Classification and Pathology

Although the classification of ILD in children remains nonstandardized, the European consortium and the North American consensus group have proposed classifications based on a multicenter review. It is helpful to separate diseases into ILD on the basis of age, disorders of known and unknown etiology, and diseases related to systemic disorders (Table 397-1). A diffuse developmental disorder of the lung is likely due to a primary aberration in lung and/or pulmonary vascular development. Growth abnormalities reflecting deficient alveolarization are largely secondary to impaired prenatal or postnatal alveolarization from restriction of fetal thoracic space, limitation of pulmonary blood supply, or chronic lung disease of prematurity (bronchopulmonary dysplasia). Abnormal alveolar growth may also be associated with a variety of chromosomal abnormalities such as trisomy 21 (Chapter 76). In neuroendocrine cell hyperplasia of infancy, which is distinct to infants and young children, the pathologic findings include hyperplasia of neuroendocrine cells within the bronchioles, and the lung histologic background is nearly normal. Pulmonary interstitial glycogenosis is characterized by diffuse accumulation of mesenchymal cells in the alveolar interstitium with accumulation of monoparticulate glycogen in the interstitial cell cytoplasm that is confirmed by ultrastructural examination. Disorders suggestive of surfactant metabolism dysfunction (Chapter 399) can explain many of formerly idiopathic pediatric ILDs. The more severe surfactant dysfunctions, such as surfactant protein (SP)–B mutations, usually manifest as respiratory failure in neonate. Congenital pulmonary alveolar proteinosis (Chapter 398) is more typical of ABCA3 mutations, and chronic pneumonitis of infancy is predominant histologic pattern seen in SP-C mutations. Diffuse ILD can occur without a known immunodeficiency or systemic disorder, but it can also be seen as a pulmonary manifestation of other systemic disease processes, such as collagen vascular disorders and sarcoidosis. Persistent pulmonary symptoms can occur after respiratory infections caused by adenoviruses (Chapter 254), influenza viruses (Chapter 250), Chlamydia pneumoniae (Chapter 217), and Mycoplasma pneumoniae (Chapter 215). Aspiration is a frequent cause of chronic lung disease in childhood. Children with developmental delay or neuromuscular weakness are at an increased risk for aspiration of food, saliva, or foreign matter secondary to swallowing dysfunction and/or gastroesophageal reflux (Chapter 315). An undiagnosed tracheoesophageal fistula (Chapter 311) can also result in pulmonary complications related to aspiration of gastric contents and interstitial pneumonia. Children experiencing an exaggerated immunologic response to organic dust, molds, or bird antigens may demonstrate hypersensitivity pneumonitis. Children with malignancies may have ILD related to the primary malignancy or an opportunistic infection or secondary to chemotherapy or radiation treatment.