The purpose of this study is to investigate the role of the pulmonary vasculature in the development and progression of chronic obstructive pulmonary disease (COPD). To accomplish this, an inhaled prostacyclin (iloprost) will be given to patients with COPD and changes in oxidative stress and lung volumes during exercise will be measured.
Chronic obstructive pulmonary disease (COPD), the 3rd leading cause of death in the US, is a progressive disorder for which new treatments are urgently needed, as existing therapies are focused primarily on symptom relief. Oxidative stress, in part arising from inducible nitric oxide synthase (iNOS) released by the pulmonary vasculature, is critical for the development and progression of COPD; a treatment strategy focused on the pulmonary vasculature is hypothesized to be beneficial in COPD patients. This will be studied with the use of an inhaled prostacyclin analogue, iloprost, which has been approved for pulmonary hypertension and investigated in small studies of COPD patients. Potential mechanisms include reductions in dynamic hyperinflation during exercise in COPD patients or improvements in oxidative stress
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
24
Single administration
Single administration
LSU Health Sciences Center
New Orleans, Louisiana, United States
Dynamic hyperinflation during maximal cardiopulmonary exercise test
Dynamic hyperinflation will be measured as EELV/TLC ratio (end-expiratory lung volume/total lung capacity ratio) during exercise
Time frame: Acute response (exercise testing performed 30 minutes after study drug administration)
Blood markers of oxidative stress
8-isoprostane, superoxide dismutase, catalase, nitrite, malondialdehyde
Time frame: Acute response (measured 10 minutes, 30 minutes, 40 minutes, and 100 minutes after study drug administration)
Blood markers of inflammation
IL-1 beta, IL-6, IL-8, IL-10, IL-13, IL-18, TNF-alpha
Time frame: Acute response (measured 10 minutes, 30 minutes, 40 minutes, and 100 minutes after study drug administration)
Dead space fraction
Time frame: Acute response (measured every 2 minutes during exercise, starting 30 minutes after study drug administration)
B-type natriuretic peptide
Time frame: Acute response (measured 30 and 40 minutes after study drug administration)
Partial pressure of oxygen
Time frame: Acute response (measured 30 minutes after study drug administration and every 2 minutes during exercise)
Metabolic and gas exchange parameters during cardiopulmonary exercise test
Time frame: Acute response (throughout exercise, starting 30 minutes after study drug administration)
Blood cyclic AMP levels
Time frame: Acute response (measured 10 minutes, 30 minutes, 40 minutes, and 100 minutes after study drug administration)
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Blood iloprost levels
Time frame: Acute response (measured 10 minutes, 30 minutes, 40 minutes, and 100 minutes after study drug administration)
Exercise time and external work performed
Time frame: measured during exercise test 30 minutes after study drug administration
Borg dyspnea and leg scores
Time frame: During exericse (starting 30 minutes after study drug administration)