Hypoxic Pulmonary Vasoconstriction Pilot Study

Phase 4

Completed

Brief Summary: The purpose of this study is to determine if the events leading to smoking-associated centrilobular and paraseptal emphysema are caused by a failure of the lungs' inherent mechanisms to block hypoxic pulmonary vasoconstriction (HPV) in areas of smoking-induced inflammation.

Detailed Description: Overall goals of this study are to 1) determine the effects on sildenafil on the heterogeneity perfused blood volume in smokers susceptible to emphysema using dual energy CT 2) utilize pulmonary blood volume heterogeneity as an image-based biomarker to differentiate normal and susceptible smokers.

Recruitment & Eligibility

Inclusion Criteria

Must be between the ages of 30 and 60.
Must be currently smoking at least 1/2 pack/day (confirmed with cotinine level).
Must have pulmonary function test (PFT) results that meet the following:
Forced Expiratory Volume at one second (FEV1)/Forced Vital Capacity (FVC) > 70%
Forced Expiratory Flow at 25-75% (FEF25-75) > 79% of predicted
FVC greater than 80% of predicted
Must be able to give informed consent for self.

Exclusion Criteria

Pregnant or breastfeeding females.
Body Mass Index (BMI) greater than 32.
Weight of greater than 220 pounds (100 kg).
Allergies to shell fish, seafood, eggs or iodine.
Heart disease, kidney disease or diabetes.
Diagnosis of asthma.
Usage of any medications that are known to affect the heart or lungs (contraceptives, anti-depressants, analgesics EXCEPT aspirin, antihypertensives, and medications for osteoporosis and gastrointestinal diseases will be allowed).
Any metal in or on the body between the nose and the abdomen.
Any major organ system disease (by judgment of study medical team).

For the subjects that will receive Sildenafil as part of the study, additional exclusion criteria are as follows:

Arm && Interventions

Group	Intervention	Description
Nonsusceptible Smokers (NS)	Sildenafil study group	8 subjects recruited to study non-contrast imaging at TLC and 20%VC and with contrast using DECT to assess perfused blood volume. For the intervention, the subject will be administered 20 mg of Sildenafil and then the same scanning will be repeated one hour after sildenafil administration.
Susceptible Smokers (SS)	Sildenafil study group	11 subjects recruited to study non-contrast imaging at TLC and 20% VC and with contrast using DECT to assess pefused blood volume. For the intervention the subject will be administered 20 mg of Sildenafil and then the same scanning will be repeated one hour after sildenafil administration.

Primary Outcome Measures

Name	Time	Method
Perfused Blood Volume Assessed for a Change in Lung Inflammation Pre and Post Dose Sildenafil Administration	Change of perfused blood volume from baseline at one hour after sildenafil administration.	Perfused blood volume will be measured by CT scan at two time points and compared at two points, pre and post the administration of sildenafil.

Secondary Outcome Measures