Chronic Obstructive Pulmonary Disease in Never-Smokers—A Distinct Entity Within the COPD Spectrum

Although smoking is the main risk factor for chronic obstructive pulmonary disease (COPD), about one-third of patients have never smoked. This phenomenon supports the idea of a distinct phenotype of the disease in never-smokers, influenced by genetic, infectious, socioeconomic, environmental, and occupational factors. The paper is based on a narrative review of recent literature on the etiology, clinical features, evolution, and therapeutic strategies of COPD in never-smokers, mainly through the analysis of published studies over the last 3 years. COPD in never-smokers occurs predominantly in women, the elderly, and individuals from rural areas or with poor socioeconomic status. Key risk factors include exposure to occupational or environmental pollutants, air pollution, previous respiratory infections, particularly due to pulmonary tuberculosis, and genetic predisposition, mainly through alpha-1 antitrypsin deficiency (A1ATD). Clinically, COPD in never-smokers is characterized by chronic cough and dyspnea, with less severe pulmonary functional impairment, slow progression, and lower prevalence of emphysema compared to smokers. Imaging often highlights bronchiectasis or post-infectious sequelae, and biological markers indicate a significant eosinophilic component. Thus, COPD in never-smokers is a distinct clinical entity with multifactorial pathogenesis and distinct clinical-functional characteristics. Prompt recognition of this form of disease is essential for prevention and adaptation of therapeutic strategies. A personalized multidisciplinary approach can improve disease prognosis and the quality of life for these patients.