Range of Factors May Heighten COPD Risk in Nonsmokers

This new study from Spain investigated risk factors for COPD among individuals without a smoking history.

As the prevalence of chronic obstructive pulmonary disease (COPD) has grown, so too has research into the disease. Yet, aside from smoking, risk factors for COPD remain understudied, according to a new review.

Corresponding author Alberto Ruano-Ravina, PhD, of the University of Santiago de Compostela, in Spain, and colleagues noted that COPD is the third-leading cause of death in the world. In Spain, in particular, more than 10% of people over the age of 40 have a COPD diagnosis.

Their findings recently were published in The Clinical Respiratory Journal.

Although smoking is known to significantly increase the risk of COPD, the investigators said that that single cause gives an incomplete picture of COPD risk. Whereas the rate varies significantly by region, 25% to 45% of patients with COPD have never smoked, they said.

“Yet despite this relatively high incidence of COPD in never-smokers, few studies have exclusively targeted these subjects, and there is a great degree of ignorance about the specific effect of various risk factors that may have an influence on the appearance of COPD in this subpopulation and the magnitude of such effects,” Ruano-Ravina and colleagues wrote.

Several other risk factors for COPD have been proposed, including biomass fumes, occupational exposure to dust and fumes, and environmental pollution. Because those factors, and others, have all been studied in recent years, the investigators sought to find out what the collective research said about COPD risk among never-smokers. They conducted a literature review on studies looking at the issue that were published after 2000.

Twenty papers met their inclusion criteria. Among these, the studies were conducted on 5 continents, and most were cross-sectional studies. The authors found a long list of potential risk factors.

“The studies reviewed show a significant association between incidence of COPD in never-smoker patients and occupational exposure, exposure to biomass, passive smoking,m and having previously suffered from asthma, tuberculosis, or respiratory infections during childhood,” they said.

Among the list, a history of respiratory diseases like asthma and tuberculosis was associated with the highest risk of developing COPD. Exposure to household radon also appeared to be linked with higher COPD mortality, although the authors said more research is required to validate this finding.

In the case of asthma, it is believed that chronic inflammation of the airway and chronic obstruction of airflow may contribute to remodeling, the investigators said. Tuberculosis’ association with COPD risk may be similar, they said.

“The biological mechanism responsible for this chronic obstruction of the respiratory tract might be the fibrosis of the airways caused by tuberculosis, as well as the immune response to mycobacteria that may cause inflammation of the respiratory tract, likewise [are] characteristic of COPD,” they said.

In addition to their findings of nonsmoking-related risk factors for COPD, the investigators said their review makes clear the lack of scientific investigation into the subject.

“The absence of a greater number of studies specifically conducted on never-smokers is extremely noteworthy, particularly when smoking in the most developed countries is progressively decreasing and the percentage of COPD in never-smokers will necessarily be gradually increasing,” they wrote.

They said future studies should have at least 500 participants, 200 of whom should be never-smokers in order to ensure meaningful results. At the same time, they said policymakers should act to find ways to reduce exposure to toxic substances that appear to heighten COPD risk.


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

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