Ventilation Heterogeneity Of Peripheral Airways (Sacin*VT) Assessed By Nitrogen Multiple Breath Washout (N2-MBW) Is An Accurate and Sensitive Marker Of Bronchiolitis Obliterans Following Haematopoietic Stem Cell Transplantation Recipients

Abstract

Bronchiolitis Obliterans (BO) initially affects terminal and respiratory bronchioles, a region of the lung largely unexplored by spirometry, which is only altered in advanced disease. In contrast, the Impulse Oscillation System (IOS) and the nitrogen multiple breath washout (N2-MBW) are techniques characterized by a high sensitivity to peripheral airway changes and potentially more suited to early detection of small airways disease. In a cross sectional study, a total of 161 patients, divided into 4 groups: healthy controls (n=41), bone marrow transplant candidates (n=47), haematopoietic stem cell transplantation (HSCT) recipients (n=65) and patients with chronic obstructive pulmonary disease (COPD; n=8), were assessed by IOS, N2-MBW, spirometry, body plethysmography and diffusing capacity for carbon monoxide (DLCO) in order to describe respiratory function changes in post-transplant patients without pulmonary graft versus host disease (GVHD) and in order to characterize the pattern of peripheral airway changes in BO. All subjects were able to perform IOS and N2-MBW without difficulty. Significant variables are illustrated in the table.ControlNo BOSpBOSpMSDMSDMSDRV/TLC %9714109240.04414422<0.001DLCO %96880160.0024911<0.001Scond* VT [l]0.020.010.030.02<0.0010.020.01<0.001Sacin* VT [l]0.050.020.130.09<0.0010.370.20<0.001Z5Hz [cmH2O/(l/s)]3.070.673.491.29NS4.932.460.017DR5-20Hz [cmH2O/(l/s)]0.300.230.560.68NS1.250.960.016X5Hz [cmH2O/(l/s)]-0.950.21-1.130.77NS-2.271.980.002fR [1/s)]10.632.5413.194.86NS20.346.39<0.001Rperipheral [cmH2O/(l/s)]1.770.802.091.46NS3.703.060.026 Stem cell transplantation, even without respiratory complications, does not affect spirometry but appears to cause an increase in air trapping, a reduction in DLCO and enhanced ventilation inhomogeneity both in conductive (Scond*VT) and acinar (Sacin*VT) airways. Patients with BO (n=8) were characterized by further DLCO reduction, increase in oscillometric indices sensible to peripheral airways involvement (Z5Hz, DR5-20Hz, X5Hz, Resonant frequency and Rperipheral) and a further three-fold increase in Sacin* VT. Compared to patients with BO, COPD patients with the same degree of spirometric obstruction (FEV1/FVC< 0.7, FEV1 50% predicted) showed only half the increase in predicted Sacin*VT (p= 0.03). At a cut off of 321% of predicted value, Sacin* VT could distinguish the subjects with BO from recipients, with good accuracy (87%), sensibility (87.5%) and specificity (89.5%). We conclude that IOS and N2-MBW are simple tests able to detect changes following HSCT as well as those specific to Bronchiolitis Obliterans. Disclosures: No relevant conflicts of interest to declare.