COPD in Never-Smokers: What Are the Risk Factors?

Mature adult man lying down on sofa in living room and using inhaler.He is wearing sleepwear
A systematic review identified risk factors for COPD among those who have never smoked.

COPD is significantly correlated with occupational and other exposures. These and other results were published in a systematic review in the Clinical Respiratory Journal.

The risk factors for COPD in never-smokers remain to be fully elucidated. To address this, researchers conducted a systematic review in PubMed and Embase of studies published since 2000. The review yielded 20 studies conducted internationally on COPD in never-smokers, including 2 case-control studies, 4 cohort studies, and 14 cross-sectional studies.

The studies in the review showed that COPD in never smokers was significantly associated with occupational exposure to toxic gases, exposure to biomass fuels for cooking and heating, passive smoking, and a previous history of asthma, tuberculosis or respiratory infections in childhood. The studies additionally indicated that residential radon exposure heightened COPD death, although more data are needed to flesh out this correlation. Inhaled radon is decayed into solid particles that stay in the lungs and expose the cell linings to alpha particles. This exposure leads to molecular changes and potentially damaged DNA.

Most exposures examined by the authors were statistically significant. Importantly, risk was highest for a history of previous respiratory disease (eg, asthma, tuberculosis) or respiratory infections compared with that of occupational/environmental exposure.

Strengths of the current study include its rigorous methodology (ie, use of the PRISMA guidelines) and the study’s basis on a specific quality assessment scale. External validity of the study is high, with included data coming from various countries.

One limitation of the current review is the heterogenous design of different studies included, which ruled out the performance of a meta-analysis. Other limitations include variations in how COPD was defined in different studies, with some studies only including airflow obstruction sans symptomatology. The authors note that bias could be secondary to the retrospective nature of studies included and challenges in measuring the accuracy of different risk factors. Of note, the quality of the included studies was determined via a nonvalidated scale, which could be a further limitation.

“The absence of a greater number of studies specifically conducted on never-smokers is extremely noteworthy,” concluded the authors, “particularly when smoking in the most developed countries is progressively decreasing and the percentage of COPD in never-smokers will necessarily be gradually increasing. The need for more research on this topic is evident. These studies should exclusively include never-smokers and assess all the potential risk factors of COPD.”


Pando-Sandoval A, Ruano-Ravina A, Candal-Pedreira C, et al. Risk factors for chronic obstructive pulmonary disease in never-smokers: A systematic review. Published online February 10, 2022. doi:10.1111/crj.13479.