Pulmonary Veno - Occlusive Disease

Introduction:

Pulmonary veno-occlusive disease refers to the blockage of the blood vessels that carry oxygenated blood from the lungs to the heart. Due to the buildup of abnormal fibrous tissue in the small veins of the lungs, the occlusion causes the narrowing of blood vessels and raises the pressure in the vessels that carry deoxygenated blood from the heart to the lungs, mainly via the pulmonary artery. The increased pressure in these vessels is referred to as pulmonary hypertension.

What Are the Causes of Pulmonary Veno-Occlusive Disease?

Various etiological factors are involved in the occurrence of this disease. These include:

• Genetic.

• Infectious.

• Immune-mediated.

• Toxic.

• Radiologic.

• Coagulopathic.

• Genetic:

  • The primary genetic cause is due to the mutations in the eukaryotic translation initiation factor-2 alpha kinase four gene (EIF2AK4 is a protein-coding gene).

  • Many cases are reported to occur in siblings with similar ages of onset.

  • Few cases are associated with mutations in bone morphogenetic protein receptor type 2 (BMPR2), a possible idiopathic or heritable pulmonary alveolar hypertension.

• Infectious: Various infections with viruses such as Epstein Barr virus, cytomegalovirus, measles virus, and concomitant toxoplasmic viral infection. Few cases associated with human immunodeficiency virus (HIV) infection have also been reported.

• Immune-Mediated: The pulmonary veno-occlusive disease occurs as a result of either autoimmune injury to veins or immune-mediated injury to venules related to viral or other environmental agents. Some cases of pulmonary hypertension with the underlying cause of scleroderma, mixed connective tissue disease, and CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) are associated with the pulmonary veno-occlusive disease.

• Toxic:

  • Pulmonary veno-occlusive disease is found to occur after the administration of certain chemotherapeutic agents such as Bleomycin, Carmustine, and Mitomycin.

  • Other factors causing this disease include powdered cleaning products containing silica, dodecyl benzyl sulfonate, soda ash, and trichloro-s-triazinetrione.

  • This disorder mostly occurs in bone marrow transplant patients than in the general population.

• Radiologic: Radiation exposure is one of the common causes of vascular injury. A case of pulmonary veno-occlusive disease that is caused due to the history of mantle irradiation for Hodgkin’s lymphoma has been reported.

• Coagulopathic: Some cases of pulmonary veno-occlusive disease are seen associated with the use of oral contraceptives or pregnancy and show support for the theory that this disease is related to coagulation disorders.

What Are the Signs and Symptoms of Pulmonary Veno-Occlusive Disease?

The signs and symptoms of pulmonary veno-occlusive disease are most commonly similar to other pulmonary and cardiac diseases. The most common symptoms include:

• Exertional dyspnea.

• Cough (productive or non-productive).

• Fatigue.

• Chest pain.

• Dizziness.

• Abdominal pressure and tenderness secondary to hepatic congestion.

• Syncope.

• Hemoptysis (coughing up blood) with diffuse alveolar hemorrhage.

• Postural dyspnea or orthopnea.

On physical examination, the following findings are observed.

• As the disease progresses, it results in pulmonary hypertension, and right-sided heart failure occurs.

• Jugular venous distension, a loud pulmonary heart sound, a right ventricular heave (heave refers to the abnormal large beating of the heart), epigastric tenderness, and pedal edema.

• Inspiratory crackles may present.

• Clubbing is an uncommon feature of pulmonary veno-occlusive disease.

• Sudden death may occur.

• Due to the increase in the pleural and pulmonary capillary pressure, the fluids may get accumulated in the pleural space, which may result in pleural effusion. But, it is found to be very rare in patients with pulmonary hypertension.

What Are the Diagnostic Approaches for Pulmonary Veno-Occlusive Disease?

The pulmonary veno-occlusive disease is suspected mostly in the presence of pulmonary arterial hypertension, with radiographic findings suggestive of left-sided heart failure. The diagnosis is based on clinical and radiographic findings.

• Laboratory Studies: In microangiopathic hemolytic anemia, proteinuria and elevations in serum immunoglobulin G and M concentrations have been reported. However, laboratory results are inaccurate and abnormal in cases of pulmonary veno-occlusive disease associated with autoimmune disease. The level of brain natriuretic peptide is high in patients with over right-sided heart failure.

• Pulmonary Function Tests: The single-breath diffusing capacity for carbon monoxide is usually reduced in pulmonary veno-occlusive disease patients. A restrictive ventilatory defect is reported in many cases.

• Echocardiography: An echocardiogram is an extensively useful initial noninvasive tool to assess right-sided pressures to rule out left ventricular abnormalities and valvular heart disease.

• Chest Radiography: The most common finding is the presence of interstitial infiltrates. As a result of interstitial edema and enlargement of pulmonary lymphatic channels, Kerley B lines are noted. Central pulmonary arteries are enlarged, which shows the presence of scattered and patchy opacities. Pleural effusion may be present mostly on the right side. However, the absence of these radiologic conditions does not exclude the presence of this condition.

• Selective Pulmonary Artery Angiogram: This test is helpful in ruling out chronic pulmonary thromboembolic disease.A ventilation-perfusion scan is sufficient to exclude significant chronic pulmonary thromboembolic disease.

• Computed Tomography (CT) Scan: A computed tomography scan shows septal thickening and diffuse or patchy ground-glass opacities. The subpleural septal thickening and diffuse, ill-defined, centrilobular ground-glass opacities are the most typical features of pulmonary veno-occlusive patients associated with pulmonary hypertension. Other findings include small nodules, lymphadenopathy, dependent areas of consolidation, and pleural effusions. Pericardial effusion may be present in advanced right-sided heart failure patients. Enlarged pulmonary arteries are seen universally in patients with pulmonary hypertension. The ground glass appearance is due to the alveolar septal thickening and epithelial hyperplasia.

• Cardiac Catheterization: The use of short-acting pulmonary arterial vasodilators, such as inhaled nitric oxide or intravenous Epoprostenol or Adenosine during acute vasoreactivity testing, may result in pulmonary edema. The edema is caused due to the increase in transcapillary hydrostatic pressure in preexisting venous occlusion and acute arterial vasodilation. The development of pulmonary edema in response to a pulmonary vasodilator strongly suggests the diagnosis of pulmonary veno-occlusive disease.

The development of acute pulmonary edema and even death is reported with the infusion of even very low doses of intravenous Epoprostenol. Thus, great caution should be used in patients with the suspected pulmonary veno-occlusive disease while administering intravenous Epoprostenol.

• Bronchoscopic Examination: Bronchoscopy helps to rule out other lung diseases in case of an atypical presentation. Hyperemia of the airway mucosa with vascular engorgement in the form of bright red, longitudinal streaks is reported. Bronchoalveolar lavage may suggest chronic alveolar hemorrhage. Transbronchial lung biopsy is contraindicated because of the presence of excessive bleeding and pulmonary hypertension.

• Surgical Lung Biopsy: Though there are controversies related to lung biopsy that it carries a severe risk of morbidity and mortality, the results of the biopsy rarely affect the treatment of pulmonary veno-occlusive disease. Other means of assessment, such as computed tomography scan findings and observation of the patient, help in making decisions about the listing and timing of lung transplantation.

What Are the Treatment Approaches for Pulmonary Veno-Occlusive Disease?

• Pulmonary Arterial Hypertension Therapy: Epoprostenol has some beneficial effects on hemodynamics and has the effect of reversing the increased vasomotor tone in pulmonary venules. Pulmonary edema may result acutely for months after initiation of therapy with the use of vasodilators.

Long-term oxygen supplementation therapy should be provided for hypoxemic patients with pulmonary veno-occlusive disease to keep oxyhemoglobin saturation levels above 90 %. This may be helpful in symptomatic and subjective improvement.

• Immunosuppressants, Steroids, and Antithrombotic Agents: These medications may be helpful in pulmonary veno-occlusive patients, particularly those associated with autoimmune disorders. The role of corticosteroids and antithrombotic agents such as Heparin does not change the course but may provide subjective treatment.

• Medications:

• Warfarin: Warfarin interrupts the hepatic synthesis of vitamin-K-dependent coagulation factors. Warfarin is used in pulmonary embolism, prophylaxis, and treatment of venous thrombosis and thromboembolic disorders.

• Epoprostenol: Epoprostenol has potent vasodilator properties and also plays a role in the inhibition of platelet aggregation and smooth muscle proliferation. Long-term infusion of this drug is helpful in patients with primary and secondary pulmonary hypertension. The disease progression is evident only in long-term administration. However, it is advisable to be used with caution.

Conclusion:

Most patients have a rapidly progressive course with the occurrence of death within two years of diagnosis without proper treatment. Currently, available treatments are insufficient to treat patients with the pulmonary veno-occlusive disease. Various studies and research are being carried out to bring out positive treatment outcomes for the disease in the future.