Abnormal Baseline Oscillometry in Subjects Undergoing Hematopoietic Stem Cell Transplantation (HSCT)

Abstract

Rationale: Oscillometry is a tidal breathing test which may have greater sensitivity to detect impairment than spirometry. It has the potential to monitor lung function and screen for early manifestations of pulmonary infection or rejection. However, little is known about oscillometry findings in patients prior to hematopoietic stem cell transplantation (HSCT). Methods: The TRANSPIRE study (NCT04098445) is an ongoing NIH sponsored multi-center prospective observational cohort study of lung injury after HSCT in children. We performed oscillometry (Tremofloã C100, Thorasys, Montreal, CA) at baseline in a cohort of 148 children at 4 centers: Cincinnati Children's Hospital, Children's Hospital of Philadelphia, University of Minnesota Children's Hospital, and Boston Children's Hospital. Operators underwent a structured training program including quality control of data. Children between the ages of 4 and 21 years were eligible for study. Of subjects enrolled so far, 69 had oscillometry pre HSCT. Following ERS 2020 Guidelines, oscillometry was measured over recording periods of 30 seconds during tidal breathing using commercial equipment (Tremoflo, Thorasys Ltd, 5-37Hz) in at least three trials targeting a coefficient of variation of <15% in respiratory system resistance at 5Hz (R5). Variables reported included resistance at 5 and 11 Hz (R5, R11), reactance at 5 and 11Hz (X5, X11), frequency dependence of R (R5-19), resonant frequency (Fres) and area under the reactance curve (AX). Linear regression analysis was used to compare Transpire subjects to a cohort of 80 normal control patients studied at Children's Hospital of Philadelphia. Results: Significant differences between subjects and controls were observed in height adjusted values for Log AX (p= 1e-04), X11 (p <0.0001), R5-R19 (p < 0.0001) and fres (p= 0.0023). No differences were observed between subjects and controls in R5 and R11. Figure: Reactance at 11 Hz (X11) cm H20/l/s; as a function of height in cm. Control subjects red and TRANSPIRE subjects green. Conclusions: In a multicenter study of oscillometry in a cohort of children undergoing HSCT, our initial results suggest that baseline oscillometry in subjects is abnormal compared to controls. These findings suggest that patients undergoing HSCT have increased small airway resistance and increased respiratory system stiffness, which may put them at increased risk for pulmonary complications after HSCT. This study provides a baseline for future analyses examining subsequent changes, both acute and long-term, after HSCT in children. .