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University of Alabama at Birmingham-led researchers have refined and validated a new framework for diagnosing chronic obstructive pulmonary disease (COPD), identifying individuals at risk for severe respiratory outcomes who would not meet current diagnostic thresholds.

COPD affects an estimated 392 million people globally and remains a leading cause of disability and mortality. Standard diagnostic practice has depended heavily on airflow obstruction measured via spirometry, with a forced expiratory volume in one second to a forced vital capacity ratio below 0.70 as the defining threshold. Multiple studies have shown this approach fails to detect significant structural abnormalities and symptomatic individuals who do not meet this numerical cutoff.

Imaging studies have revealed that individuals without airflow obstruction may still exhibit emphysema or bronchial wall thickening. Many of these individuals, especially those with a history of smoking, also report respiratory symptoms and poor quality of life.

Existing guidelines acknowledge symptoms and imaging abnormalities but have not integrated them into a cohesive diagnostic structure. Calls for a more inclusive, multidimensional model have remained largely unmet.

In the study, "A Multidimensional Diagnostic Approach for Chronic Obstructive Pulmonary Disease, " published in JAMA, researchers conducted a cohort study to determine whether a diagnostic schema incorporating respiratory symptoms and chest computed tomography (CT) findings would identify additional individuals with COPD and predict worse outcomes.

Two major cohorts were included. COPDGene enrolled 10, 305 participants at 21 sites in the United States between 2007 and 2011, with follow-up through 2022. CanCOLD enrolled 1, 561 participants across nine sites in Canada between 2009 and 2015, with follow-up through 2023.

Participants underwent spirometry and chest CT imaging. Researchers used a diagnostic framework with two paths: a major category based on airflow obstruction plus at least one minor criterion, and a minor category requiring three of five minor criteria. Minor criteria included visual emphysema, airway wall thickening, dyspnea, chronic bronchitis, and poor respiratory quality of life.

Among 9, 416 participants in COPDGene with complete data, 811 individuals without airflow obstruction were newly classified as having COPD based on minor criteria alone. Individuals in this group experienced higher all-cause mortality (adjusted hazard ratio 1.98), increased respiratory-specific mortality (hazard ratio 3.58), more frequent exacerbations (incidence rate ratio 2.09), and faster forced expiratory volume in one second decline than those without COPD.

In the Canadian CanCOLD cohort, 48 of 685 participants (7.0 %) without airflow obstruction were newly classified as having COPD under the minor-criteria path, while 105 of 656 participants (16.0 %) who did show spirometric obstruction were reclassified as not having COPD.

The newly diagnosed group experienced a higher exacerbation rate (adjusted incidence-rate ratio 2.09), but their all-cause mortality did not differ significantly from participants without COPD during follow-up.

Study authors conclude that structural lung abnormalities and respiratory symptoms predict poorer outcomes even when spirometry remains normal. Their multidimensional schema still anchors diagnosis to spirometry whenever airflow obstruction is present, yet it also allows clinicians to confirm COPD via the minor-criteria route of concordant symptoms and imaging findings.

Potential public health implications include a shift in how clinicians identify, monitor, and intervene in early or atypical cases of COPD. Diagnostic equity may also improve, particularly among Black individuals, who often exhibit emphysema without spirometric obstruction and have been historically underdiagnosed.

More information: A Multidimensional Diagnostic Approach for Chronic Obstructive Pulmonary Disease, JAMA (2025). DOI: 10.1001/jama.2025.7358  Journal information: Journal of the American Medical Association

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