This is an observational study of 1000 participants to further define the nature of early chronic obstructive pulmonary disease (COPD) in younger, at-risk individuals.

The study has three main goals:

• To use CT scan imaging to identify which smokers will develop COPD.
• To identify biomarkers predictive of smokers that will develop COPD.
• To determine if sputum (phlegm) can be analyzed to predict which smokers will develop COPD.

Procedures (methods): All participants will undergo study related questionnaires assessing medical history, smoke exposure and use, medication use, social and behavioral health, pulmonary symptoms, food frequency, and will provide nasal swab, blood, stool, and urine samples, pulmonary function testing to determine function, sputum induction to provide a sputum sample for airway biospecimen analysis, and CT imaging of the lungs.

Inclusion Criteria:

• 40 of the 1000 will be healthy controls: ages 30-55 years; with no smoking history (< 100 cigarettes in lifetime), including vaping and cannabis use; pre-bronchodilator FEV1/FVC > 0.70; pre-bronchodilator FEV1 > 80% predicted; pre-bronchodilator FVC > 80% predicted; Chronic Airway Assessment Test (CAAT) score < 10. Willingness to also participate in the bronchoscopy sub-study is only required of the 20 healthy controls recruited from the clinical centers participating in the sub-study.
• Approximately one-third of the 960 will be GOLD 0 participants: ages 30-55 years; with ≥ 10 pack-year smoking history; post-bronchodilator FEV1/FVC > 0.70 and FEV1 > 80% predicted.
• Approximately one-third of the 960 will be Preserved Ratio Impaired Spirometry (PRISm) participants: ages 30-55 years; with ≥ 10 pack-year smoking history; post-bronchodilator FEV1/FVC > 0.70 and FEV1 < 80% predicted.
• Approximately one-third of the 960 will be GOLD 1-2 participants: ages 30-55 years; with ≥ 10 pack-year smoking history; post-bronchodilator FEV1/FVC < 0.70 and FEV1 > 50% predicted.

Exclusion Criteria:

• Severe asthma, which is defined as any of the following:

  • Current (i.e., at the time of the visit) Global Initiative for Asthma (GINA) Step 4 or higher therapy (medium dose inhaled corticosteroids (ICS)/long-acting beta agonist (LABA) or high dose ICS or add-on long-acting muscarinic agonist (LAMA); Medium dose > 250 fluticasone propionate, = 100 fluticasone furoate, > 200 beclomethasone, > 400 budesonide, > 220 mometasone). We will accept low-dose ICS/LABA or medium dose ICS; or
  • Three or more unscheduled healthcare visits (provider/urgent care/ER) for asthma in the past 12 months; or
  • One asthma hospitalization in the past 12 months.

• Concurrent participation in a therapeutic trial where treatment is blinded.

• Active pregnancy at the time of the baseline visit or planning to become pregnant during the course of the study. This special population is being excluded to minimize potential for fetal radiation exposure.

• Cognitive dysfunction that prevents the participant from completing study procedures.

• BMI > 35.0 kg/m^2 at baseline, due to the effects of body weight on CT scan imaging quality.

• The presence of a respiratory condition other than COPD (including chronic bronchitis and emphysema) or asthma, such as interstitial lung disease or pulmonary fibrosis, or of a comorbid condition that in the judgment of the investigator may be the principal cause of respiratory symptoms (e.g., dyspnea or decreased exercise tolerance).

• Any illness expected to cause mortality in the next three years.

• Any implanted metallic devices or prosthesis above the waist that could degrade thoracic CT scan image quality.

• History of thoracic radiation or thoracic surgery with resection of lung tissue.

• Known HIV/AIDS infection.

• Current illicit substance abuse, excluding marijuana.

• History of or current use of IV Ritalin.

• History of or current use of heroin.

• History of illegal IV drug use within the last 10 years or more than 5 instances of illegal IV drug use ever.

14 clinical centers across the US will enroll a total of 1000 participants, 30-55 years old, both sexes, all races, and all ethnicities. The participants will include never-smokers (n=40) and GOLD stage 0-2 participants (n=960).