INTRODUCTION: Limited therapeutic options are available for treatment of pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD). The use of non-selective systemic vasodilators resulted in worsening of gas exchange and symptoms in this patient population. Preliminary data suggests favorable acute effects on gas exchange and exercise tolerance after inhalation of Iloprost in a small case series of COPD patients with PH and right ventricular (RV) dysfunction.1 We report a case of severe PH in a patient with bullous emphysema who derived a significant functional and hemodynamic improvement following treatment with inhaled Iloprost.
CASE PRESENTATION: A 61 year old male patient with history of severe bullous emphysema presented with worsening dyspnea and profound hypoxemia. He had a severely reduced diffusion capacity of the lung for carbon monoxide at 4.5 mL/mmHg/min or 13% predicted but an unexpectedly normal spirometry despite presence of very advanced bilateral parenchymal bullous lung disease on chest computed tomography. Physical exam was notable for diminished breath sounds, digital clubbing, distended jugular veins and limb edema. Arterial blood gas on 10 liters Oxygen revealed PH 7.45; PCO2 25; PO2 57. Echocardiography was consistent with a severely dilated RV, profound reduction in systolic function, a peak systolic pressure of 79 mmHg and normal left ventricular function. Work up for pulmonary embolism or other alternative causes for pulmonary vascular disease was negative. Right heart catheterization (RHC) showed a right atrial pressure, 10 mm Hg; pulmonary capillary occlusion pressure, 13 mm Hg; mean pulmonary artery pressure (mPAP), 55 mm Hg; pulmonary vascular resistance, 9.5 Wood U; and cardiac output, 4.4 L/min. Inhaled Iloprost was initiated at a dose of 2.5 mcg every 4 hours and was well tolerated with no reported adverse effects after 4 months of therapy. Treatment with Iloprost led to improved breathlessness, gas exchange and exercise tolerance. Repeat blood gas analysis revealed PO2 of 92 on same flow of supplemental oxygen and distance covered during 6 minutes walk test increased from 26 to 101 m. The mPAP was reduced to 43 mmHg on RHC after 4 months of treatment with inhaled Iloprost.
DISCUSSIONS: Multiple mechanisms can result in PH in patients with COPD. Hypoxic vasoconstriction is not the only mechanism involved. Impaired vasodilatation, remodeling of the pulmonary vasculature and other manifestations of endothelial dysfunction were shown to be present in the emphysematous lung. Furthermore prostacyclin expression was shown to be altered in smoking related lung disease. Thus treatment with inhaled PGI2 may exert protective effects in the pulmonary vasculature of COPD patients. To our knowledge, this is the second reported case of effective treatment of severe PH associated with COPD with inhaled Iloprost.2 As an inhaled agent, Iloprost has the potential to act preferentially in relatively well ventilated regions of the lung which would receive the highest dose of the drug and thereby maintain or even improve ventilation perfusion matching while reducing pulmonary pressures.
CONCLUSION: Inhaled Iloprost may represent an important advance in the treatment of severe PH associated with COPD. Randomized controlled trials are needed in this patient population where there is no known definitive therapy other than supplemental oxygen.
DISCLOSURE: Jeremy Moad, No Financial Disclosure Information; No Product/Research Disclosure Information