Ground-glass burden as a biomarker in neuroendocrine cell hyperplasia of infancy

Pediatr Pulmonol. 2019 Jun;54(6):822-827. doi: 10.1002/ppul.24301. Epub 2019 Mar 6.


Background: Neuroendocrine cell hyperplasia of infancy (NEHI) is a rare pediatric interstitial lung disease (ILD). Distinct chest computed tomography (CT) define its radiographic appearance-specifically, ground-glass (GG) opacities most prominent in the right middle lobe (RML) and lingula. We sought to quantitatively validate this description and correlate radiologic findings with clinical presentation.

Methods: Twenty-one children with NEHI were identified retrospectively, alongside 10 age-matched controls without lung disease. Clinical histories were reviewed for NEHI subjects. Semiautomated image analysis was used to measure lung volume and density. A patient-specific Hounsfield unit threshold defining GG was developed to quantify GG and assess its distribution in each subject.

Results: NEHI subjects had more GG than controls (37.9 ± 11.3% vs 14.0 ± 2.7%, P < 0.0001). The proportion of GG in the RML and lingula was greater in NEHI patients compared to controls (1.43 ± 0.37 vs 0.45 ± 0.21, P < 0.0001). GG preferentially involved the RML and lingula in 20/21 NEHI subjects. There was more GG distribution in NEHI subjects who were prescribed continuous oxygen compared with those using only nocturnal oxygen (45.7 ± 8.9% vs 29.3 ± 6.1%, P = 0.003).

Conclusions: We confirm the previously reported finding that most patients with childhood ILD and a distinctive pattern of GG distribution on CT scan are likely to have NEHI. The amount of GG may be a biomarker for severity of respiratory disease.

Keywords: childhood interstitial lung disease; quantitative computed tomography.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers
  • Child, Preschool
  • Female
  • Humans
  • Hyperplasia / diagnostic imaging*
  • Hyperplasia / pathology
  • Infant
  • Lung / diagnostic imaging
  • Lung / pathology
  • Lung Diseases, Interstitial / diagnostic imaging*
  • Lung Diseases, Interstitial / pathology*
  • Male
  • Neuroendocrine Cells / pathology*
  • Retrospective Studies
  • Tomography, X-Ray Computed


  • Biomarkers