Study design and sample collection.

SPIROMICS (ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01969344","term_id":"NCT01969344"}}NCT01969344) is an ongoing longitudinal, prospective, multicenter observational study (82) that recruited never smokers (≤1 pack-year of tobacco-smoking history) and ever smokers (current or former smokers with ≥ 20 pack-years, also referred to as smokers) without or with airflow obstruction (64). Clean-catch urine was collected and stored at –80°C before thawing and processing. For this study, urine samples were opportunistically sampled from available inventory. Clinical data were collected at the baseline and follow-up study visits, including demographics, comorbidities, questionnaires, cigarette smoke exposure, and 6MWD (82). Symptom burden was quantified with the CAT and health-related quality of life (HRQL) with the SGRQ total score. The extent of emphysema and airway-wall abnormality was characterized with HRCT scans of the lung, using Imbio (PRM) and VIDA Diagnostics software; percent emphysema was defined as LAA less than –950 HU at total lung capacity (83).