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  1. Cystic Fibrosis

    MedlinePlus

    ... for the Public » Health Topics » Cystic Fibrosis Explore Cystic Fibrosis What Is... Other Names Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Living With Clinical Trials Links Related Topics Bronchiectasis ...

  2. Cystic Fibrosis

    MedlinePlus

    ... and Diseases > Lung Disease Lookup > Cystic Fibrosis Cystic Fibrosis Cystic Fibrosis (CF) is an inherited disease that ... quality of life has improved. Learn About Cystic Fibrosis Cystic fibrosis is a genetic (inherited) condition that ...

  3. Genetics of Cystic Fibrosis: Clinical Implications.

    PubMed

    Egan, Marie E

    2016-03-01

    Cystic fibrosis (CF) is a common life-shortening autosomal recessive genetic disorder caused by mutations in the gene that encodes for the cystic fibrosis transmembrane conductance regulator protein (CFTR). Almost 2000 variants in the CFTR gene have been identified. The mutational classes are based on the functional consequences on CFTR. New therapies are being developed to target mutant CFTR and restore CFTR function. Understanding specific CF genotypes is essential for providing state-of-the art care to patients. In addition to the variation in CFTR genotype, there are several modifier genes that contribute to the respiratory phenotype. PMID:26857764

  4. Cystic fibrosis

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/000107.htm Cystic fibrosis To use the sharing features on this page, please enable JavaScript. Cystic fibrosis is a disease that causes thick, sticky mucus ...

  5. Clinical monitoring of steatorrhoea in cystic fibrosis.

    PubMed Central

    Walters, M P; Kelleher, J; Gilbert, J; Littlewood, J M

    1990-01-01

    In 100 patients with cystic fibrosis the severity of steatorrhoea was assessed by three separate methods. Using chemical faecal fat assay as the gold standard, two other rapid and inexpensive methods were compared with it. The steatocrit method proved unreliable in our hands and gave little indication of the presence or severity of steatorrhoea. The more simple microscopy method was highly sensitive (97%) and only three of 80 patients with steatorrhoea were missed. All patients with severe steatorrhoea (greater than 60 mmol fat/day) were clearly demonstrated. The method is applicable to spot faecal samples and can readily be carried out on an outpatient basis. In centres where faecal fat assays are not available, the simple and cheap microscopic examination will give some indication of the response to enzyme treatment and may also help to identify non-compliant individuals. PMID:2301990

  6. Clinical Significance of Microbial Infection and Adaptation in Cystic Fibrosis

    PubMed Central

    Hauser, Alan R.; Jain, Manu; Bar-Meir, Maskit; McColley, Susanna A.

    2011-01-01

    Summary: A select group of microorganisms inhabit the airways of individuals with cystic fibrosis. Once established within the pulmonary environment in these patients, many of these microbes adapt by altering aspects of their structure and physiology. Some of these microbes and adaptations are associated with more rapid deterioration in lung function and overall clinical status, whereas others appear to have little effect. Here we review current evidence supporting or refuting a role for the different microbes and their adaptations in contributing to poor clinical outcomes in cystic fibrosis. PMID:21233507

  7. Cystic fibrosis

    MedlinePlus

    ... or three times each week. Swimming, jogging, and cycling are good options. Clearing or bringing up mucus ... cannot be prevented. Screening those with a family history of the disease may detect the cystic fibrosis ...

  8. 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- ...

  9. Clinical Practice Guidelines From the Cystic Fibrosis Foundation for Preschoolers With Cystic Fibrosis.

    PubMed

    Lahiri, Thomas; Hempstead, Sarah E; Brady, Cynthia; Cannon, Carolyn L; Clark, Kelli; Condren, Michelle E; Guill, Margaret F; Guillerman, R Paul; Leone, Christina G; Maguiness, Karen; Monchil, Lisa; Powers, Scott W; Rosenfeld, Margaret; Schwarzenberg, Sarah Jane; Tompkins, Connie L; Zemanick, Edith T; Davis, Stephanie D

    2016-04-01

    Cystic fibrosis (CF) clinical care guidelines exist for the care of infants up to age 2 years and for individuals ≥6 years of age. An important gap exists for preschool children between the ages of 2 and 5 years. This period marks a time of growth and development that is critical to achieve optimal nutritional status and maintain lung health. Given that disease often progresses in a clinically silent manner, objective and sensitive tools that detect and track early disease are important in this age group. Several challenges exist that may impede the delivery of care for these children, including adherence to therapies. A multidisciplinary committee was convened by the CF Foundation to develop comprehensive evidence-based and consensus recommendations for the care of preschool children, ages 2 to 5 years, with CF. This document includes recommendations in the following areas: routine surveillance for pulmonary disease, therapeutics, and nutritional and gastrointestinal care. PMID:27009033

  10. Cystic Fibrosis

    MedlinePlus

    Cystic fibrosis (CF) is an inherited disease of the mucus and sweat glands. It affects mostly your lungs, pancreas, liver, intestines, sinuses, and sex organs. CF causes your mucus to be thick and sticky. The mucus clogs the lungs, causing breathing problems ...

  11. Cystic Fibrosis Research

    MedlinePlus

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

  12. Multidimensional Clinical Phenotyping of an Adult Cystic Fibrosis Patient Population

    PubMed Central

    Conrad, Douglas J.; Bailey, Barbara A.

    2015-01-01

    Background Cystic Fibrosis (CF) is a multi-systemic disease resulting from mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene and has major manifestations in the sino-pulmonary, and gastro-intestinal tracts. Clinical phenotypes were generated using 26 common clinical variables to generate classes that overlapped quantiles of lung function and were based on multiple aspects of CF systemic disease. Methods The variables included age, gender, CFTR mutations, FEV1% predicted, FVC% predicted, height, weight, Brasfield chest xray score, pancreatic sufficiency status and clinical microbiology results. Complete datasets were compiled on 211 subjects. Phenotypes were identified using a proximity matrix generated by the unsupervised Random Forests algorithm and subsequent clustering by the Partitioning around Medoids (PAM) algorithm. The final phenotypic classes were then characterized and compared to a similar dataset obtained three years earlier. Findings Clinical phenotypes were identified using a clustering strategy that generated four and five phenotypes. Each strategy identified 1) a low lung health scores phenotype, 2) a younger, well-nourished, male-dominated class, 3) various high lung health score phenotypes that varied in terms of age, gender and nutritional status. This multidimensional clinical phenotyping strategy identified classes with expected microbiology results and low risk clinical phenotypes with pancreatic sufficiency. Interpretation This study demonstrated regional adult CF clinical phenotypes using non-parametric, continuous, ordinal and categorical data with a minimal amount of subjective data to identify clinically relevant phenotypes. These studies identified the relative stability of the phenotypes, demonstrated specific phenotypes consistent with published findings and identified others needing further study. PMID:25822311

  13. Novel Outcome Measures for Clinical Trials in Cystic Fibrosis

    PubMed Central

    Tiddens, Harm AWM; Puderbach, Michael; Venegas, Jose G; Ratjen, Felix; Donaldson, Scott H; Davis, Stephanie D; Rowe, Steven M; Sagel, Scott D; Higgins, Mark; Waltz, David A

    2015-01-01

    Cystic fibrosis (CF) is a common inherited condition caused by mutations in the gene encoding the CF transmembrane regulator protein. With increased understanding of the molecular mechanisms underlying CF and the development of new therapies there comes the need to develop new outcome measures to assess the disease, its progression and response to treatment. As there are limitations to the current endpoints accepted for regulatory purposes, a workshop to discuss novel endpoints for clinical trials in CF was held in Anaheim, California in November 2011. The pros and cons of novel outcome measures with potential utility for evaluation of novel treatments in CF were critically evaluated. The highlights of the 2011 workshop and subsequent advances in technologies and techniques that could be used to inform the development of clinical trial endpoints are summarized in this review. Pediatr Pulmonol. © 2014 The Authors. Pediatric Pulmonology published by Wiley Periodicals, Inc. PMID:25641878

  14. [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. PMID:26895996

  15. 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

  16. 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. PMID:25404111

  17. Considerations for the Conduct of Clinical Trials with Antiinflammatory Agents in Cystic Fibrosis. A Cystic Fibrosis Foundation Workshop Report.

    PubMed

    Torphy, Theodore J; Allen, Janet; Cantin, André M; Konstan, Michael W; Accurso, Frank J; Joseloff, Elizabeth; Ratjen, Felix A; Chmiel, James F

    2015-09-01

    Inflammation leads to lung destruction and loss of pulmonary function in patients with cystic fibrosis (CF). Drugs that modulate the cystic fibrosis transmembrane conductance regulator (CFTR) have recently been approved. Although the impact of CFTR modulators on sweat chloride and lung function are exciting, they have not yet demonstrated an effect on inflammation. Therefore, CF antiinflammatory drug development must continue. Unfortunately, the lack of clarity with this process has left investigators and industry sponsors frustrated. The Cystic Fibrosis Foundation established a working group in early 2014 to address this issue. There are many inflammatory processes disrupted in CF, and, therefore, there are many potential targets amenable to antiinflammatory therapy. Regardless of a drug's specific mechanism of action, it must ultimately affect the neutrophil or its products to impact CF. The working group concluded that before bringing new antiinflammatory drugs to clinical trial, preclinical safety studies must be conducted in disease-relevant models to assuage safety concerns. Furthermore, although studies of antiinflammatory therapies must first establish safety in adults, subsequent studies must involve children, as they are most likely to reap the most benefit. The working group also recommended that pharmacokinetic-pharmacodynamic studies and early-phase safety studies be performed before proceeding to larger studies of longer duration. In addition, innovative study designs may improve the likelihood of adequately assessing treatment response and mitigating risk before conducting multiyear studies. Learning from past experiences and incorporating this knowledge into new drug development programs will be instrumental in bringing new antiinflammatory therapies to patients. PMID:26146892

  18. What Causes Cystic Fibrosis?

    MedlinePlus

    ... What Causes Cystic Fibrosis? A defect in the CFTR gene causes cystic fibrosis (CF). This gene makes ... and very salty sweat. Research suggests that the CFTR protein also affects the body in other ways. ...

  19. Physiologic endpoints for clinical studies for cystic fibrosis.

    PubMed

    Stanojevic, Sanja; Ratjen, Felix

    2016-07-01

    The cystic fibrosis (CF) drug development pipeline promises many exciting new treatments for patients with CF, all which will require clinical studies to prove their benefits on CF lung disease. Historically many pivotal CF studies have used the Forced Expiratory Volume in 1s (FEV1) as the primary outcome measure, and after demonstrating significant improvements in the treatment group relative to placebo have led to regulatory approval of therapies for routine clinical care. Widespread implementation of these therapies has subsequently led to significant improvements in outcomes for patients with CF. While preserving lung function has obvious benefits to CF patients, as more patients maintain FEV1 in the normal range, it has become increasingly difficult to conduct clinical trials using FEV1 as the primary outcome measure. With multiple concurrent trials competing to enroll from the same pool of patients, there is a need for novel approaches to study end points as well as new physiological outcomes for CF therapeutic trials. In this review we will discuss some of the limitations of FEV1 in the current era of CF care, describe alternative physiological endpoints and outline areas for further research. PMID:27316663

  20. Living with Cystic Fibrosis

    MedlinePlus

    ... from the NHLBI on Twitter. Living With Cystic Fibrosis If you or your child has cystic fibrosis (CF), you should learn as much as you ... about CF Care Centers, go to the Cystic Fibrosis Foundation's Care Center Network Web page. It's standard ...

  1. Learning about Cystic Fibrosis

    MedlinePlus

    ... order to digest food. Cystic Fibrosis: A Single Gene Disease Mutations in a single gene - the Cystic ... the defective gene, or correcting the defective protein. Gene Therapy Research Offers Promise of a Cure for ...

  2. How Is Cystic Fibrosis Diagnosed?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Cystic Fibrosis Diagnosed? Doctors diagnose cystic fibrosis (CF) based on ... to see whether the baby has CF. Cystic Fibrosis Carrier Testing People who have one normal CFTR ...

  3. 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. PMID:26857763

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

    PubMed

    Massie, John; Gillam, Lynn

    2014-01-01

    There is uncertainty about the diagnosis of cystic fibrosis after newborn screening (NBS) for some babies, either because of an intermediate sweat chloride test or inconclusive gene mutation analysis. There is considerable difficulty knowing how best to manage these babies, some of whom will develop cystic fibrosis, but many not. This article offers an ethics-based approach to this clinical dilemma that should be helpful to clinicians managing the baby with an uncertain diagnosis of cystic fibrosis after NBS. PMID:24166986

  5. The Cystic Fibrosis Intestine

    PubMed Central

    De Lisle, Robert C.; Borowitz, Drucy

    2013-01-01

    The clinical manifestations of cystic fibrosis (CF) result from dysfunction of the cystic fibrosis transmembrane regulator protein (CFTR). The majority of people with CF have a limited life span as a consequence of CFTR dysfunction in the respiratory tract. However, CFTR dysfunction in the gastrointestinal (GI) tract occurs earlier in ontogeny and is present in all patients, regardless of genotype. The same pathophysiologic triad of obstruction, infection, and inflammation that causes disease in the airways also causes disease in the intestines. This article describes the effects of CFTR dysfunction on the intestinal tissues and the intraluminal environment. Mouse models of CF have greatly advanced our understanding of the GI manifestations of CF, which can be directly applied to understanding CF disease in humans. PMID:23788646

  6. 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…

  7. Cystic Fibrosis Therapeutics

    PubMed Central

    Ramsey, Bonnie W.

    2013-01-01

    A great deal of excitement and hope has followed the successful trials and US Food and Drug Administration approval of the drug ivacaftor (Kalydeco), the first therapy available that targets the underlying defect that causes cystic fibrosis (CF). Although this drug has currently demonstrated a clinical benefit for a small minority of the CF population, the developmental pathway established by ivacaftor paves the way for other CF transmembrane conductance regulator (CFTR) modulators that may benefit many more patients. In addition to investigating CFTR modulators, researchers are actively developing numerous other innovative CF therapies. In this review, we use the catalog of treatments currently under evaluation with the support of the Cystic Fibrosis Foundation, known as the Cystic Fibrosis Foundation Therapeutics Pipeline, as a platform to discuss the variety of candidate treatments for CF lung disease that promise to improve CF care. Many of these approaches target the individual components of the relentless cycle of airway obstruction, inflammation, and infection characteristic of lung disease in CF, whereas others are aimed directly at the gene defect, or the resulting dysfunctional protein, that instigates this cycle. We discuss how new findings from the laboratory have informed not only the development of novel therapeutics, but also the rationales for their use and the outcomes used to measure their effects. By reviewing the breadth of candidate treatments currently in development, as well as the recent progress in CF therapies reflected by the evolution of the therapeutics pipeline over the past few years, we hope to build upon the optimism and anticipation generated by the recent success of Kalydeco. PMID:23276843

  8. Cystic Fibrosis (CF) Respiratory Screen: Sputum

    MedlinePlus

    ... Cystic Fibrosis (CF) Chloride Sweat Test Lungs and Respiratory System Cystic Fibrosis: Diet and Nutrition Cystic Fibrosis Cystic Fibrosis: Diet and Nutrition Lungs and Respiratory System Contact Us Print Resources Send to a friend ...

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

    PubMed

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

    2016-03-01

    Non-cystic fibrosis bronchiectasis (NCFB) is an increasingly prevalent disease that places a significant burden on patients and health systems globally. Although many of the therapies used to treat NCFB were originally developed as cystic fibrosis (CF) therapies, not all of them have been demonstrated to be efficacious in NCFB and some may even be harmful. This article explores the evidence for which therapeutic strategies used to treat CF have been translated into the care of NCFB. The conclusion is that therapies for adult NCFB cannot be simply extrapolated from CF clinical trials, and in some instances, doing so may actually result in harm. PMID:26857775

  10. [Rhinosinusitis in cystic fibrosis].

    PubMed

    Mainz, J G; Gerber, A; Arnold, C; Baumann, J; Baumann, I; Koitschev, A

    2015-11-01

    In cystic fibrosis (CF) mucociliary clearance of the entire respiratory system is impaired. This allows pathogens, such as Pseudomonas aeruginosa to persist and proliferate, which by progressive pulmonary destruction causes 90 % of premature deaths due to this inherited disease. The dramatic improvement in life expectation of patients due to intensive therapy has resulted in the inevitable but variably expressed sinonasal involvement coming into the clinical and scientific focus. Thereby, almost all CF patients reveal sinonasal pathology and many suffer from chronic rhinosinusitis. Recently, the sinonasal niche has been recognized as a site of initial and persistent colonization by pathogens. This article presents the pathophysiological background of this multiorgan disease as well as general diagnostic and therapeutic standards. The focus of this article is on sinonasal involvement and conservative and surgical options for treatment. Prevention of pathogen acquisition is an essential issue in the otorhinolaryngological treatment of CF patients. PMID:26495450

  11. [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. PMID:23856023

  12. Clinical impact of Achromobacter xylosoxidans colonization/infection in patients with cystic fibrosis

    PubMed Central

    Firmida, M.C.; Pereira, R.H.V.; Silva, E.A.S.R.; Marques, E.A.; Lopes, A.J.

    2016-01-01

    The rate of diagnosis of colonization/infection of the airways with Achromobacter xylosoxidans has increased in cystic fibrosis patients, but its clinical significance is still controversial. This retrospective, case-control study aimed to evaluate the clinical impact of A. xylosoxidans colonization/infection in cystic fibrosis patients. Individuals who were chronically colonized/infected (n=10), intermittently colonized/infected (n=15), and never colonized/infected with A. xylosoxidans (n=18) were retrospectively evaluated during two periods that were 2 years apart. Demographic characteristics, clinical data, lung function, and chronic bacterial co-colonization data were evaluated. Of the total study population, 87% were pediatric patients and 65.1% were female. Individuals chronically colonized/infected with A. xylosoxidans had decreased forced expiratory volume in 1 s (51.7% in the chronic colonization/infection group vs 82.7% in the intermittent colonization/infection group vs 76% in the never colonized/infected group). Compared with the other two groups, the rate of co-colonization with methicillin-resistant Staphylococcus aureus was higher in individuals chronically colonized/infected with A. xylosoxidans (P=0.002). Changes in lung function over 2 years in the three groups were not significant, although a trend toward a greater decrease in lung function was observed in the chronically colonized/infected group. Compared with the other two groups, there was a greater number of annual hospitalizations in patients chronically colonized/infected with A. xylosoxidans (P=0.033). In cystic fibrosis patients, there was an increased frequency of A. xylosoxidans colonization/infection in children, and lung function was reduced in patients who were chronically colonized/infected with A. xylosoxidans. Additionally, there were no differences in clinical outcomes during the 2-year period, except for an increased number of hospitalizations in patients with A. xylosoxidans

  13. 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. PMID:27578468

  14. IL8 gene as modifier of cystic fibrosis: unraveling the factors which influence clinical variability.

    PubMed

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

    2016-08-01

    The severity of cystic fibrosis (CF) is associated with classes of mutations in the CFTR gene (cystic fibrosis transmembrane regulator), physical environment and modifier genes interaction. The IL8 gene (interleukin 8), according to its respective polymorphisms, influences inflammatory responses. This study analyzed IL8 gene polymorphisms (rs4073, rs2227306 and rs2227307), by means of PCR/RFLP, and their association with pulmonary function markers and clinical severity scores in 186 patients with CF, considering the CFTR genotype. There was an association between rs2227307 and precocity of the disease. The severity of lung disease was associated with the following markers: transcutaneous arterial hemoglobin oxygen saturation (SaO2) (regardless of CFTR genotype, for the polymorphisms rs4073, rs2227306 and rs2227307); mucoid Pseudomonas aeruginosa (regardless of CFTR genotype, for the polymorphisms rs2227306 and rs2227307). Pulmonary function markers (SaO2 and spirometric variables) and clinical severity scores were also associated with IL8 gene polymorphisms. This study identified the IL8 gene, represented by rs4073 and rs2227306 polymorphisms, and particularly the rs2227307 polymorphism, as potentiating factors for the degree of variability in the severity of CF, especially in pulmonary clinical manifestation correlated with increased morbidity and mortality. PMID:27209008

  15. 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. PMID:26967814

  16. 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. PMID:25929952

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

    PubMed

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

    2014-04-01

    Benchmarking is the process of using outcome data to identify high-performing centres and determine practices associated with their outstanding performance. The US Cystic Fibrosis Foundation (CFF) Patient Registry contains centre-specific outcomes data for all CFF-certified paediatric and adult cystic fibrosis (CF) care programmes in the USA. The CFF benchmarking project analysed these registry data, adjusting for differences in patient case mix known to influence outcomes, and identified the top-performing US paediatric and adult CF care programmes for pulmonary and nutritional outcomes. Separate multidisciplinary paediatric and adult benchmarking teams each visited 10 CF care programmes, five in the top quintile for pulmonary outcomes and five in the top quintile for nutritional outcomes. Key practice patterns and approaches present in both paediatric and adult programmes with outstanding clinical outcomes were identified and could be summarised as systems, attitudes, practices, patient/family empowerment and projects. These included: (1) the presence of strong leadership and a well-functioning care team working with a systematic approach to providing consistent care; (2) high expectations for outcomes among providers and families; (3) early and aggressive management of clinical declines, avoiding reliance on 'rescues'; and (4) patients/families that were engaged, empowered and well informed on disease management and its rationale. In summary, assessment of practice patterns at CF care centres with top-quintile pulmonary and nutritional outcomes provides insight into characteristic practices that may aid in optimising patient outcomes. PMID:24608546

  18. Clinical significance, antimicrobial susceptibility and molecular identification of Nocardia species isolated from children with cystic fibrosis.

    PubMed

    Betrán, Ana; Villuendas, M Cruz; Rezusta, Antonio; Pereira, Javier; Revillo, M José; Rodríguez-Nava, Verónica

    2016-01-01

    Nocardia is an opportunistic pathogen that causes respiratory infections in immunocompromised patients. The aim of this study was to analyze the epidemiology, clinical significance and antimicrobial susceptibility of Nocardia species isolated from eight children with cystic fibrosis. The isolated species were identified as Nocardia farcinica, Nocardia transvalensis, Nocardia pneumoniae, Nocardia veterana and Nocardia wallacei. N. farcinica was isolated in three patients and all of them presented lung affectation with a chronic colonization and pneumonia. N. farcinica showed resistance against gentamicin, tobramycin, cefotaxime, but was susceptible to trimethoprim-sulfamethoxazole and amikacin. N. transvalensis, which was isolated from two patients, showed an association with chronic colonization. N. transvalensis was resistant to tobramycin and amikacin, but susceptible to ciprofloxacin, trimethoprim-sulfamethoxazole and cefotaxime. N. veterana, N. pneumoniae and N. wallacei were isolated from three different patients and appeared in transitory lung colonization. N. veterana and N. pneumoniae were susceptible to imipenem, trimethoprim-sulfamethoxazole, amikacin, tobramycin, and cefotaxime. N. wallacei was resistant to amikacin, tobramycin, imipenem, and trimethoprim-sulfamethoxazole and susceptible to ciprofloxacin and cefotaxime. All the isolates were identified up to species level by 16S rRNA gene sequencing. The presence of Nocardia in the sputum of patients with cystic fibrosis is not always an indication of an active infection; therefore, the need for a treatment should be evaluated on an individual basis. The detection of multidrug-resistant species needs molecular identification and susceptibility testing, and should be performed for all Nocardia infections. PMID:27155949

  19. Outcome measures for clinical trials assessing treatment of cystic fibrosis lung disease

    PubMed Central

    VanDevanter, Donald R; Konstan, Michael W

    2015-01-01

    Cystic fibrosis (CF) is a complex genetic disease characterized by death from loss of lung function. Therapies target pathophysiologic changes associated with pulmonary disease progression. Although therapeutic mechanisms differ, efficacy demonstration is limited to a few accepted outcome measures, each with shortcomings that are becoming more pronounced as CF population health improves. Pulmonary function improvement (as forced expiratory volume in 1 s [FEV1]) and reduction of pulmonary exacerbation risk are commonly used outcomes. Changes in FEV1 decline rate, quality of life, linear growth and/or weight gain are less utilized outcomes. Validated outcomes tend to work best in subjects with more aggressive or advanced lung disease and less so in healthier subjects. Assays of effects on primary therapeutic targets have yet to be validated as surrogate measures of clinical efficacy. As CF population health improves, it will become increasingly difficult to employ current clinical outcome measures to demonstrate efficacy. PMID:26146539

  20. Clinical and Genetic Correlates of Exercise Performance in Young Children with Cystic Fibrosis1,2

    PubMed Central

    McBride, Michael G.; Schall, Joan I.; Zemel, Babette S.; Stallings, Virginia A.; Ittenbach, Richard F.; Paridon, Stephen M.

    2015-01-01

    Summary Exercise performance in individuals with cystic fibrosis has been shown to be related to the degree of pulmonary dysfunction and undernutrition and genetic profile. The aim of this study was to examine these relationships in young children with cystic fibrosis. The participants were 64 children ages 8 to 11 years (M = 9.3, SD = 0.9) with cystic fibrosis and pancreatic insufficiency recruited from 13 different U.S. Cystic Fibrosis Centers. Assigned to one of three groups by ΔF508 status: ΔF508/ΔF508 homozygous, ΔF508/Other heterozygous, and Other/Other, growth, nutritional and pulmonary status, and exercise performance were measured. Differences in exercise performance, pulmonary function, and nutritional status were not observed among the three groups. However, undernutrition and decreased pulmonary function were associated with measures of exercise performance. These results imply no effect of ΔF508 status on overall functional capacity during preadolescence in children with cystic fibrosis. Rather, the degree of pulmonary disease and undernutrition were associated with functional performance. PMID:20865986

  1. Respiratory viruses in children with cystic fibrosis: viral detection and clinical findings

    PubMed Central

    Burns, Jane L.; Emerson, Julia; Kuypers, Jane; Campbell, Angela P.; Gibson, Ronald L.; McNamara, Sharon; Worrell, Kelly; Englund, Janet A.

    2011-01-01

    Please cite this paper as: Burns et al. (2011) Respiratory viruses in children with cystic fibrosis: viral detection and clinical findings. Influenza and Other Respiratory Viruses 6(3), 218–223. Background  Viral detection from different respiratory sample types in children with cystic fibrosis (CF) is facilitated by available molecular methods, but optimum sampling strategies have not been identified. In addition, associations between viral detection and respiratory symptoms are not well described. Objectives  Study goals were to compare molecular detection of viruses from concurrent upper airway and sputum samples in children with CF and to describe relative frequency of respiratory viral infections and identify potential clinical associations. Methods  We conducted a 2‐year prospective surveillance study in 44 children with CF aged 6–18 years. Upper airway and sputum samples were collected quarterly and during pulmonary exacerbations and tested for respiratory syncytial virus (RSV), influenza viruses, parainfluenza viruses types 1–4, human metapneumovirus, coronaviruses, rhinoviruses, and adenoviruses. Physical exams and symptom surveys were used to identify respiratory signs and symptoms. Results  Upper airway samples were collected at 359 visits; concordance of PCR‐based viral detection was examined in a subset of paired upper airway and sputum samples from 21 participants at 92 visits. Rhinovirus was the most commonly detected virus (23·1% overall), and rhinovirus detection was the same for both sample types (21·7% each). Sensitivity and specificity for the detection of rhinovirus in sputum relative to upper airway sampling were 70% and 91·7%, respectively. Respiratory symptoms associated with rhinovirus detection included increased cough, increased nasal congestion, increased sputum production, and wheezing. Conclusions  A relatively high frequency of rhinovirus detection was observed by either upper airway or sputum samples, and

  2. Association between clinical antibiotic resistance and susceptibility of Pseudomonas in the cystic fibrosis lung

    PubMed Central

    Jansen, Gunther; Mahrt, Niels; Tueffers, Leif; Barbosa, Camilo; Harjes, Malte; Adolph, Gernot; Friedrichs, Anette; Krenz-Weinreich, Annegret; Rosenstiel, Philip; Schulenburg, Hinrich

    2016-01-01

    Background and objectives: Cystic fibrosis patients suffer from chronic lung infections that require long-term antibiotic therapy. Pseudomonas readily evolve resistance, rendering antibiotics ineffective. In vitro experiments suggest that resistant bacteria may be treated by exploiting their collateral sensitivity to other antibiotics. Here, we investigate correlations of sensitivity and resistance profiles of Pseudomonas aeruginosa that naturally adapted to antibiotics in the cystic fibrosis lung. Methodology: Resistance profiles for 13 antibiotics were obtained using broth dilution, E-test and VITEK mass spectroscopy. Genetic variants were determined from whole-genome sequences and interrelationships among isolates were analyzed using 13 MLST loci. Result: Our study focused on 45 isolates from 13 patients under documented treatment with antibiotics. Forty percent of these were clinically resistant and 15% multi-drug resistant. Colistin resistance was found once, despite continuous colistin treatment and even though colistin resistance can readily evolve experimentally in the laboratory. Patients typically harbored multiple genetically and phenotypically distinct clones. However, genetically similar clones often had dissimilar resistance profiles. Isolates showed mutations in genes encoding cell wall synthesis, alginate production, efflux pumps and antibiotic modifying enzymes. Cross-resistance was commonly observed within antibiotic classes and between aminoglycosides and β-lactam antibiotics. No evidence was found for consistent phenotypic resistance to one antibiotic and sensitivity to another within one genotype. Conclusions and implications: Evidence supporting potential collateral sensitivity in clinical P. aeruginosa isolates remains equivocal. However, cross-resistance within antibiotic classes is common. Colistin therapy is promising since resistance to it was rare despite its intensive use in the studied patients. PMID:27193199

  3. 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.

  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. Cystic fibrosis from the gastroenterologist's perspective.

    PubMed

    Ooi, Chee Y; Durie, Peter R

    2016-03-01

    Cystic fibrosis is a life-limiting, recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Increased survival outcomes and the multisystem nature of the disease, including the involvement of hepatobiliary and gastrointestinal tracts, now require the need for more extensive knowledge and expertise in cystic fibrosis among gastroenterologists. Manifestations are either a direct consequence of the primary defect in cystic fibrosis or a secondary complication of the disease or therapy. Adult patients with cystic fibrosis also have an increased risk of malignancy in the gastrointestinal and pancreatico-biliary tracts compared with the general population. Novel treatments that target the basic defects in the CFTR protein have emerged, but to date not much is known about their effects on the gastrointestinal and hepatobiliary systems. The introduction of such therapies has provided new opportunities for the application of intestinal endpoints in clinical trials and the understanding of underlying disease mechanisms that affect the gut in cystic fibrosis. PMID:26790364

  6. Pancreatic pathophysiology in cystic fibrosis.

    PubMed

    Gibson-Corley, Katherine N; Meyerholz, David K; Engelhardt, John F

    2016-01-01

    The pancreas is one of the earliest, and most commonly affected, organs in patients with cystic fibrosis (CF). Studying the pathogenesis of pancreatic disease is limited in CF patients, due to its early clinical onset, co-morbidities and lack of tissue samples from the early phases of disease. In recent years, several new CF animal models have been developed that have advanced our understanding of both CF exocrine and endocrine pancreatic disease. Additionally, these models have helped us to better define the influence of pancreatic lesions on CF disease progression in other organs, such as the gastrointestinal tract and lung. PMID:26365583

  7. Neutrophils in cystic fibrosis.

    PubMed

    Laval, Julie; Ralhan, Anjali; Hartl, Dominik

    2016-06-01

    Cystic fibrosis (CF) lung disease is characterized by chronic infection and inflammation. Among inflammatory cells, neutrophils represent the major cell population accumulating in the airways of CF patients. While neutrophils provide the first defensive cellular shield against bacterial and fungal pathogens, in chronic disease conditions such as CF these short-lived immune cells release their toxic granule contents that cause tissue remodeling and irreversible structural damage to the host. A variety of human and murine studies have analyzed neutrophils and their products in the context of CF, yet their precise functional role and therapeutic potential remain controversial and incompletely understood. Here, we summarize the current evidence in this field to shed light on the complex and multi-faceted role of neutrophils in CF lung disease. PMID:26854289

  8. Cystic fibrosis in pregnancy.

    PubMed Central

    Kent, N E; Farquharson, D F

    1993-01-01

    OBJECTIVE: To review the outcomes of pregnancies in women with cystic fibrosis (CF) and to address issues pertinent to the obstetric care of such women. DATA SOURCES: English-language case reports and case series published from 1960 to 1991 identified through a search of MEDLINE and Index Medicus. The terms of reference were "cystic fibrosis" and "pregnancy". Not all the reports reviewed addressed all the outcomes under consideration. STUDY SELECTION: A total of 20 reports citing cases of pregnancy in women with CF. DATA EXTRACTION: Outcomes included the number of spontaneous abortions, pregnancies continued beyond 20 weeks, preterm deliveries, maternal deaths at 6 months and 2 years after delivery and perinatal deaths. Breast-feeding was addressed. Measures to assess the severity of maternal disease included the mean age at diagnosis of CF, weight gain during pregnancy, pulmonary function studies if available and the need for pancreatic enzyme replacement therapy. DATA SYNTHESIS: Of 217 pregnancies in 162 women spontaneous abortion occurred in 10 (4.6%). Pregnancy progressed beyond 20 weeks in 81.6% of cases; 24.3% of the deliveries were preterm. The maternal death rate did not exceed that among age-related women with CF who were not pregnant. The rate of perinatal death was 7.9%. Breast milk was not hypernatremic. Poor outcomes were associated with a weight gain of less than 4.5 kg and a forced vital capacity of less than 50% of the predicted value. CONCLUSIONS: Premature labour and delivery remain a significant risk for pregnant women with CF, contributing to a high rate of perinatal death. Maternal illness and death result from deteriorating pulmonary function. Breast-feeding is not contraindicated. Attention to energy intake and pulmonary function is important. PMID:8374843

  9. Current and future treatment options for cystic fibrosis lung disease: latest evidence and clinical implications

    PubMed Central

    Edmondson, Claire; Davies, Jane C.

    2016-01-01

    Treatment for cystic fibrosis (CF) has conventionally targeted downstream consequences of the defect such as mucus plugging and infection. More recently, significant advances have been made in treating the root cause of the disease, namely a defective CF transmembrane conductance regulator (CFTR) gene. This review summarizes current pulmonary treatment options and highlights advances in research and development of new therapies. PMID:27347364

  10. Current and future treatment options for cystic fibrosis lung disease: latest evidence and clinical implications.

    PubMed

    Edmondson, Claire; Davies, Jane C

    2016-05-01

    Treatment for cystic fibrosis (CF) has conventionally targeted downstream consequences of the defect such as mucus plugging and infection. More recently, significant advances have been made in treating the root cause of the disease, namely a defective CF transmembrane conductance regulator (CFTR) gene. This review summarizes current pulmonary treatment options and highlights advances in research and development of new therapies. PMID:27347364

  11. Steady Advances Against Cystic Fibrosis

    MedlinePlus

    ... age 2, he grew up playing everything from football and lacrosse to ice hockey and golf. And ... Who's at Risk? Cystic fibrosis affects males and females from all racial and ethnic groups. It is ...

  12. Genetics Home Reference: cystic fibrosis

    MedlinePlus

    ... protects the linings of the airways, digestive system, reproductive system, and other organs and tissues. In people with ... experience health problems affecting the respiratory, digestive, and reproductive systems. Most men with cystic fibrosis have congenital bilateral ...

  13. Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice

    PubMed Central

    Castellani, C.; Cuppens, H.; Macek, M.; Cassiman, J.J.; Kerem, E.; Durie, P.; Tullis, E.; Assael, B.M.; Bombieri, C.; Brown, A.; Casals, T.; Claustres, M.; Cutting, G.R.; Dequeker, E.; Dodge, J.; Doull, I.; Farrell, P.; Ferec, C.; Girodon, E.; Johannesson, M.; Kerem, B.; Knowles, M.; Munck, A.; Pignatti, P.F.; Radojkovic, D.; Rizzotti, P.; Schwarz, M.; Stuhrmann, M.; Tzetis, M.; Zielenski, J.; Elborn, J.S.

    2009-01-01

    It is often challenging for the clinician interested in cystic fibrosis (CF) to interpret molecular genetic results, and to integrate them in the diagnostic process. The limitations of genotyping technology, the choice of mutations to be tested, and the clinical context in which the test is administered can all influence how genetic information is interpreted. This paper describes the conclusions of a consensus conference to address the use and interpretation of CF mutation analysis in clinical settings. Although the diagnosis of CF is usually straightforward, care needs to be exercised in the use and interpretation of genetic tests: genotype information is not the final arbiter of a clinical diagnosis of CF or CF transmembrane conductance regulator (CFTR) protein related disorders. The diagnosis of these conditions is primarily based on the clinical presentation, and is supported by evaluation of CFTR function (sweat testing, nasal potential difference) and genetic analysis. None of these features are sufficient on their own to make a diagnosis of CF or CFTR-related disorders. Broad genotype/phenotype associations are useful in epidemiological studies, but CFTR genotype does not accurately predict individual outcome. The use of CFTR genotype for prediction of prognosis in people with CF at the time of their diagnosis is not recommended. The importance of communication between clinicians and medical genetic laboratories is emphasized. The results of testing and their implications should be reported in a manner understandable to the clinicians caring for CF patients. PMID:18456578

  14. Clinical Sensitivity of Cystic Fibrosis Mutation Panels in a Diverse Population.

    PubMed

    Hughes, Erin E; Stevens, Colleen F; Saavedra-Matiz, Carlos A; Tavakoli, Norma P; Krein, Lea M; Parker, April; Zhang, Zhen; Maloney, Breanne; Vogel, Beth; DeCelie-Germana, Joan; Kier, Catherine; Anbar, Ran D; Berdella, Maria N; Comber, Paul G; Dozor, Allen J; Goetz, Danielle M; Guida, Louis; Kattan, Meyer; Ting, Andrew; Voter, Karen Z; van Roey, Patrick; Caggana, Michele; Kay, Denise M

    2016-02-01

    Infants are screened for cystic fibrosis (CF) in New York State (NYS) using an IRT-DNA algorithm. The purpose of this study was to validate and assess clinical validity of the US FDA-cleared Illumina MiSeqDx CF 139-Variant Assay (139-VA) in the diverse NYS CF population. The study included 439 infants with CF identified via newborn screening (NBS) from 2002 to 2012. All had been screened using the Abbott Molecular CF Genotyping Assay or the Hologic InPlex CF Molecular Test. All with CF and zero or one mutation were tested using the 139-VA. DNA extracted from dried blood spots was reliably and accurately genotyped using the 139-VA. Sixty-three additional mutations were identified. Clinical sensitivity of three panels ranged from 76.2% (23 mutations recommended for screening by ACMG/ACOG) to 79.7% (current NYS 39-mutation InPlex panel), up to 86.0% for the 139-VA. For all, sensitivity was highest in Whites and lowest in the Black population. Although the sample size was small, there was a nearly 20% increase in sensitivity for the Black CF population using the 139-VA (68.2%) over the ACMG/ACOG and InPlex panels (both 50.0%). Overall, the 139-VA is more sensitive than other commercially available panels, and could be considered for NBS, clinical, or research laboratories conducting CF screening. PMID:26538069

  15. RISK OF HEMOPTYSIS IN CYSTIC FIBROSIS CLINICAL TRIALS: A RETROSPECTIVE COHORT STUDY

    PubMed Central

    Mayer-Hamblett, N.; Kloster, M.; Bilton, D.; Flume, P. A.

    2015-01-01

    Background Cystic fibrosis (CF) is characterized by airways infection and inflammation resulting in respiratory complications including hemoptysis. The objectives of this study were to characterize risk of hemoptysis attributable to the underlying disease and in the presence of standard of care therapy. Methods This retrospective cohort study estimated hemoptysis rates overall and by relevant risk factors utilizing adverse event data from longitudinal prospective CF clinical trials. Results Of the 1008 participants, 73% were ≤18 years old; of 929 with available spirometry, 27% had an FEV1 < 70% predicted. During the average 8.2 months of follow-up, 8% experienced ≥1 hemoptysis events (95% CI: 6%, 10%). Of the 125 events, 76% were mild in severity and only 9% were serious. Hemoptysis rates were greater among adults than children, those with FEV1 < 70% predicted, and participants infected with P. aeruginosa but not with S. aureus. Conclusions Hemoptysis is a common adverse event among CF clinical trial participants, and particularly in adults with more severe lung disease. These results can be used to predict event occurrence in future clinical trials. PMID:25725985

  16. Improved growth and clinical, nutritional, and respiratory changes in response to nutritional therapy in cystic fibrosis.

    PubMed

    Shepherd, R; Cooksley, W G; Cooke, W D

    1980-09-01

    To investigate the role of nutritional factors in growth and in the clinical, nurtitional, and respiratory status in cystic fibrosis, we studied 12 problem CF patients from six months before to six months after a period of supplemental parenteral nutrition. During the initial six months' observation period on appropriate conventional therapy, the patients (aged 0.5 to 11 years) had inadequate growth and weight gain, a total of 21 active pulmonary infections, and, despite dietary supplements, inadequate ad libitum nutrient intakes. After nutritional therapy, providing a balanced consistent hypercaloric intake for 21 days, catch-up weight gain occurred by one month and continued at six months; catch-up in linear growth was observed by three months and continued at six months. In addition, significantly fewer pulmonary infections were observed in the six months' post-therapy (n = 3), sustained and significant improvements were noted in clinical score and plumonary function, and there was a marked improvement in well-being and ad libitum nutrient intake. We conclude that adequate nutritional support can favorably affect growth, clinical status, and the course of chronic pulmonary disease in problem cases of CF. PMID:6774070

  17. Pseudomonas aeruginosa infection in patients with cystic fibrosis: scientific evidence regarding clinical impact, diagnosis, and treatment.

    PubMed

    Silva Filho, Luiz Vicente Ribeiro Ferreira da; Ferreira, Flavia de Aguiar; Reis, Francisco José Caldeira; Britto, Murilo Carlos Amorim de; Levy, Carlos Emilio; Clark, Otavio; Ribeiro, José Dirceu

    2013-01-01

    Evidence-based techniques have been increasingly used in the creation of clinical guidelines and the development of recommendations for medical practice. The use of levels of evidence allows the reader to identify the quality of scientific information that supports the recommendations made by experts. The objective of this review was to address current concepts related to the clinical impact, diagnosis, and treatment of Pseudomonas aeruginosa infections in patients with cystic fibrosis. For the preparation of this review, the authors defined a group of questions that would be answered in accordance with the principles of PICO-an acronym based on questions regarding the Patients of interest, Intervention being studied, Comparison of the intervention, and Outcome of interest. For each question, a structured review of the literature was performed using the Medline database in order to identify the studies with the methodological design most appropriate to answering the question. The questions were designed so that each of the authors could write a response. A first draft was prepared and discussed by the group. Recommendations were then made on the basis of the level of scientific evidence, in accordance with the classification system devised by the Oxford Centre for Evidence-Based Medicine, as well as the level of agreement among the members of the group. PMID:24068273

  18. Advancing clinical development pathways for new CFTR modulators in cystic fibrosis

    PubMed Central

    Mayer-Hamblett, Nicole; Boyle, Michael; VanDevanter, Donald

    2016-01-01

    Cystic fibrosis (CF) is a life-shortening genetic disease affecting approximately 70 000 individuals worldwide. Until recently, drug development efforts have emphasised therapies treating downstream signs and symptoms resulting from the underlying CF biological defect: reduced function of the CF transmembrane conductance regulator (CFTR) protein. The current CF drug development landscape has expanded to include therapies that enhance CFTR function by either restoring wild-type CFTR protein expression or increasing (modulating) the function of mutant CFTR proteins in cells. To date, two systemic small-molecule CFTR modulators have been evaluated in pivotal clinical trials in individuals with CF and specific mutant CFTR genotypes that have led to regulatory review and/or approval. Advances in the discovery of CFTR modulators as a promising new class of therapies have been impressive, yet work remains to develop highly effective, disease-modifying modulators for individuals of all CF genotypes. The objectives of this review are to outline the challenges and opportunities in drug development created by systemic genotype-specific CFTR modulators, highlight the advantages of sweat chloride as an established biomarker of CFTR activity to streamline early-phase development and summarise options for later phase clinical trial designs that respond to the adoption of approved genotype-specific modulators into standard of care. An optimal development framework will be needed to move the most promising therapies efficiently through the drug development pipeline and ultimately deliver efficacious and safe therapies to all individuals with CF. PMID:26903594

  19. [Effect of montelukast on lung function and clinical symptoms in patients with cystic fibrosis].

    PubMed

    Stelmach, Iwona; Korzeniewska, Aleksandra; Smejda, Katarzyna; Jarosz, Iwona; Stelmach, Włodzimierz

    2004-01-01

    Inflammatory process contributes to progressive lung tissue damage in cystic fibrosis (CF). Cysteinyl leukotrienes have been found in the sputum of CF patients at concentrations sufficient to cause potent biological effect. This study was designed to assess the effect of anti-inflammatory treatment with montelukast sodium in CF patients. Twelve patients, aged 6-29 were recruited. It was 20 week, placebo-controlled, and randomized, double blind, crossover trial. At first and last week of each treatment course spirometry and whole body plethysmography parameters (FEV1, PEF, FEF25/75%, VC, TGV, Raw and RV) and clinical wheezing and cough scale were measured. In montelukast group significant improvement in FEV1 (mean +/- SD, 54.6 +/- 22.6 before and 62 +/- 19.0 after treatment, p=0.0112) and FEF25/75% (28.9 +/- 23.0 before and 37.5 +/- 25.5 after treatment, p=0.0053) were observed. Compared with placebo montelukast significantly improved FEV1 (p=0.0032), PEF (p=0.0298) and FEF25/75% (p=0.0091). There was no significant difference in VC, TGV, Raw and RV. Montelukast compared with placebo significantly decreased cough (p<0.0001) and wheezing (p=0.0002) score. In summary, therapy with montelukast may provide clinical benefit to patients with CF. PMID:15757268

  20. Advancing clinical development pathways for new CFTR modulators in cystic fibrosis.

    PubMed

    Mayer-Hamblett, Nicole; Boyle, Michael; VanDevanter, Donald

    2016-05-01

    Cystic fibrosis (CF) is a life-shortening genetic disease affecting approximately 70,000 individuals worldwide. Until recently, drug development efforts have emphasised therapies treating downstream signs and symptoms resulting from the underlying CF biological defect: reduced function of the CF transmembrane conductance regulator (CFTR) protein. The current CF drug development landscape has expanded to include therapies that enhance CFTR function by either restoring wild-type CFTR protein expression or increasing (modulating) the function of mutant CFTR proteins in cells. To date, two systemic small-molecule CFTR modulators have been evaluated in pivotal clinical trials in individuals with CF and specific mutant CFTR genotypes that have led to regulatory review and/or approval. Advances in the discovery of CFTR modulators as a promising new class of therapies have been impressive, yet work remains to develop highly effective, disease-modifying modulators for individuals of all CF genotypes. The objectives of this review are to outline the challenges and opportunities in drug development created by systemic genotype-specific CFTR modulators, highlight the advantages of sweat chloride as an established biomarker of CFTR activity to streamline early-phase development and summarise options for later phase clinical trial designs that respond to the adoption of approved genotype-specific modulators into standard of care. An optimal development framework will be needed to move the most promising therapies efficiently through the drug development pipeline and ultimately deliver efficacious and safe therapies to all individuals with CF. PMID:26903594

  1. Pseudomonas aeruginosa infection in patients with cystic fibrosis: scientific evidence regarding clinical impact, diagnosis, and treatment*

    PubMed Central

    da Silva, Luiz Vicente Ribeiro Ferreira; Ferreira, Flavia de Aguiar; Reis, Francisco José Caldeira; de Britto, Murilo Carlos Amorim; Levy, Carlos Emilio; Clark, Otavio; Ribeiro, José Dirceu

    2013-01-01

    Evidence-based techniques have been increasingly used in the creation of clinical guidelines and the development of recommendations for medical practice. The use of levels of evidence allows the reader to identify the quality of scientific information that supports the recommendations made by experts. The objective of this review was to address current concepts related to the clinical impact, diagnosis, and treatment of Pseudomonas aeruginosa infections in patients with cystic fibrosis. For the preparation of this review, the authors defined a group of questions that would be answered in accordance with the principles of PICO–an acronym based on questions regarding the Patients of interest, Intervention being studied, Comparison of the intervention, and Outcome of interest. For each question, a structured review of the literature was performed using the Medline database in order to identify the studies with the methodological design most appropriate to answering the question. The questions were designed so that each of the authors could write a response. A first draft was prepared and discussed by the group. Recommendations were then made on the basis of the level of scientific evidence, in accordance with the classification system devised by the Oxford Centre for Evidence-Based Medicine, as well as the level of agreement among the members of the group. PMID:24068273

  2. Cystic Fibrosis: Brazilian ENT Experience

    PubMed Central

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

    2012-01-01

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

  3. Cystic Fibrosis Sinusitis.

    PubMed

    Le, Christopher; McCrary, Hilary C; Chang, Eugene

    2016-01-01

    Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the CF transmembrane conductance regulator gene(CFTR) resulting in impaired ion transport. Nearly all people with CF will develop chronic rhino-sinusitis (CRS) and present with the characteristic viscous mucus, impaired mucociliary clearance and chronic inflammation/infection of the sinonasal cavity. While some individuals with CF can appear relatively asymptomatic in terms of their sinus disease, commonly reported symptoms include anosmia, headache, facial pain, nasal obstruction, chronic congestion and nasal discharge. Nasal endoscopy typically reveals mucosal edema, purulent discharge and nasal polyposis. Computed tomography (CT) imaging classically demonstrates the distinguishing findings of sinus hypoplasia or aplasia with generalized opacification, medial bulging of the lateral sinonasal sidewall and a demineralized uncinate process. Current treatment for CF sinusitis includes the use of hypertonic saline, topical and systemic steroids, antibiotics and endoscopic surgery. Research investigating novel therapies designed at targeting the primary defect of CF is showing promise for reversal of CF sinus disease, in addition to potential for disease prevention. PMID:27466844

  4. Mucolytics in cystic fibrosis.

    PubMed

    Henke, Markus O; Ratjen, Felix

    2007-03-01

    Mucus accumulation in the lower airways is a key feature of cystic fibrosis (CF) lung disease. The major component of mucus in CF is not mucin derived from mucus producing cells but rather pus that includes viscous material such as polymerized DNA derived from degraded neutrophils. This has important implications for mucolytic therapy aiming to improve mucus clearance from the airways, since degradation of mucin may not be a suitable treatment strategy. In addition, thinning of secretions may not always be beneficial, since it may negatively affect certain aspects of mucus transport such as cough clearance. While inhaled N-acetylcysteine has been used as a mucolytic drug in CF for decades, there is little evidence that it has any beneficial effect. Dornase alfa has been shown to reduce pulmonary exacerbations and improve lung function and is currently the only mucolytic agent with proven efficacy in CF. Newer agents targeting other components of CF mucus, such as filamentous actin, are currently in development. Ultimately, drugs that are mucokinetic, which preserve viscoelasticity, rather than mucolytic may prove to be beneficial for CF lung disease in the future. PMID:17419975

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

    PubMed Central

    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. PMID:26642048

  6. Development, clinical utility, and place of ivacaftor in the treatment of cystic fibrosis

    PubMed Central

    O’Reilly, Ruth; Elphick, Heather E

    2013-01-01

    Cystic fibrosis (CF) is a life-limiting, multisystem disease characterized by thick viscous secretions leading to recurrent lung infections, bronchiectasis, and progressive deterioration in lung function. CF is caused by loss or dysfunction of the CF transmembrane conductance regulator (CFTR) protein which is responsible for transepithelial chloride and water transport. Improved understanding of CFTR protein dysfunction has allowed the development of mutation-specific small-molecule compounds which directly target the underlying CFTR defect. Ivacaftor is the first licensed small-molecule compound for CF patients which targets the CFTR gating mutation Gly551Asp (previously termed G551D) and has the potential to be truly disease-modifying. Ivacaftor is an oral medication given twice daily and has shown benefit in terms of an increase in lung function, decreased sweat chloride, weight gain, improvement in patient-reported quality of life, and reduction in number of respiratory exacerbations in clinical trials. Although ivacaftor is currently only licensed for use in approximately 5% of the CF population (those who have at least one Gly551Asp mutation), the developmental pathway established by ivacaftor paves the way for other CFTR modulators that may benefit many more patients. In particular, a CFTR modulator for those with the Phe508del deletion (previously ∆F508) would allow 90% of the CF population to benefit from disease-modifying treatment. PMID:24039402

  7. Physiotherapy for cystic fibrosis in Australia and New Zealand: A clinical practice guideline.

    PubMed

    Button, Brenda M; Wilson, Christine; Dentice, Ruth; Cox, Narelle S; Middleton, Anna; Tannenbaum, Esta; Bishop, Jennifer; Cobb, Robyn; Burton, Kate; Wood, Michelle; Moran, Fiona; Black, Ryan; Bowen, Summar; Day, Rosemary; Depiazzi, Julie; Doiron, Katherine; Doumit, Michael; Dwyer, Tiffany; Elliot, Alison; Fuller, Louise; Hall, Kathleen; Hutchins, Matthew; Kerr, Melinda; Lee, Annemarie L; Mans, Christina; O'Connor, Lauren; Steward, Ranjana; Potter, Angela; Rasekaba, Tshepo; Scoones, Rebecca; Tarrant, Ben; Ward, Nathan; West, Samantha; White, Dianne; Wilson, Lisa; Wood, Jamie; Holland, Anne E

    2016-05-01

    Physiotherapy management is a key element of care for people with cystic fibrosis (CF) throughout the lifespan. Although considerable evidence exists to support physiotherapy management of CF, there is documented variation in practice. The aim of this guideline is to optimize the physiotherapy management of people with CF in Australia and New Zealand. A systematic review of the literature in key areas of physiotherapy practice for CF was undertaken. Recommendations were formulated based on National Health and Medical Research Council (Australia) guidelines and considered the quality, quantity and level of the evidence; the consistency of the body of evidence; the likely clinical impact; and applicability to physiotherapy practice in Australia and New Zealand. A total of 30 recommendations were made for airway clearance therapy, inhalation therapy, exercise assessment and training, musculoskeletal management, management of urinary incontinence, managing the newly diagnosed patient with CF, delivery of non-invasive ventilation, and physiotherapy management before and after lung transplantation. These recommendations can be used to underpin the provision of evidence-based physiotherapy care to people with CF in Australia and New Zealand. PMID:27086904

  8. Molecular and clinical analyses of cystic fibrosis in the south of Spain.

    PubMed

    Borrego, S; Casals, T; Dapena, J; Fernández, E; Giménez, J; Cabeza, J C; Sánchez, J; Antiñolo, G

    1994-10-01

    We report molecular and clinical analyses in 71 unrelated patients with cystic fibrosis (CF) from Andalusia (South of Spain). Direct mutation analysis of six mutations of the CFTR gene (delta F508, G542X, R1162X, N1303K, W1182X and 1949de184) was performed. The proportion of CF chromosomes with the above-mentioned mutations was 58.5%. Haplotype analysis was performed with the marker/enzyme pairs XV2C/TaqI and KM19/PstI. A particular haplotype has been found associated with each of the studied mutations, while the pooled data for the unknown mutations are not associated with any particular haplotype. This lack of association indicates that there will not be a single predominant mutation amongst the other CF chromosomes. To assess the relationship between genotype and phenotype in these patients, we correlated the pancreatic status and the occurrence of chronic Pseudomona aeruginosa infection with the observed genotype. Pancreatic insufficiency was present in all patients in whom the analyzed mutations were found to be homozygous or compound heterozygous. We also found a higher rate of Pseudomonas colonization in the group of patients in whom the genotype was homozygous or compound heterozygous for the analysed mutations when compared with the group of patients with a different genotype, but the difference was not statistically significant. PMID:7530610

  9. Physiotherapy for cystic fibrosis in Australia and New Zealand: A clinical practice guideline*

    PubMed Central

    Wilson, Christine; Dentice, Ruth; Cox, Narelle S.; Middleton, Anna; Tannenbaum, Esta; Bishop, Jennifer; Cobb, Robyn; Burton, Kate; Wood, Michelle; Moran, Fiona; Black, Ryan; Bowen, Summar; Day, Rosemary; Depiazzi, Julie; Doiron, Katherine; Doumit, Michael; Dwyer, Tiffany; Elliot, Alison; Fuller, Louise; Hall, Kathleen; Hutchins, Matthew; Kerr, Melinda; Lee, Annemarie L.; Mans, Christina; O'Connor, Lauren; Steward, Ranjana; Potter, Angela; Rasekaba, Tshepo; Scoones, Rebecca; Tarrant, Ben; Ward, Nathan; West, Samantha; White, Dianne; Wilson, Lisa; Wood, Jamie; Holland, Anne E.

    2016-01-01

    Abstract Physiotherapy management is a key element of care for people with cystic fibrosis (CF) throughout the lifespan. Although considerable evidence exists to support physiotherapy management of CF, there is documented variation in practice. The aim of this guideline is to optimize the physiotherapy management of people with CF in Australia and New Zealand. A systematic review of the literature in key areas of physiotherapy practice for CF was undertaken. Recommendations were formulated based on National Health and Medical Research Council (Australia) guidelines and considered the quality, quantity and level of the evidence; the consistency of the body of evidence; the likely clinical impact; and applicability to physiotherapy practice in Australia and New Zealand. A total of 30 recommendations were made for airway clearance therapy, inhalation therapy, exercise assessment and training, musculoskeletal management, management of urinary incontinence, managing the newly diagnosed patient with CF, delivery of non‐invasive ventilation, and physiotherapy management before and after lung transplantation. These recommendations can be used to underpin the provision of evidence‐based physiotherapy care to people with CF in Australia and New Zealand. PMID:27086904

  10. Pain and its clinical associations in individuals with cystic fibrosis: A systematic review.

    PubMed

    Lee, Annemarie L; Rawlings, Sarah; Bennett, Katharine A; Armstrong, David

    2016-05-01

    Pain is recognized as a clinical complication in cystic fibrosis (CF), but the prevalence, characteristics and clinical associations of this co-morbidity have not been systematically reviewed. Electronic searches of six databases were performed. For inclusion in phase 1, studies reported a pain prevalence rate in CF and/or its clinical associations. For phase 2, included studies reported the measurement properties of validity, reliability and responsiveness of an instrument assessing pain in CF. Two independent reviewers rated the quality of evidence (phase 1) and the measurement properties using the 4-point COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist (phase 2). Of the 400 studies identified in the literature, 16 met the inclusion criteria for phase 1 and 5 for phase 2. The mean (SD) quality score (of 16) was 11.8 (2.3). The pooled prevalence of pain in adults with CF was 77% (95% confidence interval (CI): 57%-92%) and in children was 42% (95% CI: 0%-91%). Common regions of pain included back, abdomen, chest and limbs. In children and adults, pain was associated with a poorer quality of life (QOL) and significant interference with treatments. Measurement properties of three instruments (Brief Pain Inventory, Multidimensional Pain Inventory, Daily Pain Assessment-CF) were construct validity and criterion-predictive validity, with variable findings based on 'fair' to 'good' quality studies. Pain is a common problem in both children and adults with CF. It has negative clinical associations with QOL and the ability to successfully undertake treatment. Further research exploring the measurement properties of instruments assessing pain is required. PMID:26873725

  11. 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. PMID:26857767

  12. 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

  13. Aspergillus bronchitis in cystic fibrosis.

    PubMed

    Shoseyov, David; Brownlee, Keith G; Conway, Steven P; Kerem, Eitan

    2006-07-01

    Aspergillus fumigatus, a widely distributed spore-bearing fungus, is commonly grown in sputum cultures of patients with cystic fibrosis (CF). A fumigatus may cause allergic bronchopulmonary aspergillosis (ABPA), a complex condition that leads to worsening of airway inflammation and progressive damage and is diagnosed by specific criteria. In this report, we present six CF patients with respiratory deterioration that did not respond to appropriate antibiotic treatment. All had had A fumigatus in sputum cultures but did not fulfill the criteria of ABPA. Treatment with antifungal agents was followed by improvement in clinical condition. We suggest that in patients with CF, A fumigatus should be considered as a pathogen that may directly cause respiratory exacerbations. Antifungal therapy should be considered when deteriorating respiratory function is not responding to antibacterial therapy and A fumigatus is growing in sputum cultures. PMID:16840406

  14. [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. PMID:26070393

  15. Diagnostic Testing in Cystic Fibrosis.

    PubMed

    Brewington, John; Clancy, J P

    2016-03-01

    Cystic Fibrosis (CF) is a rare, multisystem disease leading to significant morbidity and mortality. CF is caused by defects in the cystic fibrosis transmembrane conductance regulator protein (CFTR), a chloride and bicarbonate transporter. Early diagnosis and access to therapies provides benefits in nutrition, pulmonary health, and cognitive ability. Several screening and diagnostic tests are available to support a diagnosis. We discuss the characteristics of screening and diagnostic tests for CF and guideline-based algorithms using these tools to establish a diagnosis. We discuss classification and management of common "diagnostic dilemmas," including the CFTR-related metabolic syndrome and other CFTR-associated diseases. PMID:26857766

  16. Rectal forceps biopsy procedure in cystic fibrosis: technical aspects and patients perspective for clinical trials feasibility

    PubMed Central

    2013-01-01

    Background Measurements of CFTR function in rectal biopsies ex vivo have been used for diagnosis and prognosis of Cystic Fibrosis (CF) disease. Here, we aimed to evaluate this procedure regarding: i) viability of the rectal specimens obtained by biopsy forceps for ex vivo bioelectrical and biochemical laboratory analyses; and ii) overall assessment (comfort, invasiveness, pain, sedation requirement, etc.) of the rectal forceps biopsy procedure from the patients perspective to assess its feasibility as an outcome measure in clinical trials. Methods We compared three bowel preparation solutions (NaCl 0.9%, glycerol 12%, mannitol), and two biopsy forceps (standard and jumbo) in 580 rectal specimens from 132 individuals (CF and non-CF). Assessment of the overall rectal biopsy procedure (obtained by biopsy forceps) by patients was carried out by telephone surveys to 75 individuals who underwent the sigmoidoscopy procedure. Results Integrity and friability of the tissue specimens correlate with their transepithelial resistance (r = −0.438 and −0.305, respectively) and are influenced by the bowel preparation solution and biopsy forceps used, being NaCl and jumbo forceps the most compatible methods with the electrophysiological analysis. The great majority of the individuals (76%) did not report major discomfort due to the short procedure time (max 15 min) and considered it relatively painless (79%). Importantly, most (88%) accept repeating it at least for one more time and 53% for more than 4 times. Conclusions Obtaining rectal biopsies with a flexible endoscope and jumbo forceps after bowel preparation with NaCl solution is a safe procedure that can be adopted for both adults and children of any age, yielding viable specimens for CFTR bioelectrical/biochemical analyses. The procedure is well tolerated by patients, demonstrating its feasibility as an outcome measure in clinical trials. PMID:23688510

  17. The Spectrum of Nocardia Lung Disease in Cystic Fibrosis.

    PubMed

    Mei-Zahav, Meir; Livnat, Galit; Bentur, Lea; Mussaffi, Huda; Prais, Dario; Stafler, Patrick; Bar-On, Ophir; Steuer, Guy; Blau, Hannah

    2015-08-01

    We reviewed all cases of Nocardia infection in cystic fibrosis patients at 2 centers. Eight of 200 patients had Nocardia in sputum. Four developed severe lung disease, including 3 with associated allergic bronchopulmonary aspergillosis; 4 remained clinically stable. Nocardia is often associated with significant lung disease in cystic fibrosis, possibly associated with allergic bronchopulmonary aspergillosis or steroids. PMID:25973994

  18. Cutaneous manifestations of cystic fibrosis.

    PubMed

    Bernstein, Megan L; McCusker, Meagen M; Grant-Kels, Jane M

    2008-01-01

    Cystic fibrosis is an autosomal recessive disease reported in 1 in 2500 live births in Northern American and Northern European Caucasian populations. Classic disease findings include chronic bacterial infection of airways and sinuses, malabsorption of fat, infertility in men, and elevated concentrations of chloride in sweat. Less well-recognized findings associated with cystic fibrosis include cutaneous findings, which can be primary or secondary manifestations of the disease process. Patients demonstrate more atopic and drug hypersensitivity reactions than the general population, but have similar rates of urticaria compared with the general population. In atypical presentations of cystic fibrosis, the nutrient deficiency dermatitis of the disease may aid with diagnosis, and notably can be the presenting sign. Other dermatologic manifestations of cystic fibrosis include early aquagenic skin wrinkling and cutaneous vasculitis, which can be associated with arthralgias. Familiarity with the nutrient deficiency dermatitis of this entity may play a role in the timely diagnosis of the disease, and the other cutaneous findings add to our understanding of the protean nature of its manifestations. PMID:18429769

  19. The Impact on Genetic Testing of Mutational Patterns of CFTR Gene in Different Clinical Macrocategories of Cystic Fibrosis.

    PubMed

    Lucarelli, Marco; Bruno, Sabina M; Pierandrei, Silvia; Ferraguti, Giampiero; Testino, Giancarlo; Truglio, Gessica; Strom, Roberto; Quattrucci, Serena

    2016-07-01

    More than 2000 sequence variations of the cystic fibrosis transmembrane conductance regulator gene are known. The marked genetic heterogeneity, poor functional characterization of the vast majority of sequence variations, and an uncertain genotype-phenotype relationship complicate the definition of mutational search strategies. We studied the effect of the marked genetic heterogeneity detected in a case series comprising 610 patients of cystic fibrosis (CF), grouped in different clinical macrocategories, on the operative characteristics of the genetic test designed to fully characterize CF patients. The detection rate in each clinical macrocategory and at each mutational step was found to be influenced by genetic heterogeneity. The definition of a single mutational panel that is suitable for all clinical macrocategories proved impossible. Only for classic CF with pancreas insufficiency did a reduced number of mutations yield a detection rate of diagnostic value. All other clinical macrocategories required an extensive genetic search. The search for specific mutational classes appears to be useful only in specific CF clinical forms. A flowchart defining a mutational search that may be adopted for different CF clinical forms, optimized in respect to those already available, is proposed. The findings also have consequences for carrier screening strategies. PMID:27157324

  20. [Therapeutic update in cystic fibrosis].

    PubMed

    Durupt, S; Nove Josserand, R; Durieu, I

    2014-06-01

    We present the recent therapeutic advances in the cystic fibrosis care. It concerns improvements in symptomatic treatment with the development of dry powder inhaled antibiotics that improved quality of life, and innovative treatments namely the modulators of the cystic fibrosis transmembrane protein conductance regulator (CFTR), molecules which act specifically at the level of the defective mechanisms implied in the disease. The life expectancy of cystic fibrosis patients born after 2000, is estimated now to be about 50 years. This improvement of survival was obtained with the organization of the care within the specialized centers for cystic fibrosis (Centre de ressource et de compétences de la mucoviscidose) and remains still based on heavy symptomatic treatments. Dry powder inhaled antibiotics constitute a significant time saving for patients to whom all the care can achieve two hours daily. Since 2012, the modulators of CFTR, molecules allowing a pharmacological approach targeted according to the type of the mutations, allows a more specific approach of the disease. Ivacaftor (Kalydeco(®)) which potentialises the function of the CFTR protein expressed on the cellular surface is now available for patients with the G551D mutation. Lumacaftor is going to be tested in association with ivacaftor in patients with the F508del mutation, that is present in at least 75% of the patients. The ataluren which allows the production of a functional protein CFTR in patients with a no sense mutation is the third representing of this new therapeutic class. We presently have numerous symptomatic treatments for the cystic fibrosis care. The development of CFTR modulators, today available to a restricted number of patients treated with ivacaftor represents a very promising therapeutic avenue. It will represent probably the first step to a personalized treatment according to CFTR genotype. PMID:24309546

  1. Diabetes mellitus in patients with cystic fibrosis.

    PubMed

    Alves, Crésio de Aragão Dantas; Aguiar, Renata Arruti; Alves, Ana Cláudia S; Santana, Maria Angélica

    2007-01-01

    Cystic fibrosis-related diabetes (CFRD) is the principal extra-pulmonary complication of cystic fibrosis, occurring in 15-30% of adult cystic fibrosis patients. The number of cystic fibrosis patients who develop diabetes is increasing in parallel with increases in life expectancy. The aim of this study was to review the physiopathology, clinical presentation, diagnosis and treatment of CFRD. A bibliographic search of the Medline and Latin American and Caribbean Health Sciences Literature databases was made. Articles were selected from among those published in the last twenty years. Insulin deficiency, caused by reduced beta-cell mass, is the main etiologic mechanism, although insulin resistance also plays a role. Presenting features of type 1 and type 2 diabetes, CFRD typically affects individuals of approximately 20 years of age. It can also be accompanied by fasting, non-fasting or intermittent hyperglycemia. Glucose intolerance is associated with worsening of nutritional status, increased morbidity, decreased survival and reduced pulmonary function. Microvascular complications are always present, although macrovascular complications are rarely seen. An oral glucose tolerance test is recommended annually for patients > or = 10 years of age and for any patients presenting unexplained weight loss or symptoms of diabetes. Patients hospitalized with severe diseases should also be screened. If fasting hyperglycemia persists for more than 48 h, insulin therapy is recommended. Insulin administration remains the treatment of choice for diabetes and fasting hyperglycemia. Calories should not be restricted, and patients with CFRD should be managed by a multidisciplinary team. PMID:17724542

  2. A first-year dornase alfa treatment impact on clinical parameters of patients with cystic fibrosis: the Brazilian cystic fibrosis multicenter study

    PubMed Central

    Rozov, Tatiana; Silva, Fernando Antônio A. e; Santana, Maria Angélica; Adde, Fabíola Villac; Mendes, Rita Heloisa

    2013-01-01

    OBJECTIVE: To describe the clinical impact of the first year treatment with dornase alfa, according to age groups, in a cohort of Brazilian Cystic Fibrosis (CF) patients. METHODS: The data on 152 eligible patients, from 16 CF reference centers, that answered the medical questionnaires and performed laboratory tests at baseline (T0), and at six (T2) and 12 (T4) months after dornase alfa initiation, were analyzed. Three age groups were assessed: six to 11, 12 to 13, and >14 years. Pulmonary tests, airway microbiology, emergency room visits, hospitalizations, emergency and routine treatments were evaluated. Student's t-test, chi-square test and analysis of variance were used when appropriated. RESULTS: Routine treatments were based on respiratory physical therapy, regular exercises, pancreatic enzymes, vitamins, bronchodilators, corticosteroids, and antibiotics. In the six months prior the study (T0 phase), hospitalizations for pulmonary exacerbations occurred in 38.0, 10.0 and 61.4% in the three age groups, respectively. After one year of intervention, there was a significant reduction in the number of emergency room visits in the six to 11 years group. There were no significant changes in forced expiratory volume in one second (VEF1), in forced vital capacity (FVC), in oxygen saturation (SpO2), and in Tiffenau index for all age groups. A significant improvement in Shwachman-Kulczychi score was observed in the older group. In the last six months of therapy, chronic or intermittent colonization by P. aeruginosa was detected in 75.0, 71.4 and 62.5% of the studied groups, respectively, while S. aureus colonization was identified in 68.6, 66.6 and 41.9% of the cases. CONCLUSIONS: The treatment with dornase alfa promoted the maintenance of pulmonary function parameters and was associated with a significant reduction of emergency room visits due to pulmonary exacerbations in the six to 11 years age group, with better clinical scores in the >14 age group, one year after the

  3. A Genotypic-Oriented View of CFTR Genetics Highlights Specific Mutational Patterns Underlying Clinical Macrocategories of Cystic Fibrosis

    PubMed Central

    Lucarelli, Marco; Bruno, Sabina Maria; Pierandrei, Silvia; Ferraguti, Giampiero; Stamato, Antonella; Narzi, Fabiana; Amato, Annalisa; Cimino, Giuseppe; Bertasi, Serenella; Quattrucci, Serena; Strom, Roberto

    2015-01-01

    Cystic fibrosis (CF) is a monogenic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The genotype–phenotype relationship in this disease is still unclear, and diagnostic, prognostic and therapeutic challenges persist. We enrolled 610 patients with different forms of CF and studied them from a clinical, biochemical, microbiological and genetic point of view. Overall, there were 125 different mutated alleles (11 with novel mutations and 10 with complex mutations) and 225 genotypes. A strong correlation between mutational patterns at the genotypic level and phenotypic macrocategories emerged. This specificity appears to largely depend on rare and individual mutations, as well as on the varying prevalence of common alleles in different clinical macrocategories. However, 19 genotypes appeared to underlie different clinical forms of the disease. The dissection of the pathway from the CFTR mutated genotype to the clinical phenotype allowed to identify at least two components of the variability usually found in the genotype–phenotype relationship. One component seems to depend on the genetic variation of CFTR, the other component on the cumulative effect of variations in other genes and cellular pathways independent from CFTR. The experimental dissection of the overall biological CFTR pathway appears to be a powerful approach for a better comprehension of the genotype–phenotype relationship. However, a change from an allele-oriented to a genotypic-oriented view of CFTR genetics is mandatory, as well as a better assessment of sources of variability within the CFTR pathway. PMID:25910067

  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. PMID:27490265

  5. [Cystic fibrosis and associated complications].

    PubMed

    Schwarz, C; Staab, D

    2015-03-01

    Cystic fibrosis (CF) is an autosomal recessive inherited metabolic disease. The mutation is located on the long arm of chromosome 7. Due to a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, chloride ion transport is reduced across the cell membrane. As a result, the disease can be described as an exocrinopathy. In all organs with exocrine glands, disorders occur in association with the defective chloride transport. The main impact of this defect is manifested in the lungs. Therefore, the most common cause of death is pulmonary disease with respiratory insufficiency due to recurrent infections. Unfortunately, a cure for the disease is still not available. However, new therapies that may affect the CFTR mutation more specifically give new hope for better therapeutic options in the future. The long-term goal of therapy is to develop a causal therapy for all six different mutation classes and thus for about 2000 mutations. PMID:25693903

  6. Respiratory Conditions Update: Cystic Fibrosis.

    PubMed

    Pritchard, Lyle L

    2016-09-01

    Cystic fibrosis (CF) is an autosomal recessive genetic disease that occurs in approximately 1 in 2,500 white live births. It is less common in nonwhite individuals. A dysfunctional epithelial chloride channel leads to excessively thick mucus affecting multiple organ systems. Common issues include mucous plugging of the airway, lung inflammation, chronic pulmonary infections, intestinal malabsorption, and malnutrition. Universal screening of newborns for CF is recommended in many countries. CF can be diagnosed based on clinical evidence of disease along with genetic testing or other laboratory evidence of chloride channel dysfunction. Pulmonary system dysfunction causes the most morbidity and mortality. Pulmonary function testing is the primary modality used to monitor CF progression. Therapies include chest physiotherapy, mucolytics, antibiotics, anti-inflammatory drugs, targeted therapies, and vaccines. Dysfunction of the exocrine pancreas and gastrointestinal tract leads to malabsorption, malnutrition, and intestinal obstruction. Nutrition should be optimized with adequate calories, pancreatic enzymes, and appropriate dietary supplements. Complications, including acute pulmonary exacerbations, gastrointestinal conditions, chronic rhinosinusitis, CF-related diabetes, osteoporosis, infertility, and psychosocial issues, must be managed. At the appropriate time, lung transplantation and end-of-life issues must be addressed. PMID:27576234

  7. Infection Control in Cystic Fibrosis

    PubMed Central

    Saiman, Lisa; Siegel, Jane

    2004-01-01

    Over the past 20 years there has been a greater interest in infection control in cystic fibrosis (CF) as patient-to-patient transmission of pathogens has been increasingly demonstrated in this unique patient population. The CF Foundation sponsored a consensus conference to craft recommendations for infection control practices for CF care providers. This review provides a summary of the literature addressing infection control in CF. Burkholderia cepacia complex, Pseudomonas aeruginosa, and Staphylococcus aureus have all been shown to spread between patients with CF. Standard precautions, transmission-based precautions including contact and droplet precautions, appropriate hand hygiene for health care workers, patients, and their families, and care of respiratory tract equipment to prevent the transmission of infectious agents serve as the foundations of infection control and prevent the acquisition of potential pathogens by patients with CF. The respiratory secretions of all CF patients potentially harbor clinically and epidemiologically important microorganisms, even if they have not yet been detected in cultures from the respiratory tract. CF patients should be educated to contain their secretions and maintain a distance of >3 ft from other CF patients to avoid the transmission of potential pathogens, even if culture results are unavailable or negative. To prevent the acquisition of pathogens from respiratory therapy equipment used in health care settings as well as in the home, such equipment should be cleaned and disinfected. It will be critical to measure the dissemination, implementation, and potential impact of these guidelines to monitor changes in practice and reduction in infections. PMID:14726455

  8. Clinical impact of laboratory error on therapeutic drug monitoring of once-daily tobramycin in cystic fibrosis: Case series

    PubMed Central

    Mancuso, Michelle A

    2014-01-01

    Once-daily dosing intravenous tobramycin is commonly used to treat cystic fibrosis pulmonary exacerbations. Clinicians often utilize historical therapeutic drug monitoring data to individualize the dose among patients who have been treated with tobramycin previously. This case series involves three patients with cystic fibrosis who had supra-therapeutic tobramycin levels despite use of a once-daily dosing that produced therapeutic drug levels during a previous hospital admission, raising questions about the validity of these levels. Investigation into several potential sources of error led to the discovery of an analyzer error in the laboratory. Once the laboratory’s tobramycin analyzer was recalibrated, the reported levels were comparable to historical levels. This case series emphasizes the clinical importance of critically analyzing reported levels, and specifically, the importance of utilizing past therapeutic drug monitoring data, if available, for all patients treated with intravenous tobramycin. If a patient was therapeutic on a similar dose of tobramycin during a previous admission, a dose adjustment may not be necessary, and clinicians should consider repeating levels while pursuing alternative explanations for the discrepant serum levels. PMID:27489639

  9. Staphylococcus aureus and Pseudomonas aeruginosa co-infection is associated with cystic fibrosis-related diabetes and poor clinical outcomes.

    PubMed

    Limoli, D H; Yang, J; Khansaheb, M K; Helfman, B; Peng, L; Stecenko, A A; Goldberg, J B

    2016-06-01

    Cystic fibrosis-related diabetes (CFRD) patients suffer from accelerated rates of pulmonary decline compared to cystic fibrosis (CF) patients with normal glucose tolerance (NGT). However, the mechanisms underlying this difference are unknown. While CFRD is associated with increased respiratory infections, a link between infection and enhanced pulmonary dysfunction remains unclear. The development of glucose intolerance is spectral, resulting in impaired glucose tolerance (IGT) prior to the diagnosis of CFRD. Inclusion of IGT patients within the NGT group may diminish the ability to identify correlations with CFRD. With this in mind, this study aimed to determine if the association between CFRD and respiratory infections is correlated with pulmonary decline. Respiratory cultures from 234 CF patients with confirmed diagnosis of NGT or CFRD were analyzed to measure rates of infection, focusing on the two most prevalent bacteria in CF, Staphylococcus aureus and Pseudomonas aeruginosa. Infection status was correlated with pulmonary function and confounding clinical variables including age, gender, blood glucose levels, and CF transmembrane conductance regulator (CFTR) phenotype were considered in multivariate analyses. CFRD patients, particularly those with extremely high blood glucose levels, were more likely than NGT patients to be co-infected with S. aureus and P. aeruginosa, compared to infection with only one pathogen. Co-infection was associated with decreased lung function and increased frequency of pulmonary exacerbations, even after adjustment for confounding variables. Alterations in the microbial community composition, as opposed to the presence of a single pathogen, may account for greater pulmonary decline in CFRD patients. PMID:26993289

  10. Systemic inflammatory mediators and cystic fibrosis genotype.

    PubMed

    Augarten, A; Paret, G; Avneri, I; Akons, H; Aviram, M; Bentur, L; Blau, H; Efrati, O; Szeinberg, A; Barak, A; Kerem, E; Yahav, J

    2004-10-01

    Morbidity and mortality in cystic fibrosis patients is mainly attributed to pulmonary infection and inflammation. Chemokines play a pivotal role in the inflammatory process. Although genotype-phenotype correlation in cystic fibrosis patients has been defined, a clear relationship between the defect in the cystic fibrosis transmembrane regulator (CFTR) gene and pulmonary inflammation has not been established. The aim of this study was to assess whether serum chemokines levels in cystic fibrosis patients correlate with genotype and pulmonary function tests, as well as with other clinical characteristics. Serum levels of interleukin-8, RANTES, and monocyte chemoattractant protein-1 were measured in 36 cystic fibrosis patients grouped according to their genotype. Group A included 25 patients who carried two mutations associated with a pathological sweat test and pancreatic insufficiency (deltaF508, W1282X, G542X, N1303K, S549R). Group B included 11 compound heterozygote patients who carried one mutation known to cause mild disease with borderline or normal sweat test and pancreatic sufficiency (3849+10kb C to T, 5T). Associations between chemokine levels, genotype, pulmonary function, Pseudomonas aeruginosa colonization, age, sweat chloride level, and pancreatic and nutritional status were examined. Mean interleukin-8 and monocyte chemoattractant protein-1 levels were significantly higher in group A than group B (11.4 +/- 2.1 pg/ml vs. 5 +/- 0.9 pg/ml and 157 +/- 16 pg/ml vs. 88.8 +/- 16.4 pg/ml, respectively) (P < 0.01). No difference in RANTES levels were found between groups. interleukin-8 levels were inversely related to forced expiratory volume in 1 s (r = -0.37, P < 0.02), while there was no association between the latter and RANTES and monocyte chemoattractant protein-1 levels. The Pseudomonas colonization rate was higher among group A patients than group B (88% vs. 40%, P < 0.01). No relationship was found between measured chemokines and age, sweat chloride

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

    PubMed

    Tümmler, B

    2016-05-01

    Personalized medicine promises that medical decisions, practices and products are tailored to the individual patient. Cystic fibrosis, an inherited disorder of chloride and bicarbonate transport in exocrine glands, is the first successful example of customized drug development for mutation-specific therapy. There are two classes of CFTR modulators: potentiators that increase the activity of CFTR at the cell surface, and correctors that either promote the read-through of nonsense mutations or facilitate the translation, folding, maturation and trafficking of mutant CFTR to the cell surface. The potentiator ivacaftor and the corrector lumacaftor are approved in Germany for the treatment of people with cystic fibrosis who carry a gating mutation such as p.Gly551Asp or who are homozygous for the most common mutation p.Phe508del, respectively. This report provides an overview of the basic defect in cystic fibrosis, the population genetics of CFTR mutations in Germany and the bioassays to assess CFTR function in humans together with the major achievements of preclinical research and clinical trials to bring CFTR modulators to the clinic. Some practical information on the use of ivacaftor and lumacaftor in daily practice and an update on pitfalls, challenges and novel strategies of bench-to-bedside development of CFTR modulators are also provided. PMID:26894479

  12. Cystic fibrosis presenting with bilateral facial palsy.

    PubMed

    Basu, Anna P; Kumar, Prashant; Devlin, Anita M; O'Brien, Christopher J

    2007-07-01

    A 15-week old male infant presented with bilateral lower motor neuron facial palsy of unknown cause. Subsequently his growth deteriorated and he developed progressively worsening cough and wheeze. A diagnosis of cystic fibrosis was confirmed and hypovitaminosis A detected. Improvement of the facial palsy was noted following standard management of cystic fibrosis including vitamin A supplementation. PMID:17287135

  13. A combination therapy for cystic fibrosis.

    PubMed

    Brodsky, Jeffrey L; Frizzell, Raymond A

    2015-09-24

    The most prevalent form of cystic fibrosis arises from an amino acid deletion in the cystic fibrosis transmembrane conductance regulator, CFTR. A recently approved treatment for individuals homozygous for this mutation combines a chemical corrector, which helps CFTR fold, and a potentiator that increases CFTR channel activity. PMID:26406363

  14. Molecular Epidemiology of Stenotrophomonas maltophilia Isolated from Clinical Specimens from Patients with Cystic Fibrosis and Associated Environmental Samples

    PubMed Central

    Denton, Miles; Todd, Neil J.; Kerr, Kevin G.; Hawkey, Peter M.; Littlewood, James M.

    1998-01-01

    Stenotrophomonas maltophilia was isolated from the respiratory tracts of 41 (25%) of 163 children attending our pediatric cystic fibrosis unit between September 1993 and December 1995. The extents of S. maltophilia contamination of environmental sites frequented by these patients were investigated with a selective medium incorporating vancomycin, imipenem, and amphotericin B. Eighty-two isolates of S. maltophilia were cultured from 67 different environmental sites sampled between January and July 1996. The organism was widespread in the home environment, with 20 (36%) and 25 (42%) of sampled sites positive in the homes of colonized and noncolonized patients, respectively. In the nosocomial setting, it was isolated from 18 (32%) sites in the hospital ward and from 4 (17%) sites in the outpatient clinic area. The most common sites of contamination were sink drains, faucets, and other items frequently in contact with water. All environmental and clinical isolates were genotyped with enterobacterial repetitive intergenic consensus sequences as primers. A total of 33 of the 41 patients were colonized with unique strains, and four pairs of patients shared strains. Further characterization by pulsed-field gel electrophoresis after digestion with XbaI found that there was no evidence of patient-to-patient transmission; however, there was some evidence that a small number of patients may have acquired the organism from the hospital environment. Resampling of environmental sites in the hospital ward in January 1997 revealed evidence of genetic drift, complicating the accurate determination of environmental sources for clinical strains. The source of the majority of S. maltophilia strains colonizing the respiratory tracts of these patients with cystic fibrosis remained uncertain but may have represented multiple, independent acquisitions from a variety of environmental sites both within and outside the hospital. PMID:9650943

  15. Endocrine Disorders in Cystic Fibrosis.

    PubMed

    Blackman, Scott M; Tangpricha, Vin

    2016-08-01

    Cystic fibrosis is frequently complicated by endocrine disorders. Diabetes can be expected to affect most with CF and pancreatic insufficiency and varies widely in age of onset, but early identification and treatment improve morbidity and mortality. Short stature can be exacerbated by relative delay of puberty and by use of inhaled corticosteroids. Bone disease in CF causes fragility fractures and should be assessed by monitoring bone mineral density and optimizing vitamin D status. Detecting and managing endocrine complications in CF can reduce morbidity and mortality in CF. These complications can be expected to become more common as the CF population ages. PMID:27469183

  16. Pulmonary complications of cystic fibrosis.

    PubMed

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

    2014-03-01

    The life expectancy of patients with cystic fibrosis (CF) has steadily increased over recent decades with a corresponding increase in the frequency of complications of the disease. Radiologists are increasingly involved with managing and identifying the pulmonary complications of CF. This article reviews the common manifestations of CF lung disease as well as updating radiologists with a number of less well-known complications of the condition. Early and accurate detection of the pulmonary effects of CF are increasingly important to prevent irreversible lung damage and give patients the greatest possibility of benefiting from the new therapies becoming available, which correct the underlying defect causing CF. PMID:24361142

  17. [Isolation of Geosmithia argillacea in a cystic fibrosis patient].

    PubMed

    Labbé, F; Babchia, S; Evreux, F; Chenal, P

    2013-09-01

    We report the case of an 11-year-old child with cystic fibrosis where Geosmithia argillacea has been isolated from sputum. This is a filamentous fungus (mold) recently described as emergent infectious agent in cystic fibrosis patients. In our case, the presence of G. argillacea was not associated with clinical disorder. However, recent evidence shows that it can be responsible for very serious invasive infection, especially in chronic granulomatous disease and may be, after lung transplantation. PMID:23856446

  18. Use of nasal potential difference and sweat chloride as outcome measures in multicenter clinical trials in subjects with cystic fibrosis.

    PubMed

    Ahrens, Richard C; Standaert, Thomas A; Launspach, Janice; Han, Seung-Ho; Teresi, Mary E; Aitken, Moira L; Kelley, Thomas J; Hilliard, Kathleen A; Milgram, Laura J H; Konstan, Michael W; Weatherly, Mark R; McCarty, Nael A

    2002-02-01

    One of the goals of current research in cystic fibrosis (CF) is to develop treatments that correct or compensate for defects in function of the cystic fibrosis transmembrane regulator (CFTR) gene. The use of outcome measures that assess CFTR function such as nasal potential difference (NPD) measurements and sweat chloride determinations will be required to evaluate the efficacy of such treatments in multicenter clinical trials. The purpose of this work was to identify the sources and magnitude of variability in NPD and sweat chloride measurements when performed at multiple centers. For the variance component analysis presented here, we used NPD and sweat chloride measurements from 37 subjects with CF participating in a phase I, four-center clinical trial of CPX (8-cyclopentyl-1,3-dipropylxanthine), a drug intended to enhance trafficking of Delta F508 CFTR to the cell membrane. The specific techniques used to measure these outcomes were not standardized, and varied between the four sites. Variability of both NPD measurements (baseline potential difference during infusion with Ringer's solution; change in response to addition of 0.1 mM amiloride; and subsequent change in response to perfusion with low chloride solution containing 0.1 mM amiloride and 0.01 mM isoproterenol) and sweat chloride measurements differed significantly between study sites. For change in NPD, one study site had significantly greater variability (lower reproducibility) of measurement than the other three sites. For sweat chloride measurements, reproducibility was lower at two of the sites relative to the other two sites. Sample size calculations showed that lower reproducibility at one or more sites can substantially reduce the power of studies using NPD or sweat chloride determinations as outcome measures. Standardization of measurement protocols, careful operator training and certification, and ongoing monitoring of individual operator performance may help to improve reliability in

  19. Cystic fibrosis in adults. From researcher to practitioner.

    PubMed Central

    Marelich, G P; Cross, C E

    1996-01-01

    The Cystic Fibrosis Foundation currently tracks about 20,000 Americans with cystic fibrosis, an autosomal recessive genetic disease that leads to multisystem complications. With the institution of better therapeutic regimens over the past 2 decades, more patients with this disease are surviving to adulthood. Within the past decade, both clinical and basic science research in the field of cystic fibrosis has progressed at a rapid rate. The intent of this review is to introduce readers to the molecular, cellular, and systemic disorders of this disease. We discuss treatment strategies involving antibiotics, nutrition, immune-response mediators, chest physiotherapy, and sputum-active agents with respect to the airway dysfunction of cystic fibrosis. Other common complications, recent developments, transplantation, and gene therapy are also reviewed. PMID:8732732

  20. Hydrator Therapies for Chronic Bronchitis. Lessons from Cystic Fibrosis.

    PubMed

    Bennett, William D; Henderson, Ashley G; Donaldson, Scott H

    2016-04-01

    Patients with the chronic bronchitis form of chronic obstructive pulmonary disease and cystic fibrosis share similar clinical features, including mucus obstruction of airways and the development of chronic/recurrent airways infections that often manifest as disease exacerbations. There is growing evidence that these diseases may have parallels in disease pathogenesis as well, including cystic fibrosis transmembrane conductance regulator dysfunction, mucus dehydration, and defective mucociliary clearance. As progress is made in the development of therapies that target the basic defects that lead to cystic fibrosis lung disease, it is possible that similar approaches could also benefit patients with chronic bronchitis. A deeper understanding of how tobacco smoke and other triggers of chronic bronchitis actually lead to disease, and exploration of the concept that therapies that restore cystic fibrosis transmembrane conductance regulator function, mucus hydration, and/or mucociliary clearance may benefit patients with chronic bronchitis, hold the prospect of significant progress in treating this prevalent disease. PMID:27115955

  1. Aspergillus infections in cystic fibrosis.

    PubMed

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

    2016-07-01

    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. PMID:27177733

  2. Managing diabetes in cystic fibrosis.

    PubMed

    Laguna, T A; Nathan, B M; Moran, A

    2010-10-01

    Cystic fibrosis related diabetes (CFRD) is the most common co-morbidity in persons with cystic fibrosis (CF). As the life expectancy of persons with CF continues to increase, the need to proactively diagnose and aggressively treat CFRD and its potential complications has become more apparent. CFRD negatively impacts lung function, growth and mortality, making its diagnosis and management crucial in a population already at high risk for early mortality. Compared to type 1 and type 2 diabetes, CFRD is a unique entity, requiring a thorough understanding of its unique pathophysiology to facilitate the creation and utilization of an effective medical treatment plan. The physiology of CFRD is complex, likely consisting of a combination of insulin deficiency, insulin resistance and a genetic predisposition towards the development of diabetes. However, the hallmark of CFRD is insulin deficiency, necessitating the use of exogenous insulin as the mainstay of therapy. Insulin administration, in combination with a multidisciplinary team of health professionals with expertise in the care of patients with CF and CFRD, is the cornerstone of the care for these patients. The goals of treatment of the CFRD population are to reverse protein catabolism, maintain a healthy weight, and reduce acute and chronic diabetes complications. Creating a partnership between the treatment team and the patient is the ideal way to accomplish these goals and is essential for successful diabetes care. PMID:20920037

  3. Biliary complications of cystic fibrosis.

    PubMed Central

    O'Brien, S; Keogan, M; Casey, M; Duffy, G; McErlean, D; Fitzgerald, M X; Hegarty, J E

    1992-01-01

    One hundred and four adult patients with cystic fibrosis were evaluated for the presence of liver disease as defined by abnormal liver function tests of six months' duration, histological evidence of fibrosis or cirrhosis, or the presence of portal hypertension, or both. Twenty patients fulfilled these criteria and were evaluated further for the presence of biliary tract abnormalities with biliary scintigraphy using 99Tc diisopropylphenyl-carboxymethyl iminodiacetic acid (DISIDA) and endoscopic retrograde cholangiography. Clearance of 99Tc DISIDA from the liver and biliary tree was diminished at 45 (E45) and 60 (E60) minutes in the patients with liver disease compared with those without liver disease; E45 = 37.8% and 65.8%, p less than 0.01; E60 = 48.2% and 77.5%, p less than 0.01 respectively. Serial analogue images of the extrahepatic biliary tree were consistent with common bile duct obstruction with retention of DISIDA and tapering of the common bile duct in seven of 18 patients with and two of 10 patients without liver disease. Endoscopic retrograde cholangiography showed changes consistent with sclerosing cholangitis, with beading and stricturing of the intrahepatic ducts in 12 of the 14 patients. In all 14 patients, including those in whom biliary scintigraphy had suggested obstruction, no abnormality of the common bile duct was identified. These results indicate that abnormalities of the bile ducts in patients with cystic fibrosis related liver disease are confined to the intrahepatic biliary tree and that common bile duct strictures do not contribute to either the progression or development of liver disease in these patients. Images Figure 2 PMID:1568661

  4. Cystic Fibrosis Transmembrane Conductance Regulator. Implications in Cystic Fibrosis and Chronic Obstructive Pulmonary Disease.

    PubMed

    Cantin, André M

    2016-04-01

    Cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) have traditionally been viewed as two distinct entities of unrelated origins. However, molecular, cellular, and clinical studies have revealed that cystic fibrosis transmembrane conductance regulator (CFTR) protein dysfunction is common to both conditions, one (CF) being defined genetically and the other (COPD) as an acquired CFTR deficiency. Multiple molecular mechanisms of cigarette smoke-induced CFTR dysfunction have been reported. More importantly, considerable evidence of cigarette smoke-induced CFTR dysfunction in several respiratory and nonrespiratory tissues have been confirmed, making CFTR a target that cannot be overlooked in our quest to understand COPD and improve therapies for individuals affected by this disease. This review summarizes the molecular, cellular, and clinical evidence that CFTR dysfunction is induced by cigarette smoke exposure both in vitro and in vivo, and explores how this may contribute to the development of COPD. PMID:27115950

  5. 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

  6. Vaccine strategies against cystic fibrosis pathogens.

    PubMed

    Le Moigne, Vincent; Gaillard, Jean-Louis; Herrmann, Jean-Louis

    2016-03-01

    A great number of cystic fibrosis (CF) pathogens such as Pseudomonas aeruginosa, the Burkholderia cepacia and the Mycobacterium abscessus complex raised difficult therapeutic problems due to their intrinsic multi-resistance to numerous antibiotics. Vaccine strategies represent one of the key weapons against these multi-resistant bacteria in a number of clinical settings like CF. Different strategies are considered in order to develop such vaccines, linked either to priming the host response, or by exploiting genomic data derived from the bacterium. Interestingly, virulence factors synthesized by various pathogens might serve as targets for vaccine development and have been, for example, evaluated in the context of CF. PMID:26618824

  7. Nontuberculous Mycobacterial Infections in Cystic Fibrosis.

    PubMed

    Martiniano, Stacey L; Nick, Jerry A; Daley, Charles L

    2016-03-01

    Nontuberculous mycobacteria (NTM) are important emerging cystic fibrosis (CF) pathogens, with estimates of prevalence ranging from 6% to 13%. Diagnosis of NTM disease in patients with CF is challenging, as the infection may remain indolent in some, without evidence of clinical consequence, whereas other patients suffer significant morbidity and mortality. Treatment requires prolonged periods of multiple drugs and varies depending on NTM species, resistance pattern, and extent of disease. The development of a disease-specific approach to the diagnosis and treatment of NTM infection in CF patients is a research priority, as a lifelong strategy is needed for this high-risk population. PMID:26857770

  8. Chronic pancreatitis and cystic fibrosis

    PubMed Central

    Witt, H

    2003-01-01

    Recent discoveries of trypsinogen and trypsin inhibitor mutations in patients with chronic pancreatitis (CP) support the hypothesis that an inappropriate activation of pancreatic zymogens to active enzymes within the pancreatic parenchyma starts the inflammatory process. Current data suggest that CP may be inherited dominant, recessive, or complex as a result of mutations in the above mentioned or yet unidentified genes. Evaluation of patients with CP should include genetic testing. Cystic fibrosis (CF) is an autosomal recessive inherited disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene and is characterised by pancreatic insufficiency and chronic bronchopulmonary infection. The progression and severity of pulmonary disease differs considerably between people with identical CFTR mutations and does not seem to correlate with the type or class of the CFTR mutation. The identification of further disease modifying genetic factors will increase the pathophysiological understanding and may help to identify new therapeutic targets. PMID:12651880

  9. Celiac Disease and Cystic Fibrosis: Challenges to Differential Diagnosis.

    PubMed

    Ramos, Alessandra Teixeira Pessoa; Figueirêdo, Manuella Machado; Aguiar, Ana Paula de B; Almeida, Carolina de Godoy; Mendes, Patrícia S A; Souza, Edna Lucia

    2016-01-01

    Cystic fibrosis and celiac disease were considered a single clinical entity for many years. Differentiation between the diseases occurred some time in the 1930s of the 20th Century. Both diseases may present the intestinal malabsorption syndrome and similar clinical manifestations that contribute to difficulties with clinical distinction. We describe a report of two patients with initial diagnosis of cystic fibrosis, who were subsequently diagnosed with celiac disease. These case reports emphasize the possibility of false positivity being shown in the sweat test in CD, which may result in delayed diagnosis and inadequate management of this disease. PMID:27552792

  10. The clinical benefits of long-term supplementation with omega-3 fatty acids in cystic fibrosis patients - A pilot study.

    PubMed

    Hanssens, L; Thiébaut, I; Lefèvre, N; Malfroot, A; Knoop, C; Duchateau, J; Casimir, G

    2016-05-01

    Effectiveness of omega-3 supplementation in cystic fibrosis (CF) remains controversial. This study sought to evaluate clinical status, exercise tolerance, inflammatory parameters, and erythrocyte fatty acid profile after 1 year of oral omega-3 supplementation in CF patients. Fifteen ΔF508-homozygous patients undergoing chronic azithromycin were randomized to receive omega-3 fish oil supplementation at a dose of 60mg/Kg/day or placebo. In comparison with the previous year, in the supplemented group, the number of pulmonary exacerbations decreased at 12 months (1.7 vs. 3.0, p<0.01), as did the duration of antibiotic therapy (26.5 days vs. 60.0 days, p<0.025). Supplementation significantly increased the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as early as <3 months of administration, with concomitant decreases in arachidonic acid (AA) levels. This pilot study suggests that long-term omega-3 supplementation offers several clinical benefits as to the number of exacerbations and duration of antibiotic therapy in CF patients. PMID:27154364

  11. Cystic fibrosis chronic rhinosinusitis: A comprehensive review

    PubMed Central

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

    2013-01-01

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

  12. Whole-Genome Sequencing of Three Clonal Clinical Isolates of B. cenocepacia from a Patient with Cystic Fibrosis

    PubMed Central

    Miller, Ruth R.; Hird, Trevor J.; Tang, Patrick; Zlosnik, James E. A.

    2015-01-01

    Burkholderia cepacia complex bacteria are amongst the most feared of pathogens in cystic fibrosis (CF). The BCC comprises at least 20 distinct species that can cause chronic and unpredictable lung infections in CF. Historically the species B. cenocepacia has been the most prevalent in CF infections and has been associated in some centers with high rates of mortality. Modeling chronic infection by B. cenocepacia in the laboratory is challenging and no models exist which effectively recapitulate CF disease caused by BCC bacteria. Therefore our understanding of factors that contribute towards the morbidity and mortality caused by this organism is limited. In this study we used whole-genome sequencing to examine the evolution of 3 clonal clinical isolates of B. cenocepacia from a patient with cystic fibrosis. The first isolate was from the beginning of infection, and the second two almost 10 years later during the final year of the patients’ life. These isolates also demonstrated phenotypic heterogeneity, with the first isolate displaying the mucoid phenotype (conferred by the overproduction of exopolysaccharide), while one of the later two was nonmucoid. In addition we also sequenced a nonmucoid derivative of the initial mucoid isolate, acquired in the laboratory by antibiotic pressure. Examination of sequence data revealed that the two late stage isolates shared 20 variant nucleotides in common compared to the early isolate. However, despite their isolation within 10 months of one another, there was also considerable variation between the late stage isolates, including 42 single nucleotide variants and three deletions. Additionally, no sequence differences were identified between the initial mucoid isolate and its laboratory acquired nonmucoid derivative, however transcript analysis indicated at least partial down regulation of genes involved in exopolysaccharide production. Our study examines the progression of B. cenocepacia throughout chronic infection

  13. Cystic fibrosis transmembrane conductance regulator protein repair as a therapeutic strategy in cystic fibrosis

    PubMed Central

    Sloane, Peter A.; Rowe, Steven M.

    2013-01-01

    Purpose of review Recent progress in understanding the production, processing, and function of the cystic fibrosis gene product, the cystic fibrosis transmembrane conductance regulator (CFTR), has revealed new therapeutic targets to repair the mutant protein. Classification of CFTR mutations and new treatment strategies to address each will be described here. Recent findings High-throughput screening and other drug discovery efforts have identified small molecules that restore activity to mutant CFTR. Compounds such as VX-770 that potentiate CFTR have demonstrated exciting results in recent clinical trials and demonstrate robust effects across several CFTR mutation classes in the laboratory. A number of novel F508del CFTR processing correctors restore protein to the cell surface and improve ion channel function in vitro and are augmented by coadministration of CFTR potentiators. Ongoing discovery efforts that target protein folding, CFTR trafficking, and cell stress have also indicated promising results. Aminoglycosides and the novel small molecule ataluren induce translational readthrough of nonsense mutations in CFTR and other genetic diseases in vitro and in vivo and have shown activity in proof of concept trials, and ataluren is now being studied in confirmatory trials. Summary An improved understanding of the molecular mechanisms underlying the basic genetic defect in cystic fibrosis have led to new treatment strategies to repair the mutant protein. PMID:20829696

  14. Abnormal Ion Permeation through Cystic Fibrosis Respiratory Epithelium

    NASA Astrophysics Data System (ADS)

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

    1983-09-01

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

  15. Non-coding small (micro) RNAs of Pseudomonas aeruginosa isolated from clinical isolates from adult patients with cystic fibrosis.

    PubMed

    Rao, J R; Nelson, D; Moore, J E; Millar, B C; Goldsmith, C E; Rendall, J; Elborn, J S

    2010-01-01

    MicroRNAs are a class of small non-coding RNAs widely reported in eukaryotic multicellular organisms. In this study, a number of small non-coding micro (mi)RNA species in clinical isolates of prokaryote Pseudomonas aeruginosa were obtained from the sputum of adult patients with cystic fibrosis (CF) utilising a DynaExpress miRNA cloning kit, and five miRNAs of 16-47 nucleotides that were smaller than those encountered or described (80-100 nucleotides) previously in bacterial systems were described. This report presents data on these unknown cellular miRNAs cloned from P. aeruginosa isolates from CF patients. Adapting a computational miRNA prediction model that takes advantage of the highly conserved known miRNA hair pin stems regions, the results revealed that the fold structure of the microRNAs had a high homology to the recently reported human bacterial infection response (BiR)-related microRNA, mi-146, associated with the Toll-like receptor (TLR) family, which is the primary evolutionarily conserved sensors of pathogen-associated molecular patterns (PAMPs), and known to trigger host inflammatory and immune responses. PMID:20973407

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

    PubMed Central

    Paulsson, Magnus; Singh, Birendra; Al-Jubair, Tamim; Su, Yu-Ching; Høiby, Niels; Riesbeck, Kristian

    2016-01-01

    Background Pseudomonas aeruginosa is a pathogen that frequently colonizes patients with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). Several pathogens are known to bind vitronectin to increase their virulence. Vitronectin has been shown to enhance P. aeruginosa adhesion to host epithelial cells. Methods We screened clinical isolates from the airways of CF patients and from the bloodstream of patients with bacteremia for binding of vitronectin. Two-dimensional SDS-PAGE and a proteomic approach was used to identify vitronectin-receptors in P. aeruginosa. Results P. aeruginosa from the airways of CF patients (n=27) bound more vitronectin than bacteremic isolates (n=15, p=0.025). Porin D (OprD) was identified as a vitronectin-binding protein. A P. aeruginosa oprD transposon insertion mutant had a decreased binding to soluble and immobilized vitronectin (p ≤ 0.001). Conclusions P. aeruginosa isolates obtained from CF patients significantly bound vitronectin. Porin D was defined as a novel P. aeruginosa vitronectin-receptor, and we postulate that the Porin D-dependent interaction with vitronectin may be important for colonization. PMID:26047937

  17. CFTR protein repair therapy in cystic fibrosis.

    PubMed

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

    2014-04-01

    Cystic fibrosis is a single gene, autosomal recessive disorder, in which more than 1,900 mutations grouped into 6 classes have been described. It is an example a disease that could be well placed to benefit from personalised medicine. There are currently 2 very different approaches that aim to correct the basic defect: gene therapy, aimed at correcting the genetic alteration, and therapy aimed at correcting the defect in the CFTR protein. The latter is beginning to show promising results, with several molecules under development. Ataluren (PTC124) is a molecule designed to make the ribosomes become less sensitive to the premature stop codons responsible for class i mutations. Lumacaftor (VX-809) is a CFTR corrector directed at class ii mutations, among which Phe508del is the most frequent, with encouraging results. Ivacaftor (VX-770) is a potentiator, the only one marketed to date, which has shown good efficacy for the class iii mutation Gly551Asp in children over the age of 6 and adults. These drugs, or a combination of them, are currently undergoing various clinical trials for other less common genetic mutations. In the last 5 years, CFTR has been designated as a therapeutic target. Ivacaftor is the first drug to treat the basic defect in cystic fibrosis, but only provides a response in a small number of patients. New drugs capable of restoring the CFTR protein damaged by the most common mutations are required. PMID:24095197

  18. 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

  19. Antibiotic allergy in cystic fibrosis.

    PubMed

    Parmar, J S; Nasser, S

    2005-06-01

    Allergic reactions to antibiotics are more common in cystic fibrosis (CF) than in the general population. This in part is due to the improving survival in adults with CF and the increased use of high dose intravenous antibiotics. While some are immediate anaphylaxis type (IgE mediated) reactions, the majority are late onset and may have non-specific features such as rash and fever. Piperacillin has consistently been found to have the highest rate of reported reactions (30-50%). There is a low risk of cross reactions between penicillins and other non-beta-lactam classes of antibiotics in penicillin skin prick positive patients. Carbapenems should only be used with extreme caution in patients with positive skin prick tests to penicillin. However, aztreonam can be used safely in patients who are penicillin allergic with positive skin prick reactions. The aminoglycosides are a relatively uncommon cause of allergic reactions, but patients who react to one member of the family may cross react with other aminoglycosides. Desensitisation relies on the incremental introduction of small quantities of the allergen and has been used for penicillins, ceftazidime, tobramycin and ciprofloxacin and must be repeated before each course. Personalized cards should be regularly updated for patients who develop allergic reactions. Written instructions on the emergency treatment of allergic reactions should be provided to patients self-administering intravenous antibiotics at home. Further research is required to identify risk factors and predictors for antibiotic allergy. PMID:15923254

  20. Cell therapy for cystic fibrosis.

    PubMed

    Murphy, Sean V; Atala, Anthony

    2015-03-01

    Currently there is no cure for cystic fibrosis (CF). Treatments are focused on addressing the disease symptoms, with varying degrees of success. Regenerative medicine holds the promise of regenerating dysfunctional or damaged tissues and to enhance the body's own endogenous repair mechanisms. The discovery of endogenous and exogenous stem cells has provided valuable tools for development of novel treatments for CF. The ability of stem cells to differentiate into functional pulmonary cells, modulate inflammatory responses and contribute to pulmonary function has provided researchers with multiple approaches to develop effective treatment strategies. Several approaches show promise to produce viable therapeutic treatments to treat the underlying cause of CF, reduce the symptoms and mitigate long-term damage, and generate functional replacement organs for end-stage transplantation. This review provides an overview of the rapidly progressing field of cell therapy for CF, focusing on the various cell types utilized and current strategies that show promise to improve life expectancy and quality of life for CF patients. PMID:23894126

  1. 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

  2. Cystic fibrosis transmembrane regulator correctors and potentiators.

    PubMed

    Rowe, Steven M; Verkman, Alan S

    2013-07-01

    Cystic fibrosis (CF) is caused by loss-of-function mutations in the CF transmembrane conductance regulator (CFTR) protein, a cAMP-regulated anion channel expressed primarily at the apical plasma membrane of secretory epithelia. Nearly 2000 mutations in the CFTR gene have been identified that cause disease by impairing its translation, cellular processing, and/or chloride channel gating. The fundamental premise of CFTR corrector and potentiator therapy for CF is that addressing the underlying defects in the cellular processing and chloride channel function of CF-causing mutant CFTR alleles will result in clinical benefit by addressing the basic defect underlying CF. Correctors are principally targeted at F508del cellular misprocessing, whereas potentiators are intended to restore cAMP-dependent chloride channel activity to mutant CFTRs at the cell surface. This article reviews the discovery of CFTR potentiators and correctors, what is known regarding their mechanistic basis, and encouraging results achieved in clinical testing. PMID:23818513

  3. Cystic Fibrosis Transmembrane Regulator Correctors and Potentiators

    PubMed Central

    Rowe, Steven M.; Verkman, Alan S.

    2013-01-01

    Cystic fibrosis (CF) is caused by loss-of-function mutations in the CF transmembrane conductance regulator (CFTR) protein, a cAMP-regulated anion channel expressed primarily at the apical plasma membrane of secretory epithelia. Nearly 2000 mutations in the CFTR gene have been identified that cause disease by impairing its translation, cellular processing, and/or chloride channel gating. The fundamental premise of CFTR corrector and potentiator therapy for CF is that addressing the underlying defects in the cellular processing and chloride channel function of CF-causing mutant CFTR alleles will result in clinical benefit by addressing the basic defect underlying CF. Correctors are principally targeted at F508del cellular misprocessing, whereas potentiators are intended to restore cAMP-dependent chloride channel activity to mutant CFTRs at the cell surface. This article reviews the discovery of CFTR potentiators and correctors, what is known regarding their mechanistic basis, and encouraging results achieved in clinical testing. PMID:23818513

  4. Sexual and reproductive health in cystic fibrosis: a life-course perspective.

    PubMed

    Frayman, Katherine B; Sawyer, Susan M

    2015-01-01

    Adolescents and adults with cystic fibrosis now approach developmental milestones, including sexual and reproductive ones, at a similar time to their healthy peers. Yet, their sexual and reproductive health (SRH) is profoundly affected by their disease, and their SRH decisions can substantially affect their health. Navigation of SRH milestones in the context of cystic fibrosis needs education, guidance, and access to SRH services. In this Review, we discuss scientific knowledge of SRH in patients with cystic fibrosis across the life course and clinical practices for SRH within cystic fibrosis care. We identify crucial gaps in SRH education of patients and their access to resources and then present a model of care for provision of developmentally appropriate SRH education and care within cystic fibrosis services across the life course. This model emphasises the central importance of the cystic fibrosis team and service links to primary and specialist SRH care. PMID:25529340

  5. 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)

  6. Breakthrough therapies: Cystic fibrosis (CF) potentiators and correctors.

    PubMed

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

    2015-10-01

    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 are also emphasized. PMID:26097168

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

    PubMed Central

    2016-01-01

    In cystic fibrosis clinics across Canada, the most common barrier that healthcare workers face when providing care to their patients is having too little time. The Health Human Resources Guidelines were developed to define specifically what amounts of time should be allocated for each discipline of cystic fibrosis clinical care and to provide a description of all the roles involved, reinforcing how these work together to provide comprehensive multidisciplinary care. With involvement from all cystic fibrosis clinics in Canada, through the use of a tailored survey, the Health Human Resources Guidelines are an exclusively Canadian document that has been developed for implementation across the country. The guidelines have been incorporated into a national Accreditation Site Visit program for use in evaluating and improving care across the country and have been distributed to all Canadian cystic fibrosis clinics. The guidelines provide hospital administrators with clear benchmarks for allocating personnel resources to the cystic fibrosis clinics hosted within their institutions. PMID:27445556

  8. Determination of the Minimal Clinically Important Difference Scores for the Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Scale in Two Populations of Patients With Cystic Fibrosis and Chronic Pseudomonas aeruginosa Airway Infection

    PubMed Central

    Quittner, Alexandra L.; Modi, Avani C.; Wainwright, Claire; Otto, Kelly; Kirihara, Jean; Montgomery, A. Bruce

    2009-01-01

    Background: The Cystic Fibrosis Questionnaire-Revised (CFQ-R) is a validated patient-reported outcome (PRO) containing both generic scales and scales specific to cystic fibrosis (CF). The minimal clinically important difference (MCID) score for a PRO corresponds to the smallest clinically relevant change a patient can detect. MCID scores for the CFQ-R respiratory symptom (CFQ-R-Respiratory) scale were determined using data from two 28 day, open-label, tobramycin inhalation solution (TIS) studies in patients with CF and chronic Pseudomonas aeruginosa airway infection. At study enrollment, patients in the study 1-exacerbation had symptoms indicative of pulmonary exacerbation (n = 84; < 14 years of age, 31 patients; ≥ 14 years of age, 53 patients); patients in study 2-stable had stable respiratory symptoms (n = 140; < 14 years of age, 14 patients; ≥ 14 years, 126 patients). Methods: The anchor-based method utilized a global rating-of-change questionnaire (GRCQ) that assessed patients' perceptions of change in their respiratory symptoms after TIS treatment. The mean change from baseline CFQ-R-Respiratory scores were mapped onto the GRCQ to estimate the MCID. The two distribution-based methods were as follows: (1) 0.5 SD of mean change in CFQ-R-Respiratory scores (baseline to end of TIS treatment); and (2) 1 SEM for baseline CFQ-R-Respiratory scores. Triangulation of these three estimates defined the MCIDs. Results: MCID scores were larger for patients in study 1-exacerbation (8.5 points) than for those in study 2-stable (4.0 points), likely reflecting differences in patient disease status (exacerbation/stable) between these studies. Conclusions: Patient benefit from new and current CF therapies can be evaluated using changes in CFQ-R-Respiratory scores. Using the MCID provides a systematic way to interpret these changes, and facilitates the identification of CF treatments that improve both symptoms and physiologic variables, potentially leading to better treatment

  9. Cystic Fibrosis Transmembrane Conductance Regulator

    PubMed Central

    Smith, Stephen S.; Steinle, Erich D.; Meyerhoff, Mark E.; Dawson, David C.

    1999-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) Cl channel exhibits lyotropic anion selectivity. Anions that are more readily dehydrated than Cl exhibit permeability ratios (PS/PCl) greater than unity and also bind more tightly in the channel. We compared the selectivity of CFTR to that of a synthetic anion-selective membrane [poly(vinyl chloride)–tridodecylmethylammonium chloride; PVC-TDMAC] for which the nature of the physical process that governs the anion-selective response is more readily apparent. The permeability and binding selectivity patterns of CFTR differed only by a multiplicative constant from that of the PVC-TDMAC membrane; and a continuum electrostatic model suggested that both patterns could be understood in terms of the differences in the relative stabilization of anions by water and the polarizable interior of the channel or synthetic membrane. The calculated energies of anion–channel interaction, derived from measurements of either permeability or binding, varied as a linear function of inverse ionic radius (1/r), as expected from a Born-type model of ion charging in a medium characterized by an effective dielectric constant of 19. The model predicts that large anions, like SCN, although they experience weaker interactions (relative to Cl) with water and also with the channel, are more permeant than Cl because anion–water energy is a steeper function of 1/r than is the anion–channel energy. These large anions also bind more tightly for the same reason: the reduced energy of hydration allows the net transfer energy (the well depth) to be more negative. This simple selectivity mechanism that governs permeability and binding acts to optimize the function of CFTR as a Cl filter. Anions that are smaller (more difficult to dehydrate) than Cl are energetically retarded from entering the channel, while the larger (more readily dehydrated) anions are retarded in their passage by “sticking” within the channel. PMID:10578016

  10. Drug disposition in cystic fibrosis.

    PubMed

    Rey, E; Tréluyer, J M; Pons, G

    1998-10-01

    There are many pathological changes in patients with cystic fibrosis (CF) which can lead to alterations in drug disposition. Although, in patients with CF, the extent of drug absorption varies widely and the rate of absorption is slower, bioavailability is not altered. Plasma protein binding for the majority of drugs studied did not differ in patients with CF compared with control groups. The difference in volume of distribution of most drugs between patients with CF and healthy individuals vanished when corrected for lean body mass. Despite hepatic dysfunction, patients with CF have enhanced clearance of many, but not all, drugs. Phase I mixed-function oxidases are selectively affected: cytochrome P450 (CYP) 1A2 and CYP2C8 have enhanced activity, while other CYP isoforms such as CYP2C9 and CYP3A4 are unaffected. Increased phase II activities are also demonstrated: glucuronyl transferase, acetyl transferase (NAT1) and sulfotransferase. The increased hepatic clearance of drugs in the presence of CF may be the consequence of disease-specific changes in both enzyme activity and/or drug transport within the liver. The renal clearance (CLR) of many drugs in patients with CF is enhanced although there has been no pathological abnormality identified which could explain this finding: glomerular filtration rate and tubular secretion appear normal in patients with CF. The precise mechanisms for enhanced drug clearance in patients with CF remain to be elucidated. The optimisation of antibiotic therapy in patients with CF includes increasing the dose of beta-lactams by 20 to 30% and monitoring plasma concentrations of aminoglycosides. The appropriate dosage of quinolones has not been definitively established. PMID:9812180

  11. Do brine shrimp diagnose cystic fibrosis?

    PubMed

    Hodes, M E; Thomas, J; Morgan, S; Merritt, A D

    1975-11-01

    The nauplii of the brine shrimp Artemia salina are dependent upon the function of their salt gland to maintain osmotic pressure within narrow limits. A number of drugs interfere with this function and are lethal to the nauplii. Saliva and serum from normal persons, patients with cystic fibrosis, and obligate heterozygotes were tested for lethal effect against brine shrimp nauplii. At salt concentrations between 100 mM and 2.5 no difference was found among the phenotypes. At lower concentrations a difference was noted occasionally between some normal subjects and some individuals carrying one or two genes for cystic fibrosis. Data from an independent series of experiments indicate that the naupliar deaths result from distorted ratios of Na+/K+ and not from a specific gene product. No difference was noted in the O2 uptake of nauplii treated with saliva or serum obtained from normal subjects, patients with cystic fibrosis, or obligate heterozygotes. PMID:1187245

  12. 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;…

  13. Developmental and psychosocial issues in cystic fibrosis.

    PubMed

    Ernst, Michelle M; Johnson, Mark C; Stark, Lori J

    2011-08-01

    Cystic fibrosis (CF) is a multisystemic life-limiting genetic disorder, primarily affecting respiratory functioning. Most patients with CF are diagnosed by 2 years of age, and the current median predicted survival rate is 37.4 years old, with 95% of patients dying from complications related to pulmonary infection. Given the chronic, progressive, and disabling nature of CF, multiple treatments are prescribed, most on a daily basis. Thus, this illness requires children, with the aid of their families, to adopt multiple health-related behaviors in addition to managing more typical developmental demands. The morbidity and mortality factors pose cognitive, emotional, and behavioral challenges for many children with CF and their families. This article applies a developmental perspective to describing the psychosocial factors affecting psychological adjustment and health-related behaviors relevant to infants, preschool and school-age children, and adolescents with CF. Topics particularly pertinent to developmental periods and medical milestones are noted, with clinical implications highlighted. PMID:21855711

  14. Treatment of pulmonary exacerbations in cystic fibrosis - could do better?

    PubMed

    Smyth, Alan

    2016-08-01

    This article describes the nature and significance of pulmonary exacerbations in cystic fibrosis (CF). The effectiveness and safety of current exacerbation treatment are explored. The article concludes with a summary of clinical trials (completed and ongoing) which aim to improve the efficacy and safety of exacerbation treatment. PMID:27349725

  15. 75 FR 45646 - Design of Clinical Trials of Aerosolized Antimicrobials for the Treatment of Cystic Fibrosis...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ... clinical trial endpoints to establish efficacy is a major challenge in the design of informative clinical.... The workshop will include discussion of clinical trial endpoints to establish efficacy, such as timing... HUMAN SERVICES Food and Drug Administration Design of Clinical Trials of Aerosolized Antimicrobials...

  16. Cystic fibrosis, intravenous antibiotics, and home therapy.

    PubMed

    Hammond, L J; Caldwell, S; Campbell, P W

    1991-01-01

    The survival rate of patients with cystic fibrosis has improved considerably in the last 20 years. Although not all of the factors accounting for this change are understood, aggressive nutritional management and treatment of pulmonary exacerbations certainly play a role. Home intravenous (IV) antibiotic delivery for pulmonary exacerbation has proved to be as effective as hospital treatment and offers significant advantages to the patient and family. This article examines the microbiology of pulmonary infections in patients with cystic fibrosis, as well as antimicrobial therapy, methods of IV administration, home IV therapy, and the nurse practitioner's role in this home program in the future. PMID:1990112

  17. Management issues for adolescents with cystic fibrosis.

    PubMed

    Withers, Adelaide Lindsay

    2012-01-01

    The healthy adolescent will encounter major changes in biological and psychosocial domains. The adolescent period can be greatly affected by a chronic illness. Cystic fibrosis is a terminal illness that can significantly affect an adolescent's biological, mental and psychosocial health. This paper discusses general issues to consider when managing an adolescent with a chronic medical condition, and specifically how cystic fibrosis may impact upon puberty, body image, risk-taking behaviours, mental health, independence, nonadherence, reproductive health, transition, lung transplantation, and end of life care. PMID:22991662

  18. Precision Genomic Medicine in Cystic Fibrosis.

    PubMed

    Chang, Eugene H; Zabner, Joseph

    2015-10-01

    The successful application of precision genomic medicine requires an understanding of how a person's genome can influence his or her disease phenotype and how medical therapies can provide personalized therapy to one's genotype. In this review, we highlight advances in precision genomic medicine in cystic fibrosis (CF), a classic autosomal recessive genetic disorder. We discuss genotype-phenotype correlations in CF, genetic and environmental modifiers of disease, and pharmacogenetic therapies that target specific genetic mutations thereby addressing the primary defect of cystic fibrosis. PMID:26073768

  19. Novel molecular approaches to cystic fibrosis gene therapy

    PubMed Central

    Lee, Tim W. R.; Matthews, David A.; Blair, G. Eric

    2005-01-01

    Gene therapy holds promise for the treatment of a range of inherited diseases, such as cystic fibrosis. However, efficient delivery and expression of the therapeutic transgene at levels sufficient to result in phenotypic correction of cystic fibrosis pulmonary disease has proved elusive. There are many reasons for this lack of progress, both macroscopically in terms of airway defence mechanisms and at the molecular level with regard to effective cDNA delivery. This review of approaches to cystic fibrosis gene therapy covers these areas in detail and highlights recent progress in the field. For gene therapy to be effective in patients with cystic fibrosis, the cDNA encoding the cystic fibrosis transmembrane conductance regulator protein must be delivered effectively to the nucleus of the epithelial cells lining the bronchial tree within the lungs. Expression of the transgene must be maintained at adequate levels for the lifetime of the patient, either by repeat dosage of the vector or by targeting airway stem cells. Clinical trials of gene therapy for cystic fibrosis have demonstrated proof of principle, but gene expression has been limited to 30 days at best. Results suggest that viral vectors such as adenovirus and adeno-associated virus are unsuited to repeat dosing, as the immune response reduces the effectiveness of each subsequent dose. Nonviral approaches, such as cationic liposomes, appear more suited to repeat dosing, but have been less effective. Current work regarding non-viral gene delivery is now focused on understanding the mechanisms involved in cell entry, endosomal escape and nuclear import of the transgene. There is now increasing evidence to suggest that additional ligands that facilitate endosomal escape or contain a nuclear localization signal may enhance liposome-mediated gene delivery. Much progress in this area has been informed by advances in our understanding of the mechanisms by which viruses deliver their genomes to the nuclei of host

  20. Guidelines for Diagnosis of Cystic Fibrosis in Newborns through Older Adults: Cystic Fibrosis Foundation Consensus Report

    PubMed Central

    Farrell, Philip M.; Rosenstein, Beryl J.; White, Terry B.; Accurso, Frank J.; Castellani, Carlo; Cutting, Garry R.; Durie, Peter R.; Legrys, Vicky A.; Massie, John; Parad, Richard B.; Rock, Michael J.; Campbell, Preston W.

    2009-01-01

    Newborn screening (NBS) for cystic fibrosis (CF) is increasingly being implemented and is soon likely to be in use throughout the United States, because early detection permits access to specialized medical care and improves outcomes. The diagnosis of CF is not always straightforward, however. The sweat chloride test remains the gold standard for CF diagnosis but does not always give a clear answer. Genotype analysis also does not always provide clarity; more than 1500 mutations have been identified in the CF transmembrane conductance regulator (CFTR) gene, not all of which result in CF. Harmful mutations in the gene can present as a spectrum of pathology ranging from sinusitis in adulthood to severe lung, pancreatic, or liver disease in infancy. Thus, CF identified postnatally must remain a clinical diagnosis. To provide guidance for the diagnosis of both infants with positive NBS results and older patients presenting with an indistinct clinical picture, the Cystic Fibrosis Foundation convened a meeting of experts in the field of CF diagnosis. Their recommendations, presented herein, involve a combination of clinical presentation, laboratory testing, and genetics to confirm a diagnosis of CF. PMID:18639722

  1. 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

  2. Zinc supplementation in children with cystic fibrosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  3. Nutritional assessment in children with cystic fibrosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  4. [Macrolides, Pseudomonas aeruginosa and cystic fibrosis].

    PubMed

    Guillot, M; Amiour, M; El Hachem, C; Harchaoui, S; Ribault, V; Paris, C

    2006-10-01

    Long-term low dose azithromycin treatment in cystic fibrosis patients with chronic Pseudomonas aeruginosa infection is safe and reduces the decline in lung function, the number of acute exacerbations and improves nutritional status; underlying efficacy mechanisms are multiple and synergistic. PMID:17370396

  5. 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

  6. Patient-reported Outcomes in Cystic Fibrosis

    PubMed Central

    Goss, Christopher H.; Quittner, Alexandra L.

    2007-01-01

    Over the past 20 years, there has been tremendous progress in the area of patient-reported outcomes (PROs). A PRO instrument is defined as any measure of a patient's health status that is elicited directly from the patient and assesses how the patient “feels or functions with respect to his or her health condition.” The advances seen in clinical research regarding PROs has been mirrored in research in cystic fibrosis (CF). A large number of instruments have been used for both therapeutic and nontherapeutic clinical research for many chronic conditions. This review will summarize a history of the development of PROs and how PROs are viewed by the U.S. Food and Drug Administration. We will then review the current state of the art of patient-reported outcomes in CF, specifically addressing the evaluation of different PRO instruments in terms of their reliability and validity. Finally, we will delineate further areas for development of PROs in CF. We believe that the future of CF research will incorporate a more diverse selection of PRO outcome measures; these outcome measures ultimately may be incorporated into clinical care to standardize symptom assessment and provide information regarding the need for specific clinical interventions to improve the quality of care delivered to these patients. PMID:17652505

  7. New and Emerging Treatments for Cystic Fibrosis.

    PubMed

    Barry, Peter J; Jones, Andrew M

    2015-07-01

    Recently, a significant number of additional key medications have become licensed in Europe for the treatment of patients with cystic fibrosis (CF), including a number of inhaled antibiotics, such as nebulised aztreonam and dry powder versions of colistin and tobramycin for inhalation; dry powder inhaled mannitol, an agent to improve airway hydration and aid airway clearance; and ivacaftor, an oral therapy that directly acts on dysfunctional CFTR to correct the basic defect encountered in CF patients with the G551D CF gene mutation. The marked success of ivacaftor both in clinical trials and in post-licensing evaluation studies in treating patients with G551D and other gating mutations has greatly encouraged the ongoing development of similar therapies that can directly target the underlying cause of CF. Other therapies, including a number of anti-infectives, anti-inflammatories and replacement pancreatic enzymes, are currently undergoing clinical studies. This article reviews those treatments that have been recently licensed for CF and highlights some of the exciting emerging therapies presently under evaluation in clinical trials. In addition, it discusses some of the potential challenges being encountered by research and clinical teams in developing and delivering treatments for this condition. PMID:26091951

  8. 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

  9. New and emerging targeted therapies for cystic fibrosis.

    PubMed

    Quon, Bradley S; 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

  10. 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. PMID:23457166

  11. Chemistry and biology of the potent endotoxin from a Burkholderia dolosa clinical isolate from a cystic fibrosis patient.

    PubMed

    Lorenzo, Flaviana Di; Sturiale, Luisa; Palmigiano, Angelo; Lembo-Fazio, Luigi; Paciello, Ida; Coutinho, Carla P; Sá-Correia, Isabel; Bernardini, MariaLina; Lanzetta, Rosa; Garozzo, Domenico; Silipo, Alba; Molinaro, Antonio

    2013-06-17

    This is the first report of the chemical and biological properties of the lipooligosaccharide (LOS) endotoxin isolated from Burkholderia dolosa IST4208, an isolate recovered from a cystic fibrosis (CF) patient in a Portuguese CF center. B. dolosa is a member of the Burkholderia cepacia complex, a group of closely related species that are highly problematic and opportunistic pathogens in CF. B. dolosa infection leads to accelerated loss of lung function and decreased survival. The structural determination of its endotoxin was achieved using a combination of chemistry and spectroscopy, and has revealed a novel endotoxin structure. The purified LOS was tested for its immunostimulatory activity on human HEK 293 cells expressing TLR-4, MD-2, and CD-14. In these assays, the LOS showed strong proinflammatory activity. PMID:23733445

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

    PubMed

    Rybacka, Anna; Karmelita-Katulska, Katarzyna

    2016-01-01

    Cystic fibrosis is the most common lethal autosomal recessive disorder in the Caucasian population. Although the survival rate in patients constantly improves, lung damage is still the major cause of morbidity and mortality in patients with cystic fibrosis. In clinical practice, evaluation of patients' pulmonary state is made by combination of monitoring of lung function and more directly by assessing the lung structure in imaging studies. Studies showed that computed tomography findings are more sensitive as compared to the pulmonary function tests. Computed tomography can identify a wide range of morphological abnormalities in patients with cystic fibrosis, such as bronchiectasis (which is progressive, irreversible and probably the most relevant structural change in cystic fibrosis) peribronchial thickening, mucous plugging and many other disorders that occur in the course of the disease. Computed tomography has a crucial role in the assessment of pulmonary damage over time, detecting complications and monitoring treatment effects in patients with cystic fibrosis. PMID:27103945

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

    PubMed Central

    Rybacka, Anna; Karmelita-Katulska, Katarzyna

    2016-01-01

    Summary Cystic fibrosis is the most common lethal autosomal recessive disorder in the Caucasian population. Although the survival rate in patients constantly improves, lung damage is still the major cause of morbidity and mortality in patients with cystic fibrosis. In clinical practice, evaluation of patients’ pulmonary state is made by combination of monitoring of lung function and more directly by assessing the lung structure in imaging studies. Studies showed that computed tomography findings are more sensitive as compared to the pulmonary function tests. Computed tomography can identify a wide range of morphological abnormalities in patients with cystic fibrosis, such as bronchiectasis (which is progressive, irreversible and probably the most relevant structural change in cystic fibrosis) peribronchial thickening, mucous plugging and many other disorders that occur in the course of the disease. Computed tomography has a crucial role in the assessment of pulmonary damage over time, detecting complications and monitoring treatment effects in patients with cystic fibrosis. PMID:27103945

  14. Inflammation and its genesis in cystic fibrosis.

    PubMed

    Nichols, David P; Chmiel, James F

    2015-10-01

    The host inflammatory response in cystic fibrosis (CF) lung disease has long been recognized as a central pathological feature and an important therapeutic target. Indeed, many believe that bronchiectasis results largely from the oxidative and proteolytic damage comprised within an exuberant airway inflammatory response that is dominated by neutrophils. In this review, we address the longstanding argument of whether or not the inflammatory response is directly attributable to impairment of the cystic fibrosis transmembrane conductance regulator or only secondary to airway obstruction and chronic bacterial infection and challenge the importance of this distinction in the context of therapy. We also review the centrality of neutrophils in CF lung pathophysiology and highlight more recent data that suggest the importance of other cell types and signaling beyond NF-κB activation. We discuss how protease and redox imbalance are critical factors in CF airway inflammation and end by reviewing some of the more promising therapeutic approaches now under development. PMID:26335954

  15. Acquired Cystic Fibrosis Transmembrane Conductance Regulator Deficiency.

    PubMed

    Cho, Do-Yeon; Woodworth, Bradford A

    2016-01-01

    In the genetic airway disease cystic fibrosis (CF), deficiency or dysfunction of the cystic fibrosis membrane conductance regulator (CFTR) alters anion transport in respiratory epithelium and consequently disrupts mucociliary clearance. An enriched understanding of the role of CFTR in the maintenance of normal epithelial function has revealed that mild and variable CFTR mutations play a causative role in a number of diseases not classically associated with CF. Furthermore, recent evidence indicates that acquired defects in wild-type CFTR protein processing, endocytic recycling and function can contribute to the pathogenesis of airway diseases, such as chronic obstructive pulmonary disease. In this chapter, we discuss emerging findings implicating acquired CFTR dysfunction in the pathogenesis of chronic rhinosinusitis and propose a new and leading edge approach to future CRS therapy using CFTR potentiators. PMID:27466849

  16. MicroRNA Dysregulation in Cystic Fibrosis

    PubMed Central

    McKiernan, Paul J.; Greene, Catherine M.

    2015-01-01

    The cystic fibrosis lung is a complex milieu comprising multiple factors that coordinate its physiology. MicroRNAs are regulatory factors involved in most biological processes and it is becoming increasingly clear that they play a key role in the development and manifestations of CF lung disease. These small noncoding RNAs act posttranscriptionally to inhibit protein production. Their involvement in the pathogenesis of CF lung disease stems from the fact that their expression is altered in vivo in the CF lung due to intrinsic and extrinsic factors; to date defective chloride ion conductance, endoplasmic reticulum stress, inflammation, and infection have been implicated in altering endogenous miRNA expression in this setting. Here, the current state-of-the-art and biological consequences of altered microRNA expression in cystic fibrosis are reviewed. PMID:26185362

  17. Pregnancy and cystic fibrosis: Approach to contemporary management.

    PubMed

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

    2014-12-01

    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

  18. 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

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

    PubMed Central

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

    2013-01-01

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

  20. 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

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

    PubMed

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

    2015-05-01

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

  2. Progress in therapies for cystic fibrosis.

    PubMed

    De Boeck, Kris; Amaral, Margarida D

    2016-08-01

    Standard follow-up and symptomatic treatment have allowed most patients with cystic fibrosis to live to young adulthood. However, many patients still die prematurely from respiratory insufficiency. Hence, further investigations to improve these therapies are important and might have relevance for other diseases-eg, exploring how to increase airway hydration, how to safely downscale the increased inflammatory response in the lung, and how to better combat lung infections associated with cystic fibrosis. In parallel, development of modulators that target the underlying dysfunction in the cystic fibrosis transmembrane conductance regulator (CFTR) is fast moving forward. Existing treatments are specific to certain mutations, or mutation class, in CFTR. An effective, although not yet entirely corrective, treatment is available for patients with class III mutations, and a treatment with modest effectiveness is available for patients who are homozygous for Phe508del, albeit at a very high cost. Corrective treatments that are non-specific to mutation class and thus applicable to all patients-eg, gene therapy, cell-based therapies, and activation of alternative ion channels that bypass CFTR-are being explored, but they are still in early stages of development. In view of the large number of patients with very rare mutations, a plan to advance personalised biomarkers to predict treatment effect is also being investigated and validated. PMID:27053340

  3. [Molecular epidemiology of cystic fibrosis in Tunisia].

    PubMed

    Messaoud, T; Bel Haj Fredj, S; Bibi, A; Elion, J; Férec, C; Fattoum, S

    2005-01-01

    Cystic fibrosis is the most frequent autosomal recessive genetic disease in North European population. This pathology seems to not be rare in Tunisia. On another hand, development of molecular biology techniques has largely contributed to implement the study of the different mutations in the CFTR gene where over 1,300 mutations were reported. Herein, we describe the strategy used to detect molecular defects responsible of cystic fibrosis on 390 children (383 families) in Tunisian population. Several techniques were performed for genotype diagnosis: DNA extraction was from peripheral blood. Polymerase chain reaction (PCR) and polyacylamide gel electrophoresis, and reverse dot blot procedures were used to detect known point mutations. Denaturant gradient gel electrophoresis (DGGE) were used in a next step searching for the unknown point mutations that are later identified by automated sequencing on ABIprism 310. This strategy allowed us to detect 17 different mutations located on the different exons of the CFTR gene. The most frequent was the F508del (50.74%) followed by three other mutations (G542X, W1282X and N1303K) known to be common in the Mediterranean area. For mutations (T665S, 2766 del8, F1166C, L1043R) were exclusively found, up to now, in the Tunisian population. Our results permitted to establish cystic fibrosis mutations and their distribution in Tunisia and to implement an appropriate prevention program of these diseases through the genetic council and prenatal diagnosis. PMID:16330381

  4. Lessons learned from the cystic fibrosis pig.

    PubMed

    Meyerholz, David K

    2016-07-01

    Deficient function in the anion channel cystic fibrosis (CF) transmembrane conductance regulator is the fundamental cause for CF. This is a monogenic condition that causes lesions in several organs including the respiratory tract, pancreas, liver, intestines, and reproductive tract. Lung disease is most notable, given it is the leading cause of morbidity and mortality in people with CF. Shortly after the identification of CF transmembrane conductance regulator, CF mouse models were developed that did not show spontaneous lung disease as seen in humans, and this spurred development of additional CF animal models. Pig models were considered a leading choice for several reasons including their similarity to humans in respiratory anatomy, physiology, and in size for translational imaging. The first CF pig models were reported in 2008 and have been extremely valuable to help clarify persistent questions in the field and advance understanding of disease pathogenesis. Because CF pigs are susceptible to lung disease like humans, they have direct utility in translational research. In addition, CF pig models are useful to compare and contrast with current CF mouse models, human clinical studies, and even newer CF animal models being characterized. This "triangulation" strategy could help identify genetic differences that underlie phenotypic variations, so as to focus and accelerate translational research. PMID:27142487

  5. New antimicrobial strategies in cystic fibrosis.

    PubMed

    van Westreenen, Mireille; Tiddens, Harm A W M

    2010-12-01

    With more antibiotic resistance and emerging pathogens in cystic fibrosis (CF) patients, the need for new strategies in the lifelong treatment of pulmonary infection has increased. Most of the focus is on chronic infection with Pseudomonas aeruginosa, which is still thought to be the main pathogen leading to advanced CF lung disease. Other bacterial species are also recognized in the pathogenesis of CF lung disease, even though their definitive role is not well established yet. Clearly, expansion of treatment options is urgently needed. This article focuses on recent developments in the field of new antimicrobial strategies for CF. It is clear that studies on new classes of antibiotics or antimicrobial-like drugs are scarce, and that most studies involve new (inhalation) formulations, new routes of delivery, or analogs of existing classes of antibiotics. Studies of new antibiotic-like drugs are, in most cases, in preclinical phases of development and only a few of these agents may reach the market. Importantly, new inhaled antibiotics, e.g. aztreonam, levofloxacin, and fosfomycin, and new, more efficient delivery systems such as dry powder inhalation and liposomes for current antibiotics are in the clinical phase of development. These developments will be of great importance in improving effective treatment and reducing the treatment burden for CF patients in the near future. PMID:21028914

  6. Cystic fibrosis: newborn screening in America.

    PubMed

    Kleven, Daniel T; McCudden, Christopher R; Willis, Monte S

    2008-07-01

    Cystic fibrosis is the most common lethal genetic disease in Caucasians, manifesting as progressive lung dysfunction, pancreatic insufficiency, and intestinal disease. CF was traditionally diagnosed clinically, either because of a family history or occurrence of meconium ileus, or as a result of intestinal malabsorption and chronic pulmonary disease. In 1979, it was discovered that immunoreactive trypsinogen was increased in neonatal dried-blood specimens on Guthrie cards, making it possible to screen neonates. During the past decades, survival rates of patients with CF have improved significantly (see Figure 5). To continue this progress, universal newborn screening has been implemented in many states as an addition to the arsenal of therapies and strategies to improve survival. National newborn-screening programs to identify CF patients after birth have been adopted for a number of years in Europe, Australia, and Canada. As expected, many benefits have been seen due to the early identification of CF patients, including improved survival, better lung function and growth with less intensive therapy, and reduced cost of therapy. To date, 37 states in the United States have adopted similar programs, in the hopes of improving CF outcomes. This welcome trend should help improve the lives of CF patients living in America. PMID:18717498

  7. Cystic fibrosis on the African continent.

    PubMed

    Stewart, Cheryl; Pepper, Michael S

    2016-07-01

    Cystic fibrosis (CF; OMIM 219700) is a life-shortening and costly autosomal recessive disease that has been most extensively studied in individuals of Caucasian descent. There is ample evidence, however, that it also affects other ethnicities. In Africa there have been several reports of CF, but there has been no concerted effort toward establishing the molecular epidemiology of this disease on the continent, which is the first step toward outlining a public health strategy to effectively address the needs of these patients. A literature search revealed reports from only 12 of the 54 African states on the molecular analysis of the mutations present in suspected CF patients, resulting in the identification of 79 mutations. Based on previous functional investigations, 39 of these cause CF, 10 are of varying clinical consequence, 4 have no associated evidence regarding whether they cause CF, 4 are synonymous, 5 are novel, and 21 are unique to Africa. We propose that CF be more thoroughly investigated on the continent to ensure that the public health needs of African CF patients-both those in Africa and those of African descent living elsewhere-are met.Genet Med 18 7, 653-662. PMID:26656651

  8. 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.

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

    PubMed

    Kraynack, Nathan C; McBride, John T

    2009-10-01

    Quality improvement (QI) using a clinical microsystems approach provides cystic fibrosis (CF) centers the opportunity to make a significant positive impact on the health of their patients. The availability of center-specific outcomes data and the support of the Cystic Fibrosis Foundation are important advantages for these quality improvement efforts. This article illustrates how the clinical microsystems methodology can improve care delivery and outcomes by describing the gradual application of quality improvement principles over the past 5 years by the CF team at the Lewis Walker Cystic Fibrosis Center at Akron Children's Hospital in Akron, Ohio. Using the example of a project to improve the pulmonary function of the pediatric patients at our center as a framework, we describe the QI process from the initial team-building phase, through the assessment of care processes, standardization of care, and developing a culture of continuous improvement. We outline how enthusiastic commitment from physician leadership, clinical managers and central administration, the availability of coaches, and an appreciation of the importance of measurement, patient involvement, communication, and standardization are critical components for successful process improvement. PMID:19760542

  10. Management of adolescent and adult inpatients with cystic fibrosis.

    PubMed

    Sterner-Allison, J L

    1999-01-15

    A program in which pharmacists help care for cystic fibrosis patients is described. The Egleston Cystic Fibrosis Center at Emory University houses outpatient clinic facilities and a 10-bed inpatient unit and is affiliated with Egleston Children's Hospital. The center provides full-service care for nearly 500 patients. Patients with mild to moderate exacerbations of pulmonary problems can receive their entire course of therapy at the center, and those with severe illness may complete their hospital stay there. A care team consisting of pharmacists, physicians, nurses, and others provides preventive and acute care. Patients can choose a "care partner" who will assist them with their care during any hospitalizations and at home. Both patient and care partner are taught drug administration, nutrition, and physical therapy and meet regularly with the care team. Patients must receive their medication education from a pharmacist before they can administer their own drugs. Pharmacists at the center also evaluate serum drug concentrations, stock the automated dispensing device, monitor for drug interactions, answer drug information questions, and attend multidisciplinary rounds. Pharmacy residents can work with the care team through rotations and clinic experience. Pharmacists at a cystic fibrosis center provide clinical services to patients and promote self-care. PMID:10030531

  11. Optimising inhaled mannitol for cystic fibrosis in an adult population

    PubMed Central

    Flume, Patrick A.; Aitken, Moira L.; Agent, Penny; Charlton, Brett; Forster, Emma; Fox, Howard G.; Hebestreit, Helge; Kolbe, John; Zuckerman, Jonathan B; Button, Brenda M.

    2015-01-01

    Abstract There has been remarkable progress in the treatment of cystic fibrosis (CF) patients over the past 20 years. However, limitations of standard therapies have highlighted the need for a convenient alternative treatment to effectively target the pathophysiologic basis of CF-related disease by improving mucociliary clearance of airway secretions and consequently improve lung function and reduce respiratory exacerbations. Mannitol is an osmotic agent available as a dry powder, dispensed in a convenient disposable inhaler device for the treatment of adult patients with CF. Inhalation of mannitol as a dry powder is thought to change the viscoelastic properties of airway secretions, increase the hydration of the airway surface liquid and contribute to increased mucociliary and cough clearance of retained secretions. In two large phase 3 studies [1, 2], long-term use of inhaled mannitol resulted in a significant and clinically meaningful improvement in lung function relative to control in adult CF subjects and had an acceptable safety profile. Clinical experience with inhaled mannitol confirms that it is safe and effective. A minority of patients are unable to tolerate the medication. However, through training in proper inhaler technique and setting clear expectations regarding therapeutic effects, both the tolerance and adherence necessary for long term efficacy can be positively influenced. Educational aims To discuss the importance of airway clearance treatments in the management of cystic fibrosis. To describe the clinical data that supports the use of mannitol in adult patients with cystic fibrosis. To highlight the role of mannitol tolerance testing in screening for hyperresponsiveness. To provide practical considerations for patient education in use of mannitol inhaler. Key points Inhaled mannitol is a safe and effective option in adult patients with cystic fibrosis. Mannitol tolerance testing effectively screens for hyperresponsiveness prior to initiation

  12. Chronic rhinosinusitis in cystic fibrosis (mucoviscidosis).

    PubMed

    Brihaye, P; Jorissen, M; Clement, P A

    1997-01-01

    The authors present two clinical studies performed in the ENT departments of two Belgian Universities. A total of 248 patients with mucoviscidosis (cystic fibrosis, CF) were assessed by means of nasal endoscopy. One hundred eighteen underwent computed tomography of the paranasal sinuses (CT) and 55 were endoscopically operated. This allowed the observation of different clinical patterns of rhinosinusitis: mucopyosinusitis (pseudomucocele) of the maxillary antrum with bulging of the lateral nasal wall (LNW), nasal polyposis with erosion of the LNW, and chronic purulent rhinosinusitis with an isolated prominent uncinate process. The treatment of those patients could be tailored to the individual clinical pattern. Medical therapy consisted of systemic antibiotics and topical drugs delivered by sprays or by lavages with a nose can. Surgery was mainly aimed at removing the massive polyposis when it interfered with the daily life activities. The use of the endoscope enabled to perform safely more extensive procedures resulting in a lower recurrence rate. In patients with chronic rhinosinusitis without polyposis, yet presenting ostiomeatal obstruction, a limited and more functional endoscopic surgery was indicated in order to restore some drainage and to improve the penetration of topical drugs into the affected sinus. A short addendum presents two studies: one about genetics and the other about prevalence of middle ear disease in CF. The first concluded that no clear correlation was found between DF508 (the most common CF mutation) and nasal polyposis. The second revealed that in contrast with the extremely high prevalence of sinus problems, there was no clear evidence of an increased prevalence of middle ear disease in CF. PMID:9444379

  13. Actin - Lysozyme Interactions in Model Cystic Fibrosis Sputum

    NASA Astrophysics Data System (ADS)

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

    2003-03-01

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

  14. Polyelectrolyte Structure and Interactions in Model Cystic Fibrosis Sputum

    NASA Astrophysics Data System (ADS)

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

    2002-03-01

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

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

    PubMed

    Kim, Roy J

    2016-09-01

    Cystic fibrosis-related diabetes mellitus (CFRD) is the most common endocrine complication of cystic fibrosis (CF), affecting more than 50% of patients by the 4th decade of life. CFRD is often preceded by worsening pulmonary status and nutritional decline. Treatment of CFRD is associated with improvements in body weight and pulmonary function and a reduction in pulmonary exacerbations. Because of the clinical significance of CFRD, diabetes screening with an oral glucose tolerance test (OGTT) is recommended annually for all patients with CF starting at age 10 years. The OGTT detects CFRD with greater sensitivity than random glucose or hemoglobin A1c testing. The first-line treatment for CFRD is insulin. The use of other treatments such as oral medications remains under study. [Pediatr Ann. 2016;45(9):e321-e326.]. PMID:27622916

  16. Emergent properties of proteostasis in managing cystic fibrosis.

    PubMed

    Balch, William E; Roth, Daniela M; Hutt, Darren M

    2011-02-01

    Cystic fibrosis (CF) is a consequence of defective recognition of the multimembrane spanning protein cystic fibrosis conductance transmembrane regulator (CFTR) by the protein homeostasis or proteostasis network (PN) (Hutt and Balch (2010). Like many variant proteins triggering misfolding diseases, mutant CFTR has a complex folding and membrane trafficking itinerary that is managed by the PN to maintain proteome balance and this balance is disrupted in human disease. The biological pathways dictating the folding and function of CFTR in health and disease are being studied by numerous investigators, providing a unique opportunity to begin to understand and therapeutically address the role of the PN in disease onset, and its progression during aging. We discuss the general concept that therapeutic management of the emergent properties of the PN to control the energetics of CFTR folding biology may provide significant clinical benefit. PMID:21421917

  17. Natural Compounds as Therapeutic Agents in the Treatment Cystic Fibrosis

    PubMed Central

    Dey, Isha; Shah, Kalpit; Bradbury, Neil A

    2016-01-01

    The recent FDA approval of two drugs to treat the basic defect in cystic fibrosis has given hope to patients and their families battling this devastating disease. Over many years, with heavy financial investment from Vertex Pharmaceuticals and the Cystic Fibrosis Foundation, pre-clinical evaluation of thousands of synthetic drugs resulted in the production of Kalydeco and Orkambi. Yet, despite the success of this endeavor, many other compounds have been proposed as therapeutic agents in the treatment of CF. Of note, several of these compounds are naturally occurring, and are present in spices from the grocery store and over the counter preparations in health food stores. In this short review, we look at three such compounds, genistein, curcumin, and resveratrol, and evaluate the scientific support for their use as therapeutic agents in the treatment of patients with CF. PMID:27081574

  18. Clinical spectrum in homozygotes and compound heterozygotes inheriting cystic fibrosis mutation 3849+10kbC>T: Significance for geneticists

    SciTech Connect

    Gilbert, F.; Li, Zhen; Arzimanoglou, I.

    1995-09-25

    We describe patients inheriting cystic fibrosis (CF) mutation 3849+10kbC>T as homozygotes or compound heterozygotes. Three unrelated homozygotes for this mutation were all pancreatic-sufficient and sweat test-negative or inconclusive. Among the compound heterozygotes, both pancreatic sufficiency and insufficiency, as well as positive and negative/inconclusive sweat test results are reported, expanding the range of clinical expression associated with inheritance of this mutation. 3849+10kbC>T is one of several CF mutations that can result in atypical or variant forms of CF. For geneticists, the diagnosis of variant CF has implications for recurrence risk and prognosis counseling of the families of affected individuals, and possibly for CF carrier screening in the general population. 19 refs., 1 tab.

  19. Cystic fibrosis database (CFDB): a new web-based tool for cystic fibrosis specialists.

    PubMed

    Buzzetti, Roberto; Cirilli, Natalia; Minicucci, Laura; Raia, Valeria; Salvatore, Donatello; Maffeis, Paolo

    2014-09-01

    In order to help specialists involved in CF care and clinical research to know the current best evidence about clinical effectiveness of interventions in CF, we designed and developed a web-based, free access tool called "CFDB"--Cystic Fibrosis DataBase (www.inetflow.it/CFDB). The database was built by searching in Medline, Embase, Cochrane Library and worldwide trials registries all studies involving clinical interventions in CF. The tool lets the user define queries starting from one or more types of pathological conditions and one or more interventions. The output of the queries is structured in three levels: (1) how many and which studies deal with the conditions formulated in the query; (2) which are the main results of these studies; (3) a critical summary of the literature related to the query. This tool, providing a quick overview of the available evidence in clinical research in CF, may help clinical decision making, designing of new trials and building guidelines. PMID:24532370

  20. 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

  1. Pandoraea pulmonicola chronic colonization in a cystic fibrosis patient, France

    PubMed Central

    Kokcha, S; Bittar, F; Reynaud-Gaubert, M; Mely, L; Gomez, C; Gaubert, J-Y; Thomas, P; Rolain, J-M

    2013-01-01

    Pandoraea are considered emerging multidrug resistant pathogens in the context of cystic fibrosis. We report herein for the first time the case of a 30-year-old woman with cystic fibrosis, living in France, who was chronically infected with Pandoraea pulmonicola and who died of Pseudomonas aeruginosa sepsis 3 weeks after bilateral lung transplantation. PMID:25356323

  2. First isolations of Segniliparus rugosus from patients with cystic fibrosis.

    PubMed

    Butler, W Ray; Sheils, Catherine A; Brown-Elliott, Barbara A; Charles, Nadege; Colin, Andrew A; Gant, Mary J; Goodill, John; Hindman, Diane; Toney, Sean R; Wallace, Richard J; Yakrus, Mitchell A

    2007-10-01

    We report three cases of the new genus Segniliparus isolated from patients with cystic fibrosis. All isolates were unambiguously identified by 16S rRNA gene sequencing as Segniliparus rugosus (GenBank accession no. AY 60892). Drug susceptibility results that may enhance treatment for cystic fibrosis patients with this opportunistic pathogen are presented. PMID:17670929

  3. The Dynamics of Disease Progression in Cystic Fibrosis

    PubMed Central

    Adler, Frederick R.; Liou, Theodore G.

    2016-01-01

    In cystic fibrosis, statistical models have been more successful in predicting mortality than the time course of clinical status. We develop a system of partial differential equations that simultaneously track mortality and patient status, with all model parameters estimated from the extensive and carefully maintained database from the Cystic Fibrosis Foundation. Cystic fibrosis is an autosomal recessive disease that leads to loss of lung function, most commonly assessed using the Forced Expiratory Volume in 1 second (FEV1%). This loss results from inflammation secondary to chronic bacterial infections, particularly Pseudomonas aeruginosa, methicillin-sensitive Staphylococcus aureus (MSSA) and members of the virulent Burkholderia complex. The model tracks FEV1% and carriage of these three bacteria over the course of a patient’s life. Analysis of patient state changes from year to year reveals four feedback loops: a damaging positive feedback loop between P. aeruginosa carriage and lower FEV1%, negative feedback loops between P. aeruginosa and MSSA and between P. aeruginosa and Burkholderia, and a protective positive feedback loop between MSSA carriage and higher FEV1%. The partial differential equations built from this data analysis accurately capture the life-long progression of the disease, quantify the key role of high annual FEV1% variability in reducing survivorship, the relative unimportance of short-term bacterial interactions for long-term survival, and the potential benefits of eradicating the most harmful bacteria. PMID:27248696

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

    PubMed

    Mou, Hongmei; Brazauskas, Karissa; Rajagopal, Jayaraj

    2015-10-01

    With over 1,500 identifiable mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that result in distinct functional and phenotypical abnormalities, it is virtually impossible to perform randomized clinical trials to identify the best therapeutics for all patients. Therefore, a personalized medicine approach is essential. The only way to realistically accomplish this is through the development of improved in vitro human model systems. The lack of a readily available and infinite supply of human CFTR-expressing airway epithelial cells is a key bottleneck. We propose that a concerted two-pronged approach is necessary for patient-specific cystic fibrosis research to continue to prosper and realize its potential: (1) more effective culture and differentiation conditions for growing primary human airway and nasal epithelial cells and (2) the development of collective protocols for efficiently differentiating disease- and patient-specific induced pluripotent stem cells (iPSC) into pure populations of adult epithelial cells. Ultimately, we need a personalized human model system for cystic fibrosis with the capacity for uncomplicated bankability, widespread availability, and universal applicability for patient-specific disease modeling, novel pharmacotherapy investigation and screening, and readily executable genetic modification. PMID:26335952

  5. 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

  6. 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. PMID:27469179

  7. Cystic Fibrosis Diagnosis and Newborn Screening.

    PubMed

    Rosenfeld, Margaret; Sontag, Marci K; Ren, Clement L

    2016-08-01

    The diagnosis of cystic fibrosis (CF) has evolved over the past decade as newborn screening has become universal in the United States and elsewhere. The heterogeneity of phenotypes associated with CF transmembrane conductance regulator (CFTR) dysfunction and mutations in the CFTR gene has become clearer, ranging from classic pancreatic-insufficient CF to manifestations in only 1 organ system to indeterminate diagnoses identified by newborn screening. The tools available for diagnosis have also expanded. This article reviews the newest diagnostic criteria for CF, newborn screening, prenatal screening and diagnosis, and indeterminate diagnoses in newborn-screened infants and symptomatic adults. PMID:27469178

  8. Nutrition and Growth in Cystic Fibrosis.

    PubMed

    Lusman, Sarah; Sullivan, Jillian

    2016-08-01

    Close attention to nutrition and growth is essential in caring for children with cystic fibrosis (CF). Growth and nutritional status should be monitored as part of routine CF care. Children with CF should achieve growth and nutritional status comparable with that of well-nourished children without CF. Children with CF are at risk for nutritional deficiencies. Optimal nutritional and growth status may be difficult to attain in this population given risk of insufficient caloric intake and likelihood of increased caloric expenditure. Various methods to attain optimal nutritional status may be used, including oral supplementation, behavioral treatment, pharmacotherapy, and enteral nutrition. PMID:27469181

  9. 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

  10. Targeting the Root Cause of Cystic Fibrosis.

    PubMed

    Trescott, Laura; Holcomb, Joshua; Spellmon, Nicholas; Mcleod, Cathy; Aljehane, Leala; Sun, Fei; Li, Chunying; Yang, Zhe

    2015-01-01

    Cystic Fibrosis (CF) is a serious genetic condition caused by CF transmembrane conductance regulator (CFTR) mutation. CF patients have shortened lifespan due to airway obstruction, infection, and end-stage lung failure. However, recent development in CF therapy suggests a brighter future for CF patients. Targeting specific CFTR mutations aims to potentiate the channel gating activity of impaired CFTR and restore protein trafficking to the plasma membrane. Gene therapy introduces correct CFTR gene into the affected airway epithelium leading to the functional expression of CFTR in CF patients. This review will sum up the current status in CF-cause targeting therapy. PMID:25316272

  11. The Changing Microbial Epidemiology in Cystic Fibrosis

    PubMed Central

    LiPuma, John J.

    2010-01-01

    Summary: Infection of the airways remains the primary cause of morbidity and mortality in persons with cystic fibrosis (CF). This review describes salient features of the epidemiologies of microbial species that are involved in respiratory tract infection in CF. The apparently expanding spectrum of species causing infection in CF and recent changes in the incidences and prevalences of infection due to specific bacterial, fungal, and viral species are described. The challenges inherent in tracking and interpreting rates of infection in this patient population are discussed. PMID:20375354

  12. Moving cystic fibrosis care from rescue to prevention by embedding adherence measurement in routine care.

    PubMed

    Wildman, Martin J; Hoo, Zhe Hui

    2014-06-01

    Cystic fibrosis [CF] is a chronic disease in which preventative treatment with nebulised antibiotics can reduce pulmonary exacerbations that otherwise require rescue therapy. However, adherence is low. Making adherence to maintenance treatment visible is a crucial step towards improving adherence. In this article, we discuss how adherence data can be used to support Quality Improvement in CF through behaviour change in both people with cystic fibrosis and their clinical teams. PMID:24835307

  13. Cystic fibrosis: need for mass deployable screening methods.

    PubMed

    Sengar, Aditya Singh; Agarwal, Anirudh; Singh, Manish K

    2014-10-01

    Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR is a member of the adenosine triphosphate (ATP)-binding cassette superfamily of proteins and it functions as a chloride channel. CFTR largely controls the working of epithelial cells of the airways, the gastrointestinal tract, exocrine glands, and genitourinary system. Cystic fibrosis is responsible for severe chronic pulmonary disorders in children. Other maladies in the spectrum of this life-limiting disorder include nasal polyposis, pansinusitis, rectal prolapse, pancreatitis, cholelithiasis, insulin-dependent hyperglycemia, and cirrhosis. This review summarizes the recent state of art in the field of cystic fibrosis diagnostic methods with the help of CF literature published so far and proposes new research domains in the field of cystic fibrosis diagnosis. PMID:24880895

  14. [Pancreatic cystic fibrosis in Mexicans over 15 years of age].

    PubMed

    Quezada, R; Hernandez, N; Sada, E

    1990-01-01

    A better knowledge of cystic fibrosis of the pancreas has contributed to raise the detection of cystic fibrosis in adults. We describe nine Mexican patients older than 15 years with cystic fibrosis. Respiratory symptoms were predominant and they were secondary to bronchiectasis. All patients were infected by mucoid Pseudomona aeruginosa and in some cases, the finding of this microorganism in sputum suggested the diagnosis. In Mexican population the cystyc fibrosis of the pancreas can be found in adult patients, and it should be considered in the differential diagnosis of chronic respiratory diseases in adults. PMID:2125356

  15. Gene therapy for the treatment of cystic fibrosis.

    PubMed

    Burney, Tabinda J; Davies, Jane C

    2012-01-01

    Gene therapy is being developed as a novel treatment for cystic fibrosis (CF), a condition that has hitherto been widely-researched yet for which no treatment exists that halts the progression of lung disease. Gene therapy involves the transfer of correct copies of cystic fibrosis transmembrane conductance regulator (CFTR) DNA to the epithelial cells in the airways. The cloning of the CFTR gene in 1989 led to proof-of-principle studies of CFTR gene transfer in vitro and in animal models. The earliest clinical trials in CF patients were conducted in 1993 and used viral and non-viral gene transfer agents in both the nasal and bronchial airway epithelium. To date, studies have focused largely on molecular or bioelectric (chloride secretion) outcome measures, many demonstrating evidence of CFTR expression, but few have attempted to achieve clinical efficacy. As CF is a lifelong disease, turnover of the airway epithelium necessitates repeat administration. To date, this has been difficult to achieve with viral gene transfer agents due to host recognition leading to loss of expression. The UK Cystic Fibrosis Gene Therapy Consortium (Imperial College London, University of Edinburgh and University of Oxford) is currently working on a large and ambitious program to establish the clinical benefits of CF gene therapy. Wave 1, which has reached the clinic, uses a non-viral vector. A single-dose safety trial is nearing completion and a multi-dose clinical trial is shortly due to start; this will be powered for clinically-relevant changes. Wave 2, more futuristically, will look at the potential of lentiviruses, which have long-lasting expression. This review will summarize the current status of translational research in CF gene therapy. PMID:23776378

  16. 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.

  17. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)

    PubMed Central

    Corradi, Valentina; Vergani, Paola; Tieleman, D. Peter

    2015-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the ATP-binding cassette (ABC) transporter superfamily. CFTR controls the flow of anions through the apical membrane of epithelia. Dysfunctional CFTR causes the common lethal genetic disease cystic fibrosis. Transitions between open and closed states of CFTR are regulated by ATP binding and hydrolysis on the cytosolic nucleotide binding domains, which are coupled with the transmembrane (TM) domains forming the pathway for anion permeation. Lack of structural data hampers a global understanding of CFTR and thus the development of “rational” approaches directly targeting defective CFTR. In this work, we explored possible conformational states of the CFTR gating cycle by means of homology modeling. As templates, we used structures of homologous ABC transporters, namely TM(287–288), ABC-B10, McjD, and Sav1866. In the light of published experimental results, structural analysis of the transmembrane cavity suggests that the TM(287–288)-based CFTR model could correspond to a commonly occupied closed state, whereas the McjD-based model could represent an open state. The models capture the important role played by Phe-337 as a filter/gating residue and provide structural information on the conformational transition from closed to open channel. PMID:26229102

  18. Targeting ion channels in cystic fibrosis.

    PubMed

    Mall, Marcus A; Galietta, Luis J V

    2015-09-01

    Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause a characteristic defect in epithelial ion transport that plays a central role in the pathogenesis of cystic fibrosis (CF). Hence, pharmacological correction of this ion transport defect by targeting of mutant CFTR, or alternative ion channels that may compensate for CFTR dysfunction, has long been considered as an attractive approach to a causal therapy of this life-limiting disease. The recent introduction of the CFTR potentiator ivacaftor into the therapy of a subgroup of patients with specific CFTR mutations was a major milestone and enormous stimulus for seeking effective ion transport modulators for all patients with CF. In this review, we discuss recent breakthroughs and setbacks with CFTR modulators designed to rescue mutant CFTR including the common mutation F508del. Further, we examine the alternative chloride channels TMEM16A and SLC26A9, as well as the epithelial sodium channel ENaC as alternative targets in CF lung disease, which remains the major cause of morbidity and mortality in patients with CF. Finally, we will focus on the hurdles that still need to be overcome to make effective ion transport modulation therapies available for all patients with CF irrespective of their CFTR genotype. PMID:26115565

  19. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)

    PubMed Central

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

    2011-01-01

    Cystic fibrosis affects about 1 in 2500 live births and involves loss of transmembrane chloride flux due to a lack of a membrane protein channel termed the cystic fibrosis transmembrane conductance regulator (CFTR). We have studied CFTR structure by electron crystallography. The data were compared with existing structures of other ATP-binding cassette transporters. The protein was crystallized in the outward facing state and resembled the well characterized Sav1866 transporter. We identified regions in the CFTR map, not accounted for by Sav1866, which were potential locations for the regulatory region as well as the channel gate. In this analysis, we were aided by the fact that the unit cell was composed of two molecules not related by crystallographic symmetry. We also identified regions in the fitted Sav1866 model that were missing from the map, hence regions that were either disordered in CFTR or differently organized compared with Sav1866. Apart from the N and C termini, this indicated that in CFTR, the cytoplasmic end of transmembrane helix 5/11 and its associated loop could be partly disordered (or alternatively located). PMID:21931164

  20. Development of cystic fibrosis and noncystic fibrosis airway cell lines.

    PubMed

    Zabner, Joseph; Karp, Phil; Seiler, Michael; Phillips, Stacia L; Mitchell, Calista J; Saavedra, Mimi; Welsh, Michael; Klingelhutz, Aloysius J

    2003-05-01

    In this study, we utilized the reverse transcriptase component of telomerase, hTERT, and human papillomavirus type 16 (HPV-16) E6 and E7 genes to transform normal and cystic fibrosis (CF) human airway epithelial (HAE) cells. One cell line, designated NuLi-1 (normal lung, University of Iowa), was derived from HAE of normal genotype; three cell lines, designated CuFi (cystic fibrosis, University of Iowa)-1, CuFi-3, and CuFi-4, were derived from HAE of various CF genotypes. When grown at the air-liquid interface, the cell lines were capable of forming polarized differentiated epithelia that exhibited transepithelial resistance and maintained the ion channel physiology expected for the genotypes. The CF transmembrane conductance regulator defect in the CuFi cell lines could be corrected by infecting from the basolateral surface using adenoviral vectors. Using nuclear factor-kappaB promoter reporter constructs, we also demonstrated that the NuLi and CuFi cell lines retained nuclear factor-kappaB responses to lipopolysaccharide. These cell lines should therefore be useful as models for studying ion physiology, therapeutic intervention for CF, and innate immunity. PMID:12676769

  1. Air Trapping and Airflow Obstruction in Newborn Cystic Fibrosis Piglets

    PubMed Central

    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.

    2013-01-01

    Rationale: 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. Objectives: To learn if air trapping and airflow obstruction are present before the onset of airway infection and inflammation in cystic fibrosis. Methods: 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. Measurements and Main Results: 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. Conclusions: 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. PMID:24168209

  2. Lumacaftor/Ivacaftor: A Review in Cystic Fibrosis.

    PubMed

    Deeks, Emma D

    2016-08-01

    Lumacaftor/ivacaftor (Orkambi™) is a fixed-dose tablet containing a corrector (lumacaftor) and potentiator (ivacaftor) of the cystic fibrosis transmembrane conductance regulator (CFTR) and is the first therapy approved to treat the underlying cause of cystic fibrosis in patients (aged ≥12 years) homozygous for the most common CFTR mutation, F508del. Lumacaftor improves the processing of F508del CFTR and its transport to the cell surface, while ivacaftor increases the channel's open probability and transport of chloride. In two 24-week trials in the approved patient population (TRAFFIC and TRANSPORT), lumacaftor 400 mg plus ivacaftor 250 mg, administered every 12 h in combination with standard therapy, was associated with an ≈3 % statistically significant improvement in lung function relative to placebo (as measured by the percent predicted forced expiratory volume in 1 s). Lumacaftor plus ivacaftor did not significantly improve respiratory symptoms, although reduced pulmonary exacerbations to a clinically meaningful extent and, in one trial (TRANSPORT), significantly improved body mass index (BMI). In an ongoing extension of these studies (PROGRESS), lumacaftor plus ivacaftor provided clinical benefit over a further 72 weeks of treatment. Lumacaftor plus ivacaftor had an acceptable tolerability profile, with the most common adverse events being respiratory or gastrointestinal in nature. Thus, lumacaftor/ivacaftor expands the treatment options available for patients with cystic fibrosis homozygous for the F508del-CFTR mutation, although its precise place in clinical practice remains to be determined. PMID:27394157

  3. The novel complex allele [A238V;F508del] of the CFTR gene: clinical phenotype and possible implications for cystic fibrosis etiological therapies.

    PubMed

    Diana, Anna; Polizzi, Angela Maria; Santostasi, Teresa; Ratclif, Luigi; Pantaleo, Maria Giuseppina; Leonetti, Giuseppina; Iusco, Danila Rosa; Gallo, Crescenzio; Conese, Massimo; Manca, Antonio

    2016-06-01

    Few mutations in cis have been annotated for F508del homozygous patients. Southern Italy patients who at a first analysis appeared homozygous for the F508del mutation (n=63) or compound heterozygous for the F508del and another mutation in the cystic fibrosis transmembrane conductance regulator gene (n=155) were searched for the A238V mutation in exon 6. The allelic frequency of the complex allele [A238V;F508del] was 0.04. When the whole data set was used (comprised also of 56 F508del/F508del and 34 F508del/other mutation controls), no differences reached the statistical significance in the clinical parameters, except chloride concentrations which were lower in [A238V;F508del]/other mutation compared with F508del/other mutation (P=0.03). The two study groups presented less complications than the control groups. Within the minimal data set (34 F508del/F508del, 27 F508del/other mutation, 4 [A238V;F508del]/F508del cases and 5 [A238V;F508del]/other mutation cases); that is, presenting all the variables in each patient, forced expiratory volume in 1 s and forced vital capacity presented a trend to lower levels in the study groups in comparison with the F508del/F508del group, and C-reactive protein approximated statistically significant higher levels in the [A238V;F508del]/other mutation as compared with F508del/F508del patients (P=0.09). The analysis of statistical dependence among the variables showed a significant anticorrelation between chloride and body mass index in the [A238V;F508del]/other mutation group. In conclusion, the complex allele [A238V;F508del] seems to be associated with less general complications than in the control groups, on the other hand possibly giving a worse pulmonary phenotype and higher systemic/local inflammatory response. These findings have implications for the correct recruitment and clinical response of F508del patients in the clinical trials testing the new etiological drugs for cystic fibrosis. PMID:26911355

  4. Familial non-cystic fibrosis mucus inspissation of respiratory tract.

    PubMed Central

    Perlman, M; Williams, J; Hirsch, M; Bar-Ziv, J

    1975-01-01

    Perlman, M., Williams, J., Hirsch, M., and Bar-Ziv, J. (1975). Archives of Disease in Childhood, 50, 727. Familial non-cystic fibrosis mucus inspissation of respiratory tract. Two sibs, whose parents are first cousins, have had chronic obstructive airways disease from birth with recurrent otitis media, sinusitis, and mastoiditis. The disease, associated with clinically abnormal mucus, differs from other familial obstructive airways diseases and probably constitutes a new entity. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 PMID:1190822

  5. Subtotal Esophagectomy for Carcinoma in a Patient with Cystic Fibrosis.

    PubMed

    Miller, Rachel; Bourke, Stephen; Immanuel, Arul; Metcalfe, Sarah

    2016-06-15

    Cystic fibrosis (CF) is a multisystem disorder characterized by progressive lung disease. Life expectancy is, however, continually improving. Patients with CF will therefore present with an increasing number of conditions, some of which will require operative management. We present our experience of the management of a patient with CF who underwent a subtotal esophagectomy for adenocarcinoma of the esophagus. No significant difficulties were encountered in the perioperative management of the patient. Despite a decline in his lung function and weight postoperatively, he remains clinically stable. Major surgery can be successfully undertaken in selected patients with CF. PMID:27301055

  6. 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. PMID:24625547

  7. Paediatric nasal polyps in cystic fibrosis.

    PubMed

    Mohd Slim, Mohd Afiq; Dick, David; Trimble, Keith; McKee, Gary

    2016-01-01

    Patients with cystic fibrosis (CF) are at increased risk of nasal polyps. We present the case of a 17-month-old Caucasian patient with CF who presented with hypertelorism causing cycloplegic astigmatism, right-sided mucoid discharge, snoring and noisy breathing. Imaging suggested bilateral mucoceles in the ethmoid sinuses. Intraoperatively, bilateral soft tissue masses were noted, and both posterior choanae were patent. Polypectomy and bilateral mega-antrostomies were performed. Histological examination revealed inflammatory nasal polyposis typical of CF. The role of early functional endoscopic sinus surgery (FESS) in children with CF nasal polyposis remains questionable as the recurrence rate is higher, and no improvement in pulmonary function has been shown. Our case, however, clearly demonstrates the beneficial upper airway symptom relief and normalisation of facial appearance following FESS in a child with this condition. PMID:27329094

  8. Imaging of Cystic Fibrosis and Pediatric Bronchiectasis.

    PubMed

    Murphy, Kevin P; Maher, Michael M; O'Connor, Owen J

    2016-03-01

    1. CT is superior to pulmonary function tests and chest radiography for the assessment and monitoring of cystic fibrosis (CF)-related lung disease and, also, of pediatric bronchiectasis not caused by CF (hereafter referred to as non-CF bronchiectasis). 2. Low-dose CT protocols that impart radiation doses similar to those used in chest radiography are feasible for the surveillance of patients with bronchiectasis. 3. Chest radiography is still most commonly used as the first-line imaging examination of choice for the assessment of acute complications related to bronchiectasis. 4. Pulmonary MRI, with or without the use of inhaled hyperpolarized gas, can be performed to obtain functional information, and, in dedicated centers, it may yield imaging results comparable to those obtained by CT. 5. Gastrointestinal and pancreaticobiliary manifestations of CF are observed with greater frequency in adults, because of increased life expectancy. PMID:26901001

  9. Scoliosis in cystic fibrosis - an appraisal

    SciTech Connect

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

    1982-03-01

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

  10. 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

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

    MedlinePlus

    ... from the NHLBI on Twitter. What Are the Signs and Symptoms of Cystic Fibrosis? The signs and ... mucus that contains blood and bacteria. Respiratory System Signs and Symptoms People who have CF have thick, ...

  12. Ciprofloxacin-induced phototoxicity in an adult cystic fibrosis population.

    PubMed

    Tolland, Julia P; Murphy, Bryan P; Boyle, Julie; Hall, Valerie; McKenna, Kevin E; Elborn, J Stuart

    2012-10-01

    The incidence of phototoxicity as a side effect of ciprofloxacin appears to be increased in patients with cystic fibrosis compared to the general population (approximately 2.4%). We used an interview-based questionnaire to determine the incidence of such phototoxic skin reactions in cystic fibrosis patients. Results from 105 respondents revealed the incidence of ciprofloxacin-induced phototoxicity in the adult cystic fibrosis population in Northern Ireland to be 48.4% with only 66% of the patients recalling being given sun care information beforehand. We concluded that the incidence of phototoxicity is increased in patients with cystic fibrosis and that it is important for all to receive good sun care information prior to taking ciprofloxacin given the high risk of developing phototoxic rash. PMID:22971191

  13. Adeno-associated virus for cystic fibrosis gene therapy.

    PubMed

    Martini, S V; Rocco, P R M; Morales, M M

    2011-11-01

    Gene therapy is an alternative treatment for genetic lung disease, especially monogenic disorders such as cystic fibrosis. Cystic fibrosis is a severe autosomal recessive disease affecting one in 2500 live births in the white population, caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR). The disease is classically characterized by pancreatic enzyme insufficiency, an increased concentration of chloride in sweat, and varying severity of chronic obstructive lung disease. Currently, the greatest challenge for gene therapy is finding an ideal vector to deliver the transgene (CFTR) to the affected organ (lung). Adeno-associated virus is the most promising viral vector system for the treatment of respiratory disease because it has natural tropism for airway epithelial cells and does not cause any human disease. This review focuses on the basic properties of adeno-associated virus and its use as a vector for cystic fibrosis gene therapy. PMID:21952739

  14. AEROSOL DEPOSITION AS A FUNCTION OF AIRWAY DISEASE: CYSTIC FIBROSIS

    EPA Science Inventory

    Progressive lung disease associated with cystic fibrosis (CF) is a continuous interaction of the processes of airway obstruction, infection and inflammation. ecent literature has suggested that the manifestation of CF could compromise the successful administration of pharmacologi...

  15. Cystic fibrosis--what are the prospects for a cure?

    PubMed

    Kumar, Shankar; Tana, Anand; Shankar, Anu

    2014-11-01

    Significant improvements in the treatment of cystic fibrosis over the last few decades have altered this lethal disease in children to a multisystem disorder with survival into adult life now common. In most developed countries the numbers of adult cystic fibrosis patients outnumber children. This is mainly due to improvements in care during early life. The principal cause of morbidity and mortality is pulmonary disease, and so the focus of new treatments has targeted the lungs. Identification of the underlying gene defect in the cystic fibrosis transmembrane conductance regulator has ushered in a new era in cystic fibrosis research, with prospects of a cure. In this article, we review the most exciting recent advances that correct defects in cellular processing, chloride channel function and gene therapy. PMID:25447947

  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. PMID:25151429

  17. Increased oral bioavailability of ciprofloxacin in cystic fibrosis patients.

    PubMed Central

    Christensson, B A; Nilsson-Ehle, I; Ljungberg, B; Lindblad, A; Malmborg, A S; Hjelte, L; Strandvik, B

    1992-01-01

    The altered pharmacokinetic properties of, e.g., aminoglycosides in cystic fibrosis patients have to be considered when pulmonary exacerbations are treated. Since reported data on ciprofloxacin, a fluorinated quinolone, are conflicting, we compared intravenous and oral administration in cystic fibrosis patients when treating them for mild symptoms of pulmonary infection. All of the patients were colonized with Pseudomonas species. Ciprofloxacin was administered orally (15 mg/kg of body weight) or intravenously (6 mg/kg) twice a day for at least 10 days during separate treatment periods. Five healthy volunteers received single intravenous and oral doses. Pharmacokinetic evaluations were performed at first dose and at steady state. The results showed that cystic fibrosis patients have increased oral bioavailability of ciprofloxacin (80% in cystic fibrosis patients versus 57% in volunteers) and increased total clearance (688 ml/min in CF patients versus 528 ml/min in volunteers). Our data indicate that the pharmacokinetic properties of ciprofloxacin are altered in cystic fibrosis patients with mild symptoms of pulmonary exacerbations and that the changes most probably are due to cystic fibrosis per se or to the impact of chronic infection. PMID:1489195

  18. Targeted therapies to improve CFTR function in cystic fibrosis.

    PubMed

    Brodlie, Malcolm; Haq, Iram J; Roberts, Katie; Elborn, J Stuart

    2015-01-01

    Cystic fibrosis is the most common genetically determined, life-limiting disorder in populations of European ancestry. The genetic basis of cystic fibrosis is well established to be mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that codes for an apical membrane chloride channel principally expressed by epithelial cells. Conventional approaches to cystic fibrosis care involve a heavy daily burden of supportive treatments to combat lung infection, help clear airway secretions and maintain nutritional status. In 2012, a new era of precision medicine in cystic fibrosis therapeutics began with the licensing of a small molecule, ivacaftor, which successfully targets the underlying defect and improves CFTR function in a subgroup of patients in a genotype-specific manner. Here, we review the three main targeted approaches that have been adopted to improve CFTR function: potentiators, which recover the function of CFTR at the apical surface of epithelial cells that is disrupted in class III and IV genetic mutations; correctors, which improve intracellular processing of CFTR, increasing surface expression, in class II mutations; and production correctors or read-through agents, which promote transcription of CFTR in class I mutations. The further development of such approaches offers great promise for future therapeutic strategies in cystic fibrosis. PMID:26403534

  19. Improved clinical and radiographic outcomes after treatment with ivacaftor in a young adult with cystic fibrosis with the P67L CFTR mutation.

    PubMed

    Yousef, Shatha; Solomon, George M; Brody, Alan; Rowe, Steven M; Colin, Andrew A

    2015-03-01

    The underlying cause of cystic fibrosis (CF) is the loss of epithelial chloride and bicarbonate transport due to mutations in the CF transmembrane conductance regulator (CFTR) gene encoding the CFTR protein. Ivacaftor is a gene-specific CFTR potentiator that augments in vivo chloride transport in CFTR mutations affecting channel gating. Originally approved for the G511D CFTR mutation, ivacaftor is now approved for eight additional alleles exhibiting gating defects and has also been tested in R117H, a CFTR mutation with residual function that exhibits abnormal gating. P67L is a class 4 conductance (nongating) mutation exhibiting residual CFTR function. We report marked clinical improvement, normalization of spirometry, and dramatic reduction in radiographic structural airway changes after > 1 year of treatment with ivacaftor in a young adult with the compound heterozygous genotype P67L/F508del CFTR. The case suggests that ivacaftor may have a potential benefit for patients with CF with nongating mutations. PMID:25732475

  20. Nontuberculous mycobacteria in cystic fibrosis and non-cystic fibrosis bronchiectasis.

    PubMed

    Park, In Kwon; Olivier, Kenneth N

    2015-04-01

    Increasing numbers of cystic fibrosis (CF) and non-CF bronchiectasis patients are affected by pulmonary nontuberculous mycobacteria (NTM) infection worldwide. Two species of NTM account for up to 95% of the pulmonary NTM infections: Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABSC). Diagnosis of pulmonary NTM infection is based on criteria specified in the 2007 American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) guidelines. While many initial positive cultures do not progress to active NTM disease, even a single positive NTM sputum culture obtained from higher risk groups such as classic CF or older women with bronchiectasis and very low body mass index should be closely monitored for progressive disease. Macrolides remain the most effective agents available against MAC and MABSC. Infection with MABSC may be associated with worse clinical outcomes, as more than half of MABSC isolates have inducible macrolide resistance conferred by an active erm(41) gene. Of growing concern in CF is that MABSC is becoming more common than MAC, seems to target younger patients with classic CF, and is more difficult to manage, often requiring prolonged courses of intravenous antibiotics. Recurrence rates of NTM after initial successful treatment remain high, likely due to nonmodifiable risk factors raising the question of whether secondary prophylaxis is feasible. More rapid and readily available methods for detecting inducible macrolide resistance and better in vitro susceptibility testing methods for other drugs that correlate with clinical responses are needed. This is crucial to identify more effective regimens of existing drugs and for development of novel drugs for NTM infection. PMID:25826589

  1. Future Directions in Early Cystic Fibrosis Lung Disease Research

    PubMed Central

    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

    2012-01-01

    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. PMID:22312017

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

    PubMed Central

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

    2016-01-01

    Patient: Female, 10 Final Diagnosis: Sepsis Symptoms: Fever • hypotension • not tollerating enteral feeds • respiratory deterioration Medication: — Clinical Procedure: IV antibiotics • lungtransplantion Specialty: Pediatrics and Neonatology Objective: Unusual clinical course Background: Achromobacter xylosoxidans is an aerobic, motile, Gram-negative, opportunistic pathogen that can be responsible for various severe nosocomial and community-acquired infections. It has been found in immunocompromised patients and patients with several other underlying conditions, but the clinical role of this microorganism in cystic fibrosis is unclear. Case Report: We describe a case of septic shock caused by A. xylosoxidans in a 10-year-old child with cystic fibrosis and severe lung disease. Conclusions: As the prevalence of A. xylosoxidans in cystic fibrosis patients is rising and patient-to-patient transmission is highly probable, further studies are warranted to determine its role and to document the appropriate treatment strategy for eradication and long-term treatment of this organism. PMID:27498677

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

    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 (PD) caused by NTM has emerged as a major threat to the health of individuals with CF, but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened a panel of 19 experts to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM-PD in individuals with CF. PICO (population, intervention, comparison, outcome) methodology and systematic literature reviews were employed to inform draft recommendations, which were then modified to achieve consensus and subsequently circulated for public consultation within the USA and European CF communities. We have thus generated a series of pragmatic, evidence-based recommendations as an initial step in optimising management for this challenging condition. PMID:26678435

  4. Lung Transplantation and Survival in Children with Cystic Fibrosis

    PubMed Central

    Liou, Theodore G.; Adler, Frederick R.; Cox, David R.; Cahill, Barbara C.

    2016-01-01

    BACKGROUND The effects of lung transplantation on the survival and quality of life in children with cystic fibrosis are uncertain. METHODS We used data from the U.S. Cystic Fibrosis Foundation Patient Registry and from the Organ Procurement and Transplantation Network to identify children with cystic fibrosis who were on the waiting list for lung transplantation during the period from 1992 through 2002. We performed proportional-hazards survival modeling, using multiple clinically relevant covariates that were available before the children were on the waiting list and the interactions of these covariates with lung transplantation as a time-dependent covariate. The data were insufficient in quality and quantity for a retrospective quality-of-life analysis. RESULTS A total of 248 of the 514 children on the waiting list underwent lung transplantation in the United States during the period from 1992 through 2002. Proportional-hazards modeling identified four variables besides transplantation that were associated with changes in survival. Burkholderia cepacia infection was associated with a trend toward decreased survival, regardless of whether the patient underwent transplantation. A diagnosis of diabetes before the patient was placed on the waiting list decreased survival while the patient was on the waiting list but did not decrease survival after transplantation, whereas older age did not affect waiting-list survival but decreased post-transplantation survival. Staphylococcus aureus infection increased waiting-list survival but decreased post-transplantation survival. Using age, diabetes status, and S. aureus infection status as covariates, we estimated the effect of transplantation on survival for each patient group, expressed as a hazard factor of less than 1 for a benefit and more than 1 for a risk of harm. Five patients had a significant estimated benefit, 283 patients had a significant risk of harm, 102 patients had an insignificant benefit, and 124 patients

  5. 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.

  6. Early Anti-Pseudomonal Acquisition in Young Patients with Cystic Fibrosis: Rationale and Design of the EPIC Clinical Trial and Observational Study

    PubMed Central

    Treggiari, Miriam M; Rosenfeld, Margaret; Mayer-Hamblett, Nicole; Retsch-Bogart, George; Gibson, Ronald L.; Williams, Judy; Emerson, Julia; Kronmal, Richard A; Ramsey, Bonnie W

    2009-01-01

    Background The primary cause of morbidity and mortality in patients with cystic fibrosis (CF) is progressive obstructive pulmonary disease due to chronic endobronchial infection, particularly with Pseudomonas aeruginosa (Pa). Risk factors for and clinical impact of early Pa infection in young CF patients are less well understood. Purpose The present studies are designed to evaluate risk factors and outcomes associated with early Pa acquisition, and the benefits and harms of four anti-pseudomonal treatment regimens in young CF patients initiated after the first Pa positive respiratory culture. Methods The Early Pseudomonas Infection Control (EPIC) program consists of two studies, a randomized multicenter trial in CF patients ages 1–12 years at first isolation of Pa from a respiratory culture, and a longitudinal cohort study enrolling Pa-negative patients. Using a factorial design, trial participants are assigned for 18 months to either anti-pseudomonal treatment on a scheduled quarterly basis (cycled therapy) or based on recovery of Pa from quarterly respiratory cultures (culture-based therapy). The study drugs include inhaled tobramycin (300 mg BID) for 28 days, combined with either oral ciprofloxacin (15–20 mg/kg BID) or oral placebo for 14 days. The primary endpoints of the trial are the time to pulmonary exacerbation requiring IV antibiotics or hospitalization for respiratory symptoms, and the proportion of patients with new Pa-positive respiratory cultures during the study. The broad goals of the observational study are to describe the risk factors and outcomes associated with early acquisition of Pa. 306 patients were randomized in the clinical trial and 1,787 were enrolled in the cohort study. Conclusions These companion studies will provide valuable epidemiological and microbiological information on early CF lung disease and Pa acquisition, and safety and clinical efficacy data on anti-pseudomonal treatment strategies for early Pa infections in the

  7. A metagenomic approach to characterize temperate bacteriophage populations from Cystic Fibrosis and non-Cystic Fibrosis bronchiectasis patients

    PubMed Central

    Tariq, Mohammad A.; Everest, Francesca L. C.; Cowley, Lauren A.; De Soyza, Anthony; Holt, Giles S.; Bridge, Simon H.; Perry, Audrey; Perry, John D.; Bourke, Stephen J.; Cummings, Stephen P.; Lanyon, Clare V.; Barr, Jeremy J.; Smith, Darren L.

    2015-01-01

    Pseudomonas aeruginosa (Pa), normally a soil commensal, is an important opportunistic pathogen in Cystic Fibrosis (CF) and non-Cystic Fibrosis Bronchiectasis (nCFBR). Persistent infection correlates with accelerated decline in lung function and early mortality. The horizontal transfer of DNA by temperate bacteriophages can add gene function and selective advantages to their bacterial host within the constrained environment of the lower lung. In this study, we chemically induce temperate bacteriophages from clonal cultures of Pa and identify their mixed viral communities employing metagenomic approaches. We compared 92 temperate phage metagenomes stratified from these clinical backgrounds (47 CF and 45 nCFBR Pa isolates) using MG-RAST and GeneWise2. KEGG analysis shows the complexity of temperate phage accessory gene carriage increases with duration and severity of the disease. Furthermore, we identify the presence of Ig-like motifs within phage structural genes linked to bacterial adhesion and carbohydrate binding including Big_2, He_Pig, and Fn3. This study provides the first clinical support to the proposed bacteriophage adherence to mucus (BAM) model and the evolution of phages interacting at these mucosal surfaces over time. PMID:25741327

  8. A metagenomic approach to characterize temperate bacteriophage populations from Cystic Fibrosis and non-Cystic Fibrosis bronchiectasis patients.

    PubMed

    Tariq, Mohammad A; Everest, Francesca L C; Cowley, Lauren A; De Soyza, Anthony; Holt, Giles S; Bridge, Simon H; Perry, Audrey; Perry, John D; Bourke, Stephen J; Cummings, Stephen P; Lanyon, Clare V; Barr, Jeremy J; Smith, Darren L

    2015-01-01

    Pseudomonas aeruginosa (Pa), normally a soil commensal, is an important opportunistic pathogen in Cystic Fibrosis (CF) and non-Cystic Fibrosis Bronchiectasis (nCFBR). Persistent infection correlates with accelerated decline in lung function and early mortality. The horizontal transfer of DNA by temperate bacteriophages can add gene function and selective advantages to their bacterial host within the constrained environment of the lower lung. In this study, we chemically induce temperate bacteriophages from clonal cultures of Pa and identify their mixed viral communities employing metagenomic approaches. We compared 92 temperate phage metagenomes stratified from these clinical backgrounds (47 CF and 45 nCFBR Pa isolates) using MG-RAST and GeneWise2. KEGG analysis shows the complexity of temperate phage accessory gene carriage increases with duration and severity of the disease. Furthermore, we identify the presence of Ig-like motifs within phage structural genes linked to bacterial adhesion and carbohydrate binding including Big_2, He_Pig, and Fn3. This study provides the first clinical support to the proposed bacteriophage adherence to mucus (BAM) model and the evolution of phages interacting at these mucosal surfaces over time. PMID:25741327

  9. Cystic fibrosis transmembrane conductance regulator mutations at a referral center for cystic fibrosis*

    PubMed Central

    Coutinho, Cyntia Arivabeni de Araújo Correia; Marson, Fernando Augusto de Lima; Ribeiro, Antônio Fernando; Ribeiro, José Dirceu; Bertuzzo, Carmen Silvia

    2013-01-01

    OBJECTIVE: To determine the frequency of six mutations (F508del, G542X, G551D, R553X, R1162X, and N1303K) in patients with cystic fibrosis (CF) diagnosed, at a referral center, on the basis of abnormal results in two determinations of sweat sodium and chloride concentrations. METHODS: This was a cross-sectional study involving 70 patients with CF. The mean age of the patients was 12.38 ± 9.00 years, 51.43% were female, and 94.29% were White. Mutation screening was performed with polymerase chain reaction (for F508del), followed by enzymatic digestion (for other mutations). Clinical analysis was performed on the basis of gender, age, ethnicity, pulmonary/gastrointestinal symptoms, and Shwachman-Kulczycki (SK) score. RESULTS: All of the patients showed pulmonary symptoms, and 8 had no gastrointestinal symptoms. On the basis of the SK scores, CF was determined to be mild, moderate, and severe in 22 (42.3%), 17 (32.7%), and 13 (25.0%) of the patients, respectively. There was no association between F508del mutation and disease severity by SK score. Of the 140 alleles analyzed, F508del mutation was identified in 70 (50%). Other mutations (G542X, G551D, R553X, R1162X, and N1303K) were identified in 12 (7.93%) of the alleles studied. In F508del homozygous patients with severe disease, the OR was 0.124 (95% CI: 0.005-0.826). CONCLUSIONS: In 50% of the alleles studied, the molecular diagnosis of CF was confirmed by identifying a single mutation (F508del). If we consider the analysis of the six most common mutations in the Brazilian population (including F508del), the molecular diagnosis was confirmed in 58.57% of the alleles studied. PMID:24310628

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

    PubMed Central

    Haber, H P; Benda, N; Fitzke, G; Lang, A; Langenberg, M; Riethmüller, J; Stern, M

    1997-01-01

    BACKGROUND: Colonic strictures represent an advanced stage of fibrosing colonopathy in patients with cystic fibrosis. AIMS: To clarify whether ultrasonography can identify patients with an early stage of fibrosing colonopathy and to determine clinical factors that influence bowel wall thickening. PATIENTS: Ninety patients with cystic fibrosis, median age 10 years, and 46 healthy controls, median age 13 years, were investigated. METHODS: Bowel wall thickness was measured by ultrasound in a prospective study. RESULTS: In cystic fibrosis, wall thickness of both small intestine and colon was significantly (p < 0.0001) higher than in controls; 81% of patients with cystic fibrosis had a maximum colon wall thickness at any site of 2 mm or more, a value that was never reached by controls. The maximum colon wall thickness was 6.5 mm. Bowel wall thickness was unchanged at re-examination after one year. There was no progression even with high dose pancreatic supplements. There was no association between bowel wall thickness and clinical features such as previous meconium ileus, intestinal resection, distal intestinal obstruction syndrome, abdominal pain, or pancreatic enzyme dose. CONCLUSIONS: There is genuine intestinal involvement in cystic fibrosis; in a few cases this could lead to fibrosing colonopathy. Images PMID:9135533

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

    NASA Astrophysics Data System (ADS)

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

    1994-10-01

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

  12. 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. PMID:27405894

  13. IgG antibodies to Aspergillus fumigatus in cystic fibrosis: a laboratory correlate of disease activity.

    PubMed Central

    Forsyth, K D; Hohmann, A W; Martin, A J; Bradley, J

    1988-01-01

    Serum was collected from 50 patients with cystic fibrosis, and IgG antibodies to Aspergillus fumigatus were measured by enzyme linked immunosorbent assay (ELISA). In addition, total IgE and Aspergillus specific IgE antibodies were measured in 41 of the 50. A close association was found between pulmonary function and clinical state, and IgG antibodies to Aspergillus. There was no association between pulmonary function or clinical state and IgE antibodies. It is postulated that in patients with cystic fibrosis, Aspergillus fumigatus may contribute to deterioration in pulmonary function by local pathogenicity, or by hypersensitivity mechanisms mediated by IgG. PMID:3046514

  14. Inflammation in cystic fibrosis lung disease: Pathogenesis and therapy.

    PubMed

    Cantin, André M; Hartl, Dominik; Konstan, Michael W; Chmiel, James F

    2015-07-01

    Lung disease is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). Although CF lung disease is primarily an infectious disorder, the associated inflammation is both intense and ineffective at clearing pathogens. Persistent high-intensity inflammation leads to permanent structural damage of the CF airways and impaired lung function that eventually results in respiratory failure and death. Several defective inflammatory responses have been linked to cystic fibrosis transmembrane conductance regulator (CFTR) deficiency including innate and acquired immunity dysregulation, cell membrane lipid abnormalities, various transcription factor signaling defects, as well as altered kinase and toll-like receptor responses. The inflammation of the CF lung is dominated by neutrophils that release oxidants and proteases, particularly elastase. Neutrophil elastase in the CF airway secretions precedes the appearance of bronchiectasis, and correlates with lung function deterioration and respiratory exacerbations. Anti-inflammatory therapies are therefore of particular interest for CF lung disease but must be carefully studied to avoid suppressing critical elements of the inflammatory response and thus worsening infection. This review examines the role of inflammation in the pathogenesis of CF lung disease, summarizes the results of past clinical trials and explores promising new anti-inflammatory options. PMID:25814049

  15. Evidence of Inhaled Tobramycin in Non-Cystic Fibrosis Bronchiectasis

    PubMed Central

    Vendrell, Montserrat; Muñoz, Gerard; de Gracia, Javier

    2015-01-01

    There is currently less experience with inhaled tobramycin in non-cystic fibrosis bronchiectasis than in cystic fibrosis (CF). Intravenous formulation and solution for inhalation (TSI) have been studied in non-CF bronchiectasis patients with chronic P. aeruginosa bronchial infection. An improvement in clinical parameters and a reduction in bacterial density have been shown with both inhaled solutions in these patients. However, further trials are needed to determine the most effective dose and administration protocol in these patients. Based on the current evidence, recommendations cannot be made regarding the use of TSI to treat exacerbations. Although no systemic toxicity has been reported in studies specifically investigating this treatment, patients with known kidney disease or ear disorders should be treated with caution. Adverse respiratory effects are reported to be more common in non-CF patients than in CF patients, who tend to be non-smokers and younger. Research is being conducted into the possibility of combining tobramycin with other antibiotics to increase its antibacterial activity. In this review we will present and discuss the published evidence regarding the use of inhaled tobramycin in non–CF bronchiectasis. PMID:25893022

  16. 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

  17. Fully automated scoring of chest radiographs in cystic fibrosis.

    PubMed

    Lee, Min-Zhao; Cai, Weidong; Song, Yang; Selvadurai, Hiran; Feng, David Dagan

    2013-01-01

    We present a prototype of a fully automated scoring system for chest radiographs (CXRs) in cystic fibrosis. The system was used to analyze real, clinical CXR data, to estimate the Shwachman-Kulczycki score for the image. Images were resampled and normalized to a standard size and intensity level, then segmented with a patch-based nearest-neighbor mapping algorithm. Texture features were calculated regionally and globally, using Tamura features, local binary patterns (LBP), gray-level co-occurrence matrix and Gabor filtering. Feature selection was guided by current understanding of the disease process, in particular the reorganization and thickening of airways. Combinations of these features were used as inputs for support vector machine (SVM) learning to classify each CXR, and evaluated using two-fold cross-validation for agreement with clinician scoring. The final computed score for each image was compared with the score assigned by a physician. Using this prototype system, we analyzed 139 CXRs from an Australian pediatric cystic fibrosis registry, for which texture directionality showed greatest discriminating power. Computed scores agreed with clinician scores in 75% of cases, and up to 90% of cases in discriminating severe disease from mild disease, similar to the level of human interobserver agreement for this dataset. PMID:24110600

  18. The role of hepatobiliary scintigraphy in cystic fibrosis.

    PubMed

    O'Connor, P J; Southern, K W; Bowler, I M; Irving, H C; Robinson, P J; Littlewood, J M

    1996-02-01

    This was a prospective open study that examined the quantitative and qualitative analysis of hepatobiliary scintigraphy (DISIDA) in detecting liver involvement in cystic fibrosis (CF). Forty-four adult and pediatric patients (median age, 12.1 years; range, 1.1-36.3 years) were divided into three groups: group 1, no evidence of liver involvement (n = 8); group 2, biochemical evidence of liver involvement on two or more occasions (n = 26); and group 3, clinical evidence of liver disease (n = 10). In groups 1 and 2, the most common qualitative scintigraphic finding was focal intrahepatic retention of tracer (26/34 patients, 12 of whom had normal findings on ultrasonography). This finding corresponds to focal cholestasis and may warrant treatment with the choleretic agent ursodeoxycholic acid (UDCA). In the group 3 patients, the abnormal qualitative scintigraphic appearances (heterogeneous uptake of tracer and nodular liver outline) added little to the findings on ultrasonography; however, these patients had a prolonged mean hepatic clearance time compared with those in groups 1 and 2 (one-way ANOVA; P < .015). It is proposed that scintigraphy with DISIDA has a role in the detection of early liver involvement in cystic fibrosis. PMID:8591853

  19. Family Stress with Chronic Childhood Illness: Cystic Fibrosis, Neuromuscular Disease, and Renal Disease.

    ERIC Educational Resources Information Center

    Holroyd, Jean; Guthrie, Donald

    1986-01-01

    Parents of children with neuromuscular disease, cystic fibrosis, and renal disease were compared with parents of control subjects matched by age to the clinical cases. The three clinical groups exhibited different patterns of stressful response, consistent with the nature of their illnesses and the requirements for care imposed on the families.…

  20. Cystic fibrosis and estrogens: a perfect storm

    PubMed Central

    Zeitlin, Pamela L.

    2008-01-01

    Irreversible destruction and widening of the airways due to acquired infections or genetic mutations as well as those of unknown cause are more severe in females. Differences between male and female anatomy, behavior, and hormonal state have been proposed to explain the increased incidence and severity in females with airway disease such as cystic fibrosis (CF); however, a mechanism to explain a sex-related difference has remained elusive. In this issue of the JCI, Coakley et al. report that elevations in the major estrogen hormone in humans — 17β-estradiol — reduce Ca2+-activated Cl– secretion by airway epithelial cells in culture, thereby disrupting ion and water balance (see the related article beginning on page 4025). They measure a similar diminution of nasal epithelial Ca2+-activated Cl– secretion in women with CF during the menstrual cycle phase at which 17β-estradiol level is at its highest. These data suggest that for about one week of a four-week menstrual cycle, women with CF will have a reduced ability to efficiently clear airway secretions, the buildup of which is a hallmark of CF. The authors suggest that these data warrant the testing of antiestrogen therapy in females with CF and propose an alternative avenue for CF therapeutic development. PMID:19033654

  1. Cephalexin pharmacokinetics in patients with cystic fibrosis.

    PubMed

    Nahata, M C; Lubin, A H; Visconti, J A

    1984-01-01

    Pharmacokinetics of cephalexin were studied in 7 pediatric and 4 adult patients with cystic fibrosis (CF) and 4 normal adult volunteers. Cephalexin, 250-500 mg, was given as a single dose in suspension. The area under the cephalexin serum concentration-time curve normalized for dose per kilogram averaged 0.185, 0.242, and 0.272 ml/min/kg-1 in pediatric CF patients, adult CF patients, and normal adults, respectively (p greater than 0.05). A threefold interindividual variation was observed in cephalexin renal clearance in CF patients. Renal clearance of cephalexin averaged 5.85 ml/min/kg in pediatric and 4.61 ml/min/kg in adult CF patients (p greater than 0.05). Elimination half-life of cephalexin averaged 0.74, 0.76, and 1.04 h in pediatric patients, adult patients, and normal adults (p greater than 0.05). Cephalexin was well absorbed based on a mean 24-hour urinary recovery of 89 and 93% in pediatric and adult patients. A trend for higher renal clearance of cephalexin was observed among pediatric compared to adult patients. These results indicate that clearance of cephalexin may not increase in patients with CF of minimal severity characterized by an excellent Shwachman score. PMID:6468223

  2. Lentiviral Vectors and Cystic Fibrosis Gene Therapy

    PubMed Central

    Castellani, Stefano; Conese, Massimo

    2010-01-01

    Cystic fibrosis (CF) is a chronic autosomic recessive syndrome, caused by mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, a chloride channel expressed on the apical side of the airway epithelial cells. The lack of CFTR activity brings a dysregulated exchange of ions and water through the airway epithelium, one of the main aspects of CF lung disease pathophysiology. Lentiviral (LV) vectors, of the Retroviridae family, show interesting properties for CF gene therapy, since they integrate into the host genome and allow long-lasting gene expression. Proof-of-principle that LV vectors can transduce the airway epithelium and correct the basic electrophysiological defect in CF mice has been given. Initial data also demonstrate that LV vectors can be repeatedly administered to the lung and do not give rise to a gross inflammatory process, although they can elicit a T cell-mediated response to the transgene. Future studies will clarify the efficacy and safety profile of LV vectors in new complex animal models with CF, such as ferrets and pigs. PMID:21994643

  3. Cystic fibrosis, atopy, and airways lability.

    PubMed Central

    Silverman, M; Hobbs, F D; Gordon, I R; Carswell, F

    1978-01-01

    In a survey of cystic fibrosis (CF) in the Avon area, 48 children with CF from 40 families together with 71 of their parents were studied by spirometry, exercise tests, and pinch tests. A control group of 42 young adults was similarly tested; control data for children were taken from previously published work. The prevalence of atopy (any positive prick test) in children with CF was 48%. Sensitivity to grass pollens and house dust mite was no more common in these children (29%) than in a normal population (34%). Hypersensitivity to Aspergillus fumigatus was found in 35% of children with CF and was associated with severe lung disease. The parents had a normal pattern and prevalence of atopy. Exercise-induced airways obstruction was present in only 22% of children with CF; its association with severe lung disease rendered interpretation difficult. The parents had a normal response to exercise. Both hypersensitivity to A. fumigatus and exercise-induced airways lability had the features of acquired characteristics. There was nothing in the present study to support the hypothesis that the possession of a CF gene predisposed to atopy. PMID:365112

  4. The Evolution of Cystic Fibrosis Care.

    PubMed

    Pittman, Jessica E; Ferkol, Thomas W

    2015-08-01

    Cystic fibrosis (CF) is the most common life-limiting inherited illness of whites. Most of the morbidity and mortality in CF stems from impaired mucociliary clearance leading to chronic, progressive airways obstruction and damage. Significant progress has been made in the care of patients with CF, with advances focused on improving mucociliary clearance, minimizing inflammatory damage, and managing infections; these advances include new antimicrobial therapies, mucolytic and osmotic agents, and antiinflammatory treatments. More recently, researchers have targeted disease-causing mutations using therapies to promote gene transcription and improve channel function, which has led to impressive physiologic changes in some patients. As we develop more advanced, allele-directed therapies for the management of CF, it will become increasingly important to understand the specific genetic and environmental interactions that cause the significant heterogeneity of lung disease seen in the CF population. This understanding of CF endotypes will allow for more targeted, personalized therapies for future patients. This article reviews the genetic and molecular basis of CF lung disease, the treatments currently available, and novel therapies that are in development. PMID:25764168

  5. Infection, inflammation and exercise in cystic fibrosis

    PubMed Central

    2013-01-01

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

  6. 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. PMID:25152272

  7. Screening policy for cystic fibrosis: the role of evidence.

    PubMed

    Wilfond, Benjamin S

    1995-01-01

    Setting priorities about medical services, including genetic testing services, often occurs in an extemporaneous fashion. Normative assumptions may not be examined critically, although doing so is a necessary component of making health policy decisions about clinical practice. The normative dimension to health policy questions suggests a need for greater public participation in the development of clinical practice guidelines. The experiences of newborn screening and carrier screening for cystic fibrosis in the United States can be examined within the framework of two models of health policy development that help explain the role in health policy development of normative assumptions and public participation. Specifically, this paper focuses on assumptions about what counts as sufficient empirical data to make health policy decisions. PMID:11654188

  8. 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. PMID:26453627

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

    PubMed

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

    2016-01-01

    BACKGROUND Achromobacter xylosoxidans is an aerobic, motile, Gram-negative, opportunistic pathogen that can be responsible for various severe nosocomial and community-acquired infections. It has been found in immunocompromised patients and patients with several other underlying conditions, but the clinical role of this microorganism in cystic fibrosis is unclear. CASE REPORT We describe a case of septic shock caused by A. xylosoxidans in a 10-year-old child with cystic fibrosis and severe lung disease. CONCLUSIONS As the prevalence of A. xylosoxidans in cystic fibrosis patients is rising and patient-to-patient transmission is highly probable, further studies are warranted to determine its role and to document the appropriate treatment strategy for eradication and long-term treatment of this organism. PMID:27498677

  10. Orthodontic and prosthetic treatment of a patient with cystic fibrosis and agenesis of maxillary lateral incisors.

    PubMed

    Slutsky, Harold; Greenberg, Joseph R

    2011-06-01

    The young dental patient with maxillary lateral incisor agenesis, maxillary canine impaction, and cystic fibrosis presents considerable challenges to the dentist. An interdisciplinary approach is described here for the orthodontist and restorative dentist to plan and work together with the patient's and parents' cooperation and consent. Despite some compromises, a successful outcome was achieved, as demonstrated in this case report. The use of conservative yet esthetic and durable fixed replacement prostheses is highlighted. Congenitally absent maxillary lateral incisors, impacted maxillary canines, and cystic fibrosis are clinical conditions that can significantly complicate and compromise dental treatment for any young patient. All three can be present simultaneously, as described in this case report. PMID:23738937