OVERVIEW
Pulmonary veno-occlusive disease (PVOD) is a clinicopathological syndrome that can cause pulmonary hypertension, characterized by progressive occlusion of small pulmonary veins leading to increased pulmonary vascular resistance and right heart failure. Pulmonary venous occlusion is considered a cause of pulmonary hypertension due to involvement of the pulmonary capillary system, and its pathology is characterized by extensive diffuse filling of lung tissue with fibrous tissue. The age of onset spans a wide range (9 days-67 years), with the majority under 50 years of age; the prevalence is similar in children of both sexes, with a higher prevalence in adult males.
Etiology
The etiology of pulmonary veno-occlusive disease is unclear, and so far it has been found that it may be related to the following factors.
1. Genetic factors
It is found that some patients have mutations in the osteogenic protein receptor II gene, and the mutation rate of this gene is more than 50% and 25% in patients with familial and sporadic pulmonary hypertension, respectively. This suggests that pulmonary veno-occlusive disease may be associated with mutations in this gene. It is also found that pulmonary veno-occlusive disease and idiopathic pulmonary hypertension are two kinds of pulmonary vascular diseases with different obstruction sites, which have similar genetic risk factors.
2. Chemotherapy
Certain chemical drugs can also cause pulmonary veno-occlusive disease. It has been found that certain chemotherapeutic drugs can cause pulmonary veno-occlusive disease, mainly mitomycin, bleomycin and carmustine. So far, it is found that these chemotherapeutic drugs themselves have certain effects on the damage, inflammation and fibrosis of pulmonary veins.
3. Malignant tumors and related transplantation
Some malignant tumors, such as leukemia, lymphoma, etc., peripheral blood stem cell transplantation, autologous and/or allogeneic bone marrow transplantation, solid organ transplantation and radiotherapy can lead to pulmonary veno-occlusive disease. However, it is difficult to determine the relationship between these factors and pulmonary veno-occlusive disease due to the rarity of related reports.
4. Immune-mediated association
Pulmonary veno-occlusive disease associated with immune disorders, such as tuberculosis, Langerhans cell granuloma, chronic active hepatitis, systemic lupus erythematosus, and scleroderma, has also been reported.
Symptoms
The clinical manifestations of pulmonary veno-occlusive disease are not specific, and its onset is insidious and easily overlooked. Dyspnea progressively worsens after activity is the main symptom. Patients with pulmonary veno-occlusive disease usually have more prominent signs of right heart failure, which are usually accompanied by some symptoms of right heart failure, including loss of appetite, abdominal distension and nausea.
Examination
Surgical lung biopsy is the gold standard for the diagnosis of pulmonary veno-occlusive disease, which is characterized by diffuse obstruction of the veins by fibrous tissue, with lesions mainly involving the interlobular septa and the pre-interlobular septal capillaries followed by the small veins and micro-veins, and rarely the large pulmonary veins. However, the risk of fatal hemorrhage is high, so the diagnosis and treatment of pulmonary veno-occlusive disease is based on imaging features.
1. High-resolution CT imaging
Pulmonary hypertension and posterior capillary congestion are the imaging basis of pulmonary veno-occlusive disease. Its imaging features mainly include main pulmonary artery dilatation, kerleyB line and pulmonary edema sign. High-resolution CT is valuable for the differential diagnosis of idiopathic pulmonary hypertension and pulmonary veno-occlusive disease. In addition to the imaging features of pulmonary hypertension such as widening of the main pulmonary artery and enlargement of the right heart, pulmonary veno-occlusive disease also has other major features such as mediastinal lymph node enlargement, thickening of the interlobular septum, and centrally located ground-glass shadows in the lobules. In idiopathic pulmonary hypertension, there is usually no abnormality in the lungs.
2. Echocardiography
Echocardiography is the most important non-invasive screening method for pulmonary hypertension. Pulmonary artery systolic pressure >40mmHg measured by tricuspid regurgitation velocity is the criterion for echocardiographic diagnosis of pulmonary hypertension, which is a sensitive but not specific indicator, and false positives often appear in the clinic, which need to be further confirmed by right heart catheterization. Echocardiography can exclude pulmonary hypertension caused by left heart disease, and can also be used to assess the severity and prognosis of patients with pulmonary veno-occlusive disease.
3. Lung function and blood gas analysis
Patients with pulmonary veno-occlusive disease may have hypoxemia, the average partial pressure of arterial oxygen in patients with pulmonary veno-occlusive disease is about 61mmHg, while the average partial pressure of arterial oxygen in patients with idiopathic pulmonary hypertension is about 75mmHg. When the measurement results are disproportionate to the severity of conventional pulmonary hypertension, we should be alerted to pulmonary veno-occlusive disease.
4. Bronchoalveolar lavage fluid (BALF) test
In patients with suspected pulmonary veno-occlusive disease, alveolar lavage fluid can be helpful in the diagnosis. patients with PVOD have a markedly increased proportion of ferritin-containing macrophages in their BALF. Although intra-alveolar hemorrhage is not a specific manifestation of pulmonary veno-occlusive disease, patients with pulmonary hypertension in the presence of intra-alveolar hemorrhage should be on high alert for pulmonary veno-occlusive disease.
Diagnosis
The disease can be suggested on the basis of clinical presentation, combined with physical examination, bronchoscopy, and imaging. Lung biopsy is the gold standard for the diagnosis of this disease.
Treatment
The current treatment program for pulmonary veno-occlusive disease is only to improve the patient’s symptoms.
1. General treatment
Limit activities, avoid drugs that aggravate pulmonary hypertension (e.g., B-blockers), inhale oxygen, etc. Oxygen inhalation can help to improve symptoms and reduce the worsening of pulmonary hypertension.
2. Diuretic, cardiotonic and anticoagulant treatment.
Patients with pulmonary hypertension are often accompanied by pulmonary edema, and a large number of diuretics can significantly improve the symptoms. Cardiac output of 100 beats/min and atrial fibrillation with fast ventricular rate are also indications for the application of digoxin. Patients with pulmonary arterial hypertension are routinely given warfarin anticoagulation to improve clinical symptoms. It should be noted that patients with pulmonary veno-occlusive disease often have hidden intra-alveolar hemorrhage, so anticoagulants should be used with caution.
3. Lung transplantation
Lung transplantation is the only method that can improve clinical symptoms and increase the survival rate, so lung transplantation should be considered as soon as possible.
Prognosis
The prognosis of pulmonary veno-occlusive disease is poor, with a high mortality rate at 1 year after diagnosis.
Prevention
Pulmonary veno-occlusive disease is a more specialized form of pulmonary hypertension. Empirical treatment based only on clinical manifestations similar to those of idiopathic pulmonary hypertension often leads to exacerbation of symptoms in patients with pulmonary veno-occlusive disease, causing severe pulmonary edema and even death. Correct and timely diagnosis is the key to treatment.