2 ml kg−1 min−1 (81% predicted). The exercise test also showed marked desaturation measured by pulse oximetry (95% at rest to 77% at peak exercise), low end-tidal partial pressure of carbon dioxide (maximum value of 32 mmHg) and high ventilatory equivalent for CO2 (nadir value of 39), all suggesting ventilation perfusion mismatch or shunt. Contrast echocardiography selleck chemicals showed no intra cardiac shunt and otherwise normal appearances.

Cardiac catheterisation showed a mean right atrial pressure of 5 mmHg, a mild increase in pulmonary artery pressure with mean of 26 mmHg, normal pulmonary capillary wedge pressure of 10 mmHg, cardiac output of 4.7 l min−1, and cardiac index of 4.13 l min−1 m−2. Pulmonary vascular resistance was slightly elevated at 3.4 Wood Units. He continued to deteriorate symptomatically. Twelve months later, spirometry was unchanged but transfer factor was 38% predicted. Arterial blood sampling breathing room air at rest showed paO2 of 56 and paCO2 of 34 mmHg. After 30 min breathing 98% O2, the values were 128 and 34 mmHg respectively,

giving a calculated shunt of approximately 27%.1 A microaggregate study showed no intrapulmonary shunt. Repeat echocardiography showed normal left and right ventricular appearances and function. There was mild tricuspid regurgitation with an estimated right ventricular Depsipeptide cost systolic pressure of 30 mmHg Adenosine triphosphate by Doppler. Magnetic resonance imaging of the heart was normal. Repeat high-resolution CT scan showed the impression of very subtle diffuse nodular opacities. Open lung biopsy showed scanty small foci of interstitial fibrosis, but no widespread pulmonary fibrosis. There were focal areas of capillary congestion within lobules, but no actual double layer of capillaries, or extension of capillaries into the interstitium, interlobular septa or bronchioles. Haemosiderin laden macrophages were prominent in alveolar spaces. Occasional small veins showed evidence of sclerosis, but there was no definite occlusion of veins and these changes were

felt to be insufficient to make a diagnosis of pulmonary veno-occlusive disease (PVOD). There were some regions of increased cellularity in the alveolar walls, reminiscent of pulmonary capillary haemangiomatosis (PCH), but again, insufficient to confirm this diagnosis. Overall, there was some suspicion of PVOD or PCH from the biopsy, but the changes were subtle and felt to be non-diagnostic. A vasculitic process was also considered possible. Warfarin and long-term oxygen therapy were commenced. On the basis that a vasculitic process was possible, a trial of methylprednisolone and pulsed cyclophosphamide was started. However, further deterioration occurred and he died approximately 3 years after initial presentation. Post mortem examination of the heart and lungs was performed. There was biventricular hypertrophy.