INTRODUCTION: Inflammation is causally related to cancer progression and cardiovascular toxicities of anticancer treatments. Fine particulate matter (PM2.5) air filtration lowers interleukin-6 and C reactive protein (CRP) levels in high-risk cardiopulmonary groups, though potential synergistic or confounding effects with routine medications-statins, cyclo-oxygenase-2 inhibitors, beta-blockers-remain poorly understood. Whether overnight in-bedroom PM2.5 air filtration effectively reduces inflammation and prothrombotic biomarkers in survivors of adult-onset cancer at high cardiovascular toxicity risk is unknown.

METHODS AND ANALYSIS: BREATHS is a series of randomised, adaptive, blinded, placebo-controlled N-of-1 trials conducted in densely populated urban areas of Valencia, Spain, during winter when PM2.5 concentrations historically exceed WHO guidelines. Eligible participants are aged ≥18 years with a history of breast, colorectal, prostate, lung or haematological cancer, prior cardiotoxic cancer therapy and CRP ≥3 mg/L. Each participant will undergo up to three cycles, each comprising two 14-day periods of advanced submicron air filtration (clean air delivery rate: 275 m3/hour nightly) or placebo (sham filtration), in random order. Sequence duration ranges from 4 weeks to 12 weeks, depending on whether a clinically meaningful CRP reduction (<2 mg/L or ≥35% relative to placebo) is achieved during active treatment of each cycle. Non-responders will enter an open-label phase (OLP) of two 14-day periods: no treatment followed by continuous filtration. The primary endpoint is change in CRP between active and placebo phases. Secondary endpoints include changes in serum amyloid A, haemoglobin A1c and blood pressure. Indoor and outdoor particulate exposure will be quantified using paired real-time monitors at each home.

ETHICS AND DISSEMINATION: The trial protocol was approved by the research ethics committees of University College London (REC UCL: 22105/001), Doctor Peset University Hospital (CEIm: 044/25) and General University Hospital of Valencia (CEIm: 1/2026 EO-PS), Spain. Results will be presented at relevant conferences and published in peer-reviewed journals.

TRIAL REGISTRATION NUMBER: NCT06778122.