Abstract
Pulmonary graft versus host disease is a pathological process arising in peripheral airways causing significant morbidity and mortality post-Bone Marrow Transplantation (BMT). Current screening and diagnosis focuses on spirometry change from baseline to identify Bronchiolitis Obliterans Syndrome (BOS), and an at-risk pre-BOS stage BOS0p (≥10% fall FEV1). Sensitive peripheral airway function tools exist but remain under-utilized and utility is unclear.
To investigate longitudinal peripheral airway function change, detected by Multiple Breath Washout (MBW) and Forced Oscillation Technique (FOT), in pediatric BMT subjects with/without BOS and BOS0p.
Children aged ≥3 years were recruited. Testing occurred at baseline, monthly during 1st year and 6-monthly to 3yrs: MBW (LCI, Scond and Sacin, ExhalyserD®, Ecomedics), FOT (Rrs and Xrs at 5Hz, AX, Fres, tremoFlo®, Thorasys) and, if feasible, spirometry, plethysmography and DLCO. Groups (BOS, BOS0p, unaffected) compared at baseline, 12, 24 and 36 months.
Of 24 recruited subjects (mean±SD (range) age 10.2±4.2 (3.3-18.1) years at BMT, 54% AML/ALL diagnosis, 71% male), 1 withdrew and 6 died (5 within 12 months). BOS and BOS0p alone were detected in 3 (12.5%) and 8 (33.3%), respectively. BOS was associated with pattern of marked abnormality, significant increases from baseline were observed in LCI, Scond, Sacin, Xrs, AX and Fres. One subject developed BOS3 at 105 days (1st feasible post-BMT test). MBW/FOT abnormality was detected 26 and 207 days prior to BOS≥1 in other cases. LCI trajectory increased with increasing BOS severity. At 3 years, statistically significant differences between BOS0p vs unaffected were observed for LCI (p=0.009), Sacin(p=0.03), Xrs (p=0.004) and approached significance for AX (p=0.09) and Fres (p=0.09).
BOS and its earlier at-risk stage BOS0p were associated with significant peripheral airway abnormality detectable on MBW and FOT. MBW and FOT abnormality predated BOS≥1 in 2/3 BOS cases.
