Towards Early Detection of Post-Allogeneic Bone Marrow Transplant Bronchiolitis Obliterans Syndrome (BOS) – the Use of Portable Airway Oscillometry

Background Bronchiolitis obliterans syndrome (BOS) is a devastating complication of allogeneic bone marrow transplantation (BMT). Detecting early small airway disease to diagnose BOS when it may be reversible could improve long term outcomes. Spirometry can be technically difficult for young and/or ill children. Oscillometry is novel pulmonary function assessment technology which superimposes pressure waves on normal tidal breathing, and the alterations in flow and pressure caused by the external waves are measured. Importantly, oscillometry is not effort dependent. Methods After IRB approved informed consent was obtained, portable airway oscillometry was attempted using the Tremoflo oscillometer on twelve BMT patients with established BOS. Due to sclerotic GVHD affecting mouth opening, one patient (aged 12yo) was unable to perform the test. The portable device was brought to the patients’ clinic room during routine follow up. Testing requires the patient to perform tidal breathing through a mouthpiece for 20-60sec (age dependent), for a minimum of three tests (Fig.1). The procedure has been successfully completed by BMT patients as young as 3 years in our other clinical studies. Results Eleven BOS patients have completed at least one test (17 separate tests performed over 6 months). Patient demographics are shown in Table 1; the median age is 18 years (10-25yo), and median time post BMT is 4.1 years (1.7-15). Six patients had malignant disease (50%), four immunodeficiency (33%), one bone marrow failure and one hemoglobinopathy. Formal spirometry was performed on the same day per routine clinical care. Patients had significantly abnormal spirometry, with mean FVC z-score -2.11 (0.3 to -5.58), mean FEV1 z-score -4.40 (-2.35 to -6.45) and mean FEV1/FVC 0.52 (0.4-0.62) (Table 1, Fig.1A).Oscillometry results are shown in Fig.1B. Reactance at 5Hz (X5) reflects elastic recoil and compliance of the peripheral airways and is a marker of respiratory system stiffness. The X5 was dramatically reduced in this cohort, with a mean X5 z-score -4.86 (Fig. 1B). X5 strongly correlates with FEV1, with correlation coefficient of 0.8091, p=0.0039 (Fig. 1C).Resistance at 5Hz (R5) provides a measure of total airway resistance, and R19 reflects proximal airway resistance. R5-19 therefore reflects peripheral airway resistance. Most BOS patients (8 of 11, 73%) had normal range R5-19 (Fig. 1C); mean R5-19 z-score 1.21 (-0.16-3.99). The R5-19 z-score correlates with the FEV1/FVC ratio (r=0.88, p=0.0007). Conclusion Our work defines the unique oscillometry characteristics of BOS, which now allows screening for early detection. This technique is portable, not effort dependent and relatively inexpensive. We have shown a dramatic reduction in reactance in BOS patients, reflecting stiff and poorly compliant lungs; these oscillometry findings may help to better understand the pathophysiology of BOS.