Pulmonary veno-occlusive disease presenting with recurrent pulmonary oedema and the use of nitric oxide to predict response to sildenafil

Abstract

Pulmonary veno-occlusive disease (PVOD) is a disorder which causes progressive pulmonary hypertension, usually presenting with worsening dyspnoea and right heart failure. Pulmonary oedema induced by pulmonary vasodilator therapy to reduce pulmonary arterial pressure has been well described in PVOD, but here we describe a case of PVOD presenting with recurrent episodes of acute non-cardiogenic pulmonary oedema, in the absence of significant pulmonary hypertension. Concern over the risk of precipitating pulmonary oedema led us to use inhaled nitric oxide to predict the safety and efficacy of sildenafil.Pulmonary veno-occlusive disease (PVOD) usually presents with worsening dyspnoea and right heart failure as a result of pulmonary arterial hypertension (PAH). Here we describe a case of PVOD presenting with recurrent episodes of acute noncardiogenic pulmonary oedema with only a borderline increase in pulmonary artery pressure, confounding the diagnosis until surgical lung biopsy was performed. In view of the risk of precipitating pulmonary oedema with vasodilator therapy, we also report on the use of inhaled nitric oxide to predict the safety and efficacy of sildenafil. CASE REPORTA previously healthy 21-year-old Afro-Caribbean male presented with a 2 h history of breathlessness. There was no associated chest pain, cough, wheeze or fever. He was apyrexial and had a saturation of 90% on high flow oxygen. He was tachycardic in sinus rhythm with a blood pressure of 110/70 mm Hg. He had widespread inspiratory crackles. His chest radiograph is shown in fig 1A. Routine blood tests revealed neutrophilia with a C reactive protein level of 4 mg/l. He started on continuous positive airway pressure (CPAP) and was treated for pneumonia with intravenous cefuroxime and clarithromycin. Pending results of an HIV test (subsequently negative), he received septrin and prednisolone for 2 days. Microbiological investigations for pneumonia were negative. Rheumatoid factor, sickle solubility test, serum ACE and autoantibodies were also negative.He improved rapidly over 2 days, with complete resolution of radiographic changes, but remained persistently hypoxaemic with exertional breathlessness and desaturation (from 93% to 76%). A CT excluded a pulmonary embolus and indirect evidence of PAH, such as dilated pulmonary arteries or right-sided cardiac chambers. There was no septal thickening, but extensive mediastinal and hilar lymphadenopathy and peripheral lung attenuation ( fig 1B). Lung function showed normal lung volumes with severely impaired gas transfer (carbon monoxide transfer factor 5.09 mmol/min/ kPa (43%), KCO 1.0 mmol/min/kPa/l (59%)). Given these findings and because of the rapid response presumed secondary to steroids, he was restarted on oral prednisolone 40 mg, with a presumptive diagnosis of sarcoidosis.Following discharge he was readmitted twice in quick succession with similar clinical and radiographic findings, responding rapidly to CPAP. On both occasions he had also reported streaky haemoptysis and frothy sputu...

Cautious epoprostenol therapy is a safe bridge to lung transplantation in pulmonary veno-occlusive disease

“…Other agents, such as sildenafil, also have venodilating properties, and there are cases of clinical improvement on sildenafil monotherapy in PVOD patients [30,31] or in combination with high-dose epoprostenol in one case [32]. However, pulmonary oedema may also occur in sildenafiltreated PVOD [33].…”

Pulmonary veno-occlusive disease

“…Unlike in pre-capillary PAH, there remains no clear-cut evidence of the value of PAH specific therapy in PVOD because of the small numbers of patients and the possibility of severe adverse effects [4]. However, clinical improvement or at least stabilisation has been observed in some patients with continuous intravenous prostacyclin [7,[74][75][76], oral sildenafil monotherapy [77,78], bosentan [79] and even chronic inhaled nitric oxide or iloprost therapy [80,81]. Combination therapy with sildenafil as an adjunct to high-dose prostacyclin has been shown to improve haemodynamics and clinical course in one case [82].…”

Lengthy Diagnostic Challenge in a Rare Case of Pulmonary Veno-Occlusive Disease: Case Report and Review of the Literature

“…According to some case reports, different specific PAH therapies (i.e., epoprostenol, bosentan and calcium channel blockers) have a risk of pulmonary vasodilator-induced pulmonary edema when taken without precautions (19). However, there have also been isolated instances of cases successfully managed using drug regimens (20,21). In the present case, we used a drug regimen of bosentan (a non-selective endothelin antagonist) in combination with diuretics and digoxin to treat the patient and relieve his symptoms.…”