This study, conducted as part of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) cohort, aimed to characterize the heterogeneity of Chronic Obstructive Pulmonary Disease (COPD) in a large, well-characterized, and controlled population. The study included 2164 clinically stable COPD patients, 337 smokers with normal lung function, and 245 never smokers. Key findings include: 1. **Clinical and Demographic Characteristics**: COPD patients were slightly older and had more pack years of smoking compared to smokers with normal lung function. They also had more comorbidities, which were prevalent regardless of GOLD stage. 2. **Airflow Limitation and Symptoms**: The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, exercise capacity, and number of exacerbations. A substantial proportion of patients with severe airflow obstruction did not report symptoms, exacerbations, or exercise limitation. 3. **Emphysema and Bronchiectasis**: The amount of emphysema increased with GOLD severity, and bronchiectasis was observed in 4% of COPD patients but not in controls. 4. **Gender Differences**: Females had less smoking exposure for the same degree of airflow limitation and reported more exacerbations. They also had higher rates of osteoporosis, inflammatory bowel disease, reflux, and depression requiring treatment. 5. **Heterogeneity by GOLD Stage and BODE Index**: The relationships between clinical, functional, and radiological variables were consistent across different GOLD stages and BODE scores, indicating that the current classification systems based on airflow limitation are poor predictors of other features of COPD. The study highlights the complexity and heterogeneity of COPD, emphasizing the need to consider multiple factors beyond just spirometry when managing patients with the disease.This study, conducted as part of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) cohort, aimed to characterize the heterogeneity of Chronic Obstructive Pulmonary Disease (COPD) in a large, well-characterized, and controlled population. The study included 2164 clinically stable COPD patients, 337 smokers with normal lung function, and 245 never smokers. Key findings include: 1. **Clinical and Demographic Characteristics**: COPD patients were slightly older and had more pack years of smoking compared to smokers with normal lung function. They also had more comorbidities, which were prevalent regardless of GOLD stage. 2. **Airflow Limitation and Symptoms**: The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, exercise capacity, and number of exacerbations. A substantial proportion of patients with severe airflow obstruction did not report symptoms, exacerbations, or exercise limitation. 3. **Emphysema and Bronchiectasis**: The amount of emphysema increased with GOLD severity, and bronchiectasis was observed in 4% of COPD patients but not in controls. 4. **Gender Differences**: Females had less smoking exposure for the same degree of airflow limitation and reported more exacerbations. They also had higher rates of osteoporosis, inflammatory bowel disease, reflux, and depression requiring treatment. 5. **Heterogeneity by GOLD Stage and BODE Index**: The relationships between clinical, functional, and radiological variables were consistent across different GOLD stages and BODE scores, indicating that the current classification systems based on airflow limitation are poor predictors of other features of COPD. The study highlights the complexity and heterogeneity of COPD, emphasizing the need to consider multiple factors beyond just spirometry when managing patients with the disease.