Study of COPD Subgroups and Biomarkers

SPIROMICS was initially funded through contracts from the NIH. That phase of SPIROMICS is now referred to as SPIROMICS I. SPIROMICS II was funded as a grant from the NIH to continue the longitudinal observation of the SPIROMICS cohort recruited in SPIROMICS I. The current phase, referred to as SPIROMICS III, is funded through a contract from the NIH to continue the longitudinal observation of the SPIROMICS cohort that remain active (not withdrawn, lost to follow-up, or deceased).

Description of SPIROMICS I:

The purpose of SPIROMICS was to learn about chronic obstructive pulmonary disease (COPD), which is sometimes called emphysema or chronic bronchitis. Millions of Americans have COPD, and it is the fourth leading cause of death in the country. The most common cause of COPD is cigarette smoking, although not all smokers get COPD. The discovery of new treatments for COPD has been slowed by a poor understanding of different types of COPD and a lack of ways to measure whether or not COPD is getting worse.

The study had two main goals. The first was to find groups of patients with COPD who share certain characteristics. Certain groups may respond differently to certain treatments. The second was to find new ways of measuring whether or not COPD is getting worse. This would provide new ways of testing whether a new treatment is working.

SPIROMICS I had three sub studies and two key ancillary studies.

Sub studies:

• Repeatability Substudy: The entire baseline clinic visit was repeated on 100 participants on a volunteer basis. The goal of this substudy was to determine reliability of measurement procedures.
• Bronchoscopy Substudy: ~300 participants were enrolled for two additional study visits, including a bronchoscopy. The goal of this substudy was to collect and assess biological specimens and relate those results to clinical measurements.
• Exacerbation Substudy: ~400 participants were enrolled in this substudy. A daily symptom diary was collected on all participants. Participants were also seen in the clinic during a pulmonary exacerbation. The goals of this substudy were to 1) better understand the relationship between symptoms and exacerbations and 2) obtain clinical data and specimens during a pulmonary exacerbation.

Ancillary Studies:

• Air Pollution Ancillary Study: The SPIROMICS Air Pollution ancillary study used state-of-the art air pollution exposure assessments to determine individual-level outdoor and indoor air pollution exposure. The goals of this substudy were to determine the effect of long-term air pollution exposure on COPD morbidity and to determine whether short-term changes in outdoor air pollution are associated with changes in COPD morbidity.
• Parametric Response Mapping in COPD: The Parametric Response Mapping (PRM) in COPD ancillary study collected an additional CT scan during the final study visit and used a new analysis technique (PRM) to assess the functional small airways of the lung and emphysema.

Description of SPIROMICS II:

Aim 1 was to define the natural history of "smokers with symptoms despite preserved spirometry" and characterize the airway mucus abnormalities underlying this condition. Aim 2 was to determine the radiographic precursor lesion(s) for emphysema and identify the molecular phenotypes underlying airway disease and emphysema. Aim 3 was to advance understanding of the biology of COPD exacerbations through analysis of predisposing baseline phenotypes, exacerbation triggers and host inflammatory response.

SPIROMICS II continued follow-up of active participants, with no new enrollment. Each participant had one clinic visit at 5-7 years of follow-up from SPIROMICS I baseline and was contacted by telephone every 4 months to assess respiratory health status.

Description of SPIROMICS III:

Aim 1 is to identify the main forms of smoking-related airway disease that are caused by pathological airway mucus, their biological underpinnings, and their physiological significance. Aim 2 is to identify longitudinal trajectories in established and novel CT measures of emphysema, test how they predict COPD progression, and define their underlying biology. Aim 3 is to identify environmental and social determinants of health that impact disease severity and progression and their influence on lung structure, biology, and health disparities in COPD.

SPIROMICS III will enroll and consent approximately 1800 participants to conduct (a) a single in-person clinic visit at approximately 11-16 years of follow-up for those originally enrolled into SPIROMICS I and approximately 5-6 years of follow-up for those originally enrolled into SOURCE (and MAP COPD) (NCT05033990), (b) follow-up telephone calls every 4 months to assess respiratory health status, and (c) to assess indoor and outdoor environmental monitoring.

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
• 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

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 <21 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 (automatic implantable cardioverter/defibrillator) 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

Temporal Exclusion Criteria for SPIROMICS III:

• Participants who present with a pulmonary exacerbation, either solely participant-identified or that has been clinically treated, in the last six weeks, can complete the study visit once a six-week window has passed.
• Participants who present with an upper respiratory infection, either solely participant-identified or that has been clinically treated, in the last six weeks, can complete the study visit once a six-week window has passed.
• Participants who present with current use of acute antibiotics or steroids can complete the study visit ≥30 days after discontinuing acute antibiotics/steroids. This does not apply to participants who are on chronic prednisone therapy of <10 mg per day or <20 mg every other day or participants who are currently on chronic, prophylactic, or suppressive antibiotic therapy.
• Participants who present with a myocardial infarction or eye, chest or abdominal surgery within six weeks can complete the study visit after a six-week window has passed.
• Female participants who present <3 months after giving birth will be asked to schedule the visit once three months have passed post-delivery.