Cystic fibrosis year in review 2025

Area of Science:

• Pulmonary Medicine
• Genetics
• Immunology

Background:

• Cystic fibrosis (CF) management is evolving due to CFTR modulators (CFTRm).
• Despite modulator benefits, challenges like infection, inflammation, and comorbidities remain.
• CF is transitioning into a chronic, heterogeneous condition requiring new care strategies.

Purpose of the Study:

• To review the 2025 literature on the evolving landscape of CF care in the modulator era.
• To summarize advancements in CFTR modulators and emerging therapeutic strategies.
• To examine persistent challenges in infection, inflammation, and multisystem comorbidities.

Main Methods:

• Literature review of 2025 publications on cystic fibrosis.
• Analysis of current and next-generation CFTR modulator therapies.
• Examination of emerging mutation-agnostic treatments, anti-inflammatory agents, and gene-based therapies.

Main Results:

• Elexacaftor/tezacaftor/ivacaftor (ETI) shows durable lung function gains but has eligibility and access gaps.
• Emerging therapies include ENaC blockers, neutrophil-directed anti-inflammatories, and gene therapies.
• While ETI reduces some inflammatory markers, chronic infections and immune defects persist.
• Bacteriophage therapy shows promise for multidrug-resistant infections; microbiome interventions have limited impact.
• Increased survival highlights the growing relevance of pregnancy, malignancy, and cardiovascular disease.

Conclusions:

• CF care is shifting towards lifelong, equitable management of a diverse, aging population.
• Next-generation modulators and novel therapies are crucial for addressing unmet needs.
• Multidisciplinary, system-level care models are essential for managing complex CF comorbidities.