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Long-standing inflammatory disorders, including COPD and GERD, signal heightened risk for lung cancer among never-smokers, according to research.

Among patients who have never smoked—“never-smokers”—those with lung cancer (LC) are more likely to have been diagnosed with an inflammatory disease, according to a study published in Nature Communications.

Lung cancer in never-smokers (LCINS) accounts for a rising share of lung-cancer deaths, yet current screening criteria focus almost exclusively on tobacco exposure. Monica E. D’Arcy, PhD, MS, of Rutgers Institute for Health, Health Care Policy, and Aging Research, and study coauthors explored whether long-standing inflammatory disorders might signal heightened LCINS susceptibility.

“Most of the medical conditions we identified involved pulmonary or systemic inflammation,” wrote corresponding author Monica E. D’Arcy, PhD, MS, of Rutgers Institute for Health, Health Care Policy, and Aging Research, and study coauthors. “Furthermore, several of the associations persisted for (more than) 10 years, hinting at the importance of long-term inflammation in the development of LCINS.”

Mining Data

The researchers mined electronic medical record data from the United Kingdom’s Clinical Practice Research Datalink. The discovery cohort (CPRD-Gold) included 1,581 patients with LCINS and 14,318 and 14,318 never-smokers without LC who served as controls. Medical diagnoses with significant associations to LCINS during the 10 years before the index date were retested in an independent validation cohort (CPRD-Aurum) comprising 2,188 patients with LCINS and 19,597 controls. Adjusted odds ratios (aORs) accounted for demographics and, in sensitivity analyses, relevant medications.

Multiple Conditions Evidence Significant Associations

In both the discovery and validation datasets, chronic obstructive pulmonary disease (COPD) was the strongest predictor of LCINS, according to the study. A COPD diagnosis 1 to 10 years before cancer carried an aOR of 2.90, while diagnoses 10 to 32 years earlier still showed an aOR of 2.52. Other conditions with significant, durable associations are noted in the table below.

Adjustment for medication use only modestly decreased the associations, the study found.

Expanding Screening Program Eligibility Criteria

The authors suggested that, because some associations span decades, chronic inflammatory diagnoses may act as practical early-warning markers. They proposed that conditions such as COPD or GERD “could be considered as part of eligibility criteria for future LCINS screening programs.”

“The potentially long latency period might provide an opportunity to identify individuals who would benefit from earlier LC detection,” researchers wrote. “The growing burden of LCINS requires developing strategies that are not reliant upon smoking history for LC risk assessment in LC screening ineligible persons.”