Intra-Subject Variance of Respiratory Oscillometry Reflects Graft Injury and is Associated with Acute Rejection and Chronic Lung Allograft Dysfunction (CLAD) Post Lung Transplant (LTx)

• Published in: The Journal of heart and lung transplantation Vol. 40; no. 4; p. S57
• Main Authors: Vasileva, A., Hanafi, N., Matelski, J., Wu, J., deHaas, E., Huang, Q., Nadj, R., Cheung, A., Martinu, T., Ghany, R., Keshavjee, S., Cypel, M., Tikkanen, J., Ryan, C., Chow, C.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-04-2021
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2021.01.1880

CLAD occurs in 50-70% of LTx patients by year 5 and is the major obstacle to longterm survival. Multiple factors contribute to CLAD, of which acute rejection (AR) is the most significant. Routine monitoring with spirometry aims to identify and treat AR early. We reported that the oscillometry (Osc) metrics of small airway obstruction and ventilatory inhomogeneity, AX, X5 and R5-19, are more sensitive than spirometry in detecting AR associated graft injury. Hypothesis Osc detects AR associated graft injury and predicts risk of CLAD.
All double LTx recipients were enrolled from Dec 2017 onwards for Osc with each routine spirometry. By Mar 13, 2020, 238/287 enrolled patients had follow-up of ≥3 months while 170 had ≥6 months, of whom 32 developed CLAD. We excluded 6 CLAD cases due to insufficient Osc measurements by CLAD-onset date. Cox regression factored in the initial, baseline (the average of 2 best achieved post LTx) and intra-subject variance of AX, X5 and R5-19; demographics, primary diagnosis, CMV match status, HLA status and biopsy A-score, a cumulative index of biopsy-proven ARs.
Cox analysis in 170 patients with ≥ 6 months follow up found higher A-scores to increase the risk of CLAD (HR 1.60, p<0.05). Higher A-scores were significantly associated with higher variance of all Osc parameters but not with variance of %predictedFEV1, i.e. Osc is more sensitivity than FEV1 in detecting AR. Higher variance of R5-19, AX and X5 was associated with increased risk of CLAD (HR 1.37, 1.42 and 1.55 respectively, p<0.001). As CLAD is defined by drop in FEV1, we saw significant associations between variance of %FEV1 and CLAD (HR 1.59, p<0.001) and a higher baseline %FEV1 with lower CLAD risk (HR 0.34, p<0.001). Lastly, we observed that initial Osc measurements post LTx were significantly associated with risk of CLAD suggesting Osc could identify risk of CLAD earlier than spirometry.
We provide evidence that 1) Osc metrics of lung function reflect graft injury associated with AR and 2) intra-subject variance in Osc measurements is a marker of ongoing graft injury that provides a risk assessment of subsequent CLAD. As such, post LTx graft monitoring with Osc can improve early detection of CLAD.