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

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.

Inherited pulmonary surfactant metabolism disorders in Argentina: Differences between patients with SFTPC and ABCA3 variants

“…Our CT findings as well as histological features are consistent with those already published 31–33 . Bilateral GGO and lung cysts in an infant born full term with rapid breathing suggest an interstitial lung disease and the possibility of a genetic surfactant disorder.…”

“…In terms of genetic findings, the SFTPC variant p.Ile73Thr appears to be the most frequent variant described for this gene also for Hispanic population 30,31 . Kröner et al have shown that genotype for SFTPC variants alone does not predict the clinical course 30 .…”

“…7,21,30 In terms of genetic findings, the SFTPC variant p.Ile73Thr appears to be the most frequent variant described for this gene also for Hispanic population. 30,31 Kröner et al have shown that genotype for SFTPC variants alone does not predict the clinical course. 30 Our patients with SFTPC variants, varied from asymptomatic to hypoxemia on exertion or pulmonary fibrosis, and these outcomes were not associated with the type of variant.…”

“…29 Wambach et al, 28 Our CT findings as well as histological features are consistent with those already published. [31][32][33] Bilateral GGO and lung cysts in an infant born full term with rapid breathing suggest an interstitial lung disease and the possibility of a genetic surfactant disorder. Most of our patients presented the typical histopathology of a surfactant dysfunction disorder:…”

Nintedanib in children and adolescents with fibrosing interstitial lung diseases

“…We also observed a stabilisation of S pO 2 at rest over 24 weeks in the nintedanib group compared with a decline in the placebo group (mean± se change 0.07±0.77% versus −2.25±1.08%). These observations need to be interpreted with caution given the paucity of data on the natural history of lung function in children with ILD [ 7 , 29 , 30 ] and the short duration of the trial. However, the observed reduction in decline in FVC % pred with nintedanib versus placebo in this paediatric population was within the range observed in adults with fibrosing ILDs treated for 24 weeks.…”