What causes pulmonary cystic disease?

From the Guidelines

Pulmonary cystic disease is primarily caused by lymphangioleiomyomatosis (LAM), pulmonary Langerhans cell histiocytosis (PLCH), and other rare conditions that lead to the formation of air-filled spaces within the lung tissue. The most common causes of pulmonary cystic disease include:

• Lymphangioleiomyomatosis (LAM), a rare lung disease that occurs sporadically or in association with tuberous sclerosis complex (TSC) 1
• Pulmonary Langerhans cell histiocytosis (PLCH), an uncommon interstitial lung disease that is strongly associated with smoking 1
• Birt-Hogg-Dubé syndrome, a genetic disorder caused by mutations in the FLCN gene
• Lymphoid interstitial pneumonia, a rare condition characterized by the accumulation of lymphoid cells in the lungs

These conditions lead to cyst formation through different mechanisms, including tissue destruction, air trapping, and abnormal tissue remodeling. Symptoms typically include shortness of breath, chest pain, and recurrent pneumothorax (collapsed lung). Diagnosis usually requires chest imaging (CT scans) and sometimes lung biopsy. Treatment depends on the underlying cause and may include smoking cessation, medications like sirolimus for LAM, or management of complications. The diagnosis and management of LAM, in particular, have been guided by the European Respiratory Society guidelines, which recommend a combination of history, high-resolution computed tomography scanning (HRCT), and tissue biopsy for diagnosis 1.

From the Research

Causes of Pulmonary Cystic Disease

• The causes of pulmonary cystic disease are diverse and can be broadly classified into several categories, including:
  • Neoplasms, such as low-grade or high-grade metastasizing neoplasms 2
  • Lymphoproliferative disorders, such as lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis 3, 2
  • Infections 2
  • Interstitial lung diseases 2
  • Smoking-related diseases 2
  • Congenital or developmental defects 2
  • Genetic syndromes with deficient tumor suppressor gene function, such as lymphangioleiomyomatosis and Birt-Hogg-Dubé syndrome 4
• Other causes of pulmonary cystic disease include:
  • Airway obstruction 3
  • Lung remodeling 3, 2
  • Inflammatory or infiltrative processes 2
  • Aberrant lung development 3

Disease-Specific Causes

• Lymphangioleiomyomatosis is caused by a genetic defect affecting the tumor suppressor gene TSC2, and can occur sporadically or in association with tuberous sclerosis complex 4
• Birt-Hogg-Dubé syndrome is caused by a genetic defect affecting the tumor suppressor gene FLCN, and is characterized by multiple pulmonary cysts, recurrent pneumothorax, skin hamartomas, and renal tumors 4
• Pulmonary Langerhans cell histiocytosis is a rare disease characterized by the proliferation of Langerhans cells in the lung, and can be associated with smoking and other environmental factors 3, 2