Cystic fibrosis year in review 2025

Cystic fibrosis (CF) is being reshaped by CFTR modulators (CFTRm), yet infection, inflammation, and multisystem comorbidities persist. This review of the 2025 CF literature summarizes how CF is evolving into a chronic, heterogeneous condition in the modulator era. First, we discuss the consolidation of elexacaftor/tezacaftor/ivacaftor (ETI) and next-generation modulators, highlighting durable gains in lung function and survival alongside persistent gaps in eligibility, access, and long-term safety, particularly for individuals with advanced structural lung damage or class I variants. Second, emerging mutation-agnostic therapy strategies are outlined, including ENaC blockade, neutrophil-directed anti-inflammatories like brensocatib, and gene and nucleic acid-based therapeutic approaches . Third, we examine airway infection and inflammation: while ETI reduces pathogen detection and systemic inflammatory markers, chronic Pseudomonas aeruginosa and heterogeneous neutrophilic endotypes frequently persist, and mucosal immune defects remain incompletely corrected. In this context, bacteriophage therapy has emerged as a candidate for multidrug-resistant infections, while microbiome-focused interventions show limited clinical impact despite clear shifts in microbial communities. Finally, as survival improves, pregnancy, age-related malignancy, and cardiovascular disease are becoming increasingly relevant, necessitating new models of multidisciplinary, lifespan care. Collectively, these developments mark a shift towards equitable, lifelong, system-level management of health in an aging and increasingly diverse CF population.