SPIROMICS Study of Early COPD Progression (SOURCE)

Study Overview
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Brief Summary
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This is an observational study of 600 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.

Official Title
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SPIROMICS Study of Early COPD Progression (SOURCE)

Conditions
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COPD, Early-Onset

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20 of the 600 will be healthy controls: ages 30-55 years; with no smoking history (< 100 cigarettes in lifetime), including vaping and cannabis use; pre-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 0.70; pre-bronchodilator FEV1 > 80% predicted; pre-bronchodilator FVC > 80% predicted; Chronic Airway Assessment Test (CAAT) score < 10; and willingness to also participate in the bronchoscopy sub-study. Approximately one-third of the 580 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. This early COPD group has been chosen because it is not currently well-represented in COPDGene and SPIROMICS cohorts. Approximately one-third of the 580 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. This early COPD group was enrolled in small numbers in COPDGene but was excluded from SPIROMICS. Approximately one-third of the 580 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. This early COPD group has been chosen because it is also not currently well-represented in the first funded phase of the COPDGene and SPIROMICS cohorts. 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.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy Controls<br>Participants with no smoking history (< 100 cigarettes in lifetime); pre-bronchodilator FEV1/FVC ≥ 0.70; pre-bronchodilator FEV1 ≥ 80% predicted; and pre-bronchodilator FVC ≥ 80% predicted. | |
| Gold 0<br>Participants graded as GOLD 0 by the GOLD grading system: ≥ 10 pack-year smoking history; post-bronchodilator FEV1/FVC ≥ 0.70 and FEV1 ≥ 80% predicted. GOLD stands for the Global initiative for Chronic Obstructive Lung Disease. | |
| Preserved Ratio Impaired Spirometry (PRISm)<br>Participants with ≥ 10 pack-year smoking history; post-bronchodilator FEV1/FVC ≥ 0.70 and FEV1 < 80% predicted. | |
| GOLD 1 - 2<br>Participants graded as GOLD 0 by the GOLD grading system: ≥ 10 pack-year smoking history; post-bronchodilator FEV1/FVC < 0.70 and FEV1 ≥ 50% predicted. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PRM fSAD | Parametric Response Mapping captures the change in lung density between matched inspiratory and expiratory images thereby enabling the distinction between normal lung parenchyma (PRMNORM), emphysema (PRMEMPH), and non-emphysematous air trapping referred to as functional small airway disease (PRMfSAD). | Year 2-5 |