2 and 3 The degree of BIBF 1120 price PH is modest in most group 3 PH cases.4 and 5 However, recent studies have highlighted a subset

of patients who exhibit disproportionately advanced or “out-of-proportion” PH.6, 7 and 8 This PH is clinically characterized by dyspnea insufficiently explained by lung mechanical disturbances1 and, more recently, a German consensus group has proposed new criteria for this population.7 It can be assumed that patients with Group 3 out-of-proportion PH have somewhat disease-specific vasculopathy and respond differently to PAH-specific drugs as compared with typical group 3 PH patients. Indeed, a few case reports have shown amelioration of pulmonary hemodynamics by PAH-specific vasodilators,9 and 10 suggesting a promising role of PAH-specific agents in this subset. In the present case report series, we document four consecutive patients with group 3 out-of-proportion PH, who favorably responded to PAH-specific vasodilators. We describe the clinical features of the four cases, and also discuss the potential benefits and risks of PAH-specific treatment in this emerging population. In July 2010, a 46-year-old man with early-onset chronic obstructive pulmonary disease (COPD) was referred to our hospital due to progressive peripheral edema. High resolution computed tomography (HRCT) exhibited severe emphysematous change

(Fig. 1A) and pulmonary function test (PFT) showed marked decrease in vital capacity (VC), forced expiratory volume in 1 s divided by forced vital capacity (FEV1/FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) (Table 1). Echocardiography suggested severe PH and right heart catheterization (RHC) Crizotinib clinical trial also noted increased MPAP, reduced cardiac index (CI) and elevated pulmonary vascular resistance (PVR). Cardiac magnetic resonance (CMR)-derived right ventricular ejection fraction (RVEF) was reduced. Overall clinical assessment suggested progression of PH and right heart

failure, rather than exacerbation of COPD. Sildenafil (20 mg, t.i.d.) and, a week later, beraprost (120 μg, t.i.d.) were started in August 2010. He tolerated treatment well without acute side effects. At follow-up admission 3 months later, his exertional dyspnea and peripheral edema had improved. RHC showed significant improvement Chorioepithelioma in MPAP, CI and PVR. CMR-derived RVEF had also improved, whereas arterial blood gas analysis (AGA) indicated deterioration of pulmonary oxygenation as compared with that before the vasodilator treatment (Table 1). PFT results did not change remarkably although tiotropium bromide inhalation (18 μg/day) was started with PAH-specific agents 3 months before. A 61-year-old man diagnosed with rheumatoid arthritis-associated interstitial pneumonia in 2009 noted progressive dyspnea, peripheral edema and hypoxemia in Dec 2011. HRCT revealed ground glass opacity and honeycomb lung in lower lobes (Fig. 1B). PFT was not performed due to advanced dyspnea.