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Cystic Fibrosis (CF) is a life-limiting, inherited condition in which a novel class of oral medicine, CFTR modulators, has revolutionised symptoms and health indicators, providing an opportunity to evaluate traditional treatment regimens with the hope of reducing burden. Additionally, there is cautious optimism that life expectancy for people with CF born today could ultimately compare to that of the general population. Given this potential, there is a need and requirement to optimise treatment to balance burden with the best clinical outcomes for each person with CF in an individualised manner. Personalised data-Linkage to Understand Treatment Optimisation (PLUTO) is a clinical framework, developed within the 14-Centre UK CFHealthHub Learning Health System collaborative, designed for use at an individual level for people with CF taking CFTR modulators. The PLUTO framework encourages use of two routinely collected clinical outcome measure (FEV1 and BMI) to determine health status. Where FEV1 or BMI trends suggest that optimal health outcomes are not being achieved for a person with CF, PLUTO supports consideration of adherence to both CFTR modulators and inhaled therapy to help guide the next steps. PLUTO is designed to support people with CF and their clinical teams to individualise care and optimise outcomes for those taking CFTR modulators, using data available in routine clinical encounters.
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http://dx.doi.org/10.1016/j.rmed.2025.108016 | DOI Listing |
Ann Am Thorac Soc
September 2025
Erasmus MC, Rotterdam, Zuid-Holland, Netherlands.
Rationale: Modulator therapies like ivacaftor have revolutionized clinical management of cystic fibrosis (CF), showing marked short-term benefits in trials but heterogeneous findings in long-term observational studies. Since newer modulators have become the standard of care for the majority living with CF in the U.S.
View Article and Find Full Text PDFAm J Physiol Lung Cell Mol Physiol
September 2025
Division of Pulmonary Medicine, Cincinnati Children's Hospital, Cincinnati, OH.
Cystic Fibrosis (CF) is characterized by impaired mucociliary clearance and pulmonary infections. Accumulating evidence suggests that fundamentally abnormal inflammatory responses also contribute to CF pathology. TGFβ, a pleiotropic cytokine, is a modifier of CF lung disease; its mechanism of action in CF is unclear.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
September 2025
Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA.
We previously demonstrated the CFTR correctors VX-445 (elexacaftor) and S-VX-121 (vanzacaftor) potentiate heterologously-expressed BK channels, as well as in primary human bronchial epithelial cells (HBEs). This potentiation of BK resulted in altered vasoreactivity and neuronal excitability. We postulated novel compounds could be identified that would potentiate BK while not affecting CFTR.
View Article and Find Full Text PDFFront Pediatr
August 2025
Division of Pediatric Pulmonology, Department of Pediatrics, Oregon Health & Science University, Portland, OR, United States.
Background: Modulator therapy restores CFTR function and has led to health benefits for persons with cystic fibrosis (CF) (PwCF), including lower rates of pulmonary exacerbations. It is unknown if modulators affect lung function trajectories after inpatient treatment of pulmonary exacerbations (PEx).
Methods: We conducted a retrospective review of hospital encounters for PEx for subjects 6-25 years old with mild to moderate lung disease admitted to a large tertiary care center from 2014 to 2021 to capture hospitalizations of PwCF before and after starting modulators.
Curr Opin Pulm Med
September 2025
4D Molecular Therapeutics, Emeryville, California, USA.
Purpose Of Review: There is a critical need for new therapies addressing the high unmet needs of individuals with rare lung diseases. This review examines the challenges industry sponsors face in developing therapeutic products for rare lung diseases, using cystic fibrosis as an example.
Recent Findings: Since the development of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, the drug development landscape for cystic fibrosis has changed.