The investigators will study the effect of pulmonary arterial vasodilation to see if it eliminates indices of persistent lung injury in smokers that are susceptible to emphysema.

The purpose of this research study is to find out if smoking cessation combined with sildenafil, an FDA approved drug for pulmonary hypertension, will decrease inflammation in the lung. Even if a smoker stops smoking, the harmful effects caused by previous smoking may recruit inflammatory cells to those affected areas, leading to lung injury. In about 30-40% of smokers, this inflammation combined with irregular blood flow in the lungs may lead to emphysema. The study goal is to measure and compare individual responses to smoking cessation, Sildenafil and placebo used three times per day, and imaging of the lungs using non-contrast and contrast CT scans to see if there is a possible decrease of inflammation and an increase of blood flow in the lungs. The study also intends to see if using Sildenafil three times per day, in addition to smoking cessation will restore blood flow to the possible injured areas of the lungs. Sildenafil is an FDA approved medication for pulmonary hypertension but will be used off-label to study the effects it may or may not have on the blood flow in possible injured areas of the lungs. Non-smokers will be enrolled to compare lung imaging and the effects of Sildenafil on their lungs with that of smokers undergoing a smoking cessation program with placebo or Sildenafil. Non-smokers will complete identical measurements as smokers, with Sildenafil used three times per day or no medication across a similar 90 day period of time. Vascular measurements of pulse wave velocity, carotid artery compliance/stiffness and pressure wave reflection will be done at baseline and 90 day visits.

Inclusion Criteria (Smokers):

• Between the age of 21 to 65 at baseline
• Be willing to participate in a smoking cessation program
• Be willing to attend all clinic visits
• Must be currently smoking at least ½ pack/day at baseline (confirmed with cotinine level and CO Smokerlyzer)
• >5 pack-year history of smoking
• Global Initiative for Chronic Obstructive Lung Disease (GOLD) 0: FEV1≥0.80 and FEV1/FVC>0.70 Forced Expiratory Volume in 1 second (FEV1), Forced Vital Capacity (FVC)
• GOLD 1: FEV1≥0.80 and FEV1/FVC < 0.70
• GOLD 2: 0.50≤FEV1<0.80 and FEV1/FVC < 0.70
• Be willing to abstain from using any nicotine patches, e-cigarettes, or marijuana for the duration of the study.

Inclusion Criteria (Non-smokers):

• Between the age of 21 to 65 at baseline
• Be willing to attend all clinic visits
• Have never smoked (confirmed with cotinine level and CO smokerlyzer)
• GOLD 0: FEV1≥0.80 and FEV1/FVC>0.70

Exclusion Criteria (Smokers and Non-smokers):

• Women only: Cannot be pregnant or nursing at baseline or plan to become pregnant during the course of the study
• Body Mass Index (BMI) > 35
• Allergies to shell fish, seafood, eggs or iodine
• Heart disease, kidney disease or diabetes
• Diagnosis of asthma
• Any metal in or on the body (that cannot be removed) between the nose and the abdomen
• Any major organ system disease (by judgment of the study medical team)
• A glomerular filtration rate of 60 cc per minute or less.
• Nitroglycerin usage or nitrates and use of phosphodiesterase 5 (PDE5) inhibitors
• Prior history of hypersensitivity to sildenafil
• Currently prescribed a phosphodiesterase (PDE) inhibitors medication (ex: Viagra, Cialis, etc)
• Known Pulmonary Hypertension
• Has used e-cigarettes and marijuana <1 years
• Use of ACE Inhibitors, Calcium Channel Blockers, Angiotensin II Receptor Blockers for control of blood pressure or any combination of these three types of medications.

CT images will be shared including non-contrast images at TLC, FRC and RV as well as dual energy CT image data used to assess regional perfused blood volume. All associated pulmonary function test results will be shared. CT-derived metrics.

Data will be made available starting 6 months after publication of the primary results of each aim.

Data will be provided to academic-based researchers upon written request to the PI, Eric A. Hoffman, PhD. A nominal charge will be made for the time it takes for a technician to prepare and transfer the requested data. These costs will not exceed $250. This service will be available for a minimum of 2 years of study close.

Subject and study team are masked to which arm subject is assigned (study drug or placebo). Investigational pharmacy will not be masked. For the non-smoker groups, both subjects and the study team will know which group they are assigned to (study drug or no medication).