An open label study in 250 subjects over five years. We are planning 130 subjects with COPD (varies stages of GOLD I-IV) and 120 normal subjects (non-smokers, ex smokers and current smokers with normal PFT’s).

Each subject will receive PFP as a contrast agent to visualize the airway and alveolar spaces in their lungs using magnetic resonance imaging of inert gas/oxygen mixtures.

Duration
Screening (V0)
1. Obtaining Informed Consent from each subject
2. History and Physical exam. The history will focus on onset of symptoms, co-morbidities, and smoking/occupational/environmental history. Also included:
a. An assessment of patterns of exacerbations (mild = use of oral antibiotics and/or steroids for an acute change in respiratory status; moderate = hospital admission
for a change in respiratory status; severe = requirement for mechanical ventilation for a change in respiratory status).
b. A measurement of the body mass index (BMI).
c. A medication history (oral steroids, chronic bronchodilator use, oxygen use) with an emphasis on whether adherence was adequate.
d. Assessment of gastro-esophageal reflux disease (10)
e. Epworth Sleepiness Scale as a marker of sleep disordered breathing
f. Estimate of daily physical activity (25)
3. Pulmonary function tests will include spirometry, plethysmographic lung volumes, and corrected carbon monoxide diffusing capacity (DLCO). All procedures will be done in accordance with ATS/ERS standards (3) (15) (17).
4. High resolution computerized scans of the chest (HRCT). Emphysema scores will be calculated per COPD Gene protocol (7). We will also explore novel approaches to quantifying airway structures (5) (16)
5. A six-minute walk test with monitoring of pulse oximetry and heart rate will be conducted in accordance with ATS standards (1)
6. Vital Signs will be measured and recorded (temperature, heart rate, blood pressure and respiratory rate)
7. Pulse oximetry will be measured and recorded.
8. Weight and height will be recorded.
9. Quality of Life (QOL) will be assessed using the St George self-administered instrument
10. A serum pregnancy test will also be performed in women with child bearing potential.

MRI will be collected at the study visit 1 after the screening visit. Where possible the screening visit (V0) and MRI visit (V1) will be accomplished on the same day for the convenience of the subject. In all cases, the MRI will be followed-up immediately following the MRI procedure for any adverse events. Finally, all subjects will be contacted 24 hours post-MRI by phone for follow-up regarding any adverse events.

Visit 1: MRI
Visit 1 will include a rescreening for MRI safety by the MR Technologist, (if not performed at screening), the MRI exam, Vital signs (temperature, heart rate, blood pressure, respiratory rate and pulse oximetry) will be collected at pre and post imaging examination. A urine pregnancy test will be performed on female of child-bearing potential if the screening serum test was given 48 or more hours earlier. They must have a negative result to further participate in the study.

Additionally, subjects will be carefully observed for any signs of hypoxia before, during, and after the MRI exam using pulse oximetry. Any SpO2 reading < 90% will result in termination of the study.

Twenty-four Hour Follow-up
Twenty-four hours post V1 (and subsequent imaging visits) the subjects will be contacted by phone and questioned regarding any post MRI adverse events.

Inclusion/Exclusion Criteria for Subjects with COPD
Inclusion criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial
1. Outpatients of either gender, age > 18.
2. Willing and able to give informed consent and adhere to visit/protocol schedules. (Consent must be given before any study procedures are performed.)
3. Women of childbearing potential must have a negative serum pregnancy test. This will be confirmed before participation in this investigational protocol.
4. Clinical diagnosis of COPD confirmed by Spirometry demonstrating FEV1/FVC <0.70.
Exclusion criteria
Subjects presenting with any of the following will not be included in the trial:
1. Recent exacerbation (within 30 days) defined by the need for antibiotics and/or systemic steroids.
2. Abuse of alcohol or illicit substances.
3. Medical conditions, which, in the opinion of the investigator, will significantly affect five-year survival.
4. Medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject’s ability to comply with the protocol requirements.
5. Conditions that will prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine, renal insufficiency with eGFR < 60 mL/min/1.73 m2)
6. Need for uninterrupted 24 hour/day O2 therapy.
7. Previously documented resting arterial pCO2 > 50 mmHg.

Inclusion/Exclusion Criteria for Normal Subjects

Inclusion criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial
1. Outpatients of either gender, age > 18.
2. Willing and able to give informed consent and adhere to visit/protocol schedules. (Consent must be given before any study procedures are performed.)
3. Women of childbearing potential must have a negative serum pregnancy test. This will be confirmed before participation in this investigational protocol.
4. Normal PFT determined by spirometry.
5. Non-smoker, ex-smoker, or current smoker.

Exclusion criteria
1. Abuse of alcohol or illicit substances.
2. Conditions that will prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine).

For more information, contact Samantha Womack at 919-684-7931.