scholarly journals “Pathogen Eradication” and “Emerging Pathogens”: Difficult Definitions in Cystic Fibrosis

2018 ◽  
Vol 56 (9) ◽  
Author(s):  
Peter H. Gilligan ◽  
Damian G. Downey ◽  
J. Stuart Elborn ◽  
Patrick A. Flume ◽  
Sebastian Funk ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pulmonary Inflammation ◽  
Airway Disease ◽  
Current Treatment ◽  
Transmembrane Conductance Regulator ◽  
Common Complication ◽  
Emerging Pathogens ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane ◽  
Chronic Use

ABSTRACTInfection is a common complication of cystic fibrosis (CF) airway disease. Current treatment approaches include early intervention with the intent to eradicate pathogens in the hope of delaying the development of chronic infection and the chronic use of aerosolized antibiotics to suppress infection. The use of molecules that help restore CFTR (cystic fibrosis transmembrane conductance regulator) function, modulate pulmonary inflammation, or improve pulmonary clearance may also influence the microbial communities in the airways. As the pipeline of these new entities continues to expand, it is important to define when key pathogens are eradicated from the lungs of CF patients and, equally important, when new pathogens might emerge as a result of these novel therapies.

scholarly journals Specialized Pro-Resolving Lipid Mediators in Cystic Fibrosis

2018 ◽  
Vol 19 (10) ◽  
pp. 2865 ◽  
Author(s):  
Réginald Philippe ◽  
Valerie Urbach
Keyword(s):  
Cystic Fibrosis ◽  
Structural Damage ◽  
Bacterial Colonization ◽  
Airway Disease ◽  
Lipid Mediators ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Persistent Inflammation ◽  
Gene Coding ◽  
Cystic Fibrosis Transmembrane

In cystic fibrosis (CF), impaired airway surface hydration (ASL) and mucociliary clearance that promote chronic bacterial colonization, persistent inflammation, and progressive structural damage to the airway wall architecture are typically explained by ion transport abnormalities related to the mutation of the gene coding for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel. However, the progressive and unrelenting inflammation of the CF airway begins early in life, becomes persistent, and is excessive relative to the bacterial burden. Intrinsic abnormalities of the inflammatory response in cystic fibrosis have been suggested but the mechanisms involved remain poorly understood. This review aims to give an overview of the recent advances in the understanding of the defective resolution of inflammation in CF including the abnormal production of specialized pro-resolving lipid mediators (lipoxin and resolvin) and their impact on the pathogenesis of the CF airway disease.

Treating the Underlying Cystic Fibrosis Transmembrane Conductance Regulator Defect in Patients with Cystic Fibrosis

2019 ◽  
Vol 40 (06) ◽  
pp. 762-774 ◽  
Author(s):  
Senne Cuyx ◽  
Kris De Boeck
Keyword(s):  
Cystic Fibrosis ◽  
Significant Proportion ◽  
Real Life ◽  
Current Treatment ◽  
Detailed Knowledge ◽  
Transmembrane Conductance Regulator ◽  
Class Iii ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane ◽  
Cftr Modulators

AbstractDetailed knowledge of how mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene disturb the trafficking or function of the CFTR protein and the use of high-throughput drug screens have allowed novel therapeutic strategies for cystic fibrosis (CF). The main goal of treatment is slowly but surely shifting from symptomatic management to targeting the underlying CFTR defect to halt disease progression and even to prevent occurrence of CF complications. CFTR potentiators for patients with class III mutations, mutation R117H (and in United States also for patients with specific residual function mutations) and the combination of a CFTR modulator plus a potentiator for patients homozygous for F508del, are the two classes of modulators that are in use in the clinic. Approval of these therapeutics has progressively expanded to include both younger patients and a wider range of CFTR mutations. For a significant proportion of patients with CF, current treatment is however still insufficient or unavailable.This review provides an overview of the clinical trial results and the real-life efficacy data of approved CFTR modulators. In addition, we discuss the entire pipeline of CFTR modulators: novel potentiators and correctors, amplifiers, stabilizers, and read-through agents. Furthermore, we discuss other strategies to improve CFTR function like nonsense-mediated decay inhibitors, modified transfer ribonucleic acids, antisense oligonucleotides, and genetic therapies.CFTR modulators are already changing the face of CF and the pipeline of new therapies continues to be exciting.

scholarly journals The porcine lung as a potential model for cystic fibrosis

2008 ◽  
Vol 295 (2) ◽  
pp. L240-L263 ◽  
Author(s):  
Christopher S. Rogers ◽  
William M. Abraham ◽  
Kim A. Brogden ◽  
John F. Engelhardt ◽  
John T. Fisher ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Potential Model ◽  
Airway Disease ◽  
Pancreatic Disease ◽  
Therapeutic Strategies ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Gene Encoding ◽  
Novel Therapeutic Strategies ◽  
Cystic Fibrosis Transmembrane

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

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