Cystic fibrosis drug trial design in the era of CFTR modulators associated with substantial clinical benefit: stakeholders' consensus view.

CFTR modulators associated with substantial clinical benefit are expected to rapidly improve the baseline condition of people with cystic fibrosis (PWCF) as well as decrease the rate of lung function decline, the occurrence of pulmonary exacerbations and likely even other disease complications. These changes in clinical status of PWCF introduced by clinically effective modulator therapy will have major repercussions on modalities of future CF drug development. As part of its 'Strategic Plan to speed up Access to new Drugs', the European Cystic Fibrosis Society (ECFS) convened a meeting in Brussels on November 27 2019 with relevant stakeholders (CF researchers and clinicians, patient organization and pharmaceutical company representatives, regulators, health technology assessors; see Acknowledgments for list of attendees) to discuss the future of clinical trials in cystic fibrosis (CF) in the context of HEMT entering the clinical arena.

Building global development strategies for cf therapeutics during a transitional cftr modulator era.

As CFTR modulator therapy transforms the landscape of cystic fibrosis (CF) care, its lack of uniform access across the globe combined with the shift towards a new standard of care creates unique challenges for the development of future CF therapies. The advancement of a full and promising CF therapeutics pipeline remains a necessary priority to ensure maximal clinical benefits for all people with CF. It is through collaboration across the global CF community that we can optimize the evaluation and approval process of new therapies.

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

Background: Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic lung infection resulting in inflammation and progressive lung damage that results in a reduced life expectancy.

Objectives: To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes, and to assess any adverse effects.

Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.

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

Background: Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic lung infection resulting in inflammation and progressive lung damage that results in a reduced life expectancy.

Objectives: To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes, and to assess any adverse effects.

Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.

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

Background: Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic lung infection resulting in inflammation and progressive lung damage that results in a reduced life expectancy.

Objectives: To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes, and to assess any adverse effects.

Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.

Prevention of chronic Pseudomonas aeruginosa infection in people with cystic fibrosis.

Cystic fibrosis is the most common genetically inherited disease in the Caucasian population, with approximately 30,000 patients in the USA and more than 50,000 patients worldwide. The primary defect in the cystic fibrosis transmembrane regulator gene affects the production and/or function of the cystic fibrosis transmembrane regulator protein. Depending on the severity of the genetic defect, patients may have minimal disease expression (e.

Serum tobramycin levels following delivery of tobramycin (Tobi) via eFlow advanced nebuliser in children with cystic fibrosis.

Background: Safety and toxicity data for nebulised tobramycin are mainly derived from use of the Pari LC Plus nebuliser, yet many centres are now using advanced nebulisers, such as the eFlow.

Methods: Ten children (ages 2-16years) receiving 300mg TOBI via eFlow for clinical reasons participated. Serum tobramycin levels were obtained 1h post nebulisation.

Eradication of early Pseudomonas infection in cystic fibrosis.

Chronic infection with the environmental bacterium Pseudomonas aeruginosa is associated with greater morbidity and mortality for people with cystic fibrosis. Strict infection control measures including segregation appear to reduce but not eliminate the risk of initial acquisition of the organism. There is now good evidence from randomized controlled trials that early eradication regimens consisting of anti-pseudomonal antibiotics are effective in clearing P.

Respiratory exacerbations in childhood associated with compound heterozygosity Phe508del/Arg117His-7T of the cystic fibrosis transmembrane regulator gene.

Unlabelled: Debate continues regarding the clinical implications for compound heterozygotes identified with Phe508del and Arg117His-7T mutations of the cystic fibrosis transmembrane regulator (CFTR) gene. We report respiratory exacerbations and airway culture of Staphylococcus aureus and Pseudomonas aeruginosa in a child with this genotype.

Conclusion: The compound heterozygote cystic fibrosis (CF) mutation Phe508del with Arg117His-7T should not necessarily be considered benign in childhood.

Longitudinal analysis of FEV1 changes related to antibiotic therapy in children with cystic fibrosis.

The measurement of FEV1 in children with cystic fibrosis has been shown to be the most important objective measurement for survival. It has been observed that children receiving intravenous antibiotics usually show a significant improvement in FEV1 with therapy in the short term. We hypothesized that the FEV1 measured pre-antibiotic therapy and followed longitudinally would show a greater rate of decline and may be a better prognostic indicator than the FEV1 post antibiotic therapy.

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

Background: Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic lung infection resulting in inflammation and progressive lung damage that results in a reduced life expectancy.

Objectives: To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes, and to assess any adverse effects.

Search Strategy: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.

Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients.

Background: Patients were defined each successive month as either 'chronic' when more than 50% of the preceding 12 months were PA culture positive, 'intermittent' when < or =50% of the preceding 12 months were PA culture positive, 'free of PA', with no growth of PA for the previous 12 months, having previously been PA culture positive, or 'never infected', when PA had never been cultured.

Methods: Cross-sectional analysis of 146 children attending the Leeds Regional Cystic Fibrosis Centre was performed to assess relationship between the new definition and clinical scores and investigations. The response variable was regressed on age and sex and the residuals analysed using the Kruskal-Wallis test.

Transmission of colistin-resistant Pseudomonas aeruginosa between patients attending a pediatric cystic fibrosis center.

We report on an outbreak of colistin-resistant Pseudomonas aeruginosa (CRPA) that occurred in a United Kingdom pediatric cystic fibrosis (CF) unit and involved six children over a period of 5 years. All CRPA-positive children had received aerosolized colistin therapy before first isolation of resistant organisms (mean duration, 3.1 years).