COPD in never-smokers: evidence, challenges, and knowledge gaps

This study aimed to summarise current evidence on chronic obstructive pulmonary disease (COPD) in never-smokers, including definitions, epidemiology, risk factors, clinical characteristics, and emerging conceptual frameworks, and identify key knowledge gaps.

Although tobacco smoking remains the predominant global risk factor for COPD, a substantial proportion of individuals with COPD are lifelong never-smokers. International data indicate that 22-51% of people with spirometry-defined COPD have never smoked, with a global COPD prevalence of 4-16% in this group. Risk factors span through the life course and include impaired lung development, early-life disadvantages, recurrent respiratory infections, asthma, indoor and outdoor air pollution, occupational exposures, environmental tobacco smoke, socioeconomic disadvantages, ageing, and genetic susceptibility. Research remains limited as most studies have historically focused on smoking-related COPD.Never-smokers with COPD show several distinct clinical features compared with those with tobacco-related disease. They tend to have an earlier age of onset, less severe airflow obstruction, and a higher prevalence of small airways disease, particularly in individuals with a history of asthma. Symptoms such as cough, sputum production, and exertional breathlessness are reported less frequently. Physiologically, never-smokers commonly demonstrate normal diffusing capacity, less emphysema, and a slower decline in lung function. Respiratory comorbidities such as asthma and allergic disease occur more often, suggesting differing inflammatory pathways. Fewer never-smokers meet GOLD stage III-IV criteria. Despite increasing recognition, COPD in never-smokers remains insufficiently characterised. Approximately one third of global COPD cases occur in never-smokers, yet they are routinely excluded from clinical trials, limiting understanding of mechanisms, natural history, and treatment response.

Never-smoker COPD represents a distinct and understudied phenotype with unique risk factors, clinical features, and comorbidity patterns. Improved diagnostic strategies, phenotyping, and dedicated clinical trials are needed to guide personalised management for this population.