Neuroendocrine cell hyperplasia of infancy (NEHI) is the pathologic correlate of the clinical syndrome persistent tachypnea of infancy. Persistent tachypnea of infancy occurs in term or near-term infants who, after an initial period of well-being, present with tachypnea, wheezing, chest retractions, exercise intolerance, or decreased oxygen saturation and supplemental oxygen requirement. Chest x-ray film typically shows hyperinflation and interstitial infiltrates. Chest CT typically demonstrates central perihilar ground-glass opacities, with predilection for the right middle lobe and lingula. Air-trapping, as in bronchiolitis obliterans syndrome, is not typically a feature. The infants usually remain stable or show gradual improvement in symptoms over a period of months to years.

Despite severity of clinical symptomatology, infants with persistent tachypnea have minimal microscopic changes on lung biopsy, except for increased numbers of neuroendocrine cells (or “clear cells”) in the mucosa of their airways. Although visible on sections stained with hematoxylin and eosin, the neuroendocrine cells are best demonstrated using immunohistochemistry for bombesin, where they may be seen in the airways in markedly increased numbers and in the parenchyma as prominent clusters (“giant” neuroepithelial bodies). It should be noted that the children described in the initial study of NEHI had no other conditions known to be associated with neuroendocrine cell hyperplasia, including bronchopulmonary dysplasia, acute lung injury, extreme altitude, smoke exposure, cystic fibrosis, and sudden infant death syndrome. Although the etiology and pathogenesis remain unclear, neuroendocrine cell hyperplasia may mediate bronchoconstriction in these children.