Causes of diffuse lung disease in children

DLD: diffuse lung disease; NEHI: neuroendocrine cell hyperplasia of infancy; GM-CSF: granulocyte-macrophage colony-stimulating factor.

* Lung growth abnormalities include structural pulmonary changes associated with chromosomal abnormalities.

¶ Genetic disorders of surfactant dysfunction include pathogenic variants in SFTPB, SFTPC, ABCA3, NKX2-1, and SFTPA1.

Δ Most pulmonary alveolar proteinosis in children are genetic, including pathogenic variants in genes encoding the GM-CSF receptor (CSF2RA and CSF2RB) or MARS1.

◊ DLD related to systemic disease processes includes connective tissue disease (especially in older children), immune-related disorders, sarcoidosis, vasculitis, and storage diseases.

§ Unlike in adults, idiopathic pulmonary fibrosis accounts for only a small proportion of unknown causes (0.2% of DLD in children <2 years and 2% of those 2 to 18 years).