Infection with Prevotella nigrescens induces TLR2 signalling and low levels of p65 mediated inflammation in Cystic Fibrosis bronchial epithelial cells
This study examined whether infection with Prevotella nigrescens, a frequently identified member of this species, contributes to inflammation in CF bronchial epithelial cells through activation of TLR- and NF- κB signalling pathways. CFBE41o- cells were infected with either P.nigrescens or Pseudomonas aeruginosa and incubated under anaerobic conditions for 4h. P.nigrescens activated TLR2 signalling but not TLR4 signalling while P.aeruginosa activated TLR4 signalling with a lesser effect on TLR2. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - October 10, 2019 Category: Respiratory Medicine Authors: A. Bertelsen, J.S. Elborn, B.C. Schock Source Type: research

GLPG2737 in lumacaftor/ivacaftor-treated CF subjects homozygous for the F508del mutation: A randomized phase 2A trial (PELICAN)
Triple combinations of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators demonstrate enhanced clinical efficacy in CF patients with F508del mutation, compared with modest effects of dual combinations. GLPG2737 was developed as a novel corrector for triple combination therapy. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - October 5, 2019 Category: Respiratory Medicine Authors: Silke van Koningsbruggen-Rietschel, Katja Conrath, Rainald Fischer, Sivagurunathan Sutharsan, Axel Kempa, Wolfgang Gleiber, Carsten Schwarz, Andreas Hector, Nancy Van Osselaer, Arian Pano, Sam Corveleyn, Dieudonn é Bwirire, Eva Santermans, Karine Muller, Source Type: research

Guidance for computed tomography (CT) imaging of the lungs for patients with cystic fibrosis (CF) in research studies
Numerous issues must be addressed when developing standard operating procedures for clinical research studies involving chest computed tomography of lung disease in patients with cystic fibrosis (CF). Study success depends on the provision of adequate funding and the identification of personnel with the necessary expertise to conduct the study, along with clear guidelines that detail the CT operating procedure at each site, including breathing maneuvers, and image reconstruction. Close coordination of the quality assurance process between sites and the central review organization is required to maintain protocol adherence....
Source: Journal of Cystic Fibrosis - September 16, 2019 Category: Respiratory Medicine Authors: Marcel van Straten, Alan S. Brody, Caroline Ernst, R. Paul Guillerman, Harm A.W.M. Tiddens, Scott K. Nagle Tags: Review Source Type: research

Micronutrient intake in children with cystic fibrosis in Sydney, Australia
Children with CF have been reported to consume significantly more energy-dense, nutrient-poor foods than controls where there are now concerns of inadequate micronutrient intake. There are no current or comprehensive dietary studies assessing micronutrient intake in CF children. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - September 14, 2019 Category: Respiratory Medicine Authors: Adrienne Tham, Tamarah E. Katz, Rosie E. Sutherland, Millie Garg, Victoria Liu, Chai Wei Tong, Rebecca Brunner, Justine Quintano, Clare Collins, Chee Y. Ooi Source Type: research

A critical review of definitions used to describe Pseudomonas aeruginosa microbiological status in patients with cystic fibrosis for application in clinical trials
Definition of Pseudomonas aeruginosa (Pa) microbiological status is essential for patients' inclusion in clinical trials. The aim of this study was to agree on the definitions of Pa infection status for initial infection, eradication and chronic infection to be used in clinical trials and to propose additional future study areas. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - September 13, 2019 Category: Respiratory Medicine Authors: G. Taccetti, M. Denton, K. Hayes, ECFS-CTN Microbiology Group, P. Drevinek, I. Sermet-Gaudelus Tags: Original Article Source Type: research

A smartphone application for reporting symptoms in adults with cystic fibrosis improves the detection of exacerbations: Results of a randomised controlled trial
Respiratory exacerbations impair lung function and health-related quality of life in people with CF, with delayed identification of exacerbations often resulting in worse outcomes. We developed a smartphone application (app) for adults with CF to report symptoms to the CF team, and investigated its impact on antibiotic use and other outcomes. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - September 12, 2019 Category: Respiratory Medicine Authors: Jamie Wood, Sue Jenkins, David Putrino, Siobhain Mulrennan, Sue Morey, Nola Cecins, Natasha Bear, Kylie Hill Source Type: research

Unwarranted use of intravenous aminoglycosides at UK paediatric cystic fibrosis centres
Due to their efficacy against Pseudomonas aeruginosa, intravenous aminoglycosides are frequently used to treat infective exacerbations in individuals with cystic fibrosis (CF). This clinical utility has to be balanced against their side effects which include acute kidney injury (AKI), chronic kidney disease (CKD), hearing impairment and vestibular toxicity [1]. The incidence of AKI in adults and children with CF is 4.6 –10.5/10,000 CF patients/year [2]. The risk increases>80 fold if an aminoglycoside was administered in the previous week [3]. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - September 12, 2019 Category: Respiratory Medicine Authors: N. Ditchfield, W.D. Carroll, F.J. Gilchrist Tags: Letter to the Editor Source Type: research

Human cystic fibrosis monocyte derived macrophages display no defect in acidification of phagolysosomes when measured by optical nanosensors
Defective macrophage phagolysosomal acidification is implicated in numerous lung diseases including Cystic Fibrosis (CF) and may contribute to defective pathogen killing. Conflicting reports relating to phagolysosomal pH in CF macrophages have been published, in part related to the use of pH-sensitive fluorescent probes where potential inadequacies in experimental design can be a contributing factor (e.g. employing probes with incorrect pKa for the cellular compartment of interest). We developed a reliable method to quantify macrophage phagolysosomal pH using surface-enhanced Raman spectroscopy-based nanosensors. (Source: ...
Source: Journal of Cystic Fibrosis - September 6, 2019 Category: Respiratory Medicine Authors: Sheonagh M. Law, Samuel J. Stanfield, Gareth R. Hardisty, Ian Dransfield, Colin J. Campbell, Robert D. Gray Source Type: research

Pharmacokinetics of colistin after nebulization or intravenous administration of colistin methanesulphonate (Colimycin ®) to cystic fibrosis patients
Colistin, administered as the prodrug colistin methanesulphonate (CMS), is an antibiotic frequently administered as aerosol in cystic fibrosis (CF) patient. Our aim was to assess the plasma PK of colistin in CF patients treated with CMS administered intravenously or as aerosol and to compare these results with those previously reported in healthy volunteers. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - September 6, 2019 Category: Respiratory Medicine Authors: Sophie Magr éault, Julie Mankikian, Sandrine Marchand, Patrice Diot, William Couet, Thomas Flament, Nicolas Grégoire Tags: Original Article Source Type: research

Single dose escalation studies with inhaled POL6014, a potent novel selective reversible inhibitor of human neutrophil elastase, in healthy volunteers and subjects with cystic fibrosis
POL6014 is a novel, orally inhaled neutrophil elastase (NE) inhibitor in development for cystic fibrosis (CF). (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - September 6, 2019 Category: Respiratory Medicine Authors: P. Barth, P. Bruijnzeel, A. Wach, O. Sellier Kessler, L. Hooftman, J. Zimmermann, N. Naue, B. Huber, I. Heimbeck, D. Kappeler, W. Timmer, E. Chevalier Tags: Original Article Source Type: research

The impact of chest computed tomography and chest radiography on clinical management of cystic fibrosis lung disease
Recent standards of care mention chest radiography (CR) but not chest computed tomography (CT) in routine annual follow-up of children with cystic fibrosis (CF). To minimise radiation risk, CT or CR should only be performed if they impact clinical decision making. We investigated whether in addition to a wide range of commonly used clinical parameters, chest CT and/or CR in routine follow-up of CF patients influence clinical decisions. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - September 4, 2019 Category: Respiratory Medicine Authors: Carla F. Bortoluzzi, Eleonora Pontello, Emily Pintani, Karin M. de Winter-de Groot, Ciro D'Orazio, Baroukh M. Assael, M.G. Myriam Hunink, Harm A.W.M. Tiddens, Daan Caudri, on behalf of the CF Clinics Study Group Source Type: research

Changing epidemiology of the respiratory bacteriology of patients with cystic fibrosis –data from the European cystic fibrosis society patient registry
Monitoring changes in the epidemiology of cystic fibrosis (CF) pathogens is essential for clinical research, quality improvement, and clinical management. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - September 3, 2019 Category: Respiratory Medicine Authors: Elpis Hatziagorou, Annalisa Orenti, Pavel Drevinek, Nataliya Kashirskaya, Meir Mei-Zahav, Kris De Boeck, on behalf of the ECFSPR Tags: Original Article Source Type: research

Important steps in the journey to highly effective CFTR modulator access for people with CF
Recent years have seen critical steps along a path beginning with characterization of the first CFTR modulator with impressive activity in a relatively small proportion of the CF population, ivacaftor for adolescents and adults with a G551D CFTR mutation [1], and leading us towards a goal of universal access to highly effective CFTR modulators for all people with CF, irrespective of CFTR genotype or age. Three articles appear in this issue of the Journal that highlight important and multifaceted steps along this pathway demonstrating the biological efficacy of new CFTR modulator candidates across multiple CF genotype popul...
Source: Journal of Cystic Fibrosis - September 1, 2019 Category: Respiratory Medicine Authors: D.R. VanDevanter, N. Mayer-Hamblett Tags: Editorial Source Type: research

Inhaled therapies for NTM disease – The way forward?
Despite improvements in the control of respiratory infections and life expectancy in cystic fibrosis (CF), highly resistant pathogens such as nontuberculous mycobacteria have emerged as an increasing challenge [1]. Disease due to M. abscessus is of particular concern as it is associated with increased healthcare utilisation, accelerated lung function decline, impaired quality of life (QoL) [2], adverse impacts on post-lung transplant outcomes [3], and increased mortality [2]. Good quality evidence to support current treatment regimens is lacking, and access to effective antimicrobial treatment options is limited. (Source: ...
Source: Journal of Cystic Fibrosis - September 1, 2019 Category: Respiratory Medicine Authors: Rachel Thomson Tags: Editorial Source Type: research

Editorial Board
(Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - September 1, 2019 Category: Respiratory Medicine Source Type: research

Transcript from Stuart Elborn's address at the ECFC award in June 2019
The following is a transcript from Stuart Elborn ’s address at the ECFC upon receiving the ECFS award in June 2019 in Liverpool. He conducted the presentation without slides, creating such positive feedback that we have printed it here with his permission. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - September 1, 2019 Category: Respiratory Medicine Source Type: research

Whole-blood transcriptomic responses to lumacaftor/ivacaftor therapy in cystic fibrosis
Cystic fibrosis (CF) remains without a definitive cure. Novel therapeutics targeting the causative defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are in clinical use. Lumacaftor/ivacaftor is a CFTR modulator approved for patients homozygous for the CFTR variant p.Phe508del, but there are wide variations in treatment responses preventing prediction of patient responses. We aimed to determine changes in gene expression related to treatment initiation and response. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - August 29, 2019 Category: Respiratory Medicine Authors: Benjamin T. Kopp, James Fitch, Lisa Jaramillo, Chandra L. Shrestha, Frank Robledo-Avila, Shuzhong Zhang, Sabrina Palacios, Fred Woodley, Don Hayes, Santiago Partida-Sanchez, Octavio Ramilo, Peter White, Asuncion Mejias Source Type: research

Addressing the burden of illness in adults with cystic fibrosis with screening and triage: An early intervention model of palliative care
This study describes such a model and its immediate impact on care delivery for CF patients during a two-year period. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - August 27, 2019 Category: Respiratory Medicine Authors: Lara Dhingra, Patricia Walker, Maria Berdella, Amy Plachta, Jack Chen, Ashley Fresenius, Julie Balzano, Malcolm Barrett, Marilyn Bookbinder, Kenya Wilder, Myra Glajchen, Elinor Langfelder-Schwind, Russell K. Portenoy Source Type: research

Amikacin liposome inhalation suspension for chronic Pseudomonas aeruginosa infection in cystic fibrosis
Shortcomings of inhaled antibiotic treatments for Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) include poor drug penetration, inactivation by sputum, poor efficiency due to protective biofilm, and short residence in the lung. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - August 23, 2019 Category: Respiratory Medicine Authors: Diana Bilton, Tacjana Pressler, Isabelle Fajac, John Paul Clancy, Dorota Sands, Predrag Minic, Marco Cipolli, Ivanka Galeva, Amparo Sol é, Alexandra L. Quittner, Keith Liu, John P. McGinnis, Gina Eagle, Renu Gupta, Michael W. Konstan, for the CLEAR-108 S Tags: Original Article Source Type: research

The presence of Aspergillus fumigatus is associated with worse respiratory quality of life in cystic fibrosis
The clinical effects of Aspergillus fumigatus in the cystic fibrosis (CF) airway, with the exception of allergic bronchopulmonary aspergillosis, is unclear. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - August 21, 2019 Category: Respiratory Medicine Authors: Gina Hong, Kevin Alby, Sharon C.W. Ng, Victoria Fleck, Christina Kubrak, Ronald C. Rubenstein, Daniel J. Dorgan, Steven M. Kawut, Denis Hadjiliadis Source Type: research

The association of pediatric cystic fibrosis-related diabetes screening on clinical outcomes by center: A CF patient registry study
This study uses CF Foundation Patient Registry to examine the impact of screening practices at centers across the United States from 2008 to 2015. We examined the association of screening practices and CFRD diagnosis at individual centers and trends in ppFEV1 and BMI percentile prior t o and after diagnosis. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - August 19, 2019 Category: Respiratory Medicine Authors: Elizabeth Franck Thompson, David Watson, Christine M. Benoit, Sandy Landvik, John McNamara Tags: Original Article Source Type: research

Total pancreatectomy with islet autotransplantation in a pancreatic-sufficient cystic fibrosis patient
We present a case of a 4  year old female with pancreatic-sufficient CF, refractory ARP, frequent hospital admissions for abdominal pain, and continued growth failure despite gastrostomy tube and parenteral nutrition. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - August 13, 2019 Category: Respiratory Medicine Authors: Ina St Onge, Jaimie D. Nathan, Maisam Abu-El-Haija, Barbara A. Chini Source Type: research

Automated glycemic control with the bionic pancreas in cystic fibrosis-related diabetes: A pilot study
Cystic fibrosis-related diabetes (CFRD) is the most common extrapulmonary manifestation of cystic fibrosis. The current standard of care for CFRD involves treatment with insulin, typically via multiple daily injections. We conducted a small pilot study comparing usual care with automated glycemic control using the bihormonal (insulin and glucagon) and insulin-only configurations of the bionic pancreas. Both configurations of the bionic pancreas achieved good glycemic control, with mean glucose levels (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - August 13, 2019 Category: Respiratory Medicine Authors: Jordan S. Sherwood, Rabab Z. Jafri, Courtney A. Balliro, Hui Zheng, Firas H. El-Khatib, Edward R. Damiano, Steven J. Russell, Melissa S. Putman Tags: Short Communication Source Type: research

The impact of CFTR modulator therapies on CF airway microbiology
Major historical advances in cystic fibrosis (CF) respiratory clinical care, including mechanical airway clearance and inhaled medications, have aimed to address the consequences of cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. In contrast, CFTR modulator therapies instead target the underlying protein defect that leads to CF lung disease. The extent to which these therapies might reduce susceptibility to chronic lung infections remains to be seen. However, by improving airway clearance, reducing the requirement for antibiotics, and in some cases, through direct antimicrobial effects, CFTR modulat...
Source: Journal of Cystic Fibrosis - August 12, 2019 Category: Respiratory Medicine Authors: Geraint B. Rogers, Steven L. Taylor, Lucas R. Hoffman, Lucy D. Burr Tags: Review Source Type: research

News
The ECFS Award is given annually to honour a person who has made an outstanding contribution to our basic understanding of CF or to the treatment or care of patients with CF and the Gerd D öring Award is given annually to honour an exceptional early career young European scientist. This year's awardees are noted below, but we will be seeking nominations for next year. Please send nominations to christine.dubois@ecfs.eu (closing date 15th February 2020). (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - August 10, 2019 Category: Respiratory Medicine Source Type: research

Fair selection of participants in clinical trials: The challenge to push the envelope further
The pipeline of new drugs being developed for cystic fibrosis (CF) is both exciting and challenging, perhaps in equal measure. Issues related to the large number of trials being conducted, some of these competing for the same group of patients, the need to ensure that more traditional drugs such as anti-infectives/ anti-inflammatories can still be trialled whilst CFTR modulators are ‘stealing the show’ and the inequity of access remain paramount. The CF Foundation's Therapeutic Development Network (TDN) and the European CF Society Clinical Trials Network (ECFS CTN) are actively engaged in tackling these issues ...
Source: Journal of Cystic Fibrosis - August 9, 2019 Category: Respiratory Medicine Authors: J.C. Davies, S. Scott, R. Dobra, R. Brendell, K. Brownlee, S.B. Carr, R. Cosgriff, N.J. Simmonds, on behalf of the London Network of Clinical Trials Accelerator Platform sites, R. Jahan, A. Jones, J. Matthews, S. Brown, K. Galono, K. Miles, C. Pao, N. Sha Tags: Letter to the Editor Source Type: research

Omalizumab for asthma and allergic bronchopulmonary aspergillosis in adults with cystic fibrosis
In cystic fibrosis (CF), omalizumab has been used for difficult-to-treat asthma and allergic bronchopulmonary aspergillosis (ABPA) but safety and efficacy data are limited for this population. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - August 9, 2019 Category: Respiratory Medicine Authors: Angela Koutsokera, Sophie Corriveau, Jenna Sykes, Adele Coriati, Daniel Cortes, Peter Vadas, Cecilia Chaparro, Kieran McIntyre, Elizabeth Tullis, Anne L. Stephenson Source Type: research

Dysregulated insulin in pancreatic insufficient cystic fibrosis with post-prandial hypoglycemia
Post-prandial and oral glucose tolerance test-related hypoglycemia is common in cystic fibrosis (CF); however, the underlying mechanisms are unclear. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - August 8, 2019 Category: Respiratory Medicine Authors: Marissa J. Kilberg, Saba Sheikh, Darko Stefanovski, Christina Kubrak, Diva D. De Leon, Denis Hadjiliadis, Ronald C. Rubenstein, Michael R. Rickels, Andrea Kelly Tags: Original Article Source Type: research

The role of endothelial cells in cystic fibrosis
Cystic fibrosis (CF) is an autosomal recessive disease caused by the loss of function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein which primarily acts as a chloride channel. CFTR has mainly been studied in epithelial cells although it is also functional and expressed in other cell types including endothelial cells. The present review summarizes current knowledge on the role of the endothelium in CF. More specifically, this review highlights the role of endothelial cells in CF in acting as a semipermeable barrier, as a key regulator of angiogenesis, coagulation, the vascular tone and the inflam...
Source: Journal of Cystic Fibrosis - August 7, 2019 Category: Respiratory Medicine Authors: M. Declercq, L. Treps, P. Carmeliet, P. Witters Tags: Review Source Type: research

Distribution and outcomes of infection of Mycobacterium avium complex species in cystic fibrosis
The majority of nontuberculous mycobacterial (NTM) pulmonary infections in people with cystic fibrosis (CF) are caused by Mycobacterium avium complex (MAC) species. Data on MAC species distribution and outcomes of infection in CF are lacking. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - August 6, 2019 Category: Respiratory Medicine Authors: Michelle Azar, Madsen Zimbric, Kerby Shedden, Lindsay J. Caverly Tags: Short Communication Source Type: research

Risk factors for adverse outcome in infancy in meconium ileus cystic fibrosis infants: A multicentre Italian study
Meconium ileus (MI) is a risk factor for poor outcomes in cystic fibrosis (CF) patients. The aim of this study was to identify the risk factors for poor 12-month clinical outcomes in MI-CF newborns. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - July 25, 2019 Category: Respiratory Medicine Authors: Rita Padoan, Natalia Cirilli, Diego Falchetti, Bruno Mario Cesana, on behalf of the Meconium Ileus Project Study Group Source Type: research

Nasal potential difference in suspected cystic fibrosis patients with 5T polymorphism
5T polymorphism is a CFTR mutation with unclear clinical consequences: the phenotype varies from healthy individuals to Cystic Fibrosis (CF). The aim of this study was to evaluate if nasal potential difference (NPD) and sweat testing correlate with symptoms and CF diagnosis in 5T patients. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - July 19, 2019 Category: Respiratory Medicine Authors: Bente L. Aalbers, Yasmin Yaakov, Nico Derichs, Nicholas J. Simmonds, Elke De Wachter, Paola Melotti, Kris De Boeck, Teresinha Leal, Burkhart T ümmler, Michael Wilschanski, Inez Bronsveld Tags: Original Article Source Type: research

Randomized controlled study of aerosolized hypertonic xylitol versus hypertonic saline in hospitalized patients with pulmonary exacerbation of cystic fibrosis
We examined the safety and efficacy of aerosolized xylitol use for 2  weeks in subjects hospitalized with a pulmonary exacerbation of CF. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - July 18, 2019 Category: Respiratory Medicine Authors: Sachinkumar Singh, Douglas Hornick, Janel Fedler, Janice L. Launspach, Mary E. Teresi, Thomas R. Santacroce, Joseph E. Cavanaugh, Rebecca Horan, George Nelson, Timothy D. Starner, Joseph Zabner, Lakshmi Durairaj Tags: Original Article Source Type: research

Theranostics by testing CFTR modulators in patient-derived materials: The current status and a proposal for subjects with rare CFTR mutations
The last decade has witnessed developments in the CF drug pipeline which are both exciting and unprecedented, bringing with them previously unconsidered challenges. The Task Force group came together to consider these challenges and possible strategies to address them. Over the last 18  months, we have discussed internally and gathered views from a broad range of individuals representing patient organizations, clinical and research teams, the pharmaceutical industry and regulatory agencies. In this and the accompanying article, we discuss two main areas of focus: i) optimising t rial design and delivery for speed/efficie...
Source: Journal of Cystic Fibrosis - July 17, 2019 Category: Respiratory Medicine Authors: Margarida D. Amaral, Kris de Boeck, ECFS Strategic Planning Task Force on ‘Speeding up access to new drugs for CF’ Tags: Review Source Type: research

Self-reported alcohol use in the cystic fibrosis community
The objective of this investigation is to examine alcohol consumption patterns in individuals with CF using a health survey administered from a social media platform. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - July 11, 2019 Category: Respiratory Medicine Authors: Erin M. Lowery, Majid Afshar, Natalie West, Elizabeth J. Kovacs, Beth Smith, Cara Joyce Source Type: research

Speeding up access to new drugs for CF: Considerations for clinical trial design and delivery
The last decade has witnessed developments in the CF drug pipeline which are both exciting and unprecedented, bringing with them previously unconsidered challenges. The Task Force group was brought together to consider these challenges and possible strategies to address them. Over the last 18  months, we have discussed internally and gathered views from a broad range of individuals representing patient organisations, clinical and research teams, the pharmaceutical industry and regulatory agencies. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - July 11, 2019 Category: Respiratory Medicine Authors: Jane C. Davies, Pavel Drevinek, J. Stuart Elborn, Eitan Kerem, Tim Lee, On behalf of the European CF Society (ECFS) Strategic Planning Task Force on ‘Speeding up access to new 4 drugs for CF’, Margarida D. Amaral, Kris de Boeck, Jane C. Davies, Pavel Tags: Original Article Source Type: research

Supersonic shear-wave elastography and APRI for the detection and staging of liver disease in pediatric cystic fibrosis
This study investigated the potential of Supersonic shear-wave elastography (SSWE) to non-invasively detect CFLD and assess hepatic fibrosis severity in children with CF. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - July 11, 2019 Category: Respiratory Medicine Authors: Diego A. Calvopina, Charlton Noble, Anna Weis, Gunter F. Hartel, Louise E. Ramm, Fariha Balouch, Manuel A. Fernandez-Rojo, Miranda A. Coleman, Peter J. Lewindon, Grant A. Ramm Tags: Original Article Source Type: research

A cystic fibrosis child with lung function decline
We report here the case of a 7-year-old cystic fibrosis child with pulmonary exacerbation and Arthrographis kalrae isolated from bronchoalveolar lavage fluid. To the best of our knowledge, this is the first reported case of lung infection due to Arhtrographis kalrae in a cystic fibrosis pediatric patient. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - July 9, 2019 Category: Respiratory Medicine Authors: Ersilia Vita Fiscarelli, Gabriella Ricciotti, Martina Rossitto, Arianna Pompilio, Vanessa Tuccio Guarna Assanti, Vincenzina Lucidi Source Type: research

Taskforce recommends coordinated effort to improve clinical research conduct and find highly effective CFTR-directed treatment for rare mutations
Through companion publications in this issue of the Journal, a group of recognized authors provide summary recommendations from a ECFS taskforce mostly of European leaders and stakeholders to consider the challenges in CF clinical research in an era of widespread access to highly effective CFTR modulator treatment (HEMT) (Editors please insert REFS for these 2 papers to be printed in this edition). The Taskforce focuses particular attention on advancing therapies for those with rare CFTR mutations. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - July 4, 2019 Category: Respiratory Medicine Authors: G.M. Solomon, D.P. Nichols Tags: Editorial Source Type: research

Pregnancy outcome in women with cystic fibrosis and poor pulmonary function
To investigate how poor pre-gestational pulmonary function influenced pregnancy outcome and clinical status evolution in women with cystic fibrosis. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - July 1, 2019 Category: Respiratory Medicine Authors: Quitterie Reynaud, Christine Rousset Jablonski, St éphanie Poupon-Bourdy, Angélique Denis, Muriel Rabilloud, Lydie Lemonnier, Raphaële Nove-Josserand, Stéphane Durupt, Sandrine Touzet, Isabelle Durieu, Participating Centers of the French Cystic Fibros Tags: Original Article Source Type: research

Mild cystic fibrosis in carriers of two nonsense mutations – a case of genetic compensation response?
Data of the cystic fibrosis (CF) registries indicate that compound heterozygosity for the most common Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutation p.Phe508del and a class 1 loss-of-function mutation is associated with the highest meconium ileus prevalence (MIP) score and a higher-than-average rate of annual decline of lung function and body mass index (BMI) [1]. Mutation class I compiles a heterogeneous group of disease-causing lesions, i.e. nonsense, frameshift and splice mutations and large deletions having variable consequences on splicing, readthrough and yield of CFTR mRNA transcripts. (Source: ...
Source: Journal of Cystic Fibrosis - June 29, 2019 Category: Respiratory Medicine Authors: Burkhard T ümmler Tags: Letter to the Editor Source Type: research

Dissociation of systemic and mucosal autoimmunity in cystic fibrosis
In this study, we sought to better understand the characteristics of systemic and mucosal autoimmunity and their relation to humoral immunity to P. aeruginosa. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - June 28, 2019 Category: Respiratory Medicine Authors: J. Theprungsirikul, S. Skopelja-Gardner, R.E. Meagher, J.P. Clancy, E.T. Zemanick, A. Ashare, W.F.C. Rigby Tags: Original Article Source Type: research

A phase 3 study of tezacaftor in combination with ivacaftor in children aged 6 through 11  years with cystic fibrosis
Tezacaftor/ivacaftor is a new treatment option in many regions for patients aged ≥12 years who are homozygous (F/F) or heterozygous for the F508del-CFTR mutation and a residual function (F/RF) mutation. This Phase 3, 2-part, open-label study evaluated the pharmacokinetics (PK), safety, tolerability, and efficacy of tezacaftor/ivacaftor in children aged 6 through 11 years w ith these mutations. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - June 27, 2019 Category: Respiratory Medicine Authors: Seth Walker, Patrick Flume, John McNamara, Melinda Solomon, Mark Chilvers, James Chmiel, R. Scott Harris, Eric Haseltine, David Stiles, Chonghua Li, Neil Ahluwalia, Honghong Zhou, Caroline A. Owen, Gregory Sawicki, on behalf of the VX15-661-113 Investigat Source Type: research

Predictors of pulmonary exacerbation treatment in cystic fibrosis
Most studies of pulmonary exacerbations (PEx) in cystic fibrosis (CF) focus on intravenous (IV)-treated PEx, though most PEx are treated with oral antibiotics. Our objectives were to describe predictors of antibiotic choice and outcomes for PEx initially identified in clinic. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - June 27, 2019 Category: Respiratory Medicine Authors: Don B. Sanders, Joshua S. Ostrenga, Margaret Rosenfeld, Aliza K. Fink, Michael S. Schechter, Gregory S. Sawicki, Patrick A. Flume, Wayne J. Morgan Tags: Original Article Source Type: research

Variation in lung function and nutritional decline in cystic fibrosis by genotype: An analysis of the Canadian cystic fibrosis registry
This study aimed to improve our understanding of the natural history of cystic fibrosis (CF) by comparing lung function and body mass index z-score (zBMI) between patients with different genotypes and identify a genotype with outcomes most comparable to homozygous ΔF508 patients. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - June 25, 2019 Category: Respiratory Medicine Authors: Garvin J. Leung, Ting J. Cho, Thomas Kovesi, Jemila S. Hamid, Dhenuka Radhakrishnan Tags: Original Article Source Type: research

Tackling bias in clinical trials
In recent years there has been a significant increase in the number of randomised controlled trials (RCTs) in CF. All eyes are focused on the therapeutic effect under investigation and what that could mean for people with CF. RCTs frequently contain a placebo (control) arm to function as a methodological safeguard for systematic bias, normal fluctuations in outcome measures, regression of outcome measures to the mean, and most importantly, the effect size of the therapeutic intervention [1]. It is recognised that participants in the placebo arm of RCTs can experience improvement in patient-reported outcomes (e.g. (Source: ...
Source: Journal of Cystic Fibrosis - June 21, 2019 Category: Respiratory Medicine Authors: Silke van Koningsbruggen-Rietschel, Damian G. Downey Tags: Editorial Source Type: research

Challenging barriers to an option for improved provision of enteral nutrition
CF clinicians have long recognized the negative effect of malnutrition on outcomes in people with CF [1] and the importance of a high-calorie diet to support weight gain and growth [2] . Nutritional status has been widely accepted as one of the critical metrics for health in people with CF. Low BMI has been identified as one factor associated with larger mean annual lung function decline [3]. Enteral feedings to increase caloric intake are used to support optimal weight gain in those at nutritional risk. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - June 21, 2019 Category: Respiratory Medicine Authors: Sarah Jane Schwarzenberg, Drucy Borowitz, on behalf of 20 gastroenterologists, 23 CF physicians, 17 CF dietitians and 1 PharmD Tags: Perspective Commentary Source Type: research

Editorial Board
(Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - June 21, 2019 Category: Respiratory Medicine Source Type: research

Do current clinical trials in cystic fibrosis match the priorities of patients and clinicans? A systematic review
There are many uncertainties regarding Cystic Fibrosis (CF) treatment. Recently, the first James Lind Alliance (JLA) Priority Setting Partnership (PSP) in CF was completed, bringing clinicians, patients and carers together to identify the Top 10 research priorities. Here we investigate how well the current clinical trials landscape reflects these priorities. Trials in CF were identified through searches of research databases (Pubmed, ANZCTR, EU clinical trials register, ClinicalTrials.gov and ISRCTN). (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - June 21, 2019 Category: Respiratory Medicine Authors: I.S. Kalaitzis, N.J. Rowbotham, S.J. Smith, A.R. Smyth Tags: Short Communication Source Type: research

Disease progression in patients with cystic fibrosis treated with ivacaftor: Data from national US and UK registries
Ivacaftor is the first in a class of drugs, CFTR modulators, that target the underlying defect in cystic fibrosis (CF). This long-term observational safety study evaluated CF disease progression in patients treated with ivacaftor in a real-world setting for up to 5  years. (Source: Journal of Cystic Fibrosis)
Source: Journal of Cystic Fibrosis - June 10, 2019 Category: Respiratory Medicine Authors: Nataliya Volkova, Kristin Moy, Jennifer Evans, Daniel Campbell, Simon Tian, Christopher Simard, Mark Higgins, Michael W. Konstan, Gregory S. Sawicki, Alexander Elbert, Susan C. Charman, Bruce C. Marshall, Diana Bilton Source Type: research