Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS)

Subpopulations and Intermediate Outcome Measures in COPD Study Description Subpopulations and intermediate outcome measures in COPD study (SPIROMICS) supports the prospective collection and analysis of phenotypic, biomarker, genetic, genomic, and clinical data from subjects with COPD for the purpose of identifying subpopulations and intermediate outcome measures. It is funded by the National Heart, Lung, and Blood Institute and is coordinated by the University of North Carolina at Chapel Hill. Molecular fingerprinting and extensive subject phenotyping will be performed to identify disease subpopulations and to identify and validate surrogate markers of disease severity which will be useful as intermediate outcome measures for future clinical trials. Secondary aims are to clarify the natural history of COPD, to develop bioinformatic resources that will enable the utilization and sharing of data in studies of COPD and related diseases, and to create a collection of clinical, biomarker, radiographic, and genetic data that can be used by external investigators for other studies of COPD. Participating Institutions: Research participants for SPIROMICS will be enrolled, phenotyped, and followed at twelve SPIROMICS Clinical Centers: Columbia University, Temple University, Johns Hopkins University, Wake Forest University, University of Michigan, University of Illinois at Chicago, University of Iowa, University of Utah, National Jewish Health, University of Alabama at Birmingham, University of California at San Francisco, and University of California at Los Angeles. The University of North Carolina at Chapel Hill serves as the Genomics and Informatics Center. The Radiology Reading Center is based at the University of Iowa. The PFT Reading Center is based at the University of California at Los Angeles. Study Design: SPIROMICS is a prospective cohort study that enrolled approximately 2,981 participants at twelve clinical centers over five years. Participants are distributed across four enrollment strata (i.e., Never-smokers, Smokers without COPD, Mild/Moderate COPD, and Severe COPD). Study Visits: Participants have up to four in-person visits (Baseline and Annual Clinic Visits at years 1, 2, 3 after Baseline). Study questionnaires and spirometry are completed at all main study visits. Blood and urine samples are collected at visits 1, 2, and 4. Sputum samples are collected at Visit 1. The CT scans are completed and Baseline and Visit 2. Participants also receive quarterly follow-up calls to assess health status and determine if an exacerbation has occurred. Substudies A. Bronchoscopy and Immunophenotyping Substudy The Bronchoscopy Substudy enrolled a total of 251 participants. These participants will be recruited across all four study strata. This substudy includes two study visits. During the first visit sputum samples are collected for Immunophenotyping analysis at the Immunophenotyping Core Lab based at the University of Michigan. Participants then return for a second visit during which samples are collected via bronchoscopy, including bronchoalveolar lavage, epithelial brushings and bronchial biopsies. Immunophenotyping analysis is also conducted on BAL and blood collected during the bronchoscopy study visit. B. Repeatability Substudy The entire baseline clinic visit was repeated on 98 volunteers to determine reliability of measurement procedures. All baseline study-related procedures and questionnaires, including the CT scan, was re-administered and new samples of blood, urine, saliva, and sputum was collected. Field center staff processed these biospecimen samples according to the same protocol. C. Exacerbation Substudy The Exacerbation Substudy is a prospective, longitudinal observational study of 204 participants, which will allow the assessment of participant driven health care utilization (HCU) events and symptom-defined exacerbation events over time. HCU driven events are defined by change in medical treatment in response to a perceived COPD Exacerbation. Symptom-based events will be defined by using EXACT-PRO (EXacerbations of Chronic Pulmonary Disease Tool - Patient Reported Outcome) a daily symptom diary developed to measure the frequency, severity, and duration of exacerbations in clinical trials. All participants are provided with a PDA on which to complete the diary. Participants reporting a possible COPD exacerbation will be brought into the study clinic for a study visit to collect biological specimens and questionnaire data. The overall objectives of the exacerbation substudy are to: Obtain clinical data and specimens on SPIROMICS participants before and during an acute COPD exacerbation defined by: Health care utilization triggered by the subject, or Symptomatic change (triggered by an EXACT defined threshold) Describe symptomatic changes occurring around HCU and symptom-defined (EXACT) events and their relationship to clinical and specimen data Characterize the non-exacerbation "stable" state in COPD using the EXACT, including: Symptom variability (EXACT), Clinical data and specimen parameters during a stable state (baseline), The relationship between clinical and specimen data and symptom severity and variability. Explore the characteristics of stable patients, defined as those who do not experience HCU or symptom-defined (EXACT) events during the sub-study period, using baseline clinical data and specimens and compare these characteristics with patients who experience HCU and/or symptom-defined events. Examine the relationship between HCU and symptom-defined exacerbation frequency during the first one-year period of follow-up for exacerbations and health outcomes, including 12-month change in lung function and COPD health status, and longer term morbidity and mortality, with the latter derived from long-term data from the larger SPIROMICS study. ]]>
LONGITUDINAL DESCRIPTIVE STATISTICS VISIT 1LONGITUDINAL DESCRIPTIVE STATISTICS VISIT 2LONGITUDINAL DESCRIPTIVE STATISTICS VISIT 3LONGITUDINAL DESCRIPTIVE STATISTICS VISIT 4Study Population Never-smokers, current and former smokers without COPD, and current and former smokers with COPD with access to one of the study clinical centers. Enrollment Strata SPIROMICS Enrollment Strata Non-Smokers (Stratum 1) Smokers (Stratum 2) Mild/Moderate COPD (Stratum 3) Severe COPD (Stratum 4) Smoking Status < 1 pack-year > 20 pack-years > 20 pack-years > 20 pack-years Bronchodilator Status for Assessing Lung Function Pre-bronchodilator Post-bronchodilator Post-bronchodilator Post-bronchodilator FEV1/FVC ratio criteria FEV1/FVC > .7 FEV1/FVC > .7 FEV1/FVC < .7 FEV1/FVC < .7 Other Lung Function Criteria FVC>LLN FVC>LLN FEV1 > 50% pred. FEV1 < 50% pred. Sample Size N = 200 (6.25%) N = 900 (28.13%) N = 1500 (46.88%) N = 600 (18.72%) Inclusion Criteria: Between 40 and 80 at baseline visit Never smokers: <1 pack-year history of smoking Never smokers: Must meet lung function criteria based on spirometry without inhaled bronchodilators (see above table) Current or former smokers: >20 pack-year history of smoking Current or former smokers: Must meet lung function criteria based on spirometry with inhaled bronchodilators (see above table) Exclusion Criteria: Dementia or other cognitive dysfunction which in the opinion of the investigator would prevent the participant from consenting to the study or completing study procedures Plans to leave the area in the next 3 years Smoking history of > 1 pack-year but < pack-years BMI > 40 kg/m2 at baseline exam Prior significant difficulties with pulmonary function testing Hypersensitivity to or intolerance of albuterol sulfate or ipratropium bromide or propellants or excipients of the inhalers Non-COPD obstructive lung disease, severe kyphoscoliosis, neuromuscular weakness, or other conditions, including clinically significant cardiovascular and pulmonary disease, that, limit the interpretability of the pulmonary function measures History of Interstitial lung disease History of Lung volume reduction surgery or lung resection History of lung or other organ transplant History of endobronchial valve therapy History of large thoracic metal implants (e.g., AICD and/or pacemaker) Currently taking ≥10mg a day/20mg every other day of prednisone or equivalent systemic corticosteroid Currently taking any immunosuppressive agent 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 Known HIV/AIDS infection History of lung cancer or any cancer that spread to multiple locations in the body History of or current exposure to chemotherapy or radiation treatments that, in the opinion of the investigator, limits the interpretability of the pulmonary function measures Diagnosis of unstable cardiovascular disease including myocardial infarction in the past 6 weeks, uncontrolled congestive heart failure, or uncontrolled arrhythmia Any illness expected to cause mortality in the next 3 years Active pulmonary infection, including tuberculosis History of pulmonary embolism in the past 2 years Known diagnosis of primary bronchiectasis Currently institutionalized (e.g., prisons, long-term care facilities) Known to be a first degree relative of another, already enrolled participant (i.e., biological parent, biological sibling) Never smokers only: Current diagnosis of asthma Women only: Cannot be pregnant at baseline or plan to become pregnant during the course of the study ]]>