Intra-subject variability in oscillometry correlates with acute rejection and CLAD post-lung transplant

Abstract

BackgroundChronic lung allograft dysfunction (CLAD) is the major cause of death post-lung transplantation, with acute cellular rejection (ACR) being the biggest contributing risk factor. Although patients are routinely monitored with spirometry, FEV1 is stable or improving in most ACR episodes. In contrast, oscillometry is highly sensitive to respiratory mechanics and shown to track graft injury associated with ACR and its improvement following treatment. We hypothesize that intra-subject variability in oscillometry measurements correlates with ACR and risk of CLAD.MethodsOf 289 bilateral lung recipients enrolled for oscillometry prior to laboratory-based spirometry between December 2017 and March 2020, 230 had ≥ 3 months and 175 had ≥ 6 months of follow-up. While 37 patients developed CLAD, only 29 had oscillometry at time of CLAD onset and were included for analysis. These 29 CLAD patients were time-matched with 129 CLAD-free recipients. We performed multivariable regression to investigate the associations between variance in spirometry/oscillometry and the A-score, a cumulative index of ACR, as our predictor of primary interest. Conditional logistic regression models were built to investigate associations with CLAD.ResultsMultivariable regression showed that the A-score was positively associated with the variance in oscillometry measurements. Conditional logistic regression models revealed that higher variance in the oscillometry metrics of ventilatory inhomogeneity, X5, AX, and R5-19, was independently associated with increased risk of CLAD (p < 0.05); no association was found for variance in %predicted FEV1.ConclusionOscillometry tracks graft injury and recovery post-transplant. Monitoring with oscillometry could facilitate earlier identification of graft injury, prompting investigation to identify treatable causes and decrease the risk of CLAD.

The diagnosis and management of chronic lung allograft dysfunction

“…They also reported that neither IOS nor spirometry was predictive for the early detection of BOS. In another study including 29 CLAD patients, Vasileva et al [6] found that intra-individual variability of IOS was independently associated with an increased risk of CLAD, suggesting that further studies on this topic are very much required. In a retrospective, cross-sectional analysis of 263 double lung transplant recipients who underwent paired testing with oscillometry and spirometry, Fu et al [7] found that different phenotypes of CLAD presented with differences in both spectral and/or intrabreath oscillometry which could prove useful in prognostication.…”

Effects of donor smoking history on early post-transplant lung function measured by oscillometry

“…In lung transplantation, oscillometry has been proposed as a tool for monitoring graft function to complement cPFTs, based on the rationale that many of the pathological processes involved in graft dysfunction, such as acute rejection and bronchiolitis obliterans (BO), affect the small airways ( 17 , 18 ), which are poorly characterized by spirometry ( 19 , 20 ). Our group has shown that oscillometry can detect episodes of acute cellular rejection which were not identified by changes in cPFT ( 21 ) and that increased intra-subject variability in X 5 , AX and R 5-19 is associated with increased risk of chronic lung allograft dysfunction (CLAD), a key cause of long-term morbidity and mortality in lung transplantation ( 22 ). Oscillometry also provides insights into the respiratory mechanics of the different phenotypes of CLAD ( 23 , 24 ).…”

Respiratory oscillometry with CT image analysis in idiopathic pulmonary fibrosis following single lung transplant

“…By contrast, oscillometry measurements of respiratory mechanics are made during quiet breathing and require only minimal cooperation from patients. Oscillometry has been shown to be surrogate marker of graft injury after double LTx; it detected biopsy-proven but spirometrically-silent acute rejection [ 3 ] and was found to be associated with chronic lung allograft dysfunction, the major long-term cause of death after LTx [ 4 ]. Oscillometry is also useful in IPF, with the reactance metrics of X5 and Xel, reactance at 5 Hz and end inspiration, respectively, being highly associated with disease severity [ 5 ].…”