COPD in never-smokers showed more symptoms and type 2 inflammation, pointing to a distinct clinical phenotype.
COPD in Never-Smokers Shows a Different Signal
Chronic obstructive pulmonary disease (COPD) in never-smokers may represent a clinically distinct phenotype, according to a population-based cohort analysis comparing never-smokers with COPD against multiple smoking and non-smoking control groups.
Investigators studied 154 never-smokers with COPD from the Swedish CArdioPulmonary bioImage Study (SCAPIS) and compared them with never-smokers with normal lung function, current smokers with normal lung function, ex-smokers with COPD, and current smokers with COPD. COPD was defined using spirometry as a post-bronchodilator ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) below the lower limit of normal, a standard threshold indicating airflow obstruction.
Never-smokers with COPD reported more respiratory symptoms and poorer health status than never-smokers with normal lung function. At the same time, they had fewer symptoms, milder airflow limitation, and better health status than ex-smokers and current smokers with COPD. This suggests that COPD in never-smokers carries a measurable burden, even if it appears less severe than smoking-related disease in some respects.
Type 2 Inflammation May Help Define This COPD Phenotype
A key finding was the inflammatory profile seen in never-smokers with COPD. Compared with never-smokers with normal lung function, this group had higher sensitization to a mix of aeroallergens, higher levels of fractional exhaled nitric oxide (FeNO), a breath test that reflects airway inflammation, and higher blood eosinophil counts, a type of immune cell associated with allergic and inflammatory responses. They also reported more asthma.
That signal did not disappear when participants with self-reported asthma were excluded. Even then, never-smokers with COPD continued to show more wheeze, more cough, and higher FeNO. These findings strengthen the argument that type 2 inflammation may be a meaningful feature of COPD in never-smokers, rather than simply a reflection of coexisting asthma.
Why COPD in Never-Smokers Could Change Clinical Follow-Up
The findings suggest that COPD in never-smokers is something more than a milder version of smoking-related disease. Instead, it may represent a separate clinical phenotype with distinct symptoms, biomarker patterns, and management needs.
For clinicians, that distinction matters. If never-smokers with COPD differ biologically and clinically from ever-smokers, a one-size-fits-all approach to monitoring and treatment may overlook important features of the condition in this group.
Reference
Sönnerfors P et al. Characterisation of chronic obstructive pulmonary disease (COPD) in never-smokers and ever-smokers from a population-based cohort. BMJ Open Respir Res. 2026;13(1):e003578.
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