Ground glass and fibrotic change in children with surfactant protein C dysfunction mutations

Pediatr Pulmonol. 2021 Jul;56(7):2223-2231. doi: 10.1002/ppul.25356. Epub 2021 May 11.

Abstract

Introduction: Therapeutics exist to treat fibrotic lung disease in adults, but these have not been investigated in children. Defining biomarkers for pediatric fibrotic lung disease in children is crucial for clinical trials. Children with surfactant protein C (SFTPC) dysfunction mutations develop fibrotic lung disease over time. We evaluated chest computed tomography (CT) changes over time in children with SFTPC dysfunction mutations.

Methods: We performed an institutional review board-approved retrospective review of children with SFTPC dysfunction mutations. We collected demographic and clinical information. Chest CT scans were evaluated using visual and computerized scores. Chest CT scores and pulmonary function tests were reviewed.

Results: Eleven children were included. All children presented in infancy and four children suffered from respiratory failure requiring mechanical ventilation. Those who performed pulmonary function tests had stable forced vital capacities over time by percent predicted, but increased forced vital capacity in liters. CT findings evolved over time in most patients with earlier CT scans demonstrating ground glass opacities and later CT scans with more fibrotic features. In a pilot analysis, data-driven textural analysis software identified fibrotic features in children with SFTPC dysfunction that increased over time and correlated with visual CT scores.

Discussion: We describe 11 children with SFTPC dysfunction mutations. Increases in forced vital capacity over time suggest that these children experience lung growth and that therapeutic intervention may maximize lung growth. Ground glass opacities are the primary early imaging findings while fibrotic features dominate later. CT findings suggest the development of and increases in fibrotic features that may serve as potential biomarkers for antifibrotic therapeutic trials.

Keywords: biomarkers; imaging; interstitial lung disease (ILD).

MeSH terms

  • Adult
  • Child
  • Humans
  • Lung / diagnostic imaging
  • Mutation
  • Protein C*
  • Pulmonary Surfactant-Associated Protein C* / genetics
  • Retrospective Studies
  • Surface-Active Agents

Substances

  • Protein C
  • Pulmonary Surfactant-Associated Protein C
  • Surface-Active Agents