Persistent tachypnea of infancy is associated with neuroendocrine cell hyperplasia

We sought to determine the clinical course and histologic findings in lung biopsies from a group of children who presented with signs and symptoms of interstitial lung disease (ILD) without identified etiology. Patients were identified from the pathology files at the Texas Children's Hospital who presented below age 2 years with persistent tachypnea, hypoxia, retractions, or respiratory crackles, and with nonspecific and nondiagnostic lung biopsy findings. Age-matched lung biopsy controls were also identified. Their clinical courses were retrospectively reviewed. Biopsies were reviewed, and immunostaining with antibodies to neuroendocrine cells was done. Fifteen pediatric ILD patients and four control patients were identified for inclusion in the study. Clinically, the mean onset of symptoms was 3.8 months (range, 0-11 months). Radiographs demonstrated hyperinflation, interstitial markings, and ground-glass densities. Oxygen was initially required for prolonged periods, and medication trials did not eliminate symptoms. After a mean of 5 years, no deaths had occurred, and patients had improved. On review of the lung biopsies, all had a similar appearance, with few abnormalities noted. Immunostaining with antibodies to neuroendocrine cell products showed consistently increased bombesin staining. Subsequent morphometric analysis showed that immunoreactivity for bombesin and serotonin was significantly increased over age-matched controls. In conclusion, we believe this may represent a distinct group of pediatric patients defined by the absence of known lung diseases, clinical signs and symptoms of ILD, and idiopathic neuroendocrine cell hyperplasia of infancy. These findings may be important for the evaluation of ILD in young children.