Characterization Of Chronic Lung Allograft Dysfunction With Oscillometry

Abstract

Chronic lung allograft dysfunction (CLAD) affects up to 70% of lung transplant (LTx) recipients and is the major impediment to long-term survival. CLAD is a retrospective diagnosis of exclusion when other causes for sustained drop of ≥20% of forced expiratory volume in 1s or forced vital capacity have been ruled out. No effective treatments exist, likely due to irreversible lung damage at diagnosis. Oscillometry (Osc) is a promising pulmonary function test that is particularly sensitive to changes in small airways, the site of CLAD onset. Our aim is to characterize Osc in patients with early CLAD. In a prospective study that began in December 2017, all new double LTx recipients are enrolled for Osc prior to routine spirometry. CLAD will be diagnosed according to ISHLT guidelines. By March 2020 we anticipate enrolment of 300 patients and 30 to have CLAD. We will compare Osc in CLAD patients with those who remain CLAD free after ≥6 mths follow-up. Univariate and mixed models will be used to examine spirometry vs Osc parameters of small airway disease: namely, X5 (reactance at 5Hz), Ax (area of reactance) and R5-19 (difference of resistance at 5 and 19 Hz). Receiver operating characteristic area under the curve (AUC) will be used to assess the predictive power of each. In interim analysis of patients enrolled by 31 July 2019, 13/197 had CLAD [all with bronchiolitis obliterans syndrome (BOS)], with median time of diagnosis at 24 wks post-LTx (range 10-59). Osc was abnormal and significantly different in CLAD vs. 87 CLAD-free recipients who had follow-up of ≥ 6 mths (median 40 wks). The mean Osc measurements at time of CLAD diagnosis vs last follow-up of CLAD-free patients are: X5 = -3.7 vs -2.1 cmH20.s/L, Ax = 31.6 vs 15.9 cmH20/L and R5-19 = 1.5 vs 0.8 cmH20.s/L (p < 0.05 for all). Using X5 to predict BOS, the AUC was 84%; a cut-off of X5 < -2.4 cmH20.s/L had sensitivity 73% and specificity 92%. Early analysis suggests Osc has excellent predictive capacity for BOS. Future work will test whether Osc can predict CLAD onset while spirometry is normal.