Pulmonary graft versus host disease (pGvHD) is a significant cause of morbidity and mortality post Bone Marrow Transplant (89AT). Histological changes such as bronchiolitisobliterans suggests significant peripheral airway involvement. However, the pattern of abnormality observed with peripheral airway function tests, such as Multiple Breath Washout (MBW) and Forced Oscillation Technique (FOT) remain unclear. The aim of this study was to investigate the pattern of peripheral airway function change with pGvHD in children following BMT.
Children aged z3 years were recruited and assessed at baseline and at monthly intervals during the first year following BMT. Tests performed included MBW (Exhalyser D, Ecomedics), FOT (Tremoflo, Thorasys) and, if feasible, spirometry. MBW outcomes included lung clearance index (LCI), and concentration normalised phase III slope (SnIII) analysis parameters (Scond and FOT outcomes included respiratory system resistance (Rrs) and reactance (Xrs), frequency dependance of Rrs (R5-19Hz), resonant frequency (fres) and area under the reactance curve (AX). pGvHD was defined using NIH Consensus criteria 01. Change from baseline was assessed at time of pGvHD diagnosis.
21 subjects have been enrolled to date with 14 subjects, median (range) 5 (1-11) months post 8MT. pGvHD criteria met in 2/21 subjects to date (10%), and occured at 3 and 8 months post-BMT, respectively. In both pGvHD cases, significant increase born pre-BMT baseline was observed in LCI, Sacin, 115-19, fres, Xrs at 5Hz and AX. No change from pre43MT testing in Scond or Rrs at 5Hz was observed. Both children subsequently died of pGVHD.
pGvHD has occurred in 10% of the cohort to date and was fatal in both cases. Significant abnormalties in peripheral airway function occurred in both cases of pGVHD with the same pattern of abnormality. Future work will try to identify if these changes can provide an early signal for intervention.