Morelli, Tommaso, Geeves, Madison E., Ahmed, Mohammed, Spalluto, Cosma Mirella, Ackland, Jodie, Freeman, Anna, Ullah, Farhan, Weeks, Jake, Page, Lee Kevin, Kong, Chia Wei, Welham, Benjamin Matthew Kelvey, Tarcan, Arda, Purcell, Martha, Simms, Claire Sally Amanda, Staples, Karl J., Watson, Alastair and Wilkinson, Tom M.A. (2025) Beyond spirometry: understanding COPD origins to support a new diagnostic approach. ERJ Open Research. (doi:10.1183/23120541.00885-2025).
Abstract
COPD remains a leading cause of morbidity and mortality, with outcomes stagnating relative to other long-term conditions. Current diagnostic pathways rely on spirometry, which detects airflow obstruction only after irreversible small-airway and parenchymal damage has accrued, whereas pathogenic processes begin decades earlier. This review examines how understanding early pathogenic processes could inform alternative approaches to diagnosis and treatment. We highlight the contribution of developmental and environmental exposures, genetic susceptibility, and epigenetic modification to disease initiation. We outline how these convergent mechanisms drive structural and functional abnormalities undetectable by conventional diagnostics but measurable with novel techniques. Advanced imaging—parametric response mapping, hyperpolarised gas MRI, and CT-based vascular metrics—can detect emphysema, small-airways disease, and vascular pruning before spirometric thresholds are reached. Physiological tools including forced oscillation techniques and capnography show promise for early detection in primary care and may be scalable, affordable alternatives to spirometry. Biofluid-based platforms—including exhaled breath analysis, extracellular matrix neo-epitopes, and blood-based inflammatory signatures—offer non-invasive phenotyping and risk stratification, though require validation and pathway integration. We argue for a shift from a spirometry-centric model to a multidimensional diagnostic framework integrating imaging, molecular, physiological, and biomarker data. Recent longitudinal evidence, including diagnostic schemas combining imaging with symptom burden, indicates that such approaches identify high-risk individuals missed by spirometry alone. Proactive COPD detection in its earliest stages is therefore an essential step to altering disease trajectory and improving patient outcomes and it is time our community looks beyond spirometry to deliver this.
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