Mechanisms of Lung Cyst Formation

Abstract

Cystic lung diseases are a group of rare diseases characterised by discrete areas of parenchymal destruction. This chapter will contrast the diverse mechanisms of parenchymal loss that occur in common cystic lung diseases such as chronic obstructive pulmonary disease (COPD) with those of rare disorders associated with dysregulation of specific molecular pathways. Four representative cystic lung diseases are described with reference to underlying molecular pathogenesis, mechanisms of cyst formation and pathological and radiological manifestations. We discuss how normal repair mechanisms may be deranged by processes such as senescence in COPD and how in lymphangioleiomyomatosis mechanistic target of rapamycin (mTOR) dysregulation leads to protease activation and a tumor-like microenvironment resulting in parenchymal destruction. In pulmonary Langerhans cell histiocytosis (PLCH), activation of the BRAF/MEK/ERK pathway in dendritic cells interacts with cigarette smoke to cause a destructive bronchiolitis. In Birt-Hogg-Dubé syndrome (BHD), loss of the tumour suppressor folliculin leads to defects in cell-cell interactions and shear-mediated lung damage. Finally, we discuss the poorly understood group of cystic lung diseases caused by abnormal immunoglobulin deposition in the lung. The end result in each case is thin-walled cystic change in the pulmonary parenchyma, which can have consequences that range from no symptoms, to recurrent pneumothorax, to chronic respiratory failure.