Early Progressive Peripheral Airway Dysfunction after Allogeneic Haematopoietic Stem Cell Transplantation is associated with chronic Graft vs Host disease not BOS-0p

Background Current spirometric-based criteria for diagnosis of bronchiolitis obliterans syndrome (BOS) may miss early peripheral airway disease associate with disease onset. Multiple breath washout (MBW) and oscillometry offer improved sensitivity, but longitudinal changes occurring in allogeneic haematopoietic stem cell transplantation (HSCT) are unknown. Objective In this longitudinal study of HSCT survivors, we investigated changes in nitrogen-based MBW, oscillometry and conventional lung function, from baseline (pre-transplant), over 36-months, and associations with BOS Stage 0p, a spirometry-defined risk classification for potential later BOS development, and chronic graft-vs-host disease (cGVHD). Study Design Longitudinal observational study of allogeneic HSCT recipients from a single adult centre. All participants underwent spirometry, plethysmography, gas transfer capacity (DLCO), oscillometry and MBW at each study visit. Tests were performed pre-HSCT and 3 monthly thereafter over 36 months. Results 64 of 69 recipients recruited were included in the final analysis. Across the entire cohort, deterioration in acinar ventilation inhomogeneity (S acin ) occurred as early as 90 days post-HSCT (0.224 z score change/month, p<0.001), prior to any significant change in spirometry or oscillometry. Progressive deteriorations in S acin were associated with cGVHD status and grade but not BOS-0p status. Conclusions Early progressive peripheral airway dysfunction occurred following HSCT and was best detected by S acin from MBW. Distal acinar ventilation inhomogeneity (S acin ) deteriorated at an earlier stage than spirometry. Longitudinal deteriorations in S acin were related to cGVHD, and independent of early changes in spirometry parameters. These findings suggest an important role of the lung in cGVHD and provide important evidence to support future studies examining the prognostic utility of MBW in long-term monitoring of HSCT patients to provide an early effective signal of BOS. Highlights The evolution of peripheral airway function abnormality assessed using Multiple Breath Washout (MBW) and oscillometry following allogeneic HSCT is unknown. Progressive abnormality is established early following HSCT and occurred in those who developed chronic graft versus host disease (cGHVD) in other organ systems. This highlights the risk of peripheral airway dysfunction in those affected by cGVHD. MBW to monitor post-HSCT subjects provides additional insight to that provided by BOS-0p criteria which did not show the same relationship to cGHVD. These findings identify a potential window for earlier targeted treatment to improve long term outcomes.