal analyzed. These findings demonstrate that CF ferrets develop lung disease during the juvenile and adult stages that is similar to patients with CF, and suggest that enteric bacterial flora may seed the lung of CF ferrets. PMID:24074402

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

    PubMed

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

    2012-02-15

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

  3. Active cycle of breathing technique for cystic fibrosis.

    PubMed

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

    2016-07-05

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

  4. Airway disease phenotypes in animal models of cystic fibrosis.

    PubMed

    McCarron, Alexandra; Donnelley, Martin; Parsons, David

    2018-04-02

    In humans, cystic fibrosis (CF) lung disease is characterised by chronic infection, inflammation, airway remodelling, and mucus obstruction. A lack of pulmonary manifestations in CF mouse models has hindered investigations of airway disease pathogenesis, as well as the development and testing of potential therapeutics. However, recently generated CF animal models including rat, ferret and pig models demonstrate a range of well characterised lung disease phenotypes with varying degrees of severity. This review discusses the airway phenotypes of currently available CF animal models and presents potential applications of each model in airway-related CF research.

  5. Sodium channel blockers for cystic fibrosis.

    PubMed

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

    2006-07-19

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

  6. Nebulized hyaluronan ameliorates lung inflammation in cystic fibrosis mice.

    PubMed

    Gavina, Manuela; Luciani, Alessandro; Villella, Valeria R; Esposito, Speranza; Ferrari, Eleonora; Bressani, Ilaria; Casale, Alida; Bruscia, Emanuela M; Maiuri, Luigi; Raia, Valeria

    2013-08-01

    Chronic lung inflammation with increased susceptibility to bacterial infections cause much of the morbidity and mortality in patients with cystic fibrosis (CF), the most common severe, autosomal recessively inherited disease in the Caucasian population. Exogenous inhaled hyaluronan (HA) can exert a protective effect against injury and beneficial effects of HA have been shown in experimental models of chronic respiratory diseases. Our objective was to examine whether exogenous administration of nebulized HA might interfere with lung inflammation in CF. F508del homozygous mice (Cftr(F508del) ) and transgenic mice overexpressing the ENaC channel β-subunit (Scnn1b-Tg) were treated with nebulized HA (0.5 mg/mouse/day for 7 days). Tumor necrosis factor-alpha (TNFα), macrophage inflammatory protein-2 (MIP-2), myeloperoxidase (MPO) levels, and macrophage infiltration were assessed on lung tissues. IB3-1 and CFBE41o-epithelial cell lines were cultured with HA (24 hr, 100 µg/ml) and Reactive Oxygen Species (ROS), Tissue Transglutaminase (TG2) SUMOylation and Peroxisome Proliferator Activated Receptor gamma (PPARγ) and phospho-p42/p44 levels were measured by dichlorodihydrofluorescein assay, or fluorescence resonance energy transfer (FRET) microscopy or immunoblots. Nebulized HA reduced TNFα expression (P < 0.005); TNFα, MIP-2, and MPO protein levels (P < 0.05); MPO activity (P < 0.05); and CD68+ cells counts (P < 0.005) in lung tissues of Cftr(F508del) and Scnn1b-Tg mice, compared with saline-treated mice. HA reduced ROS, TG2 SUMOylation, TG2 activity, phospho-p42-44, and increased PPARγ protein in both IB3-1 and CFBE41o cells (P < 0.05). Nebulized HA is effective in controlling inflammation in vivo in mice CF airways and in vitro in human airway epithelial cells. We provide the proof of concept for the use of inhaled HA as a potential anti-inflammatory drug in CF therapy. Copyright © 2012 Wiley Periodicals, Inc.

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

    PubMed

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

    2014-11-01

    We have previously reported cyanide at concentrations of up to 150 μM in the sputum of cystic fibrosis patients infected with Pseudomonas aeruginosa and a negative correlation with lung function. Our aim was to investigate possible mechanisms for this association, focusing on the effect of pathophysiologically relevant cyanide levels on human respiratory cell function. Ciliary beat frequency measurements were performed on nasal brushings and nasal air-liquid interface (ALI) cultures obtained from healthy volunteers and cystic fibrosis patients. Potassium cyanide decreased ciliary beat frequency in healthy nasal brushings (n = 6) after 60 min (150 μM: 47% fall, p<0.0012; 75 μM: 32% fall, p<0.0001). Samples from cystic fibrosis patients (n = 3) showed similar results (150 μM: 55% fall, p = 0.001). Ciliary beat frequency inhibition was not due to loss of cell viability and was reversible. The inhibitory mechanism was independent of ATP levels. KCN also significantly inhibited ciliary beat frequency in ALI cultures, albeit to a lesser extent. Ciliary beat frequency measurements on ALI cultures treated with culture supernatants from P. aeruginosa mutants defective in virulence factor production implicated cyanide as a key component inhibiting the ciliary beat frequency. If cyanide production similarly impairs mucocilliary clearance in vivo, it could explain the link with increased disease severity observed in cystic fibrosis patients with detectable cyanide in their airway. ©ERS 2014.

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

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

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

  9. About Cystic Fibrosis

    MedlinePlus

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

  10. Omega-3 fatty acids for cystic fibrosis.

    PubMed

    Oliver, Colleen; Watson, Helen

    2016-01-05

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2014-10-01

    The aim of this review is to provide an update on various relevant endocrine aspects of care in adolescents and adults with cystic fibrosis. As life expectancy in cystic fibrosis has continuously improved, endocrine complications have become more apparent. The common endocrine complications include cystic fibrosis related diabetes, cystic fibrosis related bone disease, vitamin D deficiency and poor growth and pubertal development. Thyroid and adrenal disorders have also been reported, although the prevalence appears to be less common. Endocrine diseases are an increasingly recognized complication that has a significant impact on the overall health of individuals with cystic fibrosis. This review summarizes the updated screening and management of endocrine diseases in the cystic fibrosis population.

  13. Liver Disease in Cystic Fibrosis: an Update

    PubMed Central

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

    2013-01-01

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

  14. 2-Aminoacetophenone as a potential breath biomarker for Pseudomonas aeruginosa in the cystic fibrosis lung

    PubMed Central

    2010-01-01

    Background Pseudomonas aeruginosa infections are associated with progressive life threatening decline of lung function in cystic fibrosis sufferers. Growth of Ps. aeruginosa releases a "grape-like" odour that has been identified as the microbial volatile organic compound 2-aminoacetophenone (2-AA). Methods We investigated 2-AA for its specificity to Ps. aeruginosa and its suitability as a potential breath biomarker of colonisation or infection by Solid Phase Micro Extraction and Gas Chromatography-Mass Spectrometry (GC/MS). Results Cultures of 20 clinical strains of Ps. aeruginosa but not other respiratory pathogens had high concentrations of 2-AA in the head space of in vitro cultures when analysed by GC/MS. 2-AA was stable for 6 hours in deactivated glass sampling bulbs but was not stable in Tedlar® bags. Optimisation of GC/MS allowed detection levels of 2-AA to low pico mol/mol range in breath. The 2-AA was detected in a significantly higher proportion of subjects colonised with Ps. aeruginosa 15/16 (93.7%) than both the healthy controls 5/17 (29%) (p < 0.0002) and CF patients not colonised with Ps. aeruginosa 4/13(30.7%) (p < 0.001). The sensitivity and specificity of the 2-AA breath test compared to isolation of Ps. aeruginosa in sputum and/or BALF was 93.8% (95% CI, 67-99) and 69.2% (95% CI, 38-89) respectively. The peak integration values for 2-AA analysis in the breath samples were significantly higher in Ps. aeruginosa colonised subjects (median 242, range 0-1243) than the healthy controls (median 0, range 0-161; p < 0.001) and CF subjects not colonised with Ps. aeruginosa (median 0, range 0-287; p < 0.003) Conclusions Our results report 2-AA as a promising breath biomarker for the detection of Ps. aeruginosa infections in the cystic fibrosis lung. PMID:21054900

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

    EPA Science Inventory

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

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

    PubMed

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

    2018-03-18

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

  17. Impact of Scedosporium apiospermum complex seroprevalence in patients with cystic fibrosis.

    PubMed

    Parize, Perrine; Billaud, Sandrine; Bienvenu, Anne L; Bourdy, Stéphanie; le Pogam, Marie A; Reix, Philippe; Picot, Stéphane; Robert, Raymond; Lortholary, Olivier; Bouchara, Jean-Philippe; Durieu, Isabelle

    2014-12-01

    Species of the Scedosporium apiospermum complex (S. a complex) are emerging fungi responsible for chronic airway colonization in cystic fibrosis (CF) patients. Recent studies performed on Aspergillus fumigatus suggest that the colonization of the airways by filamentous fungi may contribute to the progressive deterioration of lung function. We studied S. a complex seroprevalence, as a marker of close contact between patient and the fungi, in a large monocentric cohort of CF patients attended in a reference centre in Lyon, France. Serum samples from 373 CF patients were analysed. Antibodies against S. a complex were detected in 35 patients (9.4%). In multivariate analysis, S. a complex seropositivity was only associated with seropositivity to A. fumigatus. This study does not suggest an association between sensitization against S. a complex and poorer lung function in CF. Prospective studies are needed to evaluate the impact of both seropositivity and S. a complex colonization on the course of CF. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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

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

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

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

  19. Complement Effectors of Inflammation in Cystic Fibrosis Lung Fluid Correlate with Clinical Measures of Disease.

    PubMed

    Sass, Laura A; Hair, Pamela S; Perkins, Amy M; Shah, Tushar A; Krishna, Neel K; Cunnion, Kenji M

    2015-01-01

    In cystic fibrosis (CF), lung damage is mediated by a cycle of obstruction, infection, and inflammation. Here we explored complement inflammatory effectors in CF lung fluid. In this study soluble fractions (sols) from sputum samples of 15 CF patients were assayed for complement effectors and analyzed with clinical measurements. The pro-inflammatory peptide C5a was increased 4.8-fold (P = 0.04) in CF sols compared with controls. Incubation of CF sols with P. aeruginosa or S. aureus increased C5a concentration 2.3-fold (P = 0.02). A peptide inhibitor of complement C1 (PIC1) completely blocked the increase in C5a concentration from P. aeruginosa in CF sol in vitro (P = 0.001). C5a concentration in CF sol correlated inversely with body mass index (BMI) percentile in children (r = -0.77, P = 0.04). C3a, which has anti-inflammatory effects, correlated positively with FEV1% predicted (rs = 0.63, P = 0.02). These results suggest that complement effectors may significantly impact inflammation in CF lung fluid.

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

    PubMed

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

    2018-01-01

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

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

    PubMed

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

    2018-01-01

    centre refer only to 2014. The present Report has been organized into 10 sections. 1. Demography - number of Italian patients with cystic fibrosis (CF) in 2014 was 4,981 and their median age was 20.4 years; estimated 2014 CF prevalence was 8.2/100,000 residents in Italy; on average, 52.1% of the patients were male and CF distribution showed higher frequency in patients aged from 7 to 35 years. On average, 53.7% of CF patients are aged more than 18 years. 2. Diagnoses - most of the CF patients were diagnosed before two years of age (around 66%); a significant proportion of patients (on average, 12%) was diagnosed in adult age. 3. New diagnoses - new diagnoses were 187 in 2011, 200 in 2012, 160 in 2013, and 135 in 2014. Estimated incidence was 1/4,052 live births in 2011; 1/4,313 in 2012; 1/5,189 in 2013 and 1/8,243 in 2014. 4. Genetics - 99.5% of patients was studied at the molecular level, with identification of 90.1% of Cystic Fibrosis Transmembrane Regulator CFTR mutations; [delta]508F was the most frequent mutation (44.8% in 2014). 5. Lung function - FEV₁ (Forced Expiratory Volume in the first second) scores progressively decreased shortly before the start of adult age, in accordance with the natural history of the disease. Most of the patients between 6 and 17 years of age reported a FEV₁ % ≥ 70% of the predicted value, while the proportion of patients with severe lung disease (FEV₁ % <40% of the predicted value) is <2% over the period 2011-2014. 6. Nutrition - most critical periods come out during the first 6 months of life and during adolescence. Prevalence of malnourished male aged 12-17 years decreases over the period 2011-2014; an increasing percentage of patient (both male and female) with a suboptimal body mass index value is observed among patients aged more than 18 years 7. Complications - the presence of missing data represents an obstacle in the correct evaluation of prevalence value of complications related to Italian patients within ICFR

  2. Cystic fibrosis.

    PubMed

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

    1994-01-01

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

  3. Probability of treatment following acute decline in lung function in children with cystic fibrosis is related to baseline pulmonary function.

    PubMed

    Morgan, Wayne J; Wagener, Jeffrey S; Yegin, Ashley; Pasta, David J; Millar, Stefanie J; Konstan, Michael W

    2013-10-01

    To determine whether the association between high forced expiratory volume in 1 second (FEV1) and increased rate of decline in FEV1 in children with cystic fibrosis could be due to less frequent intervention after acute declines (sudden decline events) in FEV1. Patients with cystic fibrosis aged 6-17 years enrolled in the Epidemiologic Study of Cystic Fibrosis were assessed for a sudden decline event, defined as a 10% relative decline in FEV1% predicted from an average of 3 consecutive stable baseline spirometries. The likelihood of therapeutic intervention within 14 days before and 56 days after this event was then related to their baseline FEV1% predicted age-specific decile using a logistic regression adjusting for age group (6-12 years, 13-17 years) and presence of Pseudomonas aeruginosa on respiratory culture. A total of 10 888 patients had at least 1 sudden decline event in FEV1. Patients in the highest FEV1 decile were significantly less likely than those in the lowest decile to receive intravenous antibiotics (OR, 0.14; 95% CI, 0.11-0.18; P < .001) or be hospitalized (OR, 0.18; 95% CI, 0.14-0.23; P < .001) following decline. Children and adolescents with high baseline lung function are less likely to receive a therapeutic intervention following an acute decline in FEV1, which may explain their greater rate of FEV1 decline. Copyright © 2013 Mosby, Inc. All rights reserved.

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

    PubMed

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

    2006-01-01

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

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

    ERIC Educational Resources Information Center

    Cystic Fibrosis Foundation, Atlanta, GA.

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

  6. Associations between Academic Achievement and Psychosocial Variables in Adolescents with Cystic Fibrosis

    ERIC Educational Resources Information Center

    Grieve, Adam J.; Tluczek, Audrey; Racine-Gilles, Caroline N.; Laxova, Anita; Albers, Craig A.; Farrell, Philip M.

    2011-01-01

    Background: Cystic fibrosis (CF) is a chronic genetic disease that leads to the accumulation of thick mucus in multiple organ systems, leading to chronic lung infection and affecting the body's ability to absorb nutrients necessary for growth and development. This cross-sectional, correlational study examined the potential effects of CF on…

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

    ERIC Educational Resources Information Center

    Goldberg, Richard T.; And Others

    1980-01-01

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

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

    PubMed

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

    2005-02-01

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

  9. A model for predicting life expectancy of children with cystic fibrosis.

    PubMed

    Aurora, P; Wade, A; Whitmore, P; Whitehead, B

    2000-12-01

    In this study the authors aimed to produce a model for predicting the life expectancy of children with severe cystic fibrosis (CF) lung disease. The survival of 181 children with severe CF lung disease referred for transplantation assessment 1988-1998 (mean age 11.5 yrs, median survival without transplant 1.9 yrs from date of assessment) were studied. Proportional hazards modelling was used to identify assessment measurements that are of value in predicting longevity. The resultant model included low height predicted forced expiratory volume in one second (FEV1), low minimum oxygen saturation (Sa,O2min) during a 12-min walk, high age adjusted resting heart rate, young age, female sex, low plasma albumin, and low blood haemoglobin as predictors for poor prognosis. Extrapolation from the model suggests that a 12-yr old male child with an FEV1 of 30% pred and a Sa,O2min of 85% has a 44% risk of death within 2 yrs (95% confidence interval (CI) 35-54%), whilst a female child with the same measurements has a 63% risk of death (95% CI 52-73%) within the same period. The model produced may be of value in predicting the life expectancy of children with severe cystic fibrosis lung disease and in optimizing the timing of lung transplantation.

  10. Chitinase activation in patients with fungus-associated cystic fibrosis lung disease.

    PubMed

    Hector, Andreas; Chotirmall, Sanjay H; Lavelle, Gillian M; Mirković, Bojana; Horan, Deirdre; Eichler, Laura; Mezger, Markus; Singh, Anurag; Ralhan, Anjai; Berenbrinker, Sina; Mack, Ines; Ensenauer, Regina; Riethmüller, Joachim; Graepler-Mainka, Ute; Murray, Michelle A; Griese, Matthias; McElvaney, N Gerry; Hartl, Dominik

    2016-10-01

    Chitinases have recently gained attention in the field of pulmonary diseases, particularly in asthma and chronic obstructive pulmonary disease, but their potential role in patients with cystic fibrosis (CF)-associated lung disease remains unclear. The aim of this study was to assess chitinase activity systemically and in the airways of patients with CF and asthma compared with healthy subjects. Additionally, we assessed factors that regulate chitinase activity within the lungs of patients with CF. Chitinase activities were quantified in serum and bronchoalveolar lavage fluid from patients with CF, asthmatic patients, and healthy control subjects. Mechanistically, the role of CF airway proteases and genetic chitinase deficiency was assessed. Chitinase activity was systemically increased in patients with CF compared with that in healthy control subjects and asthmatic patients. Further stratification showed that chitinase activity was enhanced in patients with CF colonized with Candida albicans compared with that in noncolonized patients. CF proteases degraded chitinases in the airway microenvironment of patients with CF. Genetic chitinase deficiency was associated with C albicans colonization in patients with CF. Patients with CF have enhanced chitinase activation associated with C albicans colonization. Therefore chitinases might represent a novel biomarker and therapeutic target for CF-associated fungal disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  11. Ion Channel Modulators in Cystic Fibrosis.

    PubMed

    Gentzsch, Martina; Mall, Marcus A

    2018-05-08

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

  12. A cystic fibrosis handbook for teachers.

    PubMed

    Ryan, L L; Williams, J K

    1996-01-01

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

  13. Exhaled breath condensate adenosine tracks lung function changes in cystic fibrosis

    PubMed Central

    Olsen, Bonnie M.; Lin, Feng-Chang; Fine, Jason; Boucher, Richard C.

    2013-01-01

    Measurement of exhaled breath condensate (EBC) biomarkers offers a noninvasive means to assess airway disease, but the ability of EBC biomarkers to track longitudinal changes in disease severity remains unproven. EBC was collected from pediatric patients with cystic fibrosis (CF) during regular clinic visits over 1 yr. EBC biomarkers urea, adenosine (Ado), and phenylalanine (Phe) were measured by mass spectrometry, and biomarker ratios were used to control for variable dilution of airway secretions. EBC biomarker ratios were assessed relative to lung function in longitudinal, multivariate models and compared with sputum inflammatory markers and quality of life assessment (CFQ-R). EBC was successfully analyzed from 51 subjects during 184 visits (3.6 ± 0.9 visits per subject). EBC Ado/urea ratio was reproducible in duplicate samples (r = 0.62, P < 0.01, n = 20) and correlated with sputum neutrophil elastase (β = 2.5, P < 0.05). EBC Ado/urea correlated with the percentage predicted of forced expiratory volume in 1 s in longitudinal, multivariate models (β = −2.9, P < 0.01); EBC Ado/Phe performed similarly (β = −2.1, P < 0.05). In contrast, IL-8 and elastase measured in spontaneously expectorated sputum (n = 57 samples from 25 subjects) and the CFQ-R respiratory scale (n = 90 tests from 47 subjects) were not significantly correlated with lung function. EBC was readily collected in a clinic setting from a wide range of subjects. EBC Ado tracked longitudinal changes in lung function in CF, with results similar to or better than established measures. PMID:23355385

  14. Cystic Fibrosis Transmembrane Conductance Regulator is an Epithelial Cell Receptor for Clearance of Pseudomonas aeruginosa from the Lung

    NASA Astrophysics Data System (ADS)

    Pier, Gerald B.; Grout, Martha; Zaidi, Tanweer S.

    1997-10-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride ion channel, but its relationship to the primary clinical manifestation of CF, chronic Pseudomonas aeruginosa pulmonary infection, is unclear. We report that CFTR is a cellular receptor for binding, endocytosing, and clearing P. aeruginosa from the normal lung. Murine cells expressing recombinant human wild-type CFTR ingested 30-100 times as many P. aeruginosa as cells lacking CFTR or expressing mutant Δ F508 CFTR protein. Purified CFTR inhibited ingestion of P. aeruginosa by human airway epithelial cells. The first extracellular domain of CFTR specifically bound to P. aeruginosa and a synthetic peptide of this region inhibited P. aeruginosa internalization in vivo, leading to increased bacterial lung burdens. CFTR clears P. aeruginosa from the lung, indicating a direct connection between mutations in CFTR and the clinical consequences of CF.

  15. Dental treatment for people with cystic fibrosis.

    PubMed

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

    2016-06-01

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

  16. Determination of right ventricular ejection fraction in children with cystic fibrosis

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

    Piepsz, A.; Ham, H.R.; Millet, E.

    1987-01-01

    The radionuclide right ventricular ejection fraction (RVEF) determined by means of Krypton-81m represents a simple, noninvasive, and accurate procedure to quantify the right ventricular contractility. This procedure was applied to 25 young patients with cystic fibrosis. The RVEF tended to decrease with the progression of the lung disease, as assessed by the clinical S-K score, the degree of the defects on lung scintigraphy, the PaO/sub 2/, and the lung function tests. However, the decrease of RVEF in patients with marked lung function tests. However, the decrease of RVEF in patients with marked lung involvement was moderate, and terminal lung diseasemore » was sometimes associated with normal right heart contractility.« less

  17. Physical exercise training for cystic fibrosis.

    PubMed

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

    2017-11-01

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

  18. Comparison of Microbiomes from Different Niches of Upper and Lower Airways in Children and Adolescents with Cystic Fibrosis

    PubMed Central

    Boutin, Sébastien; Graeber, Simon Y.; Weitnauer, Michael; Panitz, Jessica; Stahl, Mirjam; Clausznitzer, Diana; Kaderali, Lars; Einarsson, Gisli; Tunney, Michael M.; Elborn, J. Stuart

    2015-01-01

    Changes in the airway microbiome may be important in the pathophysiology of chronic lung disease in patients with cystic fibrosis. However, little is known about the microbiome in early cystic fibrosis lung disease and the relationship between the microbiomes from different niches in the upper and lower airways. Therefore, in this cross-sectional study, we examined the relationship between the microbiome in the upper (nose and throat) and lower (sputum) airways from children with cystic fibrosis using next generation sequencing. Our results demonstrate a significant difference in both α and β-diversity between the nose and the two other sampling sites. The nasal microbiome was characterized by a polymicrobial community while the throat and sputum communities were less diverse and dominated by a few operational taxonomic units. Moreover, sputum and throat microbiomes were closely related especially in patients with clinically stable lung disease. There was a high inter-individual variability in sputum samples primarily due to a decrease in evenness linked to increased abundance of potential respiratory pathogens such as Pseudomonas aeruginosa. Patients with chronic Pseudomonas aeruginosa infection exhibited a less diverse sputum microbiome. A high concordance was found between pediatric and adult sputum microbiomes except that Burkholderia was only observed in the adult cohort. These results indicate that an adult-like lower airways microbiome is established early in life and that throat swabs may be a good surrogate in clinically stable children with cystic fibrosis without chronic Pseudomonas aeruginosa infection in whom sputum sampling is often not feasible. PMID:25629612

  19. Deleterious impact of hyperglycemia on cystic fibrosis airway ion transport and epithelial repair.

    PubMed

    Bilodeau, Claudia; Bardou, Olivier; Maillé, Émilie; Berthiaume, Yves; Brochiero, Emmanuelle

    2016-01-01

    Cystic fibrosis (CF)-related diabetes (CFRD) is associated with faster pulmonary function decline. Thus, we evaluated the impact of hyperglycemia on airway epithelial repair and transepithelial ion transport, which are critical in maintaining lung integrity and function. Non-CF and CF airway epithelial cells were exposed to low (LG) or high (HG) glucose before ion current and wound repair rate measurements. CFTR and K+ currents decreased after HG treatments. HG also reduced the wound healing rates of non-CF and CF cell monolayers. Although CFTR correction with VRT-325 accelerated the healing rates of CF cells monolayers under LG conditions, this improvement was significantly abrogated under HG conditions. Our data highlights a deleterious impact of hyperglycemia on ion transport and epithelial repair functions, which could contribute to the deterioration in lung function in CFRD patients. HG may also interfere with the beneficial effects of CFTR rescue on airway epithelial repair. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  20. Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening.

    PubMed

    Sly, Peter D; Brennan, Siobhain; Gangell, Catherine; de Klerk, Nicholas; Murray, Conor; Mott, Lauren; Stick, Stephen M; Robinson, Philip J; Robertson, Colin F; Ranganathan, Sarath C

    2009-07-15

    The promise of newborn screening (NBS) for cystic fibrosis (CF) has not been fully realized, and the extent of improvement in respiratory outcomes is unclear. We hypothesized that significant lung disease was present at diagnosis. To determine the extent of lung disease in a geographically defined population of infants with CF diagnosed after detection by NBS. Fifty-seven infants (median age, 3.6 mo) with CF underwent bronchoalveolar lavage and chest computed tomography (CT) using a three-slice inspiratory and expiratory protocol. Despite the absence of respiratory symptoms in 48 (84.2%) of infants, a substantial proportion had lung disease with bacterial infection detected in 12 (21.1%), including Staphylococcus aureus (n = 4) and Pseudomonas aeruginosa (n = 3); neutrophilic inflammation (41. 4 x 10(3) cells/ml representing 18.7% of total cell count); proinflammatory cytokines, with 44 (77.2%) having detectable IL-8; and 17 (29.8%) having detectable free neutrophil elastase activity. Inflammation was increased in those with infection and respiratory symptoms; however, the majority of those infected were asymptomatic. Radiologic evidence of structural lung disease was common, with 46 (80.7%) having an abnormal CT; 11 (18.6%) had bronchial dilatation, 27 (45.0%) had bronchial wall thickening, and 40 (66.7%) had gas trapping. On multivariate analysis, free neutrophil elastase activity was associated with structural lung disease. Most children with structural lung disease had no clinically apparent lung disease. These data support the need for full evaluation in infancy and argue for new treatment strategies, especially those targeting neutrophilic inflammation, if the promise of NBS for CF is to be realized.

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

    NASA Astrophysics Data System (ADS)

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

    1995-09-01

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

  2. Inadequate erythroid response to hypoxia in cystic fibrosis.

    PubMed

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

    1984-07-01

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

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

    PubMed

    Goralski, Jennifer L; Donaldson, Scott H

    2014-06-01

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

  4. Serum lipoprotein concentrations in cystic fibrosis

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

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

    1978-02-17

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

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

    PubMed

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

    2017-01-01

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

  6. Sodium channel blockers for cystic fibrosis.

    PubMed

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

    2014-04-09

    clinically relevant outcomes. We found no evidence that the topical administration of a short-acting sodium channel blocker improves respiratory condition in people with cystic fibrosis and some limited evidence of deterioration in lung function.

  7. Sodium channel blockers for cystic fibrosis.

    PubMed

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

    2012-03-14

    evidence that the topical administration of a short-acting sodium channel blocker improves respiratory condition in people with cystic fibrosis and some limited evidence of deterioration in lung function.

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

    PubMed

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

    2014-01-01

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

  9. Voriconazole pharmacokinetic variability in cystic fibrosis lung transplant patients.

    PubMed

    Berge, M; Guillemain, R; Boussaud, V; Pham, M-H; Chevalier, P; Batisse, A; Amrein, C; Dannaoui, E; Loriot, M-A; Lillo-Le Louet, A; Billaud, E M

    2009-06-01

    Aspergillosis is a high-risk complication in cystic fibrosis (CF) lung transplant patients. Azole antifungal drugs inhibit CYP3A4, resulting in significant metabolic drug-drug interactions. Voriconazole (VRZ) was marketed without therapeutic drug monitoring (TDM) recommendations, consistent with favorable pharmacokinetics, but regular determinations of plasma VRZ concentration were introduced in our center to manage interactions with calcineurin inhibitors and to document the achievement of therapeutic levels. VRZ TDM data analysis for trough concentration (C0) and peak concentration (C2) was carried out, using validated liquid chromatography assay with ultraviolet detection, for 35 CF lung transplant patients (mean age 25 years, mean weight 47 kg, balanced sex ratio) since 2003. Therapeutic range (C0: 1.5 +/- 0.5 - C2 : 4.0 +/- 1.0 mg/L) was expressed relative to pivotal pharmacokinetic trial data. The duration of VRZ treatment ranged from 9 days to 22 months. The recommended standard dose of VRZ (200 mg twice a day, following the loading dose) resulted in significant plasma concentrations (>0.5 mg/L) in 20% of CF lung transplant patients. Therapeutic concentrations were obtained using higher doses (average 570 +/- 160 mg/day, +43%, P<0.01). Despite adaptation, C0 remained <0.5 mg/L (11%), even when the drug was administered intravenously, highlighting the variability of VRZ pharmacokinetics, possibly enhanced by CYP2C19 polymorphism. The risk of inefficacy during periods of underdosage was overcome by treatment with antifungal drug combinations (caspofungin, n=10). The therapeutic index was limited by neurologic effects (14%) and hepatic abnormalities (30%). VRZ concentrations correlated significantly (P<0.01) with aspartate aminotransferase levels but not with bilirubin levels. VRZ acted as a metabolic inhibitor of tacrolimus (C0 to dose ratio 5.8 +/- 2.6, n=31/VRZ versus 1.7 +/- 0.9 alone, P<0.001). Large changes in azole concentration affected the magnitude of

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

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

  11. Festival food coma in cystic fibrosis.

    PubMed

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

    2013-07-01

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

  12. The outcome of pregnancies in women with cystic fibrosis--single centre experience 1998-2011.

    PubMed

    Thorpe-Beeston, J G; Madge, S; Gyi, K; Hodson, M; Bilton, D

    2013-02-01

    To describe the maternal and fetal outcomes of pregnancies in women with cystic fibrosis. Retrospective study. Single obstetric hospital and adult cystic fibrosis centre. Retrospective case-note review of pregnant women with cystic fibrosis referred for antenatal care and delivery. Maternal and fetal outcomes, mode of delivery, lung function and pregnancy complications. Forty-eight pregnancies were studied in 41 women. There were two miscarriages, 44 singleton pregnancies and two sets of twins. All babies were liveborn and survived. The mean gestational age at delivery was 35.9 ± 3.3 weeks. There were no fetal abnormalities or terminations of pregnancy. The median birthweight centile was 31.9 (interquartile range 14.9-55.6). Twenty-five (52.1%) of the women had pancreatic insufficiency and 17 (35.4%) required insulin. There was a positive correlation between booking predicted forced expiratory volume in 1 second (FEV(1) ) and gestational age at delivery (P < 0.01). Women with FEV(1) ≤60% were more likely to deliver earlier and by caesarean section compared with women with FEV(1) >60% (35.0 ± 3.2 weeks versus 37.1 ± 3.0 weeks; P = 0.02 and 75.0% versus 25.0%; P = 0.01). Three of the seven women with an FEV(1) <40% died within 18 months of delivery. Four of the eight women with FEV(1) 40-50% died between 2 and 8 years after delivery. Pregnancy for women with cystic fibrosis is possible and results in favourable maternal and fetal outcomes, but the incidence of preterm delivery and caesarean section is increased. Women with pre-existing poor lung function should be counselled antenatally to ensure that they understand the implications of their shortened life-expectancy and parenthood. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

  13. Allergic Bronchopulmonary Aspergillosis in Patient with Cystic Fibrosis - a Case Report

    PubMed Central

    IONESCU, Marcela Daniela; BALGRADEAN, Mihaela; MARCU, Veronica

    2014-01-01

    Asthma with allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity disease of the lungs due to an immune response to Aspergillus fumigattus (Af) antigens, is rarely seen in children, other than complicating cystic fibrosis. We present the case of a 14 – year- old female teenager with cystic fibrosis (CF), admitted in our hospital with respiratory failure and persistent cyanosis. Chest X-ray showed perihilar and upper lobes pulmonary infiltrates. Her airway cultures were positive for methicillin resistant staphilococcus aureus (MRSA) and non-mucoid Pseudomonas aeruginosa. She was prescribed intravenous antibiotherapy with ceftazidime and vancomycine (to which MRSA and Pseudomonas aeruginosa were susceptible). Pulmonary function testing (PFT) revealed severe obstructive lung disease. After ten days of intravenous antibiotics and first five days of corticosteroid, the patient's FEV1 was 68% of predicted. Total serum IgE and IgE antibodies to Aspergillus fumigatus were elevated. These results raised the possibility of allergic bronchopulmonary aspergillosis (ABPA). The possibility of ABPA should be considered in all pulmonary exacerbation and in order to determine if ABPA is developing or if an exacerbation is occurring, a serial monitoring of IgE levels should be performed. PMID:25705310

  14. Higher mobility scores in patients with cystic fibrosis are associated with better lung function.

    PubMed

    Thobani, Aneesha; Alvarez, Jessica A; Blair, Shaina; Jackson, Kaila; Gottlieb, Eric R; Walker, Seth; Tangpricha, Vin

    2015-01-01

    The purpose of this study was to determine whether mobility and physical activity were associated with lung function in adults with cystic fibrosis (CF). This was a prospective cohort observational study in an urban, academic, specialized care center. Participants were ambulatory, nonhospitalized adults with CF. Mobility was assessed monthly by the Life-Space Assessment (LSA) questionnaire and quarterly by pedometer. Lung function was assessed by spirometry. 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. 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.

  15. CFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease.

    PubMed

    Fernandez Fernandez, Elena; de Santi, Chiara; De Rose, Virginia; Greene, Catherine M

    2018-05-11

    Obstructive lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are causes of high morbidity and mortality worldwide. CF is a multiorgan genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is characterized by progressive chronic obstructive lung disease. Most cases of COPD are a result of noxious particles, mainly cigarette smoke but also other environmental pollutants. Areas covered: Although the pathogenesis and pathophysiology of CF and COPD differ, they do share key phenotypic features and because of these similarities there is great interest in exploring common mechanisms and/or factors affected by CFTR mutations and environmental insults involved in COPD. Various molecular, cellular and clinical studies have confirmed that CFTR protein dysfunction is common in both the CF and COPD airways. This review provides an update of our understanding of the role of dysfunctional CFTR in both respiratory diseases. Expert Commentary: Drugs developed for people with CF to improve mutant CFTR function and enhance CFTR ion channel activity might also be beneficial in patients with COPD. A move toward personalized therapy using, for example, microRNA modulators in conjunction with CFTR potentiators or correctors, could enhance treatment of both diseases.

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

    PubMed

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

    2016-07-20

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

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

    PubMed

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

    2014-05-22

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

  18. Therapies for Cystic Fibrosis

    MedlinePlus

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

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

    PubMed

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

    2017-11-01

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

  20. Distorted body image and anorexia complicating cystic fibrosis in an adolescent.

    PubMed

    Gilchrist, Francis J; Lenney, Warren

    2008-09-01

    A 15 year old girl with cystic fibrosis has been dieting and losing weight for 2 years. Despite being underweight she aims to lose a further 6 kg to become a "size zero". Her falling weight has been associated with deteriorations in her general health and lung function, which is exacerbated by poor compliance. The situation has been complicated further by her becoming pregnant.

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

    PubMed

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

    2017-01-01

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

  2. Genetic counselling issues in cystic fibrosis.

    PubMed

    Culling, Bronwyn; Ogle, Robert

    2010-06-01

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

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

    PubMed

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

    2014-07-01

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

  4. Randomised controlled trial of inhaled corticosteroids (fluticasone propionate) in cystic fibrosis

    PubMed Central

    Balfour-Lynn, I.; Klein, N.; Dinwiddie, R.

    1997-01-01

    Accepted 29 April 1997
 BACKGROUND—Controlling lung inflammation may be the key to improving morbidity and mortality in cystic fibrosis.
OBJECTIVE—To assess the effects of inhaled corticosteroids on lung inflammation in cystic fibrosis.
DESIGN—Double blind placebo controlled randomised sequence crossover trial. Fluticasone propionate (400 µg/day) was given as a dry powder inhaler for six weeks with a four week washout period before crossover.
OUTCOME MEASURES—Sputum inflammatory markers (interleukin-8, tumour necrosis factor-α (TNF-α) and neutrophil elastase—both free and bound to α1-antiprotease), sputum interleukin-10, lung function, and symptomatology.
SUBJECTS—Twenty three children from a regional cystic fibrosis centre were enrolled into the study, with mean age 10.3 years (range 7 to 17 years) and mean baseline forced expiratory volume in one second (FEV1) of 64% (range 21% to 102%) predicted for sex and height. One patient was excluded for non-compliance to the study protocol.
RESULTS—No significant benefit was shown for the use of fluticasone propionate in any of the outcomes. For sputum interleukin-8 there was an estimated true treatment median difference of 142 pg/ml (95% confidence interval (CI) 8 to 2866 pg/ml) in favour of placebo; while for maximal expiratory flow at 25% (MEF25%) remaining forced vital capacity predicted for sex and height there was a 15 percentage points (pp) (95% CI 4 to 26 pp) mean treatment difference in favour of placebo. Sputum interleukin-10 was undetected in any samples and unaffected by fluticasone propionate. Neither atopic status, baseline FEV1, nor concomitant DNase therapy had any effect on response to treatment.
CONCLUSIONS—Lack of benefit from fluticasone propionate was most likely due to failure of the drug to penetrate the viscid mucus lining the airways. It is suggested a large multicentre trial with higher doses given for a longer time by a different delivery system is required to

  5. Vitamin E supplementation in people with cystic fibrosis.

    PubMed

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

    2014-12-09

    study, mean difference 11.61 (95% confidence interval 4.77 to 18.45); and at six months, one study, mean difference 19.74 (95% confidence interval 13.48 to 26.00). At one month fat-soluble vitamin E significantly improved serum vitamin E levels compared with control: one month, two studies, mean difference 13.59 (95% CI 9.52 to 17.66). The findings at three months were imprecise; one study; mean difference 6.40 (95% CI -1.45 to 14.25).None of the studies report the review's primary outcomes of vitamin E total lipid ratio or the incidence of vitamin E-specific deficiency disorders, or the secondary outcomes lung function or quality of life. Only one study, comparing water-soluble vitamin E with placebo, reported the secondary outcome of growth and nutritional status (weight), but the results are uncertain due to imprecision around the effect estimate.There was limited detail about randomisation and blinding in the included studies which compromises the quality of the evidence base for the review. The heterogeneous mix of the formulations with differing biovailabilities among these studies also limits the generalisability of the data to the wider cystic fibrosis population. Vitamin E supplementation led to an improvement in vitamin E levels in people with cystic fibrosis, although the studies may have been at risk of bias. No data on other outcomes of interest were available to allow conclusions about any other benefits of this therapy.In future, larger studies are needed, especially in people already being treated with enteric-coated pancreatic enzymes and supplemented with vitamin E, to look at more specific outcome measures such as vitamin E status, lung function and nutritional status. Future studies could also look at the optimal dose of vitamin E required to achieve maximal clinical effectiveness.

  6. Vitamin E supplementation in people with cystic fibrosis.

    PubMed

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

    2017-03-06

    interval 10.59 to 24.74); at three months, one study, mean difference 11.61 (95% confidence interval 4.77 to 18.45); and at six months, one study, mean difference 19.74 (95% confidence interval 13.48 to 26.00). At one month fat-soluble vitamin E significantly improved serum vitamin E levels compared with control: one month, two studies, mean difference 13.59 (95% CI 9.52 to 17.66). The findings at three months were imprecise; one study; mean difference 6.40 (95% confidence interval -1.45 to 14.25).None of the studies report the review's primary outcomes of vitamin E total lipid ratio or the incidence of vitamin E-specific deficiency disorders, or the secondary outcomes lung function or quality of life. Only one study, comparing water-soluble vitamin E with placebo, reported the secondary outcome of growth and nutritional status (weight), but the results are uncertain due to imprecision around the effect estimate.There was limited detail about randomisation and blinding in the included studies which compromises the quality of the evidence base for the review. The heterogeneous mix of the formulations with differing biovailabilities among these studies also limits the generalisability of the data to the wider cystic fibrosis population. Vitamin E supplementation led to an improvement in vitamin E levels in people with cystic fibrosis, although the studies may have been at risk of bias. No data on other outcomes of interest were available to allow conclusions about any other benefits of this therapy.In future, larger studies are needed, especially in people already being treated with enteric-coated pancreatic enzymes and supplemented with vitamin E, to look at more specific outcome measures such as vitamin E status, lung function and nutritional status. Future studies could also look at the optimal dose of vitamin E required to achieve maximal clinical effectiveness.

  7. "No Time to Play": Perceptions toward Physical Activity in Youth with Cystic Fibrosis

    ERIC Educational Resources Information Center

    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…

  8. Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

    PubMed Central

    Tyrrell, Jean

    2016-01-01

    Iron acquisition is vital to microbial survival and is implicated in the virulence of many of the pathogens that reside in the cystic fibrosis (CF) lung. The multifaceted nature of iron acquisition by both bacterial and fungal pathogens encompasses a range of conserved and species-specific mechanisms, including secretion of iron-binding siderophores, utilization of siderophores from other species, release of iron from host iron-binding proteins and haemoproteins, and ferrous iron uptake. Pathogens adapt and deploy specific systems depending on iron availability, bioavailability of the iron pool, stage of infection and presence of competing pathogens. Understanding the dynamics of pathogen iron acquisition has the potential to unveil new avenues for therapeutic intervention to treat both acute and chronic CF infections. Here, we examine the range of strategies utilized by the primary CF pathogens to acquire iron and discuss the different approaches to targeting iron acquisition systems as an antimicrobial strategy. PMID:26643057

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

    PubMed Central

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

    2011-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1990-09-01

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

  11. Nutrient Status of Adults with Cystic Fibrosis

    PubMed Central

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

    2011-01-01

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

  12. YEAR-TO-YEAR CHANGES IN LUNG FUNCTION IN INDIVIDUALS WITH CYSTIC FIBROSIS

    PubMed Central

    Liou, Theodore G.; Elkin, Eric P.; Pasta, David J.; Jacobs, Joan R.; Konstan, Michael W.; Morgan, Wayne J.; Wagener, Jeffrey S.

    2014-01-01

    Background We examined the year-to-year change in FEV1 for individuals and the overall cystic fibrosis population to better understand how individual trends may differ from population trends. Methods We calculated individual yearly changes using the largest annual FEV1 percent predicted (FEV1%) measurement in 20,644 patients (6–45 years old) included in the Epidemiologic Study of Cystic Fibrosis. We calculated yearly population changes using age-specific medians. Results FEV1% predicted decreased 1–3 points per year for individuals, with maximal decreases in 14–15 year olds. Population changes agreed with individual changes up to age 15; however after age 30, yearly population change approximated zero while individual FEV1% predicted decreases were 1–2 points per year. Conclusions Adolescents have the greatest FEV1% predicted decreases; however. loss of FEV1 is a persistent risk in 6–45 year old CF patients. Recognizing individual year-to-year changes may improve patient-specific care and may suggest new methods for measuring program quality. PMID:20471331

  13. Breathing pattern and chest wall volumes during exercise in patients with cystic fibrosis, pulmonary fibrosis and COPD before and after lung transplantation.

    PubMed

    Wilkens, H; Weingard, B; Lo Mauro, A; Schena, E; Pedotti, A; Sybrecht, G W; Aliverti, A

    2010-09-01

    Pulmonary fibrosis (PF), cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) often cause chronic respiratory failure (CRF). In order to investigate if there are different patterns of adaptation of the ventilatory pump in CRF, in three groups of lung transplant candidates with PF (n=9, forced expiratory volume in 1 s (FEV(1))=37+/-3% predicted, forced vital capacity (FVC)=32+/-2% predicted), CF (n=9, FEV(1)=22+/-3% predicted, FVC=30+/-3% predicted) and COPD (n=21, FEV(1)=21+/-1% predicted, FVC=46+/-2% predicted), 10 healthy controls and 16 transplanted patients, total and compartmental chest wall volumes were measured by opto-electronic plethysmography during rest and exercise. Three different breathing patterns were found during CRF in PF, CF and COPD. Patients with COPD were characterised by a reduced duty cycle at rest and maximal exercise (34+/-1%, p<0.001), while patients with PF and CF showed an increased breathing frequency (49+/-6 and 34+/-2/min, respectively) and decreased tidal volume (0.75+/-0.10 and 0.79+/-0.07 litres) (p<0.05). During exercise, end-expiratory chest wall and rib cage volumes increased significantly in patients with COPD and CF but not in those with PF. End-inspiratory volumes did not increase in CF and PF. The breathing pattern of transplanted patients was similar to that of healthy controls. There are three distinct patterns of CRF in patients with PF, CF and COPD adopted by the ventilatory pump to cope with the underlying lung disease that may explain why patients with PF and CF are prone to respiratory failure earlier than patients with COPD. After lung transplantation the chronic adaptations of the ventilatory pattern to advanced lung diseases are reversible and indicate that the main contributing factor is the lung itself rather than systemic effects of the disease.

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

    PubMed

    Kintu, Brett; Brightwell, Alex

    2014-06-01

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

  15. Randomized, single blind, controlled trial of inhaled glutathione vs placebo in patients with cystic fibrosis.

    PubMed

    Calabrese, C; Tosco, A; Abete, P; Carnovale, V; Basile, C; Magliocca, A; Quattrucci, S; De Sanctis, S; Alatri, F; Mazzarella, G; De Pietro, L; Turino, C; Melillo, E; Buonpensiero, P; Di Pasqua, A; Raia, V

    2015-03-01

    In cystic fibrosis (CF) the defective CF transmembrane conductance regulator protein may be responsible for the impaired transport of glutathione (GSH), the first line defense of the lung against oxidative stress. The aim of this single-blind, randomized, placebo-controlled trial was to evaluate the effect of inhaled GSH in patients with CF. 54 adult and 51 pediatric patients were randomized to receive inhaled GSH or placebo twice daily for 12 months. Twelve month treatment with inhaled GSH did not achieve our predetermined primary outcome measure of 15% improvement in FEV1%. Only in patients with moderate lung disease, 3, 6 and 9 months therapy with GSH resulted in a statistically significant increase of FEV1 values from the baseline. Moreover GSH therapy improved 6-minute walking test in pediatric population. GSH was well tolerated by all patients. Inhaled GSH has slight positive effects in CF patients with moderate lung disease warranting further study. ClinicalTrials.gov; No.: NCT01450267; URL: www.clinicaltrialsgov. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  16. Neutrophil Membrane Cholesterol Content is a Key Factor in Cystic Fibrosis Lung Disease.

    PubMed

    White, Michelle M; Geraghty, Patrick; Hayes, Elaine; Cox, Stephen; Leitch, William; Alfawaz, Bader; Lavelle, Gillian M; McElvaney, Oliver J; Flannery, Ryan; Keenan, Joanne; Meleady, Paula; Henry, Michael; Clynes, Martin; Gunaratnam, Cedric; McElvaney, Noel G; Reeves, Emer P

    2017-09-01

    Identification of mechanisms promoting neutrophil trafficking to the lungs of patients with cystic fibrosis (CF) is a challenge for next generation therapeutics. Cholesterol, a structural component of neutrophil plasma membranes influences cell adhesion, a key step in transmigration. The effect of chronic inflammation on neutrophil membrane cholesterol content in patients with CF (PWCF) remains unclear. To address this we examined neutrophils of PWCF to evaluate the cause and consequence of altered membrane cholesterol and identified the effects of lung transplantation and ion channel potentiator therapy on the cellular mechanisms responsible for perturbed membrane cholesterol and increased cell adhesion. PWCF homozygous for the ΔF508 mutation or heterozygous for the G551D mutation were recruited (n=48). Membrane protein expression was investigated by mass spectrometry. The effect of lung transplantation or ivacaftor therapy was assessed by ELISAs, and calcium fluorometric and μ-calpain assays. Membranes of CF neutrophils contain less cholesterol, yet increased integrin CD11b expression, and respond to inflammatory induced endoplasmic reticulum (ER) stress by activating μ-calpain. In vivo and in vitro, increased μ-calpain activity resulted in proteolysis of the membrane cholesterol trafficking protein caveolin-1. The critical role of caveolin-1 for adequate membrane cholesterol content was confirmed in caveolin-1 knock-out mice. Lung transplant therapy or treatment of PWCF with ivacaftor, reduced levels of circulating inflammatory mediators and actuated increased caveolin-1 and membrane cholesterol, with concurrent normalized neutrophil adhesion. Results demonstrate an auxiliary benefit of lung transplant and potentiator therapy, evident by a reduction in circulating inflammation and controlled neutrophil adhesion. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Exopolysaccharides produced by Inquilinus limosus, a new pathogen of cystic fibrosis patients: novel structures with usual components.

    PubMed

    Herasimenka, Yury; Cescutti, Paola; Impallomeni, Giuseppe; Rizzo, Roberto

    2007-11-26

    The major cause of morbidity and mortality in patients with cystic fibrosis, an autosomal recessive disorder, is chronic microbial colonisation of the major airways that leads to exacerbation of pulmonary infection. Several different microbes colonise cystic fibrosis lungs, and Pseudomonas aeruginosa is one of the most threatening, since the establishment of mucoid (alginate producing) strains is ultimately associated with the patient's death. Very recently a new bacterium, named Inquilinus limosus, was repeatedly found infecting the respiratory tract of cystic fibrosis patients. Its multi-resistance characteristic to antibiotics might result in the spreading of I. limosus infection among the cystic fibrosis community, as recently happened with strains of the Burkholderia cepacia complex. Since exopolysaccharides are recognised as important virulence factors in lung infections, the primary structure of the polysaccharide produced by I. limosus strain LMG 20952(T) was investigated as the first step in understanding its role in pathogenesis. The structure was determined by means of methylation analysis, acid degradations, mass spectrometry and NMR spectroscopy. The results showed that the bacterium produced a mixture constituted of the following polymers: [3)-[4,6-O-(1-carboxyethylidene)]-beta-D-Glcp(1-->]n; [2)-[4,6-O-(1-carboxyethylidene)]-alpha-D-Manp(1-->]n. Both polymers were completely substituted with pyruvyl ketal groups, a novel structural characteristic not previously found in bacterial polysaccharides. The absolute configuration of all pyruvyl groups was S. Inspection of possible local conformations assumed by the two polysaccharide chains showed features, which might provide interesting clues for understanding structure-function relationships.

  18. Lung function, symptoms and inflammation during exacerbations of non-cystic fibrosis bronchiectasis: a prospective observational cohort study.

    PubMed

    Brill, Simon E; Patel, Anant R C; Singh, Richa; Mackay, Alexander J; Brown, Jeremy S; Hurst, John R

    2015-02-07

    Exacerbations of non-cystic fibrosis bronchiectasis cause significant morbidity but there are few detailed data on their clinical course and associated physiological changes. The biology of an exacerbation has not been previously described. This was a prospective observational cohort study of 32 outpatients with non-cystic fibrosis bronchiectasis conducted between August 2010 and August 2012. Patients completed a symptom diary card and measured their peak expiratory flow rate (PEFR) daily. Exacerbations were defined as oral antibiotic treatment taken for a worsening of respiratory symptoms. Symptoms and peak flow at exacerbation were analysed, and further measurements including the COPD Assessment Test (CAT) and inflammatory markers were also compared to baseline values. At baseline, health status was significantly related to lung function, prognostic severity and systemic inflammation. 51 exacerbations occurred in 22 patients. Exacerbation symptoms began a median (interquartile range) of 4 (2, 7) days before treatment started and the median exacerbation duration was 16 (10, 29) days. 16% had not recovered by 35 days. At exacerbation, mean PEFR dropped by 10.6% (95% confidence interval 6.9-14.2, p < 0.001) and mean CAT score increased by 6.3 units (3.6-9.1, p = 0.001), median symptom count by 4 (2.25, 6, p < 0.001), and mean CRP by 9.0mg/L (2.3-15.8, p = 0.011). Exacerbations where PEFR fell by ≥10% were longer with more symptoms at onset. Exacerbations of non-CF bronchiectasis are inflammatory events, with worsened symptoms, lung function and health status, and a prolonged recovery period. Symptom diary cards, PEFR and CAT scores are responsive to changes at exacerbation and may be useful tools for their detection and monitoring.

  19. New horizons for cystic fibrosis treatment.

    PubMed

    Fajac, Isabelle; De Boeck, Kris

    2017-02-01

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

  20. [Historical compilation of cystic fibrosis].

    PubMed

    Navarro, Salvador

    2016-01-01

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

  1. Early cystic fibrosis lung disease: Role of airway surface dehydration and lessons from preventive rehydration therapies in mice.

    PubMed

    Mall, Marcus A; Graeber, Simon Y; Stahl, Mirjam; Zhou-Suckow, Zhe

    2014-07-01

    Cystic fibrosis (CF) lung disease starts in the first months of life and remains one of the most common fatal hereditary diseases. Early therapeutic interventions may provide an opportunity to prevent irreversible lung damage and improve outcome. Airway surface dehydration is a key disease mechanism in CF, however, its role in the in vivo pathogenesis and as therapeutic target in early lung disease remains poorly understood. Mice with airway-specific overexpression of the epithelial Na(+) channel (βENaC-Tg) recapitulate airway surface dehydration and phenocopy CF lung disease. Recent studies in neonatal βENaC-Tg mice demonstrated that airway surface dehydration produces early mucus plugging in the absence of mucus hypersecretion, which triggers airway inflammation, promotes bacterial infection and causes early mortality. Preventive rehydration therapy with hypertonic saline or amiloride effectively reduced mucus plugging and mortality in neonatal βENaC-Tg mice. These results support clinical testing of preventive/early rehydration strategies in infants and young children with CF. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

    2013-01-01

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

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

    ERIC Educational Resources Information Center

    Strawhacker, MaryAnn Tapper; Wellendorf, Joyce

    2004-01-01

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

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

    PubMed

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

    1980-09-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2011-11-01

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

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

    PubMed

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

    2018-02-23

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

  9. Epidemic Pseudomonas aeruginosa infection in patients with cystic fibrosis is not a risk factor for poor clinical Outcomes following lung transplantation.

    PubMed

    Pritchard, Julia; Thakrar, Mitesh V; Somayaji, Ranjani; Surette, Michael G; Rabin, Harvey R; Helmersen, Doug; Lien, Dale; Purighalla, Swathi; Waddell, Barbara; Parkins, Michael D

    2016-05-01

    Epidemic strains of Pseudomonas aeruginosa (ePA) causing infection in cystic fibrosis (CF) have been commonly identified from clinics around the world. ePA disproportionally impacts CF patient pre-transplant outcomes manifesting in increased exacerbation frequency, worsened treatment burden and increased rate of lung function decline, and disproportionally leads to death and/or transplantation. As other CF factors such as pre-transplant infection with multi-resistant organisms, and isolation of P. aeruginosa in the post transplant graft, may impact post-transplant outcomes, we sought to determine if infection with ePA similarly adversely impact post-transplant outcomes. Between 1991-2014, 53 CF patients from our center received lung transplants. Bacterial strain typing was performed retrospectively on isolates collected prior to transplantation. Comprehensive chart reviews were performed to obtain baseline patient characteristics and post-transplant outcomes. Of the 53 transplanted patients, 57% of patients were infected with ePA prior to transplant; the other 43% of patients had unique strains of P. aeruginosa. Mean age at transplant was 29.0years for ePA and 33.3years for unique (p=0.04). There were no differences in overall survival (HR=0.75, 95% CI 0.31-1.79), bronchiolitis obliterans syndrome (BOS) free survival (HR 1.43, 95% CI 0.54-4.84) or all other assessed outcomes including exacerbation frequency, chronic renal failure, acute cellular rejections, Aspergillus infection, airway stenosis, and post-transplant lymphoproliferative disorder. Unlike pre-transplant outcomes, CF patients infected with ePA do not experience worse post-transplant outcomes than those infected with unique strains. Therefore, lung transplantation should be considered for all patients with P. aeruginosa infection and end stage lung disease, irrespective of infection with ePA. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2015-01-01

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

  11. Immunological mechanisms behind the cystic fibrosis-ABPA link.

    PubMed

    Hartl, Dominik

    2009-01-01

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

  12. Fungal infection of cystic fibrosis patients - single center experience.

    PubMed

    Garczewska, Barbara; Jarzynka, Sylwia; Kuś, Jan; Skorupa, Wojciech; Augustynowicz-Kopeć, Ewa

    2016-01-01

    Cystic fibrosis (CF) is the most common monogenetic autosomal recessive disease in the human population. This systemic disease is characterized by changes in multiple organs, mainly in the lung tissue and digestive tract. More than 59% of CF patients become sensitized to fungal spores, mostly Aspergillus fumigatus. 5-15% of CF patients develop allergic bronchopulmonary aspergillosis. The aim of the study was to analyse the occurrence of yeast and filamentous fungi of the respiratory infections in CF patients and evaluation of drug resistance. Between 2006 and 2014, mycological evaluation of 42 patients hospitalized at the National Institute of Tuberculosis and Lung Diseases was carried out. 217 specimens from pulmonary tract were collected from 42 patients with cystic fibrosis. 205 (68%) strains of yeast and 96 (32%) filamentous fungi strains were cultured. The most common mould strain was A. fumigatus - 22,2% (67 species). All isolates of filamentous fungi were in vitro 100% susceptible to itraconazole, voriconazole, posaconazole and amphotericin B. A. fumigatus and C. albicans were the most common etiological agents of fungal respiratory pathogens associated with CF patients. A. fumigatus strains were in vitro 100% susceptible to azole and amphotericin B. Two strains of C. albicans and one strain of C. tropicalis were non-susceptible to azole (fluconazole, itraconazole and voriconazole). Scedosporium apiospermum was resistant to amphotericin B (MIC > 32 mg/l) and susceptible to voriconazole (MIC 0.094 mg/l).

  13. A Different Microbiome Gene Repertoire in the Airways of Cystic Fibrosis Patients with Severe Lung Disease

    PubMed Central

    Bacci, Giovanni; Fiscarelli, Ersilia; Taccetti, Giovanni; Dolce, Daniela; Paganin, Patrizia; Morelli, Patrizia; Tuccio, Vanessa; De Alessandri, Alessandra; Lucidi, Vincenzina

    2017-01-01

    In recent years, next-generation sequencing (NGS) was employed to decipher the structure and composition of the microbiota of the airways in cystic fibrosis (CF) patients. However, little is still known about the overall gene functions harbored by the resident microbial populations and which specific genes are associated with various stages of CF lung disease. In the present study, we aimed to identify the microbial gene repertoire of CF microbiota in twelve patients with severe and normal/mild lung disease by performing sputum shotgun metagenome sequencing. The abundance of metabolic pathways encoded by microbes inhabiting CF airways was reconstructed from the metagenome. We identified a set of metabolic pathways differently distributed in patients with different pulmonary function; namely, pathways related to bacterial chemotaxis and flagellar assembly, as well as genes encoding efflux-mediated antibiotic resistance mechanisms and virulence-related genes. The results indicated that the microbiome of CF patients with low pulmonary function is enriched in virulence-related genes and in genes encoding efflux-mediated antibiotic resistance mechanisms. Overall, the microbiome of severely affected adults with CF seems to encode different mechanisms for the facilitation of microbial colonization and persistence in the lung, consistent with the characteristics of multidrug-resistant microbial communities that are commonly observed in patients with severe lung disease. PMID:28758937

  14. Scoliosis in cystic fibrosis - an appraisal

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

    Paling, M.R.; Spasovsky-Chernick, M.

    1982-03-01

    An unusually high prevalence (10%) of scoliosis is described in a series of 151 patients aged four years and older with cystic fibrosis. The scolioses were of the late onset (juvenile and adolescent) type, being typically thoracic with the curve convex to the right, although there was no significant preference for either sex. No direct relationship was found between the spinal curvature and the severity or distribution of the lung disease, although the worse scolioses tended to occur in patients with relatively severe pulmonary involvement. There was no evidence of metabolic bone disease as a predisposing cause. Some indication ofmore » a familial tendency towards scoliosis was apparent, and a genetic or constitutional basis is postulated with an unknown precipitating factor.« less

  15. Aspergillus Bronchitis in Patients with Cystic Fibrosis.

    PubMed

    Brandt, Claudia; Roehmel, Jobst; Rickerts, Volker; Melichar, Volker; Niemann, Nadja; Schwarz, Carsten

    2018-02-01

    Aspergillus fumigatus frequently colonizes the airways of patients with cystic fibrosis (CF) and may cause various severe infections, such as bronchitis. Serological data, sputum dependent markers and longitudinal data of treated cases of Aspergillus bronchitis were evaluated for further description of this infection. This study, which comprises three substudies, aimed to analyze epidemiological data of Aspergillus in CF and the entity of Aspergillus bronchitis. In a first step, data of the German Cystic Fibrosis Registry were used to evaluate the frequency of Aspergillus colonization in patients with CF (n = 2599). Then a retrospective analysis of 10 cases of Aspergillus bronchitis was performed to evaluate longitudinal data for lung function and clinical presentation parameters: sputum production, cough and physical capacity. Finally, a prospective cohort study (n = 22) was conducted to investigate serological markers for Aspergillus bronchitis: total serum IgE, specific serum IgE, specific serum IgG, as well as sputum galactomannan, real-time PCR detection of Aspergillus DNA in sputum and fungal cultures. Analysis of the German CF registry revealed an Aspergillus colonization rate of 32.5% among the 2599 patients. A retrospective data analysis of 10 treated cases revealed the clinical course of Aspergillus bronchitis, including repeated positive sputum culture findings for A. fumigatus, no antibiotic treatment response, total serum IgE levels <200 kU/l, no observation of new pulmonary infiltrates and appropriate antifungal treatment response. Antifungal treatment durations of 4 ± 1.6 (2-6) weeks significantly reduced cough (P = 0.0067), sputum production (P < 0.0001) and lung function measures (P = 0.0358) but not physical capacity (P = 0.0794). From this retrospective study, a prevalence of 1.6% was calculated. In addition, two cases of Aspergillus bronchitis were identified in the prospective cohort study according to immunological, molecular

  16. Chronic Rhinosinusitis in Patients with Cystic Fibrosis.

    PubMed

    Hamilos, Daniel L

    2016-01-01

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

  17. Lumacaftor/Ivacaftor in Patients Aged 6-11 Years with Cystic Fibrosis and Homozygous for F508del-CFTR.

    PubMed

    Milla, Carlos E; Ratjen, Felix; Marigowda, Gautham; Liu, Fang; Waltz, David; Rosenfeld, Margaret

    2017-04-01

    Combination lumacaftor/ivacaftor has been shown to improve lung function and other endpoints in patients aged 12 years and older with cystic fibrosis and homozygous for F508del-CFTR, but it has not been assessed in younger patients. In this open-label phase III trial, we evaluated the safety, tolerability, pharmacodynamics, and efficacy of lumacaftor/ivacaftor combination therapy in patients aged 6-11 years with cystic fibrosis who were homozygous for F508del-CFTR. Patients (N = 58) received 200 mg lumacaftor/250 mg ivacaftor orally every 12 hours for 24 weeks in addition to their existing cystic fibrosis medications. Lumacaftor/ivacaftor was well tolerated; the safety profile was generally similar to that observed in larger lumacaftor/ivacaftor trials with older patients. Four patients discontinued (two because of drug-related adverse events: elevated liver transaminases, n = 1; rash, n = 1). No safety concerns were associated with spirometry. No significant changes in percent predicted FEV 1 were observed (change from baseline at Week 24, +2.5 percentage points; 95% confidence interval [CI], -0.2 to 5.2; P = 0.0671). At Week 24, significant improvements from baseline were observed in sweat chloride (-24.8 mmol/L; 95% CI, -29.1 to -20.5; P < 0.0001), body mass index z score (+0.15; 95% CI, 0.08 to 0.22; P < 0.0001), Cystic Fibrosis Questionnaire-Revised respiratory domain score (+5.4; 95% CI, 1.4 to 9.4; P = 0.0085), and lung clearance index based on lung volume turnover required to reach 2.5% of starting N 2 concentration (-0.88; 95% CI, -1.40 to -0.37; P = 0.0018). Lumacaftor/ivacaftor was well tolerated in this young population; no new safety concerns were identified. Improvements in lung clearance index, sweat chloride, nutritional status, and health-related quality of life were observed after 24 weeks of treatment. Clinical trial registered with www.clinicaltrials.gov (NCT01897233).

  18. Short-Term Effect of Autogenic Drainage on Ventilation Inhomogeneity in Adult Subjects With Stable Non-Cystic Fibrosis Bronchiectasis.

    PubMed

    Poncin, William; Reychler, Grégory; Leeuwerck, Noémie; Bauwens, Nathalie; Aubriot, Anne-Sophie; Nader, Candice; Liistro, Giuseppe; Gohy, Sophie

    2017-05-01

    Lung clearance index (LCI), a measure of ventilation inhomogeneity derived from a multiple-breath washout test, is a promising tool for assessing airway function in patients with non-cystic fibrosis bronchiectasis. However, it is unknown whether ventilation inhomogeneity could improve after successful elimination of excessive secretions within bronchiectasis. The objective of this work was to assess the short-term effects of lung secretion clearance using the autogenic drainage technique on standard lung function tests and LCI in subjects with non-cystic fibrosis bronchiectasis. Nitrogen-based multiple-breath washout, spirometry, and body plethysmography tests were performed 30 min before autogenic drainage in adults with stable non-cystic fibrosis bronchiectasis. The autogenic drainage session was followed by a 5-min break, after which the tests were repeated in the same order. Sputum expectorated during autogenic drainage was quantified as dry weight and correlated with change between post- and pre-measurements (Δ). Paired t test or Wilcoxon signed-rank tests were used to compare pre- and post-autogenic drainage measurement outcomes. A P value of ≤.05 was considered as statistically significant. Twenty-four subjects were studied (18 females, median age [range]: 65 [21-81] y). Mean ± SD LCI significantly improved after autogenic drainage (10.88 ± 2.62 vs 10.53 ± 2.35, P = .042). However, only 20% of subjects with mucus hyperproduction during autogenic drainage had a ΔLCI that exceeded measurement variability. The percent of predicted slow vital capacity (SVC%) also slightly improved (88.7 ± 19.3% vs 90 ± 19.1%, P = .02). ΔLCI was inversely related to dry sputum weight (r = -.48, P = .02) and ΔSVC% (r = -.64, P = .001). ΔSVC% also correlated with dry sputum weight (r = 0.46, P = .02). In adults with non-cystic fibrosis bronchiectasis and mucus hypersecretion, autogenic drainage improved ventilation inhomogeneity. LCI change may be the result of the

  19. What is Cystic Fibrosis?

    MedlinePlus

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

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

    PubMed

    Cholon, Deborah M; Gentzsch, Martina

    2018-03-01

    Significant progress has been achieved in developing precision therapies for cystic fibrosis; however, highly effective treatments that target the ion channel, CFTR, are not yet available for many patients. As numerous CFTR therapeutics are currently in the clinical pipeline, reliable screening tools capable of predicting drug efficacy to support individualized treatment plans and translational research are essential. The utilization of bronchial, nasal, and rectal tissues from individual cystic fibrosis patients for drug testing using in vitro assays such as electrophysiological measurements of CFTR activity and evaluation of fluid movement in spheroid cultures, has advanced the prediction of patient-specific responses. However, for precise prediction of drug effects, in vitro models of CFTR rescue should incorporate the inflamed cystic fibrosis airway environment and mimic the complex tissue structures of airway epithelia. Furthermore, novel assays that monitor other aspects of successful CFTR rescue such as restoration of mucus characteristics, which is important for predicting mucociliary clearance, will allow for better prognoses of successful therapies in vivo. Additional cystic fibrosis treatment strategies are being intensively explored, such as development of drugs that target other ion channels, and novel technologies including pluripotent stem cells, gene therapy, and gene editing. The multiple therapeutic approaches available to treat the basic defect in cystic fibrosis combined with relevant precision medicine models provide a framework for identifying optimal and sustained treatments that will benefit all cystic fibrosis patients. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  1. Upper lobe fibrosis: a novel manifestation of chronic allograft dysfunction in lung transplantation.

    PubMed

    Pakhale, Smita Sakha; Hadjiliadis, Denis; Howell, David N; Palmer, Scott M; Gutierrez, Carlos; Waddell, Thomas K; Chaparro, Cecilia; Davis, R Duane; Keshavjee, Shaf; Hutcheon, Michael A; Singer, Lianne G

    2005-09-01

    Lung transplantation is an established treatment modality for a number of chronic lung diseases. Long-term survival after lung transplantation is limited by chronic allograft dysfunction, usually manifested by bronchiolitis obliterans syndrome. We describe a case series with upper lobe fibrosis, a novel presentation of chronic allograft dysfunction. We reviewed lung transplants at the Toronto General Hospital and Duke University Hospital from 1990 to 2002 and identified patients with upper lobe fibrosis. Thirteen of 686 patients (6 women) developed upper lobe fibrosis (Toronto, 9; Duke, 4); 12 of 13 had bilateral transplants. The median age at diagnosis was 42 years (range, 19-70). Primary diagnoses were cystic fibrosis, 6; emphysema, 4; sarcoidosis, 1; and pulmonary fibrosis, 2 patients. Radiographic diagnosis was made at a median of 700 days post-transplant (range, 150-2,920). Pulmonary function tests demonstrated predominantly a progressively worsening restrictive pattern. Open lung biopsy specimens revealed dense interstitial fibrosis, with occasional features of obliterative bronchitis, bronchiolitis obliterans obstructive pneumonia, and aspiration. Nine patients died at a median follow-up of 2,310 days (range, 266-3,740), 8 due to respiratory failure. Upper lobe fibrosis is a novel presentation of chronic allograft dysfunction in lung transplant recipients and is differentiated from bronchiolitis obliterans syndrome on the basis of physiologic and radiologic findings.

  2. New and emerging targeted therapies for cystic fibrosis

    PubMed Central

    Rowe, Steven M

    2016-01-01

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

  3. Chronic infection sustained by a Pseudomonas aeruginosa High-Risk clone producing the VIM-1 metallo-β-lactamase in a cystic fibrosis patient after lung transplantation.

    PubMed

    Pollini, Simona; Mugnaioli, Claudia; Dolce, Daniela; Campana, Silvia; Neri, Anna Silvia; Taccetti, Giovanni; Rossolini, Gian Maria

    2018-02-12

    The significance of chronic lung infection by multidrug-resistant (MDR) pathogens in Cystic Fibrosis (CF) transplanted patients remains controversial, and the available information is overall limited. Here we describe the case of a chronic infection, sustained by a metallo-β-lactamase (MBL)-producing P. aeruginosa strain, in a CF patient following lung transplantation. Twelve P. aeruginosa isolates collected from a CF patient over a 15-years follow-up period after lung transplantation were analysed for their antibiotic susceptibility profile, MBL production and clonal relatedness. Available clinical and microbiological records were reviewed. The transplanted CF patient was chronically infected by an MBL-producing P. aeruginosa strain which harboured a bla VIM-1 determinant inserted into a novel class 1 integron. The strain exhibited an MDR phenotype and belonged to the globally widespread ST235 epidemic clonal lineage, which however is not a typical CF-associated epidemic clone. Despite the chronic infection, the long-term outcome of this patient during the post-transplant period was characterized by the absence of acute exacerbations and by a mostly stable pulmonary function. This report provides one of the few descriptions of MBL-producing P. aeruginosa infections in CF patients, and the first description of such an infection after lung transplantation in these patients. Infection with the MBL-producing strain apparently did not significantly affect the patient pulmonary function. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  4. Pharmacogenetics of cystic fibrosis treatment.

    PubMed

    Carter, Suzanne C; McKone, Edward F

    2016-08-01

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

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

    PubMed

    Yamada, Akihiro; Komaki, Yuga; Komaki, Fukiko; Micic, Dejan; Zullow, Samantha; Sakuraba, Atsushi

    2018-04-26

    The management and life expectancy of patients with cystic fibrosis have improved substantially in the past three decades, which has resulted in an increased number of these patients being diagnosed with malignancies. Our aim was to assess the risk of gastrointestinal cancers in patients with cystic fibrosis. In this systematic review and meta-analysis, we searched PubMed, MEDLINE, Google Scholar, Scopus, Embase, and Cochrane databases with no language restrictions for studies published from inception of the databases to Aug 1, 2017, assessing the risk of gastrointestinal cancers in patients with cystic fibrosis. We also searched abstracts from scientific meetings and the bibliographies of identified articles for additional references. Studies were included if they reported the standardised incidence ratio (SIR) or incidence ratio per person-years. No exclusion criteria with regard to patient characteristics (age, sex, comorbidities, cystic fibrosis mutation type), study setting (location and time period), or method of reporting cancer diagnoses were applied. The primary outcome was risk of gastrointestinal cancer and site-specific gastrointestinal cancers in patients with cystic fibrosis compared with the general population. Pooled summary estimates were calculated using a random-effects model, and subgroup analyses were done to establish whether risk of gastrointestinal cancer varied according to patient lung transplant status. The study is registered with PROSPERO, number CRD42017075396. Our search identified 95 681 records, of which six cohort studies including 99 925 patients (544 695 person-years) were eligible for the meta-analysis. The overall risk of gastrointestinal cancer was significantly higher in patients with cystic fibrosis than in the general population (pooled SIR 8·13, 95% CI 6·48-10·21; p<0·0001; log SIR 2·10, 95% CI 1·87-2·32; p<0·0001, I 2 =93·93%). Subgroup analyses showed that the risk of gastrointestinal cancer among patients

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

    PubMed

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

    2018-02-01

    relevant confounders, lung function and body mass index were associated with V.O2peak. CFTR functional genotype class was not associated with maximal exercise capacity in patients with cystic fibrosis overall, but those with at least one copy of a F508del-CFTR mutation and a single class V mutation had lower maximal exercise capacity.

  7. Expression of the cystic fibrosis transmembrane conductance regulator gene in the respiratory tract of normal individuals and individuals with cystic fibrosis

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

    Trapnell, B.C.; Chinshyan Chu; Paakko, P.K.

    1991-08-01

    The most common mutation of the cystic fibrosis transmembrane conductance regulator gene, CFTR, associated with the clinical disorder cystic fibrosis (CF) is called {Delta}Phe{sup 508}, a triple-base deletion resulting in loss of phenylalanine at residue 508 of the predicted 1480-amino acid CFTR protein. In the context that the lung is the major site of morbidity and mortality in CF, the authors evaluated airway epithelial cells for CFTR mRNA transcripts in normal individuals, normal-{Delta}Phe{sup 508} heterozygotes, and {Delta}Phe{sup 508} homozygotes to determine if the normal and {Delta}Phe{sup 508} CFTR alleles are expressed in the respiratory epithelium, to what extent they aremore » expressed, and whether there are relative differences in the expression of the normal and abnormal alleles at the mRNA level. Respiratory tract epithelial cells recovered by fiberoptic bronchoscopy with a cytology brush demonstrated CFTR mRNA transcripts with sequences appropriately reflecting the normal and {Delta}Phe{sup 508} CFTR alleles of the various study groups. CFTR gene expression quantified by limited polymerase chain reaction amplification showed that in normal individuals, CFTR mRNA transcripts are expressed in nasal, tracheal, and bronchial epithelial cells.« less

  8. Drug therapies for reducing gastric acidity in people with cystic fibrosis.

    PubMed

    Ng, Sze May; Francini, Angelo J

    2012-04-18

    Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, abstract books and conference proceedings.Most recent search of the Group's Trials Register: 15 February 2012. All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment. Both authors independently selected trials, assessed trial quality and extracted data. Thirty-eight trials were identified from the searches. Sixteen trials, with 256 participants, were suitable for inclusion. Seven trials were limited to children and three trials enrolled only adults. Meta-analysis was not performed. However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures

  9. Nutrition Status Parameters and Hydration Status by Bioelectrical Impedance Vector Analysis Were Associated With Lung Function Impairment in Children and Adolescents With Cystic Fibrosis.

    PubMed

    Hauschild, Daniela Barbieri; Barbosa, Eliana; Moreira, Emilia Addison Machado; Ludwig Neto, Norberto; Platt, Vanessa Borges; Piacentini Filho, Eduardo; Wazlawik, Elisabeth; Moreno, Yara Maria Franco

    2016-06-01

    (1) To compare nutrition and hydration status between a group of children/adolescents with cystic fibrosis (CFG; n = 46; median age, 8.5 years) and a control group without cystic fibrosis (CG). (2) To examine the association of nutrition and hydration status with lung function in the CFG. A cross-sectional study. Nutrition screening, anthropometric parameters, and bioelectrical impedance analysis (BIA) were assessed. The z scores for body mass index for age, height for age, mid upper arm circumference, triceps and subscapular skinfold thickness, mid upper arm muscle area, resistance/height, and reactance/height were calculated. Bioelectrical impedance vector analysis was conducted. Forced expiratory volume in 1 second <80% was considered lung function impairment. An adjusted logistic regression was applied (P < .05). In the CFG, lung function impairment was observed in 51.1%. All anthropometric parameters were lower, and the mean z-resistance/height and z-reactance/height were higher in the CFG (P < .05) compared with the CG. In the CFG, 43% were severely/mildly dehydrated, while none were in the CG (P = .007). In the CFG, there was an association between high nutrition risk-via nutrition screening (odds ratio [OR], 22.28; P < .05), lower values of anthropometric parameters, higher z-resistance/height (OR, 2.23; P < .05) and z-reactance/height (OR, 1.81; P < .05), and dehydration (OR, 4.94; P < .05)-and lung function impairment. The CFG exhibited a compromised nutrition status assessed by anthropometric and BIA parameters. Nutrition screening, anthropometric and BIA parameters, and hydration status were associated with lung function. © 2016 American Society for Parenteral and Enteral Nutrition.

  10. Transcriptional Activation of Mucin by Pseudomonas aeruginosa Lipopolysaccharide in the Pathogenesis of Cystic Fibrosis Lung Disease

    NASA Astrophysics Data System (ADS)

    Li, Jian-Dong; Dohrman, Austin F.; Gallup, Marianne; Miyata, Susumu; Gum, James R.; Kim, Young S.; Nadel, Jay A.; Prince, Alice; Basbaum, Carol B.

    1997-02-01

    An unresolved question in cystic fibrosis (CF) research is how mutations of the CF transmembrane conductance regulator, a CI ion channel, cause airway mucus obstruction leading to fatal lung disease. Recent evidence has linked the CF transmembrane conductance regulator mutation to the onset and persistence of Pseudomonas aeruginosa infection in the airways, and here we provide evidence directly linking P. aeruginosa infection to mucus overproduction. We show that P. aeruginosa lipopolysaccharide profoundly upregulates transcription of the mucin gene MUC 2 in epithelial cells via inducible enhancer elements and that this effect is blocked by the tyrosine kinase inhibitors genistein and tyrphostin AG 126. These findings improve our understanding of CF pathogenesis and suggest that the attenuation of mucin production by lipopolysaccharide antagonists and tyrosine kinase inhibitors could reduce morbidity and mortality in this disease.

  11. Technological advances shed light on left ventricular cardiac disturbances in cystic fibrosis.

    PubMed

    Sayyid, Zahra N; Sellers, Zachary M

    2017-07-01

    Cystic fibrosis (CF), the most common autosomal recessive lethal disease in Caucasians, causes chronic pulmonary disease and can lead to cor pulmonale with right ventricular dysfunction. The presence of the cystic fibrosis transmembrane conductance regulator (CFTR) in cardiac myocardia has prompted debate regarding possible defective ion channel-induced cardiomyopathy. Clinical heart disease in CF is considered rare and is restricted to case reports. It has been unclear if this is due to the lack of physiological importance of CFTR in the heart, the relatively short lifespan of those with CF, or a technical inability to detect subclinical disease. Extensive echocardiographic investigations have yielded contradictory results, leading to the dogma that left ventricular defects in CF occur secondary to lung disease. In this review, we consider why studies examining heart function in CF have not provided clarity on this topic. We then focus on data from new echocardiographic and magnetic resonance imaging technology, which are providing greater insight into cardiac function in CF and demonstrating that, in addition to secondary effects from pulmonary disease, there may be an intrinsic primary defect in the CF heart. With advancing lifespans and activity levels, understanding the risk of cardiac disease is vital to minimizing morbidity in adults with CF. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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

    PubMed

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

    2017-07-15

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

  13. The clinical presentations of pulmonary aspergillosis in children with cystic fibrosis - preliminary report.

    PubMed

    Walicka-Serzysko, Katarzyna; Sands, Dorota

    2015-01-01

    Pulmonary aspergillosis is a very serious complication in cystic fibrosis (CF) patients due to the great variety of its clinical presentations and the fact that it worsens the prognosis. We can distinguish the following: Aspergillus colonization (AC), Aspergillus infection (AI) and allergic bronchopulmonary aspergillosis (ABPA). Aspergillus colonization (AC) is defined as isolation of Aspergillus spp. from 50% ormore sputum samples over six months to one year without observing deterioration in lung function and an increase in such respiratory symptoms as cough. Aspergillus infection (AI) is diagnosed in subjects with Aspergillus colonization and a decline in lung function, respiratory exacerbation with and without cough or with an incomplete response to a 2-4 week course of appropriate broad-spectrum antibiotics. Aspergillus can also cause allergic bronchopulmonary aspergillosis (ABPA). The classic diagnostic criteria of allergic bronchopulmonary aspergillosis in cystic fibrosis have been established during the Cystic Fibrosis Foundation Conference in 2001. To establish the prevalence of pulmonary aspergillosis in children with cystic fibrosis under the care of our centre and to investigate the potential predisposing factors to Aspergillus infection (AI) and allergic bronchopulmonary aspergillosis (ABPA). An analysis was conducted of the medical documentation of 374 children aged 0-18 years monitored regularly in the Cystic Fibrosis Centre of the Institute of Mother and Child in Warsaw from 01.01.2010 to 31.08.2014. We selected 13 patients who presented an evidently worsening clinical status and course of the bronchopulmonary disease (decline in lung function parameters, respiratory exacerbations with increased cough, new or recent abnormalities in chest imaging) despite standard treatment with a high calorie diet, supplementation of pancreatic enzymes and vitamins, dornase alpha, inhaled and/or oral antibiotics, inhaled or oral corticosteroids, bronchodilators

  14. Pharmacokinetics and Tolerability of Oral Sildenafil in Adults with Cystic Fibrosis Lung Disease

    PubMed Central

    Taylor-Cousar, JL; Wiley, C; Felton, LA; St Clair, C; Jones, M; Curran-Everett, D; Poch, K; Nichols, DP; Solomon, GM; Saavedra, MT; Accurso, FJ; Nick, JA

    2014-01-01

    Rationale Airway inflammation is central to cystic fibrosis (CF) pathophysiology. Pre-clinical models have shown that phosphodiesterase inhibitors (PDEi) like sildenafil have anti-inflammatory activity. PDEi have not been studied in CF subjects. Objectives We evaluated the pharmacokinetics, tolerability, and safety of sildenafil in subjects with CF. Sputum biomarkers were used to explore efficacy. Methods An open-label pilot study of oral sildenafil administration was conducted in adults with mild to moderate CF lung disease. Subjects received oral sildenafil 20 or 40 mg p.o. t.i.d. for 6 weeks. Measurements and Main Results Twenty subjects completed the study. Estimated elimination rate constants were statistically different in subjects with CF compared to previously published non-CF subjects. Side effects were generally mild. There were no drug-related serious adverse events. Sputum neutrophil elastase activity decreased. Conclusions Subjects with CF may eliminate sildenafil at a faster rate than non-CF subjects. Sildenafil administration was safe in subjects with CF, and decreased sputum elastase activity. Sildenafil warrants further study as an anti-inflammatory in CF. PMID:25466700

  15. Differences between WHO AND CDC early growth measurements in the assessment of Cystic Fibrosis clinical outcomes.

    PubMed

    Usatin, Danielle; Yen, Elizabeth H; McDonald, Catherine; Asfour, Fadi; Pohl, John; Robson, Jacob

    2017-07-01

    Early childhood growth status has been used to predict long-term clinical outcomes in Cystic Fibrosis (CF) patients. Adulthood CF outcomes based on early weight-for-length (WFL) measurements, using either World Health Organization (WHO) or Centers for Disease Control (CDC) scales, have not been compared. Cystic Fibrosis Foundation registry patients were studied (n=3014). Participants were categorized at age two years as WFL <50th percentile on both WHO and CDC scales, ≥50th percentile on WHO but not CDC, or ≥50th percentile on both. Pulmonary function and overall survival were assessed at age 18years. Stepwise gains in pulmonary function and lung transplant-free survival were noted across the three increasing WFL categories. Children with CF who achieve higher WFL at age two years have improved pulmonary and survival outcomes into adulthood. CF providers should continue to utilize current early growth recommendations, with goal WFL ≥50th percentile on CDC growth charts before age two. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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

    PubMed

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

    2017-05-01

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

  17. Enteral tube feeding in adults with cystic fibrosis; patient choice and impact on long term outcomes.

    PubMed

    White, H; Morton, A M; Conway, S P; Peckham, D G

    2013-12-01

    Enteral tube feeding (ETF) has been evaluated in paediatric and mixed child and adult populations with cystic fibrosis, demonstrating positive outcomes from 6 months to 2 years post insertion. No studies have examined the longer term nutritional and clinical outcomes in an exclusively adult population with cystic fibrosis or compared the outcomes for those who meet standard criteria and opt to undertake or decline ETF. Twenty three out of 380 patients attending the Leeds Regional Adult CF unit fulfilled the standard criteria for commencing ETF (CF Trust, 2002) between 2004 and 2008. Weight, BMI, FEV1, FVC, CFRD, and number of intravenous antibiotic treatment days were collected at 1 year pre baseline, at baseline, and at 1, 2, and 3 years post baseline for all these patients whether they accepted or declined ETF. Seventeen of the 23 patients agreed to accept a programme of ETF, two of whom died within the first year of ETF. In the remaining patients (n=15), weight increased by 19.5% from baseline (p<0.001), BMI increased to within the normal range and lung function stabilised. There was no reduction in the requirement for intravenous antibiotic treatment. The six patients who declined ETF had a decline in lung function and no weight gain. Supplemental enteral tube feeding improves clinical outcomes when administered over 3 years, resulting in significant weight gain, a normal BMI and stabilisation of lung function. It does not reduce intravenous antibiotic treatment days. In contrast those patients eligible for, but who declined ETF, showed a deterioration in lung function and a failure to gain weight and to achieve normal BMI status. Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  18. Respiratory muscle training for cystic fibrosis.

    PubMed

    Hilton, Nathan; Solis-Moya, Arturo

    2018-05-24

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

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

    PubMed Central

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

    1992-01-01

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

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

    ERIC Educational Resources Information Center

    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)

  1. Pro-resolving lipid mediator Resolvin D1 serves as a marker of lung disease in cystic fibrosis.

    PubMed

    Eickmeier, Olaf; Fussbroich, Daniela; Mueller, Klaus; Serve, Friederike; Smaczny, Christina; Zielen, Stefan; Schubert, Ralf

    2017-01-01

    Cystic fibrosis (CF) is an autosomal recessive genetic disorder that affects multiple organs, including the lungs, pancreas, liver and intestine. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) locus lead to defective proteins and reduced Cl- secretion and Na+ hyperabsorption in the affected organs. In addition, patients suffering from CF display chronic inflammation that contributes to the pathogenesis of CF. Recent work suggests that CF patients have a reduced capacity to biosynthesize specialized pro-resolving lipid mediators (SPMs), which contributes to the development and duration of the unwanted inflammation. Alterations in the metabolism of arachidonic acid (AA) and docosahexaenoic acid (DHA) to specialized pro-resolving mediators (SPMs), like lipoxins (LXs), maresins (MaRs), protectins (PDs) and resolvins (Rvs), may play a major role on clinical impact of airway inflammation in CF. In this study, our aims were to detect and quantitate Resolvin D1 (RvD1) in sputum and plasma from patients with CF and compare levels of RvD1 with biomarkers of inflammation and lung function. We studied 27 CF patients aged 6 to 55 years (median 16 years) in a prospective approach. DHA can be found in the plasma of our CF patients in the milligram range and is decreased in comparison to a healthy control group. The DHA-derived pro-resolving mediator Resolvin D1 (RvD1) was also present in the plasma (286.4 ± 50 pg/ mL, mean ± SEM) and sputum (30.0 ± 2.6 pg/ mL, mean ± SEM) samples from our patients with CF and showed a positive correlation with sputum inflammatory markers. The plasma concentrations of RvD1 were ten times higher than sputum concentrations. Interestingly, sputum RvD1/ IL-8 levels showed a positive correlation with FEV1 (rs = 0.3962, p< 0.05). SPMs, like RvD1, are well known to down-regulate inflammatory pathways. Our study shows that the bioactive lipid mediator RvD1, derived from DHA, was present in sputum and plasma of CF patients

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

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

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  5. 21 CFR 866.5910 - Quality control material for cystic fibrosis nucleic acid assays.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  6. The altered gut microbiota in adults with cystic fibrosis.

    PubMed

    Burke, D G; Fouhy, F; Harrison, M J; Rea, M C; Cotter, P D; O'Sullivan, O; Stanton, C; Hill, C; Shanahan, F; Plant, B J; Ross, R P

    2017-03-09

    Cystic Fibrosis (CF) is an autosomal recessive disease that affects the function of a number of organs, principally the lungs, but also the gastrointestinal tract. The manifestations of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction in the gastrointestinal tract, as well as frequent antibiotic exposure, undoubtedly disrupts the gut microbiota. To analyse the effects of CF and its management on the microbiome, we compared the gut microbiota of 43 individuals with CF during a period of stability, to that of 69 non-CF controls using 454-pyrosequencing of the 16S rRNA gene. The impact of clinical parameters, including antibiotic therapy, on the results was also assessed. The CF-associated microbiome had reduced microbial diversity, an increase in Firmicutes and a reduction in Bacteroidetes compared to the non-CF controls. While the greatest number of differences in taxonomic abundances of the intestinal microbiota was observed between individuals with CF and the healthy controls, gut microbiota differences were also reported between people with CF when grouped by clinical parameters including % predicted FEV 1 (measure of lung dysfunction) and the number of intravenous (IV) antibiotic courses in the previous 12 months. Notably, CF individuals presenting with severe lung dysfunction (% predicted FEV 1  ≤ 40%) had significantly (p < 0.05) reduced gut microbiota diversity relative to those presenting with mild or moderate dysfunction. A significant negative correlation (-0.383, Simpson's Diversity Index) was also observed between the number of IV antibiotic courses and gut microbiota diversity. This is one of the largest single-centre studies on gut microbiota in stable adults with CF and demonstrates the significantly altered gut microbiota, including reduced microbial diversity seen in CF patients compared to healthy controls. The data show the impact that CF and it's management have on gut microbiota, presenting the opportunity to

  7. The Influence of Genetics on Cystic Fibrosis Phenotypes

    PubMed Central

    Knowles, Michael R.; Drumm, Mitchell

    2012-01-01

    Technological advances in genetics have made feasible and affordable large studies to identify genetic variants that cause or modify a trait. Genetic studies have been carried out to assess variants in candidate genes, as well as polymorphisms throughout the genome, for their associations with heritable clinical outcomes of cystic fibrosis (CF), such as lung disease, meconium ileus, and CF-related diabetes. The candidate gene approach has identified some predicted relationships, while genome-wide surveys have identified several genes that would not have been obvious disease-modifying candidates, such as a methionine sulfoxide transferase gene that influences intestinal obstruction, or a region on chromosome 11 proximate to genes encoding a transcription factor and an apoptosis controller that associates with lung function. These unforeseen associations thus provide novel insight into disease pathophysiology, as well as suggesting new therapeutic strategies for CF. PMID:23209180

  8. Appetite stimulants for people with cystic fibrosis.

    PubMed

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

    2014-07-27

    Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic anorexia attain optimal body mass index and nutritional status. However, these may have adverse effects on clinical status. The aim of this review is to systematically search for and evaluate evidence on the beneficial effects of appetite stimulants in the management of CF-related anorexia and synthesize reports of any side-effects. Trials were identified by searching the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, MEDLINE, Embase, CINAHL, handsearching reference lists and contacting local and international experts.Last search of online databases: 01 April 2014.Last search of the Cystic Fibrosis Trials Register: 08 April 2014. Randomised and quasi-randomised controlled trials of appetite stimulants, compared to placebo or no treatment for at least one month in adults and children with cystic fibrosis. Authors independently extracted data and assessed the risk of bias within eligible trials. Meta-analyses were performed. Three trials (total of 47 recruited patients) comparing appetite stimulants (cyproheptadine hydrochloride and megesterol acetate) to placebo were included; the numbers of adults or children within each trial were not always reported. The risk of bias of the included trials was graded as moderate.A meta-analysis of all three trials showed appetite stimulants produced a larger increase in weight z score at three months compared to placebo, mean difference 0.61 (95% confidence interval 0.29 to 0.93) (P < 0.001) (n = 40) with no evidence of a difference in effect between two different appetite stimulants. One of these trials also reported a significant weight increase with megesterol acetate compared to placebo at six months (n = 17). The three trials reported no significant differences in forced expiratory volume at one second (per cent predicted

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

    PubMed

    Gini, Andrea; Zauber, Ann G; Cenin, Dayna R; Omidvari, Amir-Houshang; Hempstead, Sarah E; Fink, Aliza K; Lowenfels, Albert B; Lansdorp-Vogelaar, Iris

    2017-12-27

    Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared to the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. We adjusted the existing Microsimulation Screening Analysis-Colon microsimulation model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess whether optimal screening strategies would change. Colonoscopy every 5 years, starting at age 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in population is not clear. Using a Microsimulation Screening Analysis-Colon microsimulation model, we found screening of patients with cystic fibrosis for CRC to be cost-effective. Due to the higher risk in these patients for CRC, screening should start at an earlier age with a shorter screening interval. The findings of this study

  10. Circulating RNA transcripts identify therapeutic response in cystic fibrosis lung disease.

    PubMed

    Saavedra, Milene T; Hughes, Grant J; Sanders, Linda A; Carr, Michelle; Rodman, David M; Coldren, Christopher D; Geraci, Mark W; Sagel, Scott D; Accurso, Frank J; West, James; Nick, Jerry A

    2008-11-01

    Circulating leukocyte RNA transcripts are systemic markers of inflammation, which have not been studied in cystic fibrosis (CF) lung disease. Although the standard assessment of pulmonary treatment response is FEV(1), a measure of airflow limitation, the lack of systemic markers to reflect changes in lung inflammation critically limits the testing of proposed therapeutics. We sought to prospectively identify and validate peripheral blood leukocyte genes that could mark resolution of pulmonary infection and inflammation using a model by which RNA transcripts could increase the predictive value of spirometry. Peripheral blood mononuclear cells were isolated from 10 patients with CF and acute pulmonary exacerbations before and after therapy. RNA expression profiling revealed that 10 genes significantly changed with treatment when compared with matched non-CF and control subjects with stable CF to establish baseline transcript abundance. Peripheral blood mononuclear cell RNA transcripts were prospectively validated, using real-time polymerase chain reaction amplification, in an independent cohort of acutely ill patients with CF (n = 14). Patients who responded to therapy were analyzed using general estimating equations and multiple logistic regression, such that changes in FEV(1)% predicted were regressed with transcript changes. Three genes, CD64, ADAM9, and CD36, were significant and independent predictors of a therapeutic response beyond that of FEV(1) alone (P < 0.05). In both cohorts, receiver operating characteristic analysis revealed greater accuracy when genes were combined with FEV(1). Circulating mononuclear cell transcripts characterize a response to the treatment of pulmonary exacerbations. Even in small patient cohorts, changes in gene expression in conjunction with FEV(1) may enhance current outcomes measures for treatment response.

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

    PubMed

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

    2016-11-01

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

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

    PubMed

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

    2011-09-22

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

  13. The relationship between insulin secretion, the insulin-like growth factor axis and growth in children with cystic fibrosis.

    PubMed

    Ripa, Paulus; Robertson, Ian; Cowley, David; Harris, Margaret; Masters, I Brent; Cotterill, Andrew M

    2002-03-01

    Cystic fibrosis-related diabetes mellitus (CFRD) is an increasingly common complication of cystic fibrosis. CFRD is preceded by a progressive decline in insulin secretion but there is no accepted definition of the prediabetic state in CFRD. This prediabetic state appears to have adverse effects on clinical status, nutrition and lung function, but there is no direct evidence that the impaired glucose homeostasis is the cause of these deteriorations. This study examined the prevalence of glucose intolerance and impaired insulin secretion in a population of children with CF without CFRD. Severe CF lung disease is often associated with poor weight gain and slower growth but the mechanism for this is still unclear. The relationships between the current state of glucose homeostasis, insulin secretion and the insulin-like growth factor axis, height velocity, nutrition status and lung function were therefore studied. Eighteen children with cystic fibrosis aged 9.5-15 years had oral glucose tolerance tests and 14 of these also had intravenous glucose tolerance tests (four refused). Blood samples were collected for insulin, C-peptide, glucose, HbA1c, insulin-like growth factor (IGF)-I, IGF-II, IGF-binding protein (IGFBP)-1 and IGFBP-3. Data on height, weight, puberty status, clinical score (Shwachman score) and lung function were recorded. Height velocity, height and weight standard deviation scores (SDS) were calculated using WHO/CDC data. The mean height SDS (-0.52 +/- 0.17) was less than the normal population (P = 0.007) and the mean height velocity was 4.6 +/- 0.5 cm/year, 39% with a height velocity less than the third percentile for age. The weight SDS and body mass index (BMI) were similar to the normal population. Four children had impaired glucose tolerance. The first-phase insulin response (FPIR) was below the first percentile of normal population values in nine (65%). Impaired FPIR or impaired glucose tolerance did not correlate with the Shwachman score

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2008-04-01

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

  16. A roadmap to the brittle bones of cystic fibrosis.

    PubMed

    Gore, Ashwini P; Kwon, Soon Ho; Stenbit, Antine E

    2010-12-16

    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.

  17. Aspergillus-induced superoxide production by cystic fibrosis phagocytes is associated with disease severity.

    PubMed

    Brunel, Shan F; Willment, Janet A; Brown, Gordon D; Devereux, Graham; Warris, Adilia

    2018-04-01

    Aspergillus fumigatus infects up to 50% of cystic fibrosis (CF) patients and may play a role in progressive lung disease. As cystic fibrosis transmembrane conductance regulator is expressed in cells of the innate immune system, we hypothesised that impaired antifungal immune responses play a role in CF-related Aspergillus lung disease. Peripheral blood mononuclear cells, polymorphonuclear cells (PMN) and monocytes were isolated from blood samples taken from CF patients and healthy volunteers. Live-cell imaging and colorimetric assays were used to assess antifungal activity in vitro . Production of reactive oxygen species (ROS) was measured using luminol-induced chemiluminescence and was related to clinical metrics as collected by case report forms. CF phagocytes are as effective as those from healthy controls with regards to phagocytosis, killing and restricting germination of A. fumigatus conidia. ROS production by CF phagocytes was up to four-fold greater than healthy controls (p<0.05). This effect could not be replicated in healthy phagocytes by priming with lipopolysaccharide or serum from CF donors. Increased production of ROS against A. fumigatus by CF PMN was associated with an increased number of clinical exacerbations in the previous year (p=0.007) and reduced lung function (by forced expiratory volume in 1 s) (p=0.014). CF phagocytes mount an intrinsic exaggerated release of ROS upon A. fumigatus stimulation which is associated with clinical disease severity.

  18. Aspergillus-induced superoxide production by cystic fibrosis phagocytes is associated with disease severity

    PubMed Central

    Brunel, Shan F.; Brown, Gordon D.; Devereux, Graham; Warris, Adilia

    2018-01-01

    Aspergillus fumigatus infects up to 50% of cystic fibrosis (CF) patients and may play a role in progressive lung disease. As cystic fibrosis transmembrane conductance regulator is expressed in cells of the innate immune system, we hypothesised that impaired antifungal immune responses play a role in CF-related Aspergillus lung disease. Peripheral blood mononuclear cells, polymorphonuclear cells (PMN) and monocytes were isolated from blood samples taken from CF patients and healthy volunteers. Live-cell imaging and colorimetric assays were used to assess antifungal activity in vitro. Production of reactive oxygen species (ROS) was measured using luminol-induced chemiluminescence and was related to clinical metrics as collected by case report forms. CF phagocytes are as effective as those from healthy controls with regards to phagocytosis, killing and restricting germination of A. fumigatus conidia. ROS production by CF phagocytes was up to four-fold greater than healthy controls (p<0.05). This effect could not be replicated in healthy phagocytes by priming with lipopolysaccharide or serum from CF donors. Increased production of ROS against A. fumigatus by CF PMN was associated with an increased number of clinical exacerbations in the previous year (p=0.007) and reduced lung function (by forced expiratory volume in 1 s) (p=0.014). CF phagocytes mount an intrinsic exaggerated release of ROS upon A. fumigatus stimulation which is associated with clinical disease severity. PMID:29651422

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

    PubMed

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

    1989-09-01

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

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

    PubMed

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

    2017-09-01

    Acid neutralization during chemical clearance is significantly prolonged in children with cystic fibrosis, compared to symptomatic children without cystic fibrosis. The absence of available reference values impeded identification of abnormal findings within individual patients with and without cystic fibrosis. The present study aimed to test the hypothesis that significantly more children with cystic fibrosis have acid neutralization durations during chemical clearance that fall outside the physiological range. Published reference value for acid neutralization duration during chemical clearance (determined using combined impedance/pH monitoring) was used to assess esophageal acid neutralization efficiency during chemical clearance in 16 children with cystic fibrosis (3 to <18 years) and 16 age-matched children without cystic fibrosis. Duration of acid neutralization during chemical clearance exceeded the upper end of the physiological range in 9 of 16 (56.3%) children with and in 3 of 16 (18.8%) children without cystic fibrosis ( p =0.0412). The likelihood ratio for duration indicated that children with cystic fibrosis are 2.1-times more likely to have abnormal acid neutralization during chemical clearance, and children with abnormal acid neutralization during chemical clearance are 1.5-times more likely to have cystic fibrosis. Significantly more (but not all) children with cystic fibrosis have abnormally prolonged esophageal clearance of acid. Children with cystic fibrosis are more likely to have abnormal acid neutralization during chemical clearance. Additional studies involving larger sample sizes are needed to address the importance of genotype, esophageal motility, composition and volume of saliva, and gastric acidity on acid neutralization efficiency in cystic fibrosis children.

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

    PubMed

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

    2012-08-01

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

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

    PubMed Central

    Alton, Eric W.F.W.

    2015-01-01

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

  3. Variation in lung function is associated with worse clinical outcomes in cystic fibrosis

    PubMed Central

    Heinzmann-Filho, João Paulo; Pinto, Leonardo Araujo; Marostica, Paulo José Cauduro; Donadio, Márcio Vinícius Fagundes

    2015-01-01

    ABSTRACT OBJECTIVE: To determine whether the variation in lung function over one year is associated with worse clinical outcomes, as well as with a decline in lung function in the following years, in patients with cystic fibrosis (CF). METHODS: This was a retrospective study involving CF patients (4-19 years of age), evaluated over a three-year period. We evaluated demographic characteristics, chronic Pseudomonas aeruginosa infection, antibiotic use, hospitalization, six-minute walk distance (6MWD), and lung function. The inclusion criterion was having undergone pulmonary function testing at least three times in the first year and at least once in each of the next two years. RESULTS: We evaluated 35 CF patients. The variation in FEV1 in the first year (ΔFEV1) was greater among those who, in the third year, showed reduced FEV1, had a below-average 6MWD, or were hospitalized than among those with normal FEV1, normal 6MWD, or no hospital admissions, in that same year (p < 0.05), although no such difference was found for antibiotic use in the third year. Subjects showing a ΔFEV1 ≥ 10% also showed a greater decline in FEV1 over the two subsequent years (p = 0.04). The ΔFEV1 also showed an inverse correlation with absolute FEV1 in the third year (r = −0.340, p = 0.04) and with the rate of FEV1 decline (r = −0.52, p = 0.001). Linear regression identified ΔFEV1 as a predictor of FEV1 decline (coefficient of determination, 0.27). CONCLUSIONS: Significant variation in lung function over one year seems to be associated with a higher subsequent rate of FEV1 decline and worse clinical outcomes in CF patients. Short-term ΔFEV1 might prove useful as a predictor of CF progression in clinical practice. PMID:26785959

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

    PubMed Central

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

    2017-01-01

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

  5. Novel end points for clinical trials in young children with cystic fibrosis.

    PubMed

    Simpson, Shannon J; Mott, Lauren S; Esther, Charles R; Stick, Stephen M; Hall, Graham L

    2013-06-01

    Cystic fibrosis (CF) lung disease commences early in the disease progression and is the most common cause of mortality. While new CF disease-modifying agents are currently undergoing clinical trial evaluation, the implementation of such trials in young children is limited by the lack of age-appropriate clinical trial end points. Advances in infant and preschool lung function testing, imaging of the chest and the development of biochemical biomarkers have led to increased possibility of quantifying mild lung disease in young children with CF and objectively monitoring disease progression over the course of an intervention. Despite this, further standardization and development of these techniques is required to provide robust objective measures for clinical trials in this age group.

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

    PubMed

    Fischman, Daniel; Nookala, Vinod K

    2008-12-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2001-04-01

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

  9. Allergic bronchopulmonary aspergillosis and Aspergillus infection in cystic fibrosis.

    PubMed

    Moss, Richard B

    2010-11-01

    Recent literature on Aspergillus fumigatus infection and allergy in cystic fibrosis have expanded our understanding of many aspects of allergic bronchopulmonary aspergillosis, and bring new attention to A. fumigatus airways infection and A. fumigatus allergy without allergic bronchopulmonary aspergillosis (ABPA). ABPA, A. fumigatus infection and A. fumigatus allergy without ABPA all likely worsen cystic fibrosis (CF) lung disease. Studies examining utility of new serologic assays for diagnosing ABPA include evaluations of standardized measurement of A. fumigatus-specific IgG, serum chemokine TARC levels, and recombinant A. fumigatus allergens; as yet, none appear ideal. Although oral glucocorticoids remain primary therapy, toxicity and incomplete control have led to an ongoing search for further safe and effective agents including itraconazole and voriconazole, intravenous pulse methylprednisolone, nebulized amphotericin B and omalizumab. Little controlled treatment data is available. Diagnosis of CF-ABPA remains difficult, but improvements in serologic assays are occurring. Treatment remains in many cases unsatisfactory, and new agents offer promise but await proper controlled trials of safety and efficacy. A. fumigatus airway infection and A. fumigatus allergy without ABPA are emerging as further complications of A. fumigatus respiratory colonization in patients with CF, but prospective studies are needed to corroborate largely retrospective findings.

  10. New and emerging targeted therapies for cystic fibrosis.

    PubMed

    Quon, Bradley S; Rowe, Steven M

    2016-03-30

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

  11. Chest physiotherapy can affect the lung clearance index in cystic fibrosis patients.

    PubMed

    Grosse-Onnebrink, Joerg; Mellies, Uwe; Olivier, Margarete; Werner, Claudius; Stehling, Florian

    2017-05-01

    The lung clearance index (LCI) is determined by multiple-breath washout lung function (MBW). It is increasingly used as an endpoint in clinical trials. Chest physiotherapy (CP) is part of routine cystic fibrosis (CF) care. Whether the LCI is useful in detecting short-term treatment effects of CP has not been sufficiently investigated. We assessed the short-term influence of CP with highly standardized high-frequency chest wall oscillation (HFCWO) on the LCI in CF patients. In this randomized controlled study, the LCI was obtained in 20 CF patients (7-34 years) hospitalized for infective pulmonary exacerbation prior to and immediately after a single treatment of HFCWO. Twenty-one control group CF patients (7-51 years) received no treatment. We calculated the coefficient of repeatability (CR) to estimate the clinical relevance of possible treatment effects. HFCWO improved (ie, decreased) the LCI by a median of 0.9 (range -0.45; 3.47; P = 0.002); the LCI decreased in 15 of 20 intervention group patients. In five patients the decrease in LCI exceeded the CR (2.15), indicating a clinically relevant treatment effect; in five patients the LCI increased but did not exceed the CR. The LCI did not change significantly in the control group patients. HFCWO can have a short-term decreasing effect on the LCI, but the treatment response is heterogeneous. In future trials using LCI as an endpoint, the timing of CP in relation to MBW should be considered a possible bias. © 2017 Wiley Periodicals, Inc.

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

    PubMed

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

    2014-01-01

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

  13. Pulmonary function outcomes for assessing cystic fibrosis care.

    PubMed

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

    2015-05-01

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

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

    PubMed

    Maqbool, Asim; Stallings, Virginia A

    2008-11-01

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

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

    PubMed

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

    2015-06-01

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

  16. Sweat Chlorides in Salt-Deprived Cystic Fibrosis Heterozygotes

    PubMed Central

    Myers, Michael F.

    1965-01-01

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

  17. Aminoglycoside exposure and renal function before lung transplantation in adult cystic fibrosis patients.

    PubMed

    Novel-Catin, Etienne; Pelletier, Solenne; Reynaud, Quitterie; Nove-Josserand, Raphaele; Durupt, Stephane; Dubourg, Laurence; Durieu, Isabelle; Fouque, Denis

    2018-04-18

    Patients with cystic fibrosis (CF) are at risk of kidney injury even before undergoing lung transplantation, because of prolonged exposure to aminoglycosides (AGs), chronic dehydration and complications of diabetes mellitus. The usual equations estimating the glomerular filtration rate (GFR), such as Cockcroft-Gault and Modification of Diet in Renal Disease, are not adapted to the CF population due to patients' low body weight and reduced muscle mass. The aim of this study was to precisely measure GFR in adult CF patients and to see whether repeated AG treatment would impair renal function before lung transplantation. Inulin or iohexol clearances were performed in 25 adult CF patients when they entered the lung transplant waiting list. No patient was treated with AGs at the time of GFR measurement. Body mass index (BMI), history of diabetes mellitus and blood pressure were recorded. Exposure to intravenous (IV) AGs within 5 years prior to the GFR measurement was obtained from the patient's medical files. Urine samples were collected to check for albuminuria and proteinuria. The population was predominantly female (67%). The mean age was 32 years, the mean BMI was 19 kg/m2 and 28% had CF-related diabetes. Median exposure to IV AG within 5 years before GFR measurement was 155 days with a mean dosage of 7.7mg/kg/day. The mean measured GFR was 106 mL/min/1.73 m2 and the mean estimated GFR according to the Chronic Kidney Disease Epidemiology Collaboration formula was 124 mL/min/1.73 m2. Despite prolonged exposure to high-dose IV AG, no decline in GFR was observed in these patients.

  18. Constrictive Bronchiolitis in Cystic Fibrosis Adolescents with Refractory Pulmonary Decline.

    PubMed

    Harris, William T; Boyd, J Todd; McPhail, Gary L; Brody, Alan S; Szczesniak, Rhonda D; Korbee, Leslie L; Baker, Michael L; Clancy, John P

    2016-12-01

    Refractory lung function decline in association with recurrent pulmonary exacerbations is a common, yet poorly explained finding in cystic fibrosis (CF). To investigate the histopathologic mechanisms of pulmonary deterioration during adolescence and early adulthood, we reviewed clinically-indicated lung biopsy specimens obtained during a period of persistent decline. To determine if peribronchiolar remodeling is prominent in lung biopsy specimens obtained in adolescents with CF refractory to conventional therapy. Six adolescents with CF (mean age, 16.2 y; mean FEV 1 , 52% predicted at biopsy) with significant pulmonary deterioration over 12-24 months (mean FEV 1 decline of 14% predicted/year) despite aggressive intervention underwent computed tomography imaging and ultimately lung biopsy to aid clinical management. In addition to routine clinical evaluation, histopathologic investigation included staining for transforming growth factor-β (TGF-β, a genetic modifier of CF lung disease), collagen deposition (a marker of fibrosis), elastin (to evaluate for bronchiectasis), and α-smooth muscle actin (to identify myofibroblasts). All computed tomography scans demonstrated a mix of bronchiectasis and hyperinflation that was variable across lung regions and within patients. Lung biopsy revealed significant peribronchiolar remodeling, particularly in patients with more advanced disease, with near complete obliteration of the peribronchiolar lumen (constrictive bronchiolitis). Myofibroblast differentiation (a TGF-β-dependent process) was prominent in specimens with significant airway remodeling. Constrictive bronchiolitis is widely present in the lung tissue of adolescents with CF with advanced disease and may contribute to impaired lung function that is refractory to conventional therapy (antibiotics, antiinflammatories, and mucolytics). TGF-β-dependent myofibroblast differentiation is prominent in areas of active fibrogenesis and may foster small airway remodeling in

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

    PubMed

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

    1993-04-01

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

  20. Antibiotic management of lung infections in cystic fibrosis. II. Nontuberculous mycobacteria, anaerobic bacteria, and fungi.

    PubMed

    Chmiel, James F; Aksamit, Timothy R; Chotirmall, Sanjay H; Dasenbrook, Elliott C; Elborn, J Stuart; LiPuma, John J; Ranganathan, Sarath C; Waters, Valerie J; Ratjen, Felix A

    2014-10-01

    Airway infections are a key component of cystic fibrosis (CF) lung disease. Whereas the approach to common pathogens such as Pseudomonas aeruginosa is guided by a significant body of evidence, other infections often pose a considerable challenge to treating physicians. In Part I of this series on the antibiotic management of difficult lung infections, we discussed bacterial organisms including methicillin-resistant Staphylococcus aureus, gram-negative bacterial infections, and treatment of multiple bacterial pathogens. Here, we summarize the approach to infections with nontuberculous mycobacteria, anaerobic bacteria, and fungi. Nontuberculous mycobacteria can significantly impact the course of lung disease in patients with CF, but differentiation between colonization and infection is difficult clinically as coinfection with other micro-organisms is common. Treatment consists of different classes of antibiotics, varies in intensity, and is best guided by a team of specialized clinicians and microbiologists. The ability of anaerobic bacteria to contribute to CF lung disease is less clear, even though clinical relevance has been reported in individual patients. Anaerobes detected in CF sputum are often resistant to multiple drugs, and treatment has not yet been shown to positively affect patient outcome. Fungi have gained significant interest as potential CF pathogens. Although the role of Candida is largely unclear, there is mounting evidence that Scedosporium species and Aspergillus fumigatus, beyond the classical presentation of allergic bronchopulmonary aspergillosis, can be relevant in patients with CF and treatment should be considered. At present, however there remains limited information on how best to select patients who could benefit from antifungal therapy.

  1. Antibiotic Management of Lung Infections in Cystic Fibrosis. II. Nontuberculous Mycobacteria, Anaerobic Bacteria, and Fungi

    PubMed Central

    Aksamit, Timothy R.; Chotirmall, Sanjay H.; Dasenbrook, Elliott C.; Elborn, J. Stuart; LiPuma, John J.; Ranganathan, Sarath C.; Waters, Valerie J.; Ratjen, Felix A.

    2014-01-01

    Airway infections are a key component of cystic fibrosis (CF) lung disease. Whereas the approach to common pathogens such as Pseudomonas aeruginosa is guided by a significant body of evidence, other infections often pose a considerable challenge to treating physicians. In Part I of this series on the antibiotic management of difficult lung infections, we discussed bacterial organisms including methicillin-resistant Staphylococcus aureus, gram-negative bacterial infections, and treatment of multiple bacterial pathogens. Here, we summarize the approach to infections with nontuberculous mycobacteria, anaerobic bacteria, and fungi. Nontuberculous mycobacteria can significantly impact the course of lung disease in patients with CF, but differentiation between colonization and infection is difficult clinically as coinfection with other micro-organisms is common. Treatment consists of different classes of antibiotics, varies in intensity, and is best guided by a team of specialized clinicians and microbiologists. The ability of anaerobic bacteria to contribute to CF lung disease is less clear, even though clinical relevance has been reported in individual patients. Anaerobes detected in CF sputum are often resistant to multiple drugs, and treatment has not yet been shown to positively affect patient outcome. Fungi have gained significant interest as potential CF pathogens. Although the role of Candida is largely unclear, there is mounting evidence that Scedosporium species and Aspergillus fumigatus, beyond the classical presentation of allergic bronchopulmonary aspergillosis, can be relevant in patients with CF and treatment should be considered. At present, however there remains limited information on how best to select patients who could benefit from antifungal therapy. PMID:25167882

  2. Cystic fibrosis gene therapy: a mutation-independent treatment.

    PubMed

    Griesenbach, Uta; Davies, Jane C; Alton, Eric

    2016-11-01

    Since cloning of the disease-causing gene 27 years ago, the development of cystic fibrosis (CF) gene therapy has been pursued. Here, we will summarize key findings with a particular focus on recent developments. Almost 3 decades of research have highlighted the complexity of lung gene transfer and have generated a body of data that has recently led to the completion of a large phase IIB study. This trial has, for the first time, shown that nonviral gene transfer can, albeit modestly, stabilize lung function in CF and provides the impetus for further development of more potent gene transfer agents. Lentiviral vectors, specifically pseudotyped to enable entry into airway epithelial cells have most recently been developed. Persistent expression after a single dose and the ability to be administered repeatedly suggest that these viral vectors hold promise for the treatment of CF; a first-in-man clinical trial will shortly be initiated. Although the development of CF gene therapy has been slower than initially anticipated, recent progress has been encouraging and has renewed the interest of academics and industry to pursue lung gene therapy.

  3. Effect of bronchoalveolar lavage-directed therapy on Pseudomonas aeruginosa infection and structural lung injury in children with cystic fibrosis: a randomized trial.

    PubMed

    Wainwright, Claire E; Vidmar, Suzanna; Armstrong, David S; Byrnes, Catherine A; Carlin, John B; Cheney, Joyce; Cooper, Peter J; Grimwood, Keith; Moodie, Marj; Robertson, Colin F; Tiddens, Harm A

    2011-07-13

    Early pulmonary infection in children with cystic fibrosis leads to increased morbidity and mortality. Despite wide use of oropharyngeal cultures to identify pulmonary infection, concerns remain over their diagnostic accuracy. While bronchoalveolar lavage (BAL) is an alternative diagnostic tool, evidence for its clinical benefit is lacking. To determine if BAL-directed therapy for pulmonary exacerbations during the first 5 years of life provides better outcomes than current standard practice relying on clinical features and oropharyngeal cultures. The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) randomized controlled trial, recruiting infants diagnosed with cystic fibrosis through newborn screening programs in 8 Australasian cystic fibrosis centers. Recruitment occurred between June 1, 1999, and April 30, 2005, with the study ending on December 31, 2009. BAL-directed (n = 84) or standard (n = 86) therapy until age 5 years. The BAL-directed therapy group underwent BAL before age 6 months when well, when hospitalized for pulmonary exacerbations, if Pseudomonas aeruginosa was detected in oropharyngeal specimens, and after P. aeruginosa eradication therapy. Treatment was prescribed according to BAL or oropharyngeal culture results. Primary outcomes at age 5 years were prevalence of P. aeruginosa on BAL cultures and total cystic fibrosis computed tomography (CF-CT) score (as a percentage of the maximum score) on high-resolution chest CT scan. Of 267 infants diagnosed with cystic fibrosis following newborn screening, 170 were enrolled and randomized, and 157 completed the study. At age 5 years, 8 of 79 children (10%) in the BAL-directed therapy group and 9 of 76 (12%) in the standard therapy group had P. aeruginosa in final BAL cultures (risk difference, -1.7% [95% confidence interval, -11.6% to 8.1%]; P = .73). Mean total CF-CT scores for the BAL-directed therapy and standard therapy groups were 3.0% and 2.8%, respectively (mean difference, 0.19% [95

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

    PubMed

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

    2017-10-01

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

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

    PubMed

    Gini, Andrea; Zauber, Ann G; Cenin, Dayna R; Omidvari, Amir-Houshang; Hempstead, Sarah E; Fink, Aliza K; Lowenfels, Albert B; Lansdorp-Vogelaar, Iris

    2018-02-01

    Individuals with cystic fibrosis are at increased risk of colorectal cancer (CRC) compared with the general population, and risk is higher among those who received an organ transplant. We performed a cost-effectiveness analysis to determine optimal CRC screening strategies for patients with cystic fibrosis. We adjusted the existing Microsimulation Screening Analysis-Colon model to reflect increased CRC risk and lower life expectancy in patients with cystic fibrosis. Modeling was performed separately for individuals who never received an organ transplant and patients who had received an organ transplant. We modeled 76 colonoscopy screening strategies that varied the age range and screening interval. The optimal screening strategy was determined based on a willingness to pay threshold of $100,000 per life-year gained. Sensitivity and supplementary analyses were performed, including fecal immunochemical test (FIT) as an alternative test, earlier ages of transplantation, and increased rates of colonoscopy complications, to assess if optimal screening strategies would change. Colonoscopy every 5 years, starting at an age of 40 years, was the optimal colonoscopy strategy for patients with cystic fibrosis who never received an organ transplant; this strategy prevented 79% of deaths from CRC. Among patients with cystic fibrosis who had received an organ transplant, optimal colonoscopy screening should start at an age of 30 or 35 years, depending on the patient's age at time of transplantation. Annual FIT screening was predicted to be cost-effective for patients with cystic fibrosis. However, the level of accuracy of the FIT in this population is not clear. Using a Microsimulation Screening Analysis-Colon model, we found screening of patients with cystic fibrosis for CRC to be cost effective. Because of the higher risk of CRC in these patients, screening should start at an earlier age with a shorter screening interval. The findings of this study (especially those on FIT

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

    PubMed

    Tomaszek, Lucyna; Cepuch, Grazyna; Pawlik, Lidia

    2018-03-21

    The purpose of the study was to assess the incidence of insomnia in adolescents and young adults with cystic fibrosis and its impact on the quality of life, and to examine whether demographic and clinical factors and negative emotional states are predictors of insomnia in these patients. The study was conducted among 95 cystic fibrosis patients aged 14-25 years. The study used a personal questionnaire survey, the Athens Insomnia Scale, the Cystic Fibrosis Quality of Life Questionnaire, the Hospital Anxiety and Depression Scale, and the Numeric Rating Scale. Insomnia was diagnosed in 38% of cystic fibrosis patients. In patients with insomnia, the level of anxiety (Me: 10 vs. 4; P=0.000) and depression (Me: 6.5 vs. 2; P=0.000) was significantly higher than in the good sleep quality group. The risk of insomnia increases as anxiety (OR: 4.31; 95% CI: 2.20 to 8.41) and depressive symptoms exacerbate (OR: 4.98; 95% CI: 1.84 to 13.43). Insomnia significantly worsens the quality of life in cystic fibrosis patients (ß =-0.5, P=0.000). Insomnia affects a large percentage of cystic fibrosis patients, and anxiety and depression are factors that increase the risk of insomnia. Insomnia decreases the quality of life in cystic fibrosis patients.

  7. Diagnosis of Adult Patients with Cystic Fibrosis.

    PubMed

    Nick, Jerry A; Nichols, David P

    2016-03-01

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

  8. Beta-defensin genomic copy number is not a modifier locus for cystic fibrosis

    PubMed Central

    Hollox, Edward J; Davies, Jane; Griesenbach, Uta; Burgess, Juliana; Alton, Eric WFW; Armour, John AL

    2005-01-01

    Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2) is a salt-sensitive antimicrobial protein that is expressed in lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic fibrosis (CF), and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with CF. No significant association was found. PMID:16336654

  9. Gene delivery to the lungs: pulmonary gene therapy for cystic fibrosis.

    PubMed

    Villate-Beitia, Ilia; Zarate, Jon; Puras, Gustavo; Pedraz, José Luis

    2017-07-01

    Cystic fibrosis (CF) is a monogenic autosomal recessive disorder where the defective gene, the cystic fibrosis transmembrane conductance regulator (CFTR), is well identified. Moreover, the respiratory tract can be targeted through noninvasive aerosolized formulations for inhalation. Therefore, gene therapy is considered a plausible strategy to address this disease. Conventional gene therapy strategies rely on the addition of a correct copy of the CFTR gene into affected cells in order to restore the channel activity. In recent years, genome correction strategies have emerged, such as zinc-finger nucleases, transcription activator-like effector nucleases and clustered regularly interspaced short palindromic repeats associated to Cas9 nucleases. These gene editing tools aim to repair the mutated gene at its original genomic locus with high specificity. Besides, the success of gene therapy critically depends on the nucleic acids carriers. To date, several clinical studies have been carried out to add corrected copies of the CFTR gene into target cells using viral and non-viral vectors, some of them with encouraging results. Regarding genome editing systems, preliminary in vitro studies have been performed in order to repair the CFTR gene. In this review, after briefly introducing the basis of CF, we discuss the up-to-date gene therapy strategies to address the disease. The review focuses on the main factors to take into consideration when developing gene delivery strategies, such as the design of vectors and plasmid DNA, in vitro/in vivo tests, translation to human use, administration methods, manufacturing conditions and regulatory issues.

  10. Ataluren in cystic fibrosis: development, clinical studies and where are we now?

    PubMed

    Zainal Abidin, Noreen; Haq, Iram J; Gardner, Aaron I; Brodlie, Malcolm

    2017-09-01

    Cystic fibrosis (CF) is one of the most common genetically-acquired life-limiting conditions worldwide. The underlying defect is dysfunction of the cystic fibrosis transmembrane-conductance regulator (CFTR) which leads to progressive lung disease and other multi-system effects. Around 10% of people with CF have a class I nonsense mutation that leads to production of shortened CFTR due to a premature termination codon (PTC). Areas covered: We discuss the discovery of the small-molecule drug ataluren, which in vitro has been shown to allow read-through of PTCs and facilitate synthesis of full-length protein. We review clinical studies that have been performed involving ataluren in CF. Early-phase short-term cross-over studies showed improvement in nasal potential difference. A follow-up phase III randomised controlled trial did not show a significant difference for the primary outcome of lung function, however a post-hoc analysis suggested possible benefit in patients not receiving tobramycin. A further randomised controlled trial in patients not receiving tobramycin has been reported as showing no benefit but has not yet been published in full peer-reviewed form. Expert opinion: A small-molecule approach to facilitate read-through of PTCs in nonsense mutations makes intuitive sense. However, at present there is no high-quality evidence of clinical efficacy for ataluren in people with CF.

  11. Functional genomic responses to cystic fibrosis transmembrane conductance regulator (CFTR) and CFTR(delta508) in the lung.

    PubMed

    Xu, Yan; Liu, Cong; Clark, Jean C; Whitsett, Jeffrey A

    2006-04-21

    Cystic fibrosis (CF), a common lethal pulmonary disorder in Caucasians, is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) that disturbs fluid homeostasis and host defense in target organs. The effects of CFTR and delta508-CFTR were assessed in transgenic mice that 1) lack CFTR expression (Cftr-/-); 2) express the human delta508 CFTR (CFTR(delta508)); 3) overexpress the normal human CFTR (CFTR(tg)) in respiratory epithelial cells. Genes were selected from Affymetrix Murine Gene-Chips analysis and subjected to functional classification, k-means clustering, promoter cis-elements/modules searching, literature mining, and pathway exploring. Genomic responses to Cftr-/- were not corrected by expression of CFTR(delta508). Genes regulating host defense, inflammation, fluid and electrolyte transport were similarly altered in Cftr-/- and CFTR(delta508) mice. CFTR(delta508) induced a primary disturbance in expression of genes regulating redox and antioxidant systems. Genomic responses to CFTR(tg) were modest and were not associated with lung pathology. CFTR(tg) and CFTR(delta508) induced genes encoding heat shock proteins and other chaperones but did not activate the endoplasmic reticulum-associated degradation pathway. RNAs encoding proteins that directly interact with CFTR were identified in each of the CFTR mouse models, supporting the hypothesis that CFTR functions within a multiprotein complex whose members interact at the level of protein-protein interactions and gene expression. Promoters of genes influenced by CFTR shared common regulatory elements, suggesting that their co-expression may be mediated by shared regulatory mechanisms. Genes and pathways involved in the response to CFTR may be of interest as modifiers of CF.

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

    PubMed

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

    2014-12-15

    Abnormal biliary secretion leads to the thickening of bile and the formation of plugs within the bile ducts; the consequent obstruction and abnormal bile flow ultimately results in the development of cystic fibrosis-related liver disease. This condition peaks in adolescence with up to 20% of adolescents with cystic fibrosis developing chronic liver disease. Early changes in the liver may ultimately result in end-stage liver disease with people needing transplantation. One therapeutic option currently used is ursodeoxycholic acid. To analyse evidence that ursodeoxycholic acid improves indices of liver function, reduces the risk of developing chronic liver disease and improves outcomes in general in cystic fibrosis. We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also contacted drug companies.Date of the most recent search of the Group's trials register: 29 May 2014. Randomised controlled trials of the use of ursodeoxycholic acid for at least three months compared with placebo or no additional treatment in people with cystic fibrosis. Two authors independently assessed trial eligibility and quality. Ten trials have been identified, of which three trials involving 118 participants were included; the dose of ursodeoxycholic acid ranged from 10 to 20 mg/kg/day for up to 12 months. The complex design used in two trials meant that data could only be analysed for subsets of participants. There was no significant difference in weight change, mean difference -0.90 kg (95% confidence interval -1.94 to 0.14) based on 30 participants from two trials. Improvement in biliary excretion was reported in only one trial and no significant change after treatment was shown. There were no data available for analysis for long-term outcomes such as death or need for liver transplantation. There are few

  13. Early detection of lung function decrements in children and adolescents with cystic fibrosis using new reference values.

    PubMed

    Zacharasiewicz, Angela; Renner, Sabine; Haderer, Flora; Weber, Michael; Dehlink, Eleonore; Szepfalusi, Zsolt; Frischer, Thomas

    2017-08-01

    Interpretation of lung function values in children with cystic fibrosis (CF) depends on the applied reference values. We hypothesize that differences between the new global lung function initiative (GLI) values and the formerly used Zapletal et al. values produce significantly different clinical results. We analyzed 3719 lung function measurements of 108 children and adolescents (n = 54 male; aged 6-18 years) with CF treated between September 1991 and July 2009. Data were analyzed in milliliters (ml) and % predicted (pred.) and interpreted using Zapletal and GLI reference values. Applying GLI compared to Zapletal resulted in significantly lower mean forced expiratory volume in 1s (FEV1)% pred. Zapletal 86.6% (SD 20.6), GLI 79.9% (SD 20.3) and 32% (n = 497/1543) were misclassified as normal when using Zapletal. Despite showing no overall differences in FEV1 and forced vital capacity (FVC) between concomitant Pseudomonas detection (PA+) in n = 938 and Pseudomonas negative (PA-) (n = 2781) using either reference PA+ resulted in lower FEV1 and FVC values with increasing age; however, measurement of small airway obstruction with forced expiratory flow at 75% of FVC (FEF75) values - available for Zapletal -showed significant differences. Reassurance regarding lung function when using old reference values may occur with potential clinical significance. Discrepancies in lung function interpretation underline the importance of using uniform and best available reference values.

  14. Host-pathogen interplay in the respiratory environment of Cystic Fibrosis

    PubMed Central

    Hurley, Bryan P.; Bragonzi, Alessandra

    2015-01-01

    Significant advances have been made in the understanding of disease progression in cystic fibrosis (CF), revealing a complex interplay between host and pathogenic organisms. The diverse CF microbiota within the airway activates an aberrant immune response that is ineffective in clearing infection. An appreciation of how the CF host immune system interacts with these organisms is crucial to understanding the pathogenesis of CF pulmonary disease. Here we discuss the microbial complexity present in the lungs of individuals with CF, review emerging concepts of innate and adaptive immune responses to pathogens that chronically inhabit the CF lung, and discuss therapies that target the aberrant inflammatory response that characterizes CF. A greater understanding of the underlying mechanisms will shed light on pathogenesis and guide more targeted therapies in the future that serve to reduce infection, minimize lung pathology, and improve the quality of life for patients with CF. PMID:25800687

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

    PubMed

    Gupta, R; Jentoft, N

    1992-02-15

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

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

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    1996-01-01

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

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

    PubMed

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

    2017-01-01

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

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

    PubMed

    Schippa, Serena; Iebba, Valerio; Santangelo, Floriana; Gagliardi, Antonella; De Biase, Riccardo Valerio; Stamato, Antonella; Bertasi, Serenella; Lucarelli, Marco; Conte, Maria Pia; Quattrucci, Serena

    2013-01-01

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

  20. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Allelic Variants Relate to Shifts in Faecal Microbiota of Cystic Fibrosis Patients

    PubMed Central

    Santangelo, Floriana; Gagliardi, Antonella; De Biase, Riccardo Valerio; Stamato, Antonella; Bertasi, Serenella; Lucarelli, Marco

    2013-01-01

    Introduction In this study we investigated the effects of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene variants on the composition of faecal microbiota, in patients affected by Cystic Fibrosis (CF). CFTR mutations (F508del is the most common) lead to a decreased secretion of chloride/water, and to mucus sticky secretions, in pancreas, respiratory and gastrointestinal tracts. Intestinal manifestations are underestimated in CF, leading to ileum meconium at birth, or small bowel bacterial overgrowth in adult age. Methods Thirty-six CF patients, fasting and under no-antibiotic treatment, were CFTR genotyped on both alleles. Faecal samples were subjected to molecular microbial profiling through Temporal Temperature Gradient Electrophoresis and species-specific PCR. Ecological parameters and multivariate algorithms were employed to find out if CFTR variants could be related to the microbiota structure. Results Patients were classified by two different criteria: 1) presence/absence of F508del mutation; 2) disease severity in heterozygous and homozygous F508del patients. We found that homozygous-F508del and severe CF patients exhibited an enhanced dysbiotic faecal microbiota composition, even within the CF cohort itself, with higher biodiversity and evenness. We also found, by species-specific PCR, that potentially harmful species (Escherichia coli and Eubacterium biforme) were abundant in homozygous-F508del and severe CF patients, while beneficial species (Faecalibacterium prausnitzii, Bifidobacterium spp., and Eubacterium limosum) were reduced. Conclusions This is the first report that establishes a link among CFTR variants and shifts in faecal microbiota, opening the way to studies that perceive CF as a ‘systemic disease’, linking the lung and the gut in a joined axis. PMID:23613805

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

    PubMed

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

    2015-12-24

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

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

    PubMed

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

    2017-01-01

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

  3. Macrolide antibiotics for cystic fibrosis.

    PubMed

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

    2012-11-14

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

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

    NASA Astrophysics Data System (ADS)

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

    1981-11-01

    The Na and K dependence of the Na/K pump was measured in skin fibroblasts from patients with cystic fibrosis and age/sex-matched controls. Under basal conditions, there was no difference between control and cystic fibrosis cells in protein per cell, intracellular Na and K content, or Na/K pump activity (measured as ouabain-sensitive 86Rb uptake). There was no difference in the Na dependence of the Na/K pump between cystic fibrosis cells and control cells. In cells from patients with cystic fibrosis, the Na/K pump had a significantly lower affinity for K (Km = 1.6 mM) when compared to normals (Km = 0.9 mM). This difference was demonstrated by using two independent experimental designs.

  5. Transplant center volume and outcomes in lung transplantation for cystic fibrosis.

    PubMed

    Hayes, Don; Sweet, Stuart C; Benden, Christian; Kopp, Benjamin T; Goldfarb, Samuel B; Visner, Gary A; Mallory, George B; Tobias, Joseph D; Tumin, Dmitry

    2017-04-01

    Transplant volume represents lung transplant (LTx) expertise and predicts outcomes, so we sought to determine outcomes related to center volumes in cystic fibrosis (CF). United Network for Organ Sharing data were queried for patients with CF in the United States (US) receiving bilateral LTx from 2005 to 2015. Multivariable Cox regression was used to model survival to 1 year and long-term (>1 year) survival, conditional on surviving at least 1 year. A total of 2025 patients and 67 centers were included in the analysis. The median annual LTx volumes were three in CF [interquartile range (IQR): 2, 6] and 17 in non-CF (IQR: 8, 33). Multivariable Cox regression in cases with complete data and surviving at least 1 year (n = 1510) demonstrated that greater annual CF LTx volume (HR per 10 LTx = 0.66; 95% CI: 0.49, 0.89; P = 0.006) but not greater non-CF LTx volume (HR = 1.00; 95% CI: 0.96, 1.05; P = 0.844) was associated with improved long-term survival in LTx recipients with CF. A Wald interaction test confirmed that CF LTx volume was more strongly associated with long-term outcomes than non-CF LTx volume (P = 0.012). In a US cohort, center volume was not associated with 1-year survival. CF-specific expertise predicted improved long-term outcomes of LTx for CF, whereas general LTx expertise was unassociated with CF patients' survival. © 2016 Steunstichting ESOT.

  6. Cystic fibrosis transmembrane conductance regulator regulates epithelial cell response to Aspergillus and resultant pulmonary inflammation.

    PubMed

    Chaudhary, Neelkamal; Datta, Kausik; Askin, Frederic B; Staab, Janet F; Marr, Kieren A

    2012-02-01

    Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) alter epithelial cell (EC) interactions with multiple microbes, such that dysregulated inflammation and injury occur with airway colonization in people with cystic fibrosis (CF). Aspergillus fumigatus frequently colonizes CF airways, but it has been assumed to be an innocent saprophyte; its potential role as a cause of lung disease is controversial. To study the interactions between Aspergillus and EC, and the role of the fungus in evoking inflammatory responses. A. fumigatus expressing green fluorescent protein was developed for in vitro and in vivo models, which used cell lines and mouse tracheal EC. Fungal spores (conidia) are rapidly ingested by ECs derived from bronchial cell lines and murine tracheas, supporting a role for EC in early airway clearance. Bronchial ECs harboring CFTR mutations (ΔF508) or deletion demonstrate impaired uptake and killing of conidia, and ECs with CFTR mutation undergo more conidial-induced apoptosis. Germinated (hyphal) forms of the fungus evoke secretion of inflammatory mediators, with CFTR mutation resulting in increased airway levels of macrophage inflammatory protein 2 and KC, and higher lung monocyte chemotactic protein-1. After A. fumigatus inhalation, CFTR(-/-) mice develop exaggerated lymphocytic inflammation, mucin accumulation, and lung injury. Data demonstrate a critical role for CFTR in mediating EC responses to A. fumigatus. Results suggest that the fungus elicits aberrant pulmonary inflammation in the setting of CFTR mutation, supporting the potential role of antifungals to halt progressive CF lung disease.

  7. Determination of right ventricular ejection fraction in children with cystic fibrosis, using krypton-81m

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

    Piepsz, A.; Ham, H.R.; Millet, E.

    1984-01-01

    The diagnosis of cor pulmonale and incipient heart failure remains difficult to assess in cystic fibrosis (CF) on the basis of the clinical as well as the biological parameters. The measurement of the right ventricular ejection fraction has been facilitated these last years by the introduction of the radionuclide methods. Methodological difficulties are however encountered when Tc-99m RBC are used, and are mainly related to heart chambers superposition (equilibrium method) or the low count density (first pass method). Few papers have been published on RVEF in cystic fibrosis and the results are somewhat contradictory. The authors have recently introduced amore » new method for the determination of RVEF, using equilibrium study during continuous injection of Kr-81m in glucose solution. This method offers several advantages related to an increased accuracy and a favorable dosimetry. In 25 patients aged 2 to 23 years with CF, one or more RVEF studies were performed. The severity of the disease was evaluated on the basis of the clinical Schwachman score, the lung function tests, the ventilation scan and the pa02. RVEF tended to decrease with the progression of the lung disease, although, owing to the spread of the results, no RVEF could be predicted on the basis of the other parameters. The decrease of RVEF in patients with advanced lung disease was moderate and terminal lung disease was sometimes associated with normal right heart contractility.« less

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

    PubMed

    Derichs, Nico

    2013-03-01

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

  9. The L441P mutation of cystic fibrosis transmembrane conductance regulator and its molecular pathogenic mechanisms in a Korean patient with cystic fibrosis.

    PubMed

    Gee, Heon Yung; Kim, Chang Keun; Kim, So Won; Lee, Ji Hyun; Kim, Jeong-Ho; Kim, Kyung Hwan; Lee, Min Goo

    2010-01-01

    Cystic fibrosis (CF) is an autosomal recessive disorder usually found in populations of white Caucasian descent. CF is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. A 5-yr-old Korean girl was admitted complaining of coughing and greenish sputum. Chest radiographs and computed tomographic (CT) scan revealed diffuse bronchiectasis in both lungs. The patient had chronic diarrhea and poor weight gain, and the abdominal pancreaticobiliary CT scan revealed atrophy of the pancreas. Finally, CF was confirmed by the repeated analysis of the quantitative pilocarpine iontophoresis test. The chloride concentration of sweat samples taken from both forearms of the pateint was an average of 88.7 mM/L (normal value <40 mM/L). After a comprehensive search for mutations in the CFTR gene, the patient was found to carry the non-synonymous L441P mutation in one allele. Molecular physiologic analysis of the L441P mutation of CFTR revealed that the L441P mutation completely abolished the CFTR Cl(-) channel activity by disrupting proper protein folding and membrane trafficking of CFTR protein. These results confirmed the pathogenicity of the L441P mutation of CFTR circulating in the Korean population. The possibility of CF should be suspected in patients with chronic bronchiectasis, although the frequency of CF is relatively rare in East Asia.

  10. Role of vitamin D in cystic fibrosis and non-cystic fibrosis bronchiectasis

    PubMed Central

    Moustaki, Maria; Loukou, Ioanna; Priftis, Kostas N; Douros, Konstantinos

    2017-01-01

    Bronchiectasis is usually classified as cystic fibrosis (CF) related or CF unrelated (non-CF); the latter is not considered an orphan disease any more, even in developed countries. Irrespective of the underlying etiology, bronchiectasis is the result of interaction between host, pathogens, and environment. Vitamin D is known to be involved in a wide spectrum of significant immunomodulatory effects such as down-regulation of pro-inflammatory cytokines and chemokines. Respiratory epithelial cells constitutively express 1α-hydroxylase leading to the local transformation of the inactive 25(OH)-vitamin D to the active 1,25(OH)2-vitamin D. The latter through its autocrine and paracrine functions up-regulates vitamin D dependent genes with important consequences in the local immunity of lungs. Despite the scarcity of direct evidence on the involvement of vitamin D deficiency states in the development of bronchiectasis in either CF or non-CF patients, it is reasonable to postulate that vitamin D may play some role in the pathogenesis of lung diseases and especially bronchiectasis. The potential contribution of vitamin D deficiency in the process of bronchiectasis is of particular clinical importance, taking into consideration the increasing prevalence of vitamin D deficiency worldwide and the significant morbidity of bronchiectasis. Given the well-established association of vitamin D deficiency with increased inflammation, and the indicative evidence for harmful consequences in lungs, it is intriguing to speculate that the administration of vitamin D supplementation could be a reasonable and cost effective supplementary therapeutic approach for children with non-CF bronchiectasis. Regarding CF patients, maybe in the future as more data become available, we have to re-evaluate our policy on the most appropriate dosage scheme for vitamin D. PMID:28828295

  11. Analysis of Lung Microbiota in Bronchoalveolar Lavage, Protected Brush and Sputum Samples from Subjects with Mild-To-Moderate Cystic Fibrosis Lung Disease

    PubMed Central

    Hogan, Deborah A.; Willger, Sven D.; Dolben, Emily L.; Hampton, Thomas H.; Stanton, Bruce A.; Morrison, Hilary G.; Sogin, Mitchell L.; Czum, Julianna; Ashare, Alix

    2016-01-01

    Individuals with cystic fibrosis (CF) often acquire chronic lung infections that lead to irreversible damage. We sought to examine regional variation in the microbial communities in the lungs of individuals with mild-to-moderate CF lung disease, to examine the relationship between the local microbiota and local damage, and to determine the relationships between microbiota in samples taken directly from the lung and the microbiota in spontaneously expectorated sputum. In this initial study, nine stable, adult CF patients with an FEV1>50% underwent regional sampling of different lobes of the right lung by bronchoalveolar lavage (BAL) and protected brush (PB) sampling of mucus plugs. Sputum samples were obtained from six of the nine subjects immediately prior to the procedure. Microbial community analysis was performed on DNA extracted from these samples and the extent of damage in each lobe was quantified from a recent CT scan. The extent of damage observed in regions of the right lung did not correlate with specific microbial genera, levels of community diversity or composition, or bacterial genome copies per ml of BAL fluid. In all subjects, BAL fluid from different regions of the lung contained similar microbial communities. In eight out of nine subjects, PB samples from different regions of the lung were also similar in microbial community composition, and were similar to microbial communities in BAL fluid from the same lobe. Microbial communities in PB samples were more diverse than those in BAL samples, suggesting enrichment of some taxa in mucus plugs. To our knowledge, this study is the first to examine the microbiota in different regions of the CF lung in clinically stable individuals with mild-to-moderate CF-related lung disease. PMID:26943329

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

    PubMed

    Azimi, Arsalan

    2015-12-01

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

  13. Disease-causing Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator Determine the Functional Responses of Alveolar Macrophages*

    PubMed Central

    Deriy, Ludmila V.; Gomez, Erwin A.; Zhang, Guangping; Beacham, Daniel W.; Hopson, Jessika A.; Gallan, Alexander J.; Shevchenko, Pavel D.; Bindokas, Vytautas P.; Nelson, Deborah J.

    2009-01-01

    Alveolar macrophages (AMs) play a major role in host defense against microbial infections in the lung. To perform this function, these cells must ingest and destroy pathogens, generally in phagosomes, as well as secrete a number of products that signal other immune cells to respond. Recently, we demonstrated that murine alveolar macrophages employ the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel as a determinant in lysosomal acidification (Di, A., Brown, M. E., Deriy, L. V., Li, C., Szeto, F. L., Chen, Y., Huang, P., Tong, J., Naren, A. P., Bindokas, V., Palfrey, H. C., and Nelson, D. J. (2006) Nat. Cell Biol. 8, 933–944). Lysosomes and phagosomes in murine cftr−/− AMs failed to acidify, and the cells were deficient in bacterial killing compared with wild type controls. Cystic fibrosis is caused by mutations in CFTR and is characterized by chronic lung infections. The information about relationships between the CFTR genotype and the disease phenotype is scarce both on the organismal and cellular level. The most common disease-causing mutation, ΔF508, is found in 70% of patients with cystic fibrosis. The mutant protein fails to fold properly and is targeted for proteosomal degradation. G551D, the second most common mutation, causes loss of function of the protein at the plasma membrane. In this study, we have investigated the impact of CFTR ΔF508 and G551D on a set of core intracellular functions, including organellar acidification, granule secretion, and microbicidal activity in the AM. Utilizing primary AMs from wild type, cftr−/−, as well as mutant mice, we show a tight correlation between CFTR genotype and levels of lysosomal acidification, bacterial killing, and agonist-induced secretory responses, all of which would be expected to contribute to a significant impact on microbial clearance in the lung. PMID:19837664

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

    PubMed

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

    2017-02-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

    Morrison, Lisa; Agnew, Jennifer

    2014-07-20

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

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

    PubMed

    Zhang, Zhe; Chen, Jue

    2016-12-01

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

  18. Drug therapies for reducing gastric acidity in people with cystic fibrosis.

    PubMed

    Ng, Sze May; Franchini, Angelo J

    2014-07-13

    Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, abstract books and conference proceedings.Most recent search of the Group's Trials Register: 17 March 2014. All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment. Both authors independently selected trials, assessed trial quality and extracted data. The searches identified 39 trials; 17 of these, with 273 participants, were suitable for inclusion, but the number of trials assessing each of the different agents was small. Seven trials were limited to children and four trials enrolled only adults. Meta-analysis was not performed, 14 trials were of a cross-over design and we did not have the appropriate information to conduct comprehensive meta-analyses. The included trials were generally not reported adequately enough to allow judgements on risk of bias.However, one trial found that drug therapies

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

    MedlinePlus

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

  20. Is sweat chloride predictive of severity of cystic fibrosis lung disease assessed by chest computed tomography?

    PubMed

    Caudri, Daan; Zitter, David; Bronsveld, Inez; Tiddens, Harm

    2017-09-01

    Cystic Fibrosis (CF) lung disease is characterized by a marked heterogeneity. Sweat chloride-level is a functional marker of the CF Transmembrane Regulator (CFTR) protein and could be an important predictor of later disease severity. In this retrospective analysis children from the Rotterdam CF clinic with available sweat chloride level at diagnosis and at least one routine spirometry-controlled volumetric chest CT scan in follow-up were included. CT scans were scored using the CF-CT scoring system (% of maximum). Associations between sweat chloride-levels and CF-CT scores were calculated using linear regression models, adjusting for age at sweat test and age at follow-up. Because structural lung damage develops over the course of many years, effect modification by the age at follow-up CT-scan was tested for by age-stratification. In 59 children (30 male) sweat chloride was measured at diagnosis (median age 0.5 years, range 0-13) and later chest CT performed (median age 14 years, range 6-18). Sweat chloride was associated with significantly higher CT-CT total score, bronchiectasis score, and mucus plugging score. Stratification for age at follow-up in tertiles showed this association remained only in the oldest age group (range 15-18 years). In that subgroup associations were found with all but one of the CF-CT subscores, as well as with all tested lung functions parameters. Sweat chloride-level is a significant predictor of CF lung disease severity as determined by chest CT and lung function. This association could only be demonstrated in children with follow-up to age 15 years and above. © 2017 Wiley Periodicals, Inc.

  1. Airway inflammation in cystic fibrosis: molecular mechanisms and clinical implications.

    PubMed

    Cohen-Cymberknoh, Malena; Kerem, Eitan; Ferkol, Thomas; Elizur, Arnon

    2013-12-01

    Airway epithelial cells and immune cells participate in the inflammatory process responsible for much of the pathology found in the lung of patients with cystic fibrosis (CF). Intense bronchial neutrophilic inflammation and release of proteases and oxygen radicals perpetuate the vicious cycle and progressively damage the airways. In vitro studies suggest that CF transmembrane conductance regulator (CFTR)-deficient airway epithelial cells display signalling abnormalities and aberrant intracellular processes which lead to transcription of inflammatory mediators. Several transcription factors, especially nuclear factor-κB, are activated. In addition, the accumulation of abnormally processed CFTR in the endoplasmic reticulum results in unfolded protein responses that trigger 'cell stress' and apoptosis leading to dysregulation of the epithelial cells and innate immune function in the lung, resulting in exaggerated and ineffective airway inflammation. Measuring airway inflammation is crucial for initiating treatment and monitoring its effect. No inflammatory biomarker predictive for the clinical course of CF lung disease is currently known, although neutrophil elastase seems to correlate with lung function decline. CF animal models mimicking human lung disease may provide an important insight into the pathogenesis of lung inflammation in CF and identify new therapeutic targets.

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

    PubMed

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

    2006-08-01

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

  3. Longitudinal study of Stenotrophomonas maltophilia antibody levels and outcomes in cystic fibrosis patients.

    PubMed

    Wettlaufer, Jillian; Klingel, Michelle; Yau, Yvonne; Stanojevic, Sanja; Tullis, Elizabeth; Ratjen, Felix; Waters, Valerie

    2017-01-01

    Previous studies have shown an association between higher Stenotrophomonas maltophilia antibody levels and decreased lung function in patients with cystic fibrosis (CF). The purpose of this study was to assess the serologic response to S. maltophilia over time and to determine whether changes in antibody levels could predict clinical outcomes. Changes in S. maltophilia antibody levels in adult and pediatric patients with CF from 2008 to 2014 were assessed between groups of infection patterns. Regression models accounting for repeated measures were used to assess whether antibody levels could predict subsequent S. maltophilia microbiological status, and whether they are associated with lung function and subsequent pulmonary exacerbation. A total of 409 S. maltophilia antibody samples from 135 CF patients showed that antibody levels did not change significantly between study visits, regardless of infection group. Higher antibody levels were independently associated with future culture positivity (OR 1.62; 95% CI 1.09, 2.41; p=0.02). While higher antibody levels were not independently associated with decreases in FEV 1 % predicted, they were associated with an increased hazard ratio for subsequent pulmonary exacerbation (HR 1.3; 95% CI 1.1, 1.6; p<0.001). S. maltophilia antibody levels may be helpful to identify individuals at risk of exacerbation who may benefit from earlier antimicrobial treatment. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  4. Detection of Cystic Fibrosis Serological Biomarkers Using a T7 Phage Display Library.

    PubMed

    Talwar, Harvinder; Hanoudi, Samer Najeeb; Geamanu, Andreea; Kissner, Dana; Draghici, Sorin; Samavati, Lobelia

    2017-12-18

    Cystic fibrosis (CF) is an autosomal recessive disorder affecting the cystic fibrosis transmembrane conductance regulator (CFTR). CF is characterized by repeated lung infections leading to respiratory failure. Using a high-throughput method, we developed a T7 phage display cDNA library derived from mRNA isolated from bronchoalveolar lavage (BAL) cells and leukocytes of sarcoidosis patients. This library was biopanned to obtain 1070 potential antigens. A microarray platform was constructed and immunoscreened with sera from healthy (n = 49), lung cancer (LC) (n = 31) and CF (n = 31) subjects. We built 1,000 naïve Bayes models on the training sets. We selected the top 20 frequently significant clones ranked with student t-test discriminating CF antigens from healthy controls and LC at a False Discovery Rate (FDR) < 0.01. The performances of the models were validated on an independent validation set. The mean of the area under the receiver operating characteristic (ROC) curve for the classifiers was 0.973 with a sensitivity of 0.999 and specificity of 0.959. Finally, we identified CF specific clones that correlate highly with sweat chloride test, BMI, and FEV1% predicted values. For the first time, we show that CF specific serological biomarkers can be identified through immunocreenings of a T7 phage display library with high accuracy, which may have utility in development of molecular therapy.

  5. Precision Medicine In Action: The Impact Of Ivacaftor On Cystic Fibrosis-Related Hospitalizations.

    PubMed

    Feng, Lisa B; Grosse, Scott D; Green, Ridgely Fisk; Fink, Aliza K; Sawicki, Gregory S

    2018-05-01

    Cystic fibrosis is a life-threatening genetic disease that causes severe damage to the lungs. Ivacaftor, the first drug that targeted the underlying defect of the disease caused by specific mutations, is a sterling example of the potential of precision medicine. Clinical trial and registry studies showed that ivacaftor improved outcomes and reduced hospitalizations. Our study used US administrative claims data to assess the real-world effectiveness of ivacaftor. Comparing twelve-month rates before and after starting the use of ivacaftor among people who initiated therapy during 2012-2015, we found that overall and cystic fibrosis-related inpatient admissions fell by 55 percent and 81 percent, respectively. There was a comparable reduction in inpatient spending. Ivacaftor appears to be effective for multiple mutations that cause the disease, as suggested by the fact that during the study period, ivacaftor's use was extended to nine additional mutations in 2014. Examination of evidence from clinical trial, clinical care, and administrative data sources is important for understanding the real-world effectiveness of precision medicines such as ivacaftor.

  6. High incidence of non-tuberculous mycobacteria-positive cultures among adolescent with cystic fibrosis.

    PubMed

    Cavalli, Zoé; Reynaud, Quitterie; Bricca, Romain; Nove-Josserand, Raphaële; Durupt, Stéphane; Reix, Philippe; Perceval, Marie; de Montclos, Michèle Pérouse; Lina, Gérard; Durieu, Isabelle

    2017-09-01

    We evaluated the prevalence of non-tuberculous mycobacteria (NTM)-positive cultures among our cystic fibrosis (CF) center patients, reviewed risk factors for NTM positivity, and determined its impact on lung function evolution. From 2009 to 2014, CF adults and children attending the CF center of Lyon (France) and having at least one positive NTM isolate were included. Each case was matched by age and gender with two CF patients with no NTM isolate (controls). 48 CF patients with NTM-positive isolates were matched to 96 controls. The age group for whom incident NTM was higher was young adolescents aged 13 to 17. A significant association for NTM positivity was found with Staphylococcusaureus in multivariate analysis and with allergic bronchopulmonary aspergillosis, corticosteroid and itraconazole in univariate analysis. Mean annual FEV1 decline was faster for NTM-positive patients compared to controls. These data highlight the high incidence of NTM-positive cultures among young adolescents with CF. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  7. Pretransplant Aspergillus colonization of cystic fibrosis patients and the incidence of post-lung transplant invasive aspergillosis.

    PubMed

    Luong, Me-Linh; Chaparro, Cecilia; Stephenson, Anne; Rotstein, Coleman; Singer, Lianne G; Waters, Valerie; Azad, Sassan; Keshavjee, Shaf; Tullis, Elizabeth; Husain, Shahid

    2014-02-15

    Invasive aspergillosis (IA) is an important cause of morbidity and mortality among patients undergoing lung transplant. Cystic fibrosis-lung transplant recipients (CF-LTRs) may be at greater risk of IA following lung transplantation because of the presence of Aspergillus in their airways before transplantation. This study evaluated the impact of pretransplant Aspergillus colonization on the risk for IA among CF-LTRs. A single-center retrospective cohort study of CF-LTRs was conducted between 2006 and 2010. Respiratory tract cultures before transplantation were reviewed to identify patients with pretransplant Aspergillus colonization. Patients with positive Aspergillus sputum culture or positive bronchoalvelolar lavage (BAL) galactomannan after transplantation were classified as having colonization or disease according to the International Society of Heart and Lung Transplantation criteria. A total of 93 CF patients underwent lung transplantation. Seventy percent (65/93) of CF-LTRs had pretransplant Aspergillus colonization. Thirty-six patients had positive intraoperative Aspergillus culture from the native lung BAL. Overall, 22.5% (20/93) of CF-LTRs developed IA. Median time to IA was 42 days following transplantation. Positive intraoperative Aspergillus culture (OR 4.36, 95% CI 1.35-14.05, P=0.01) and treatment for acute cellular rejection within 90 days after transplantation (OR 3.53, 95% CI 1.03-12.15, P=0.05) were independent risk factors for IA. Antifungal prophylaxis was administered to 61% (57/93) of CF-LTRs. One-year mortality rate was 16% (15/93). IA was not associated with increased risk of death (OR 2.10, 95% CI 0.62-7.06, P=0.23). Pretransplant Aspergillus colonization is frequent among CF-LTRs and a positive intraoperative Aspergillus culture produced a fourfold higher risk of developing IA.

  8. Aerosolized recombinant human DNase I for the treatment of cystic fibrosis.

    PubMed

    Shak, S

    1995-02-01

    Respiratory symptoms, recurrent infectious exacerbations, and progressive lung destruction in cystic fibrosis can be attributed to bacterial persistence and the accumulation of viscous purulent secretions in the airways. Purulent secretions contain high concentrations of extracellular DNA, a viscous material released by leukocytes. To evaluate the potential clinical utility of recombinant human DNase I (rhDNase or Pulmozyme), the human enzyme was cloned, sequenced, and expressed. In in vitro studies, rhDNase has been shown to reduce the viscoelasticity, reduce the adhesiveness, and improve the mucociliary transportability of cystic fibrosis sputum. In short-term phase 1 and phase 2 clinical trials, rhDNase has been shown to be safely tolerated and to improve the FEV1, FVC, and symptoms of dyspnea. A long-term placebo-controlled phase 3 study was performed in 968 adults and children (> or = 5 years) with cystic fibrosis to determine the effect of rhDNase on the risk of respiratory exacerbations requiring parenteral antibiotics and on the FEV1. Compared with placebo-treated patients, patients treated with rhDNase once daily or twice daily experienced a reduced risk of respiratory exacerbations by 28% (p = 0.04) and 37% (p = 0.01), respectively, and had a mean improvement in FEV1 of 5.8% (p < 0.01) and 5.6% (p < 0.01), respectively. Compared with placebo-treated patients, patients treated with rhDNase spent 2.7 fewer days receiving parenteral antibiotics (p = 0.04) and spent 1.3 fewer days in the hospital (p = 0.06) over the 6-month treatment period. Inhalation of rhDNase did not cause anaphylaxis but was associated with upper airway symptoms (ie, voice alteration, hoarseness, pharyngitis) that were generally mild and transient. In conclusion, aerosol administration of rhDNase was safely tolerated, reduced the risk of infectious exacerbations requiring parenteral antibiotics, and improved pulmonary function and patient well-being.

  9. Individual Patterns of Complexity in Cystic Fibrosis Lung Microbiota, Including Predator Bacteria, over a 1-Year Period

    PubMed Central

    de Dios Caballero, Juan; Vida, Rafael; Cobo, Marta; Máiz, Luis; Suárez, Lucrecia; Galeano, Javier; Baquero, Fernando; Cantón, Rafael

    2017-01-01

    ABSTRACT Cystic fibrosis (CF) lung microbiota composition has recently been redefined by the application of next-generation sequencing (NGS) tools, identifying, among others, previously undescribed anaerobic and uncultivable bacteria. In the present study, we monitored the fluctuations of this ecosystem in 15 CF patients during a 1-year follow-up period, describing for the first time, as far as we know, the presence of predator bacteria in the CF lung microbiome. In addition, a new computational model was developed to ascertain the hypothetical ecological repercussions of a prey-predator interaction in CF lung microbial communities. Fifteen adult CF patients, stratified according to their pulmonary function into mild (n = 5), moderate (n = 9), and severe (n = 1) disease, were recruited at the CF unit of the Ramón y Cajal University Hospital (Madrid, Spain). Each patient contributed three or four induced sputum samples during a 1-year follow-up period. Lung microbiota composition was determined by both cultivation and NGS techniques and was compared with the patients’ clinical variables. Results revealed a particular microbiota composition for each patient that was maintained during the study period, although some fluctuations were detected without any clinical correlation. For the first time, Bdellovibrio and Vampirovibrio predator bacteria were shown in CF lung microbiota and reduced-genome bacterial parasites of the phylum Parcubacteria were also consistently detected. The newly designed computational model allows us to hypothesize that inoculation of predators into the pulmonary microbiome might contribute to the control of chronic colonization by CF pathogens in early colonization stages. PMID:28951476

  10. Vitamin K supplementation for cystic fibrosis.

    PubMed

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

    2015-01-18

    Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 08 October 2014. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). Two authors independently screened papers, extracted trial details and assessed their risk of bias. Two trials (total of 32 participants) each lasting one month were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial in children (aged 8 to 18 years); and the other (with an older cohort) had a cross-over design comparing supplements to no treatment, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of

  11. Vitamin K supplementation for cystic fibrosis.

    PubMed

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

    2011-01-19

    Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 15 April 2010. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). Two authors independently screened papers, extracted trial details and assessed their risk of bias. Two trials (total of 32 participants) were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial; and the other had a cross-over design, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K. Evidence from randomised controlled trials on the benefits of routine

  12. Vitamin K supplementation for cystic fibrosis.

    PubMed

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

    2013-04-30

    Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 11 October 2012. Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). Two authors independently screened papers, extracted trial details and assessed their risk of bias. Two trials (total of 32 participants) were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial; and the other had a cross-over design, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration of serum vitamin K and undercarboxylated osteocalcin levels to the normal range after one month of daily supplementation with 1 mg of vitamin K. Evidence from randomised controlled trials on the benefits of routine

  13. No survival benefit to gaining private health insurance coverage for post-lung transplant care in adults with cystic fibrosis.

    PubMed

    Tumin, Dmitry; Foraker, Randi E; Tobias, Joseph D; Hayes, Don

    2016-03-01

    The use of public insurance is associated with diminished survival in patients with cystic fibrosis (CF) following lung transplantation. No data exist on benefits of gaining private health insurance for post-transplant care among such patients previously using public insurance. The United Network for Organ Sharing database was used to identify first-time lung transplant recipients participating in Medicare or Medicaid, diagnosed with CF, and transplanted between 2005 and 2015. Survival outcomes were compared between recipients gaining private insurance after transplantation and those maintaining public coverage throughout follow-up. Since implementation of the lung allocation score, 575 adults with CF received lung transplantation funded by Medicare or Medicaid and contributed data on insurance status post-transplant. There were 128 (22%) patients who gained private insurance. Multivariable analysis of time-varying insurance status found no survival benefit of gaining private insurance (HR = 0.822; 95% CI = 0.525, 1.286; p = 0.390). Further analysis demonstrated that resuming public insurance coverage was detrimental, relative to gaining and keeping private insurance (HR = 2.315; 95% CI = 1.020, 5.258; p = 0.045). Survival disadvantages of lung transplant recipients with CF who have public health insurance were not ameliorated by a switch to private coverage for post-transplant care. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    PubMed

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

    2014-10-10

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

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

    PubMed

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

    2010-06-01

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

  16. Aspergillus fumigatus chronic colonization and lung function decline in cystic fibrosis may have a two-way relationship.

    PubMed

    Noni, M; Katelari, A; Dimopoulos, G; Doudounakis, S-E; Tzoumaka-Bakoula, C; Spoulou, V

    2015-11-01

    Aspergillus fumigatus is commonly found in cystic fibrosis (CF) airways. Our aim was to assess the relationship between A. fumigatus chronic colonization and lung function in CF patients. A case-control study of CF patients born from 1989 to 2002 was performed. Medical records were reviewed from the time of initial diagnosis until December 2013. Chronic colonization was defined as two or more positive sputum cultures in a given year. Each patient chronically colonized with A. fumigatus was matched with three control patients (never colonized by A. fumigatus) for age, sex, and year of birth (±3 years). A number of parameters were recorded and analyzed prospectively. The primary outcome measure was the difference in forced expiratory volume in 1 s (FEV1) in percent predicted between groups. Linear mixed models were used for longitudinal analyses to evaluate the relationship between A. fumigatus chronic colonization and lung function during a 7-year period and study the lung function 4 years before the time of enrollment (t0). Twenty patients had chronic colonization and were matched with 60 controls. A significant difference in lung function was detected throughout the 7-year period after adjustment for confounders (est = 8.66, p = 0.020). Four years before t0, FEV1 baseline was the only factor associated with the course of lung function (est = 0.64, p < 0.001) and was significantly different between groups (p = 0.001). In conclusion, a decreased FEV1 baseline appears to be a risk factor for chronic colonization by A. fumigatus, which, in turn, may cause a faster deterioration of lung function.

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

    PubMed

    Castanet, M; Wieliczko, M-C

    2012-05-01

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

  18. Evidence for a Cystic Fibrosis Enteropathy

    PubMed Central

    Adriaanse, Marlou P. M.; van der Sande, Linda J. T. M.; van den Neucker, Anita M.; Menheere, Paul P. C. A.; Dompeling, Edward; Buurman, Wim A.; Vreugdenhil, Anita C. E.

    2015-01-01

    Background 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. Methods 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. Results 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. Conclusion 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. PMID:26484665

  19. Epidemiology of Cystic Fibrosis.

    PubMed

    Spoonhower, Kimberly A; Davis, Pamela B

    2016-03-01

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

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

    PubMed

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

    2013-05-23

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

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

    PubMed

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

    2017-10-01

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

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

    PubMed

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

    2010-11-01

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

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

    PubMed

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

    2013-09-01

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

  4. Cystic fibrosis transmembrane conductance regulator modulators: precision medicine in cystic fibrosis.

    PubMed

    Burgener, Elizabeth B; Moss, Richard B

    2018-06-01

    The aim of this study was to describe the newest development in cystic fibrosis (CF) care, CF transmembrane conductance regulator (CFTR) modulator therapies. Phase II results showing CFTR modulator triple therapies are more effective than current CFTR modulators. CFTR modulator therapy targets the protein defective in CF and boosts its function, but the drug must match mutation pathobiology. Ivacaftor, a CFTR potentiator, was the first modulator approved in 2012, with impressive improvement in lung function and other measures of disease in patients with gating and other residual function mutations (∼10% of CF patients). In 2015, the combination of lumacaftor, a CFTR corrector, and ivacaftor was approved for patients homozygous for the F508del mutation (∼40-50% of the CF population) with positive but less impressive clinical response and 10-20% incidence of intolerance. A next-generation CFTR corrector, tezacaftor, with ivacaftor equally effective and better tolerated than lumacaftor, has also received US Food and Drug Administration approval. Novel CFTR correctors, entering Phase 3 trials in triple modulator combination with tezacaftor-ivacaftor, appear substantially more effective for patients who are homozygous for the F508del mutation and can provide benefit for patients with a single F508del mutation. This offers promise of effective CFTR modulator therapy for nearly 90% of CF patients.

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

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

    Wilfond, B.S.; Fost, N.

    1990-05-23

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

  6. Association between glucose intolerance and bacterial colonisation in an adult population with cystic fibrosis, emergence of Stenotrophomonas maltophilia.

    PubMed

    Lehoux Dubois, C; Boudreau, V; Tremblay, F; Lavoie, A; Berthiaume, Y; Rabasa-Lhoret, R; Coriati, A

    2017-05-01

    Diabetes is common in cystic fibrosis (CF). Glucose can be detected in the airway when the blood glucose is elevated, which favours bacterial growth. We investigated the relationship between dysglycemia and lung pathogens in CF. Cross-sectional and prospective analysis of CF patients (N=260) who underwent a 2h-oral glucose tolerance test. Clinical data was collected. Stenotrophomonas maltophilia (S. maltophilia) was the sole bacteria increased in dysglycemic (AGT: 20.2%, CFRD: 21.6%) patients compared to normotolerants (NGT: 8.7%). S. maltophilia positive patients with dysglycemia had more pulmonary exacerbation events compared to NGTs (1.22 vs 0.63, P=0.003). The interaction between S. maltophilia colonisation and glucose tolerance status significantly increases the risk of lower lung function (P=0.003). Its growth was not affected by the evolution of the glucose tolerance after three years follow-up. Prevalence of S. maltophilia was higher in dysglycemic patients, supporting the idea that S. maltophilia is a marker of disease severity in CF. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  7. Bone Mineral Density and Fat-Soluble Vitamin Status in Adults with Cystic Fibrosis Undergoing Lung Transplantation: A Pilot Study.

    PubMed

    Hubert, Grace; Chung, Theresa Tam; Prosser, Connie; Lien, Dale; Weinkauf, Justin; Brown, Neil; Goodvin, Marianne; Jackson, Kathy; Tabak, Joan; Salgado, Josette; Alzaben, Abeer Salman; Mager, Diana R

    2016-12-01

    Patients with cystic fibrosis (CF) often experience low bone mineral density (BMD) pre- and post-lung transplantation (LTX). The study purpose was to describe BMD and micronutrient status in adults with CF pre- and post-LTX. Twelve patients with CF (29 ± 8 years) were recruited from the CF clinic at the University of Alberta Lung Transplant Program. BMD and vitamins A, D, E, K status, and parathyroid hormone were measured pre- and post-LTX. No significant differences pre- and post-LTX were observed at the different bone sites measured (lumber-spine, femoral-neck (FN), hip, and femoral-trochlea) (P > 0.05). BMD T-scores (<-2) was present in lumbar-spine, FN, hip, and femoral-trochlea in 33%, 17%, 17%, and 25% of individuals pre-LTX and 58%, 33%, 58%, and 33% of individuals post-LTX, respectively. More than 50% of patients had suboptimal vitamin K levels (PIVKA-II values >3 ng/mL) pre- and post-LTX. Adults with CF pre- and post-LTX had reduced BMD and suboptimal vitamin K status.

  8. Cystic Fibrosis Transmembrane Conductance Regulator Regulates Epithelial Cell Response to Aspergillus and Resultant Pulmonary Inflammation

    PubMed Central

    Chaudhary, Neelkamal; Datta, Kausik; Askin, Frederic B.; Staab, Janet F.

    2012-01-01

    Rationale: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) alter epithelial cell (EC) interactions with multiple microbes, such that dysregulated inflammation and injury occur with airway colonization in people with cystic fibrosis (CF). Aspergillus fumigatus frequently colonizes CF airways, but it has been assumed to be an innocent saprophyte; its potential role as a cause of lung disease is controversial. Objectives: To study the interactions between Aspergillus and EC, and the role of the fungus in evoking inflammatory responses. Methods: A. fumigatus expressing green fluorescent protein was developed for in vitro and in vivo models, which used cell lines and mouse tracheal EC. Measurements and Main Results: Fungal spores (conidia) are rapidly ingested by ECs derived from bronchial cell lines and murine tracheas, supporting a role for EC in early airway clearance. Bronchial ECs harboring CFTR mutations (ΔF508) or deletion demonstrate impaired uptake and killing of conidia, and ECs with CFTR mutation undergo more conidial-induced apoptosis. Germinated (hyphal) forms of the fungus evoke secretion of inflammatory mediators, with CFTR mutation resulting in increased airway levels of macrophage inflammatory protein 2 and KC, and higher lung monocyte chemotactic protein-1. After A. fumigatus inhalation, CFTR−/− mice develop exaggerated lymphocytic inflammation, mucin accumulation, and lung injury. Conclusions: Data demonstrate a critical role for CFTR in mediating EC responses to A. fumigatus. Results suggest that the fungus elicits aberrant pulmonary inflammation in the setting of CFTR mutation, supporting the potential role of antifungals to halt progressive CF lung disease. PMID:22135344

  9. Cystic fibrosis year in review 2016.

    PubMed

    Savant, Adrienne P; McColley, Susanna A

    2017-08-01

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

  10. Hyaluronic acid improves "pleasantness" and tolerability of nebulized hypertonic saline in a cohort of patients with cystic fibrosis.

    PubMed

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

    2010-11-01

    Inhaled hypertonic saline improves lung function and decreases pulmonary exacerbations in people with cystic fibrosis. However, side effects such as cough, narrowing of airways and saltiness cause intolerance of the therapy in 8% of patients. The aim of our study was to compare the effect of an inhaled solution of hyaluronic acid and hypertonic saline with hypertonic solution alone on safety and tolerability. A total of 20 patients with cystic fibrosis aged 6 years and over received a single treatment regimen of 7% hypertonic saline solution or hypertonic solution with 0.1% hyaluronate for 2 days nonconsecutively after a washout period in an open crossover study. Cough, throat irritation, and salty taste were evaluated by a modified ordinal score for assessing tolerability; "pleasantness" was evaluated by a five-level, Likert-type scale. Forced expiratory volume in 1 second was registered before and after the end of the saline inhalations. All 20 patients (nine males, 11 females, mean age 13 years, range 8.9-17.7) completed the study. The inhaled solution of 0.1% hyaluronic acid and hypertonic saline significantly improved tolerability and pleasantness compared to hypertonic saline alone. No major adverse effects were observed. No difference was documented in pulmonary function tests between the two treatments. Hyaluronic acid combined with hypertonic saline solution may contribute to improved adherence to hypertonic saline therapy. Further clinical trials are needed to confirm our findings. Considering the extraordinary versatility of hyaluronic acid in biological reactions, perspective studies could define its applicability to halting progression of lung disease in cystic fibrosis.

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

    PubMed

    Li, Li; Somerset, Shawn

    2014-10-01

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

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

    PubMed Central

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

    1996-01-01

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

  13. ABPA diagnosis in cystic fibrosis patients: the clinical utility of IgE specific to recombinant Aspergillus fumigatus allergens.

    PubMed

    Almeida, Marina B; Bussamra, Maria Helena C F; Rodrigues, Joaquim C

    2006-01-01

    Allergic bronchopulmonary aspergillosis (ABPA) is a complicating factor of cystic fibrosis which can result in a devastating combination as lung disease progresses. The overlap between the signs and symptoms of the two conditions makes diagnosis problematic, even if standardized criteria are used. The objective of this study was to identify, in a group of cystic fibrosis patients, cases of ABPA by assaying IgE specific to recombinant Aspergillus fumigatus antigens and to compare the method with the Cystic Fibrosis Foundation diagnostic criteria. Fifty-four patients, aged 2 to 20 years, presenting characteristics that could occur with ABPA in isolation, were systematically assessed based on the following: clinical data, a chest CT scan, immediate hypersensitivity skin test for A. fumigatus, total serum IgE assay, RAST for A. fumigatus and serum IgE specific for the recombinant allergens Asp f1, f2, f3, f4 and f6. Thirty-nine patients were eligible for the study. Thirty-two of these were investigated. Sensitization to A. fumigatus was observed in 34%. Both the Cystic Fibrosis Foundation criteria and the recombinant antigen specific IgE assay defined three patients as suffering from ABPA; however, only two of these patients were diagnosed by both methods. The detection of A. fumigatus recombinant antigen specific IgE was a useful tool for the early detection of sensitization and diagnosis of ABPA. Nevertheless, diagnostic confirmation cannot be divorced from clinical findings, and before this method can be used for ABPA diagnosis, for detecting relapses and for defining cure criteria, longitudinal studies with larger numbers of patients are required.

  14. 21 CFR 866.5910 - Quality control material for cystic fibrosis nucleic acid assays.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  15. Modeling cystic fibrosis disease progression in patients with the rare CFTR mutation P67L.

    PubMed

    MacKenzie, Isobel E R; Paquette, Valerie; Gosse, Frances; George, Sheenagh; Chappe, Frederic; Chappe, Valerie

    2017-05-01

    The progression of cystic fibrosis (CF) in patients with the rare mutation P67L was examined to determine if it induced a milder form of CF compared to the common severe ΔF508 mutation. Parameters of lung function, level of bacterial infection, nutritional status and hospitalization were used to represent CF progression. Age at diagnosis and pancreatic status were used to assess CF presentation. Analysis of data from the CF Canada Registry collected over a 15-year period included 266 ΔF508/ΔF508 homozygote patients from CF clinics in Atlantic Canada and 26 compound heterozygote patients with the rare P67L mutation from clinics across Canada. Late age at diagnosis, high incidence of pancreatic sufficiency, maintained Body Mass Index (BMI) with age, delayed life-threatening bacterial infection, and fewer days in hospital were observed for P67L heterozygote patients included in this study. Although the decline of lung function did not differ from ΔF508 homozygotes, the fact that a greater proportion of P67L heterozygotes live to an older age suggests that lung function is not the primary factor determining CF progression for P67L heterozygote patients. The P67L mutation is associated with a mild disease, even when combined with the severe ΔF508 mutation. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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

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

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

    1986-05-01

    Intestinal permeability was investigated in 14 children with cystic fibrosis making use of (/sup 51/Cr)EDTA as probe molecule. Ten normal young adults and 11 children served as controls. After oral administration of (/sup 51/Cr)EDTA, 24 h urine was collected. Urinary radioactivity was calculated and results expressed as percentage of oral dose excreted in 24 h urine. Mean and SEM were as follows: 2.51 +/- 0.21, 2.35 +/- 0.24, and 13.19 +/- 1.72 for control children, normal adults, and cystic fibrosis patients, respectively. The permeability differences between cystic fibrosis patients and either control children or control adults are significant (p lessmore » than 0.001).« less

  17. The clinical utility of lung clearance index in early cystic fibrosis lung disease is not impacted by the number of multiple-breath washout trials

    PubMed Central

    Foong, Rachel E.; Harper, Alana J.; King, Louise; Turkovic, Lidija; Davis, Miriam; Clem, Charles C.; Davis, Stephanie D.; Ranganathan, Sarath; Hall, Graham L.

    2018-01-01

    The lung clearance index (LCI) from the multiple-breath washout (MBW) test is a promising surveillance tool for pre-school children with cystic fibrosis (CF). Current guidelines for MBW testing recommend that three acceptable trials are required. However, success rates to achieve these criteria are low in children aged <7 years and feasibility may improve with modified pre-school criteria that accepts tests with two acceptable trials. This study aimed to determine if relationships between LCI and clinical outcomes of CF lung disease differ when only two acceptable MBW trials are assessed. Healthy children and children with CF aged 3–6 years were recruited for MBW testing. Children with CF also underwent bronchoalveolar lavage fluid collection and a chest computed tomography scan. MBW feasibility increased from 46% to 75% when tests with two trials were deemed acceptable compared with tests where three acceptable trials were required. Relationships between MBW outcomes and markers of pulmonary inflammation, infection and structural lung disease were not different between tests with three acceptable trials compared with tests with two acceptable trials. This study indicates that pre-school MBW data from two acceptable trials may provide sufficient information on ventilation distribution if three acceptable trials are not possible. PMID:29707562

  18. Cystic fibrosis: psychological issues.

    PubMed

    Götz, I; Götz, M

    2000-06-01

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

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

    PubMed

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

    2005-03-01

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

  20. Multilocus sequence typing of Scedosporium apiospermum and Pseudallescheria boydii isolates from cystic fibrosis patients.

    PubMed

    Bernhardt, A; Sedlacek, L; Wagner, S; Schwarz, C; Würstl, B; Tintelnot, K

    2013-12-01

    Scedosporium and Pseudallescheria species are the second most common lung-colonising fungi in cystic fibrosis (CF) patients. For epidemiological reasons it is important to trace sources of infection, routes of transmission and to determine whether these fungi are transient or permanent colonisers of the respiratory tract. Molecular typing methods like multilocus sequence typing (MLST) help provide this data. Clinical isolates of the P. boydii complex (including S. apiospermum and P. boydii) from CF patients in different regions of Germany were studied using MLST. Five gene loci, ACT, CAL, RPB2, BT2 and SOD2, were analysed. The S. apiospermum isolates from 34 patients were assigned to 32 sequence types (STs), and the P. boydii isolates from 14 patients to 8 STs. The results revealed that patients can be colonised by individual strains for years. The MLST scheme developed for S. apiospermum and P. boydii is a highly effective tool for epidemiologic studies worldwide. The MLST data are accessible at http://mlst.mycologylab.org/. Copyright © 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

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

    PubMed Central

    Li, Ziyi; Engelhardt, John F

    2003-01-01

    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 adequately replicate spontaneous bacterial infections observed in the human CF lung. Hence, several laboratories are pursuing alternative animal models of CF in larger species such as the pig, sheep, rabbits, and ferrets. Our laboratory has focused on developing the ferret as a CF animal model. Over the past few years, we have investigated several experimental parameters required for gene targeting and nuclear transfer (NT) cloning in the ferret using somatic cells. In this review, we will discuss our progress and the hurdles to NT cloning and gene-targeting that accompany efforts to generate animal models of genetic diseases in species such as the ferret. PMID:14613541

  2. Free DNA in Cystic Fibrosis Airway Fluids Correlates with Airflow Obstruction

    PubMed Central

    Marcos, Veronica; Zhou-Suckow, Zhe; Önder Yildirim, Ali; Bohla, Alexander; Hector, Andreas; Vitkov, Ljubomir; Krautgartner, Wolf Dietrich; Stoiber, Walter; Griese, Matthias; Eickelberg, Oliver; Mall, Marcus A.; Hartl, Dominik

    2015-01-01

    Chronic obstructive lung disease determines morbidity and mortality of patients with cystic fibrosis (CF). CF airways are characterized by a nonresolving neutrophilic inflammation. After pathogen contact or prolonged activation, neutrophils release DNA fibres decorated with antimicrobial proteins, forming neutrophil extracellular traps (NETs). NETs have been described to act in a beneficial way for innate host defense by bactericidal, fungicidal, and virucidal actions. On the other hand, excessive NET formation has been linked to the pathogenesis of autoinflammatory and autoimmune disease conditions. We quantified free DNA structures characteristic of NETs in airway fluids of CF patients and a mouse model with CF-like lung disease. Free DNA levels correlated with airflow obstruction, fungal colonization, and CXC chemokine levels in CF patients and CF-like mice. When viewed in combination, our results demonstrate that neutrophilic inflammation in CF airways is associated with abundant free DNA characteristic for NETosis, and suggest that free DNA may be implicated in lung function decline in patients with CF. PMID:25918476

  3. Drug therapies for reducing gastric acidity in people with cystic fibrosis.

    PubMed

    Ng, Sze May; Moore, Helen S

    2016-08-22

    Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. This is an update of a previously published review. To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, abstract books and conference proceedings.Most recent search of the Group's Trials Register: 12 May 2016. All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment. Both authors independently selected trials, assessed trial quality and extracted data. The searches identified 39 trials; 17 of these, with 273 participants, were suitable for inclusion, but the number of trials assessing each of the different agents was small. Seven trials were limited to children and four trials enrolled only adults. Meta-analysis was not performed, 14 trials were of a cross-over design and we did not have the appropriate information to conduct comprehensive meta-analyses. All the trials were run in single centres and duration ranged from five days to six months. The

  4. Effective silencing of ENaC by siRNA delivered with epithelial-targeted nanocomplexes in human cystic fibrosis cells and in mouse lung.

    PubMed

    Tagalakis, Aristides D; Munye, Mustafa M; Ivanova, Rositsa; Chen, Hanpeng; Smith, Claire M; Aldossary, Ahmad M; Rosa, Luca Z; Moulding, Dale; Barnes, Josephine L; Kafetzis, Konstantinos N; Jones, Stuart A; Baines, Deborah L; Moss, Guy W J; O'Callaghan, Christopher; McAnulty, Robin J; Hart, Stephen L

    2018-05-10

    Loss of the cystic fibrosis transmembrane conductance regulator in cystic fibrosis (CF) leads to hyperabsorption of sodium and fluid from the airway due to upregulation of the epithelial sodium channel (ENaC). Thickened mucus and depleted airway surface liquid (ASL) then lead to impaired mucociliary clearance. ENaC regulation is thus a promising target for CF therapy. Our aim was to develop siRNA nanocomplexes that mediate effective silencing of airway epithelial ENaC in vitro and in vivo with functional correction of epithelial ion and fluid transport. We investigated translocation of nanocomplexes through mucus and their transfection efficiency in primary CF epithelial cells grown at air-liquid interface (ALI).Short interfering RNA (SiRNA)-mediated silencing was examined by quantitative RT-PCR and western analysis of ENaC. Transepithelial potential (V t ), short circuit current (I sc ), ASL depth and ciliary beat frequency (CBF) were measured for functional analysis. Inflammation was analysed by histological analysis of normal mouse lung tissue sections. Nanocomplexes translocated more rapidly than siRNA alone through mucus. Transfections of primary CF epithelial cells with nanocomplexes targeting αENaC siRNA, reduced αENaC and βENaC mRNA by 30%. Transfections reduced V t , the amiloride-sensitive I sc and mucus protein concentration while increasing ASL depth and CBF to normal levels. A single dose of siRNA in mouse lung silenced ENaC by approximately 30%, which persisted for at least 7 days. Three doses of siRNA increased silencing to approximately 50%. Nanoparticle-mediated delivery of ENaCsiRNA to ALI cultures corrected aspects of the mucociliary defect in human CF cells and offers effective delivery and silencing in vivo. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

    PubMed

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

    2017-09-11

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

  6. Intrapulmonary percussive ventilation improves lung function in cystic fibrosis patients chronically colonized with Pseudomonas aeruginosa: a pilot cross-over study.

    PubMed

    Dingemans, Jozef; Eyns, Hanneke; Willekens, Julie; Monsieurs, Pieter; Van Houdt, Rob; Cornelis, Pierre; Malfroot, Anne; Crabbé, Aurélie

    2018-06-01

    High levels of shear stress can prevent and disrupt Pseudomonas aeruginosa biofilm formation in vitro. Intrapulmonary percussive ventilation (IPV) could be used to introduce shear stress into the lungs of cystic fibrosis (CF) patients to disrupt biofilms in vivo. We performed a first-of-its-kind pilot clinical study to evaluate short-term IPV therapy at medium (200 bursts per minute, bpm) and high frequency (400 bpm) as compared to autogenic drainage (AD) on lung function and the behavior of P. aeruginosa in the CF lung in four patients who are chronically colonized by P. aeruginosa. A significant difference between the three treatment groups was observed for both the forced expiratory volume in 1 s (FEV1) and the forced vital capacity (FVC) (p < 0.05). More specifically, IPV at high frequency significantly increased FEV1 and FVC compared to AD (p < 0.05) and IPV at medium frequency (p < 0.001). IPV at high frequency enhanced the expression levels of P. aeruginosa planktonic marker genes, which was less pronounced with IPV at medium frequency or AD. In conclusion, IPV at high frequency could potentially alter the behavior of P. aeruginosa in the CF lung and improve lung function. The trail was retrospectively registered at the ISRCTN registry on 6 June 2013, under trial registration number ISRCTN75391385.

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

    PubMed

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

    1992-09-01

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

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

    PubMed Central

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

    1992-01-01

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

  9. Assessment of Aspergillus sensitization or persistent carriage as a factor in lung function impairment in cystic fibrosis patients.

    PubMed

    Fillaux, Judith; Brémont, François; Murris, Marléne; Cassaing, Sophie; Rittié, Jean-Luc; Tétu, Laurent; Segonds, Christine; Abbal, Michel; Bieth, Eric; Berry, Antoine; Pipy, Bernard; Magnaval, Jean-François

    2012-11-01

    Cystic fibrosis (CF) patients presenting with persistent carriage of, or sensitization to, Aspergillus fumigatus are often treated with antifungal therapies because the presence of the fungus is commonly thought to impede lung function, even in the absence of allergic bronchopulmonary aspergillosis (ABPA). The aim of this study was to assess Aspergillus-related status modulating the forced expiratory volume in 1 s (FEV₁) of CF patients. From 1995 to 2007, 251 patients were evaluated. Demographic data, cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations, body mass index, and FEV(1) were recorded. The presence of A. fumigatus and Pseudomonas aeruginosa in sputum and the levels of A. fumigatus precipitin, total IgE (t-IgE), and specific anti-A. fumigatus IgE (Af-IgE) were determined. Patients were divided into 3 groups: (1) ABPA: A. fumigatus precipitin ≥3 lines, Af-IgE > 0.35 IU/ml, and t-IgE ≥500 IU/ml; (2) sensitization: Af-IgE > 0.35 IU/ml but t-IgE < 500 IU/ml; and (3) persistent carriage: Af-IgE ≤ 0.35 IU/ml with either an A. fumigatus persistent positive culture or an A. fumigatus precipitin ≥3 lines, provided this serological finding had been found associated with at least 1 A. fumigatus-positive culture. The remaining patients represented the control group. A multivariate analysis was carried out with FEV(1) as the outcome variable. ABPA, sensitization, and persistent carriage were significantly associated with a larger decline in FEV₁ compared with the control group, with odds ratios of 15.9, 14.9, and 10.7, respectively. This association was independent of other associated factors (P. aeruginosa transient detection, age, being underweight, and low FEV₁ at baseline). In addition to ABPA, sensitization and persistent carriage appear to have an impact on pulmonary function in CF patients.

  10. Vitamin K supplementation for cystic fibrosis.

    PubMed

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

    2017-08-22

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

  11. Vitamin K supplementation for cystic fibrosis

    PubMed Central

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

    2015-01-01

    Background Cystic fibrosis is a genetic disorder which can lead to multiorgan dysfunction. Malabsorption of fat and fat-soluble vitamins (A, D, E, K) may occur and can cause subclinical deficiencies of some of these vitamins. Vitamin K is known to play an important role in both blood coagulation and bone formation. Supplementation with vitamin K appears to be one way of addressing the deficiency, but there is very limited agreement on the appropriate dose and frequency of use of these supplements. Objectives To assess the effects of vitamin K supplementation in people with cystic fibrosis and to determine the optimal dose and route of administration of vitamin K for both routine and therapeutic use. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 08 October 2014. Selection criteria Randomised and quasi-randomised controlled trials of all preparations of vitamin K used as a supplement compared to either no supplementation (or placebo) at any dose or route and for any duration, in children or adults diagnosed with cystic fibrosis (by sweat test or genetic testing). Data collection and analysis Two authors independently screened papers, extracted trial details and assessed their risk of bias. Main results Two trials (total of 32 participants) each lasting one month were included in the review and were assessed as having a moderate risk of bias. One was a dose-ranging parallel group trial in children (aged 8 to 18 years); and the other (with an older cohort) had a crossover design comparing supplements to no treatment, but no separate data were reported for the first intervention period. Neither of the trials addressed any of the primary outcomes (coagulation, bone formation and quality of life). Both trials reported the restoration

  12. Intravenous immunoglobulin for cystic fibrosis lung disease: a case series of 16 children

    PubMed Central

    Balfour-Lynn, I; Mohan, U; Bush, A; Rosenthal, M

    2004-01-01

    Background and objective: Some children with severe cystic fibrosis (CF) lung disease develop chest tightness, recurrent dry cough, and intractable wheeze, often accompanied by deteriorating lung function and failure to expectorate sputum. In an attempt to reduce the use of regular oral corticosteroids, we treated a group of such children with monthly courses of intravenous immunoglobulin (IVIG). Methods: This is a retrospective case note review of 16 children, aged 3–16 years (median 13.0 years) who received 1–66 (median 7.5) courses of monthly IVIG, at a dose of 1 g/kg on two successive days for the first dose, followed by 1 g/kg monthly as a 12 hour infusion, with corticosteroid and antihistamine cover. Results: FEV1 improved from a median (95% confidence interval (CI)) of 50% (39 to 61%) to 54% (48 to 66%), with a median (95% CI) difference of +7.5% (-1.5 to 14.5%; NS). FVC improved from 65% (60 to 77%) to 83% (70 to 89%), with a difference of +13% (4 to 22%, p = 0.01). The total daily dose/kg body weight of oral prednisolone was reduced from 0.6 (0.3 to 1.0) to 0 (0 to 0.1) mg/kg/day, with a reduction of -0.6 (-1.0 to -0.1, p = 0.006) mg/kg/day. The total daily dose of inhaled corticosteroid (budesonide equivalent) was a median (range) of 2000 µg (800–6000 µg), which was reduced to 1500 µg (0–3200 µg). The median (95% CI) difference was -400 µg (-1600 to 0 µg), p<0.05. IVIG was well tolerated and the regimen acceptable to all but one of the children. The following transient adverse reactions were seen in only one patient each: headache, fever, hypotension, aseptic meningitis, and chest tightness. Conclusion: We suggest that an n = 1 trial of IVIG in carefully selected patients with severe obstructive CF lung disease is worth considering, as for some it may lead to significant benefit. PMID:15033837

  13. Cystic fibrosis: a clinical view.

    PubMed

    Castellani, Carlo; Assael, Baroukh M

    2017-01-01

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

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

    PubMed

    Ravert, Russell D; Crowell, Toni L

    2008-11-01

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

  15. Clinical outcomes in cystic fibrosis patients with Trichosporon respiratory infection.

    PubMed

    Esther, Charles R; Plongla, Rongpong; Kerr, Alan; Lin, Feng-Chang; Gilligan, Peter

    2016-09-01

    Relationships between clinical outcomes and novel respiratory pathogens such as Trichosporon are not well understood. Respiratory cultures from CF patients were screened for novel pathogens Trichosporon and Chryseobacterium as well as other pathogens over 28months. Relationships between microbiologic and clinical data were assessed using univariate and multivariate methods. Of 4934 respiratory cultures from 474 CF patients, 37 cultures from 10 patients were Trichosporon positive. Patients with positive Trichosproron cultures had a greater decline in FEV1 over time (-3.9%/year vs. -1.3%/year, p<0.05), whereas Chryseobacterium did not influence lung function. These findings were confirmed in multivariate analyses that included age, gender, and other common pathogens as confounders. Treatment of Trichosporon infected patients was associated with improved lung function. Trichosporon can be recovered from a small but clinically meaningful fraction of CF patients. The presence of Trichosporon, but not Chryseobacterium, is associated with greater declines in lung function. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  16. Localization of Burkholderia cepacia Complex Bacteria in Cystic Fibrosis Lungs and Interactions with Pseudomonas aeruginosa in Hypoxic Mucus

    PubMed Central

    Abdullah, Lubna H.; Perlmutt, Olivia S.; Albert, Daniel; Davis, C. William; Arnold, Roland R.; Yankaskas, James R.; Gilligan, Peter; Neubauer, Heiner; Randell, Scott H.; Boucher, Richard C.

    2014-01-01

    The localization of Burkholderia cepacia complex (Bcc) bacteria in cystic fibrosis (CF) lungs, alone or during coinfection with Pseudomonas aeruginosa, is poorly understood. We performed immunohistochemistry for Bcc and P. aeruginosa bacteria on 21 coinfected or singly infected CF lungs obtained at transplantation or autopsy. Parallel in vitro experiments examined the growth of two Bcc species, Burkholderia cenocepacia and Burkholderia multivorans, in environments similar to those occupied by P. aeruginosa in the CF lung. Bcc bacteria were predominantly identified in the CF lung as single cells or small clusters within phagocytes and mucus but not as “biofilm-like structures.” In contrast, P. aeruginosa was identified in biofilm-like masses, but densities appeared to be reduced during coinfection with Bcc bacteria. Based on chemical analyses of CF and non-CF respiratory secretions, a test medium was defined to study Bcc growth and interactions with P. aeruginosa in an environment mimicking the CF lung. When test medium was supplemented with alternative electron acceptors under anaerobic conditions, B. cenocepacia and B. multivorans used fermentation rather than anaerobic respiration to gain energy, consistent with the identification of fermentation products by high-performance liquid chromatography (HPLC). Both Bcc species also expressed mucinases that produced carbon sources from mucins for growth. In the presence of P. aeruginosa in vitro, both Bcc species grew anaerobically but not aerobically. We propose that Bcc bacteria (i) invade a P. aeruginosa-infected CF lung when the airway lumen is anaerobic, (ii) inhibit P. aeruginosa biofilm-like growth, and (iii) expand the host bacterial niche from mucus to also include macrophages. PMID:25156735

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

    PubMed Central

    Siwamogsatham, Oranan; Alvarez, Jessica

    2015-01-01

    Purpose of review The aim of this review is to provide an update on various relevant endocrine aspects of care in adolescents and adults with cystic fibrosis (CF). Recent findings As life expectancy in CF has continuously improved, endocrine complications have become more apparent. The common endocrine complications include cystic fibrosis related diabetes (CFRD), cystic fibrosis related bone disease, vitamin D deficiency and poor growth and pubertal development. Thyroid and adrenal disorders have also been reported, although the prevalence appears to be less common. Summary Endocrine diseases are an increasingly recognized complication that has a significant impact on the overall health of individuals with CF. This review summarizes the updated screening and management of endocrine diseases in the CF population. PMID:25105995

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

    PubMed

    Thornton, Judith; Rangaraj, Satyapal

    2016-01-21

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

  19. Cystic fibrosis Δf508 mutation screening in Brazilian women with altered fertility.

    PubMed

    Brunoro, G V F; Wolfgramm, E V; Louro, I D; Degasperi, I I; Busatto, V C W; Perrone, A M S; Batitucci, M C P

    2011-10-01

    Cystic Fibrosis (CF) is an autosomal recessive disease, caused by mutations in the Cystic Fibrosis Transmembrane Regulator gene (CFTR). The most frequent mutation in CF is ΔF508. The disease is clinically characterized by elevated concentrations of sweat chlorides and abnormally thick mucus. It affects organs such as lung, pancreas, gastrointestinal and reproductive tract. Women with CF commonly present delayed puberty and amenorrhea due to malnutrition. Our objective was to screen the presence of ΔF508 mutation in 24 women with altered fertility. Nine of these women presented reduced fertility without a known cause, four showed polycystic ovaries and two had early menopause. One woman with early menopause was a carrier of the ΔF508 mutation. Our study demonstrates that it is possible that the frequency of CF mutations among patients with altered fertility may be higher than expected. Previous data showed that fibrocystic women can show reduced fertility, maternal mortality associated with pregnancy and increased incidence of spontaneous abortion. We therefore recommend that women with reduced fertility undertake genetic tests for a better evaluation of pregnancy risks and clinical monitoring.

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

    PubMed

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

    2014-06-01

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

  1. Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

    PubMed Central

    Chmiel, James F.; Konstan, Michael W.; Elborn, J. Stuart

    2013-01-01

    Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. PMID:23880054

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

    PubMed Central

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

    1996-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2003-03-01

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

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

    PubMed Central

    Cutting, Garry R.

    2015-01-01

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

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

    PubMed

    Cutting, Garry R

    2015-01-01

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

  7. Cystic Fibrosis Revisited - a Review Study.

    PubMed

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

    2017-01-01

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

  8. The lipid A of Burkholderia multivorans C1576 smooth-type lipopolysaccharide and its pro-inflammatory activity in a cystic fibrosis airways model.

    PubMed

    Ieranò, Teresa; Cescutti, Paola; Leone, Maria Rosaria; Luciani, Alessandro; Rizzo, Roberto; Raia, Valeria; Lanzetta, Rosa; Parrilli, Michelangelo; Maiuri, Luigi; Silipo, Alba; Molinaro, Antonio

    2010-12-01

    Cystic fibrosis is an autosomal recessive disorder and it is characterised by chronic bacterial airway infection which leads to progressive lung deterioration, sometimes with fatal outcome. Burkholderia multivorans and Burkholderia cenocepacia are the species responsible for most of the infections of cystic fibrosis patients. Lipopolysaccharide endotoxins (LPSs) are among the foremost factors of pathogenesis of Gram-negative infection and, in particular, lipid A is the endotoxic portion of LPS responsible for eliciting host innate immune response. In this work, the complete primary structure of the lipid A from B. multivorans C1576 has been defined and, further, its pro-inflammatory activity in a cystic fibrosis airways model is shown. The structure of B. multivorans lipid A was attained by chemical, mass spectrometry and nuclear magnetic resonance analyses whereas its biological activity was assessed on the intestinal epithelial cell line CACO-2 cells, on the airway epithelial IB3-1 cells, carrying the ΔF508/W1282X CFTR mutation and on an ex vivo model of culture explants of nasal polyps.

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

    PubMed

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

    1994-01-01

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

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

    PubMed

    Witt, D M; Anderson, L

    1996-01-01

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

  11. Relationship of Antibiotic Treatment to Recovery after Acute FEV1 Decline in Children with Cystic Fibrosis.

    PubMed

    Morgan, Wayne J; Wagener, Jeffrey S; Pasta, David J; Millar, Stefanie J; VanDevanter, Donald R; Konstan, Michael W

    2017-06-01

    Children with cystic fibrosis often experience acute declines in lung function. We previously showed that such declines are not always treated with antibiotics, but we did not assess whether treatment improves the likelihood of recovery. To determine whether new antibiotic treatment was associated with recovery from acute FEV 1 decline. We studied episodes of FEV 1 decline (≥10% from baseline) in the Epidemiologic Study of Cystic Fibrosis. Treatments were hospitalization, home intravenous antibiotic, new inhaled oral quinolone, or other oral antibiotic. We used logistic regression to evaluate whether treatment was associated with recovery to baseline or near baseline. Logistic regression of 9,875 patients showed that new antibiotic treatment was associated with an increased likelihood of recovery to 90% of baseline (P < 0.001), especially for hospitalization compared with no new antibiotic (odds ratio [OR], 2.79; 95% confidence interval, 2.41-3.23). All four outpatient treatments were associated with greater likelihood of recovery compared with no treatment (OR, 1.27-1.64). Inpatient treatment was better than outpatient treatment (OR, 1.94; 95% confidence interval, 1.68-2.23). Treatment-type ORs were similar across recovery criteria and levels of baseline lung function. New antibiotic therapy, and especially inpatient treatment, is associated with greater likelihood of recovery after acute decline in FEV 1 . Benefits extend across all disease stages and are especially important in patients with high lung function, who are at greatest risk for FEV 1 decline.

  12. Ethnicity impacts the cystic fibrosis diagnosis: A note of caution.

    PubMed

    Bosch, Barbara; Bilton, Diana; Sosnay, Patrick; Raraigh, Karen S; Mak, Denise Y F; Ishiguro, Hiroshi; Gulmans, Vincent; Thomas, Muriel; Cuppens, Harry; Amaral, Margarida; De Boeck, Kris

    2017-07-01

    The diagnosis of Cystic Fibrosis (CF) is by consensus based on the same parameters in all patients, yet the influence of ethnicity has only scarcely been studied. We aimed at elucidating the impact of Asian descent on the diagnosis of CF. We performed a retrospective analysis of the CFTR2 and UK CF databases for clinical phenotype, sweat chloride values and CFTR mutations and compared the diagnostic characteristics of Asian to non-Asian patients with CF. Asian patients with CF do not have a worse clinical phenotype. The repeatedly reported lower FEV 1 of Asian patients with CF is attributable to the influence of ethnicity on lung function in general. However, pancreatic sufficiency is more common in Asian patients with CF. The diagnosis of CF in people with Asian ancestry is heterogeneous as mean sweat chloride values are lower (92±26 versus 99±22mmol/L in controls) and 14% have sweat chloride values below 60mmol/L (versus 6% in non-Asians). Also, CFTR mutations differ from those in Caucasians: 55% of British Asian patients with CF do not have one mutation included in the routine newborn screening panel. Bringing together the largest cohort of patients with CF and Asian ethnicity, we demonstrate that Asian roots impact on all three CF diagnostic pillars. These findings have implications for clinical practice in the increasingly ethnically diverse Western population. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  13. Acidic pH increases airway surface liquid viscosity in cystic fibrosis

    PubMed Central

    Tang, Xiao Xiao; Ostedgaard, Lynda S.; Hoegger, Mark J.; Moninger, Thomas O.; Karp, Philip H.; McMenimen, James D.; Choudhury, Biswa; Varki, Ajit; Stoltz, David A.; Welsh, Michael J.

    2016-01-01

    Cystic fibrosis (CF) disrupts respiratory host defenses, allowing bacterial infection, inflammation, and mucus accumulation to progressively destroy the lungs. Our previous studies revealed that mucus with abnormal behavior impaired mucociliary transport in newborn CF piglets prior to the onset of secondary manifestations. To further investigate mucus abnormalities, here we studied airway surface liquid (ASL) collected from newborn piglets and ASL on cultured airway epithelia. Fluorescence recovery after photobleaching revealed that the viscosity of CF ASL was increased relative to that of non-CF ASL. CF ASL had a reduced pH, which was necessary and sufficient for genotype-dependent viscosity differences. The increased viscosity of CF ASL was not explained by pH-independent changes in HCO3– concentration, altered glycosylation, additional pH-induced disulfide bond formation, increased percentage of nonvolatile material, or increased sulfation. Treating acidic ASL with hypertonic saline or heparin largely reversed the increased viscosity, suggesting that acidic pH influences mucin electrostatic interactions. These findings link loss of cystic fibrosis transmembrane conductance regulator–dependent alkalinization to abnormal CF ASL. In addition, we found that increasing Ca2+ concentrations elevated ASL viscosity, in part, independently of pH. The results suggest that increasing pH, reducing Ca2+ concentration, and/or altering electrostatic interactions in ASL might benefit early CF. PMID:26808501

  14. Airway surface liquid homeostasis in cystic fibrosis: pathophysiology and therapeutic targets.

    PubMed

    Haq, Iram J; Gray, Michael A; Garnett, James P; Ward, Christopher; Brodlie, Malcolm

    2016-03-01

    Cystic fibrosis (CF) is a life-limiting disease characterised by recurrent respiratory infections, inflammation and lung damage. The volume and composition of the airway surface liquid (ASL) are important in maintaining ciliary function, mucociliary clearance and antimicrobial properties of the airway. In CF, these homeostatic mechanisms are impaired, leading to a dehydrated and acidic ASL. ASL volume depletion in CF is secondary to defective anion transport by the abnormal cystic fibrosis transmembrane conductance regulator protein (CFTR). Abnormal CFTR mediated bicarbonate transport creates an unfavourable, acidic environment, which impairs antimicrobial function and alters mucus properties and clearance. These disease mechanisms create a disordered airway milieu, consisting of thick mucopurulent secretions and chronic bacterial infection. In addition to CFTR, there are additional ion channels and transporters in the apical airway epithelium that play a role in maintaining ASL homeostasis. These include the epithelial sodium channel (ENaC), the solute carrier 26A (SLC26A) family of anion exchangers, and calcium-activated chloride channels. In this review we discuss how the ASL is abnormal in CF and how targeting these alternative channels and transporters could provide an attractive therapeutic strategy to correct the underlying ASL abnormalities evident in CF. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  15. One time quantitative PCR detection of Pseudomonas aeruginosa to discriminate intermittent from chronic infection in cystic fibrosis.

    PubMed

    Boutin, Sébastien; Weitnauer, Michael; Hassel, Selina; Graeber, Simon Y; Stahl, Mirjam; Dittrich, A Susanne; Mall, Marcus A; Dalpke, Alexander H

    2018-05-01

    Chronic airway infection with Pseudomonas aeruginosa is a major risk factor of progression of lung disease in patients with cystic fibrosis (CF). Chronic P. aeruginosa infection evolves from intermittent infection that is amenable to antibiotic eradication, whereas chronically adapted P. aeruginosa becomes resistant to antibiotic therapy. Discrimination of intermittent versus chronic infection is therefore of high therapeutic relevance, yet the available diagnostic methods are only partly satisfactory. The aim of the present study was, therefore, to evaluate the usage of quantitative PCR (qPCR) to measure pathogen abundance and to discriminate between intermittent and chronic Pseudomonas infection in patients with CF. Using an established qPCR protocol, we analyzed the abundance of P. aeruginosa in 141 throats swabs and 238 sputa from CF patients with intermittent or chronic infection with P. aeruginosa, as determined by standard culture based diagnostics. We observed a large increase of abundance of P. aeruginosa in throat swabs and sputum samples from patients with chronic compared to intermittent infections with P. aeruginosa. The data show that abundance of P. aeruginosa as measured by qPCR is a valuable tool to discriminate intermittent from chronic infection. Of note, P. aeruginosa burden seems more sensitive than mucoidity phenotype to discriminate chronic from intermittent strains. Furthermore we observed that molecular detection in throat swabs was linked to a viable culture in the sputum when sputum was available. This result is of special interest in young patients with cystic fibrosis that often cannot expectorate sputum. We also observed that qPCR in comparison to culture detected the infection earlier. The results suggest that qPCR detection and quantification of P. aeruginosa is a precious tool to be added to the diagnostic toolbox in cystic fibrosis. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  16. Is bronchoscopy an obsolete tool in cystic fibrosis? The role of bronchoscopy in cystic fibrosis and its clinical use

    PubMed Central

    2017-01-01

    Cystic fibrosis (CF) is a progressive life threatening multisystem genetic disease which affects the CF transmembrane conductance regulator channel. Respiratory causes remain the most common mortality in CF. With the onset of newborn screening, initiating treatments both for prophylaxis and disease management, optimizing nutritional support, and developing therapies targeting CF transmembrane conductance regulator protein, this has significantly changed the face of managing this devastating disease. Bronchoscopy and related procedures such as bronchoalveolar lavage (BAL), transbronchial biopsies, and protected brush sampling have been looked at in the management of CF as patients with CF continue to live longer with the help of newer therapies, the microbiome in the lung becomes less diverse along with increased occurrences for noninfectious causes of airway diseases. Though bronchoscopy has been used in conjunction with other modalities such as computed tomography and sputum induction providing a better understanding of the progression of the disease, it still remains valuable in the diagnosis and management of CF. PMID:29214071

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

    PubMed

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

    2018-02-15

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

  18. Pulmonary Bacteriophage Therapy on Pseudomonas aeruginosa Cystic Fibrosis Strains: First Steps Towards Treatment and Prevention

    PubMed Central

    Morello, Eric; Saussereau, Emilie; Maura, Damien; Huerre, Michel; Touqui, Lhousseine; Debarbieux, Laurent

    2011-01-01

    Multidrug-resistant bacteria are the cause of an increasing number of deadly pulmonary infections. Because there is currently a paucity of novel antibiotics, phage therapy—the use of specific viruses that infect bacteria—is now more frequently being considered as a potential treatment for bacterial infections. Using a mouse lung-infection model caused by a multidrug resistant Pseudomonas aeruginosa mucoid strain isolated from a cystic fibrosis patient, we evaluated bacteriophage treatments. New bacteriophages were isolated from environmental samples and characterized. Bacteria and bacteriophages were applied intranasally to the immunocompetent mice. Survival was monitored and bronchoalveolar fluids were analysed. Quantification of bacteria, bacteriophages, pro-inflammatory and cytotoxicity markers, as well as histology and immunohistochemistry analyses were performed. A curative treatment (one single dose) administrated 2 h after the onset of the infection allowed over 95% survival. A four-day preventive treatment (one single dose) resulted in a 100% survival. All of the parameters measured correlated with the efficacy of both curative and preventive bacteriophage treatments. We also showed that in vitro optimization of a bacteriophage towards a clinical strain improved both its efficacy on in vivo treatments and its host range on a panel of 20 P. aeruginosa cystic fibrosis strains. This work provides an incentive to develop clinical studies on pulmonary bacteriophage therapy to combat multidrug-resistant lung infections. PMID:21347240

  19. Increase in interleukin-8 production from circulating neutrophils upon antibiotic therapy in cystic fibrosis patients.

    PubMed

    Montemurro, Pasqualina; Mariggiò, Maria A; Barbuti, Giovanna; Cassano, Amalia; Vincenti, Alessandra; Serio, Gabriella; Guerra, Lorenzo; Diana, Anna; Santostasi, Teresa; Polizzi, Angela; Fumarulo, Ruggiero; Casavola, Valeria; Manca, Antonio; Conese, Massimo

    2012-12-01

    It is not known whether antibiotic therapy for lung disease in cystic fibrosis (CF) has an influence on circulating polymorphonuclear neutrophil (PMN) function and apoptosis. Blood PMNs were obtained from 14 CF patients before and after antibiotic treatment for an acute exacerbation, and from 10 healthy controls. PMNs were evaluated for production of reactive oxygen species (ROS) by spectrophotometry, of cytokines in the conditioned medium by ELISA, and apoptotic response by cytofluorimetry. ROS and interleukin (IL)-8 were produced at higher levels by CF PMNs pre-therapy than control PMNs under basal conditions. IL-8 levels further increased after therapy. Early apoptotic response was higher in CF PMNs pre-therapy than in control PMNs, and this pattern did not change after antibiotic treatment. Circulating PMNs are primed in CF acute patients. Further studies are needed to consider PMN-produced IL-8 as a biomarker to evaluate response to antibiotic therapy in CF patients. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  20. [Lung transplantation in cystic fibrosis. The results of the Clínica Puerta de Hierro (Madrid) and the Hospital La Fe (Valencia)].

    PubMed

    Lázaro-Carrasco, M T; Morales, P; Ferreiro, M J; Borro, J M; Varela, A; Vicente, R; Ramos, F; Estada, J A

    1999-05-01

    Retrospective analysis of cystic fibrosis patients who underwent pulmonary transplantation at Clínica Puerta de Hierro, Madrid, and at Hospital La Fe, Valencia. Since the beginning of the programme and until March 1998, a total of 63 patients with cystic fibrosis were studied. Among transplanted patients, 18 were males and 16 females, with a mean age of 18.9 years. All patients underwent sequential bilateral pulmonary transplantation. After transplantation, the most common complication was bacterial pneumonia which affected all patients. Six patients had dehiscence or stenosis of the bronchial suture. Other specific complications of this condition by frequency were intestinal obstruction and diabetes mellitus. Six patients developed obliterans bronchiolitis and one of them underwent a repeat transplantation. Three out of the 34 patients died, and the likelihood of survival after one and three years was 94%. Respiratory function tests and PaO2 peaked at sixth post-transplantation month. Pulmonary transplantation is a therapeutic option to be considered for the patient with cystic fibrosis and severe involvement of his/her pulmonary disease.