CF-Tracker study: protocol for a multicentre prospective longitudinal study investigating triggers and mechanisms of pulmonary exacerbations in cystic fibrosis
Year: 2026
Type: article
Study design: Study Protocol
Abstract: Background Pulmonary exacerbations remain a major cause of morbidity in cystic fibrosis (CF), despite advances in cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. These events are associated with reduced quality of life, accelerated lung function decline, and increased healthcare utilisation. Their underlying mechanisms remain poorly understood, and traditional models centred on bacterial overgrowth confound our understanding based on observations from microbiome and susceptibility studies. Exacerbations are likely driven by heterogeneous triggers, including viral infection, changes to microbiome composition, host inflammatory response, and environmental exposures, which are not well captured by current clinical assessments. Methods CF-Tracker is a multicentre, prospective, longitudinal observational study recruiting 300 adults with CF and up to 40 healthy controls across UK centres. Participants undergo a baseline assessment followed by 6-months of intensive home monitoring and 12-months longitudinal follow-up. A tiered design includes a subgroup undergoing enhanced in-person assessments. Fortnightly home sampling includes respiratory viral swabs, saliva collection, spirometry, and symptom reporting, with additional sampling during exacerbations. Certain biofluids (sputum, nasal, and plasma) will undergo omics analyses. A systems biology approach will integrate clinical, microbiology, immunology, and multi-omics data. Additionally, a subset of patients will provide environmental exposure data, including optional air pollution and mould monitoring, for hypothesis generation. The primary outcome is time to first exacerbation requiring antibiotic treatment, alongside exacerbation frequency over 12 months. Results This study will generate a longitudinal dataset linking clinical outcomes with biological, microbiological, and environmental measures. It is expected to identify distinct exacerbation phenotypes, quantify contributions of different triggers, and identify biomarkers associated with exacerbation susceptibility and severity. Conclusions CF-Tracker will provide a comprehensive characterisation of pulmonary exacerbations in CF, enabling improved understanding of underlying mechanisms. These findings are expected to inform targeted, evidence-based prevention strategies and reduce reliance on antibiotics, addressing a major unmet need in CF care.
Authors: Weinberg, Sharon E, Caamaño-Gutiérrez, Eva, Tunney, Michael M, Ahmad, Shazaad, Bannan, Thomas J, Barry, Peter, Beattie, Laura J, Brockhurst, Michael A, Doe, Simon, Duckers, Jamie, Einarsson, Gisli G; id_orcid 0000-0003-1353-950X, Emmott, Edward, Felton, Tim, Fowler, Stephen J, Frost, Freddy, Gilpin, Deirdre F, Jones, Andrew, Lord, Robert W, Maher, Rosemary, Mann, Elizabeth, McFiggans, Gordon, Peckham, Daniel, Sahin, Zeliha Gozde, Villis, Laura, Whelan, Fiona, Smyth, Alan R; id_orcid 0000-0001-5494-5438, Bell, Scott, Flume, Patrick A, Horsley, Alexander
Institutions: University of Manchester, Manchester University NHS Foundation Trust, University of Liverpool, Queen's University Belfast, Newcastle upon Tyne Hospitals NHS Foundation Trust, Cardiff and Vale University Health Board, National Health Service Wales, NIHR Manchester Biomedical Research Centre, Liverpool Heart and Chest Hospital NHS Trust, Liverpool Heart and Chest Hospital, University of Leeds, St James's University Hospital, Nottingham Biomedical Research Centre, Prince Charles Hospital, Medical University of South Carolina
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1483213741, G1798610363
OpenAlex ID: W7210629906