Monitoring for paediatric pulmonary graft versus host disease with multiple breath washout.

Background: Current diagnostic tests for pulmonary chronic graft versus host disease (p-cGvHD) are either invasive or challenging for children to perform. Multiple breath washout (MBW) has been proposed as a feasible and sensitive tool for the diagnosis of p-cGvHD. In this study, we aimed to determine the feasibility and sensitivity of MBW to monitor for p-cGvHD in children after haematopoietic stem cell transplantation (HSCT). Methods: This was a prospective, single-centre cohort study, recruiting children >3 years of age undergoing HSCT between February 2019 and January 2024. MBW and spirometry were performed at regular follow-up visits out to 2 years post-HSCT. Results: 46 children were included in the longitudinal analysis, five (10.9%) of whom developed p-cGvHD. MBW success rate was 93.9% (229 out of 244 visits), compared to 78.3% for spirometry (191 out of 244 visits). In children who developed p-cGvHD, compared to those who did not, peak lung clearance index (LCI) was higher (12.6 versus 6.8, p=0.0003), nadir forced expiratory volume in 1 s z-score (zFEV1) was lower (-3.5 versus -0.7, p=0.005) and nadir zFEV1:forced vital capacity (FVC) was lower (-2.4 versus -0.3, p=0.01). The sensitivity and specificity for p-cGvHD were 100%/97.6% for peak LCI, 100%/71.1% for nadir FEV1 and 75.0%/94.7% for nadir FEV1:FVC. In those who do not develop p-cGvHD, longitudinal LCI remained normal or mildly abnormal (LCI <8.0) in 98.1% of visits, compared to FEV1 (z > -1.9) in 90.2% and zFEV1:FVC in 95.5% of visits. Conclusions: MBW is longitudinally feasible in a post-HSCT population as young as 3 years of age. LCI is highly sensitive and specific for p-cGvHD and may help to distinguish different phenotypes of post-HSCT lung disease.