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 is now funded as a grant from the NIH. The current
phase is referred to as SPIROMICS II.

Brief summary of SPIROMICS I:

The purpose of SPIROMICS is 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 has two main goals. The first is to find groups of patients with COPD who share
certain characteristics. Certain groups may respond differently to certain treatments. The
second is 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 has three substudies and two ancillary studies.

Substudies:

1. Repeatability Substudy: The entire baseline clinic visit will be repeated on 100
volunteers. The goal of this substudy is to determine reliability of measurement
procedures.

2. Bronchoscopy Substudy: 300 participants will be enrolled for two additional study
visits, including a bronchoscopy. The goal of this substudy is to collect and assess
biological specimens and relate those results to clinical measurements.

3. Exacerbation Substudy: Up to 400 participants will be enrolled in this substudy. A daily
symptom diary will be collected on all participants. Participants will also be seen in
the clinic during a pulmonary exacerbation. The goals of this substudy are to 1) better
understand the relationship between symptoms and exacerbations and 2) obtain clinical
data and specimens during a pulmonary exacerbation.

Ancillary Studies:

1. Air Pollution Ancillary Study: The SPIROMICS Air Pollution ancillary study uses
state-of-the art air pollution exposure assessments to determine individual-level
outdoor and indoor air pollution exposure. The goals of this substudy are 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.

2. Parametric Response Mapping in COPD: The Parametric Response Mapping (PRM) in COPD
ancillary study collects an additional CT scan during the final study visit and uses a
new analysis technique (PRM) to assess the functional small airways of the lung and
emphysema.

Brief summary of SPIROMICS II:

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

SPIROMICS II will continue follow-up of current participants, with no new enrollment. Each
participant will have one clinic visit and will be contacted by telephone every 4 months.

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 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