LAM Lung Disease - Types, Causes, Symptoms, and Management

Introduction

Lymphangioleiomyomatosis is also referred to as LAM lung disease. It is a rare disorder caused by abnormal and uncontrolled growth of muscle-like cells. It usually affects women of childbearing age. It causes breathing difficulties. It results in the formation of cysts in the lungs and affects the healthy lung tissues.

What Is LAM Lung Disease?

LAM is a rare lung disorder caused by the uncontrolled growth of smooth muscle-like cells in the lungs and the lymphatic system. It leads to the formation of cystic lesions in the lungs. It affects the healthy tissues of the lungs, disrupts the oxygen supply, and results in breathing difficulties. These abnormal growths can enlarge and cause bleeding.

What Are the Types of LAM Lung Disease?

LAM lung disease is divided into two types:

• TSC-LAM: TSC (tuberous sclerosis complex) LAM disease is seen in individuals with rare genetic diseases.

• Sporadic LAM: It occurs in individuals who do not have TSC. It is not a hereditary disease.

What Are the Causes of LAM Lung Disease?

Mutations cause LAM lung disease in the TSC1 or TSC2 genes. A germline mutation in the TSC1 or TSC2 genes causes TSC-LAM. Sporadic LAM is caused by somatic mutation in the TSC2 genes.

How Does LAM Lung Disease Occur?

The cells within the LAM lesion contain mutational inactivation of the TSC1 or TSC2 genes. Loss of these genes induces abnormal cell growth and increases cell viability. LAM cells arise from the extrapulmonary region and migrate to the lungs. It also behaves like metastatic cells. LAM cells proliferate and obstruct bronchioles. This results in airflow obstruction, air trapping, formation of bullae, and pneumothoraces. The obstruction of the lymphatic system forms lymphangioleiomyomatosis. It affects the healthy lung tissues and results in the formation of fluid-filled pockets called cysts that prevent air movement in the lungs and reduce the oxygen supply. It metastasizes to the lungs through the lymphatic system. It causes progressive cystic lesions and lung failure. It causes noncancerous spread to other organs in the abdomen and pelvis.

What Are the Symptoms Associated With LAM Lung Disease?

Individuals with LAM lung disease may have the following symptoms:

• Chest pain that worsens while breathing in.

• Shortness of breath.

• Chest pain and shortness of breath due to collapsed lung.

• Tiredness.

• Cough with bloody phlegm.

• Wheezing.

Tuberous sclerosis complex may present with the following signs:

• Facial angiofibroma.

• Hypomelanotic macules, ash-leaf spots.

• Periungual fibroma.

• Shagreen patch - A cluster of hamartoma on the lower back.

• Forehead plaque.

• Retinal hamartoma.

What Are the Complications Associated With LAM Lung Disease?

The complications caused by LAM lung disease are

• Angiomyolipomas are also called fatty kidney tumors. It causes bleeding, pain, or low blood pressure.

• Cystic lymphangiomas that resemble necrotizing lymphomas, ovarian or renal cancers.

• Hemoptysis.

• Pneumothorax.

• Chylothorax.

• Chylous ascites.

• Chylopericardium.

• Chyloptysis.

• Chyluria.

• Chyle in vaginal discharge.

• Chyle in the stool.

• Hematuria.

• Pericardial effusion.

• Pneumoperitoneum.

• Lymphedema.

• Respiratory failure.

• Osteoporosis.

• Meningioma.

How Is LAM Lung Disease Diagnosed?

The diagnosis is based on history, imaging tests, and laboratory tests. This includes the following:

• Chest Radiograph - The chest X-ray appears normal or shows the presence of hyperinflation in the initial stages of the disease. It presents with diffuse, bilateral, and symmetric reticulonodular opacities, cysts, bullae, or honeycomb appearance in advanced cases of this disease. Pleural effusion and pneumothorax may also be seen.

• Computed Tomography Scan (CT) - The high-resolution CT scan detects cystic lesions better than chest X-rays. It shows the presence of diffuse, round, bilateral, thin-walled cysts of varying sizes. It also detects the presence of linear densities, hilar or mediastinal lymphadenopathy, pneumothorax, lymphangioma, and thoracic duct dilation.

• Ventilation-Perfusion Scans showed a speckling pattern in perfusion imaging with the peripheral collection of radioisotopes.

• Positron Emission Tomography - LAM lesions do not uptake 18F-fluorodeoxyglucose on positron emission tomography scans. Hence, other neoplasms should be suspected.

• Abdominal Imaging - Abdominal imaging shows enlarged lymphatic structures and fat density within the renal mass. Abdominal lymphangiomatosis with cystic and solid components are seen.

• Central Nervous System Imaging - Abnormalities like cortical or subependymal tubers and astrocytomas are seen.

• Pulmonary Function Tests - The decreased diffusion capacity for carbon monoxide is markedly reduced. Spirometry tests show airflow obstruction. Lung volumes show an increased ratio of residual volume to total lung capacity.

• Laboratory Studies - Lymphangioleiomyomatosis shows a significant increase in vascular endothelial growth factor-D (VEGF-D). An increase in VEGF-D levels is associated with lymphatic involvement, like lymphangioleiomyomas and adenopathy.

• Histological Findings - Histological examination is done by obtaining tissue via an open lung, video-assisted thoracoscopic, or transbronchial biopsy. Microscopic examination reveals the presence of cystic lesions, large lymph nodes, chyle-filled cysts, and a large thoracic duct. The proliferation of LAM cells, loss of alveoli, distal airway narrowing, and thickened arterial walls with venous occlusion are present.

How Is LAM Lung Disease Managed?

The treatment for LAM lung disease involves the following:

• Pneumothorax - Pneumothorax is managed by performing chemical pleurodesis and surgical obliteration of the pleural space. Medium-chain triglycerides and a lipid-free diet are advised to reduce chyle flow.

• Ascites - It is managed by performing paracentesis. A medium-chain triglyceride diet is advised.

• Airway Disease - Bronchodilators and oxygen therapy are given. Smoking cessation and pulmonary rehabilitation are advised.

• Lung transplantation is recommended for severe cases.

• Standard vaccination is recommended for respiratory infections.

• Medical Care - Sirolimus drug is recommended for LAM lung disease. It reduces the size of angiomyolipomas, lymphangioleiomyomas, and chylous effusions.

• Hormone Therapy - Medroxyprogesterone, gonadotropin-releasing hormone, and tamoxifen are used.

• Surgical Care - Recurrent pneumothoraces or pleural effusions require surgical treatment. Arterial embolization is recommended over surgical resection. Lung transplantation is done for end-stage disease.

Conclusion

LAM lung disease is a rare respiratory disorder that affects women of childbearing age. It is a progressive disease that cannot be cured but can be treated. It is a low-grade, slow-growing tumor that is noncancerous. Early diagnosis of the disease and management can prevent the progression of the disease, its spread to other organs, and the risk of complications.