Assessment of FEV1 Decline after Lung Transplantation Using Functional Respiratory Imaging

The current definition of chronic lung allograft dysfunction after lung transplantation (LTx) mainly relies on an observed sustained decline in the forced expiratory volume in one second (FEV1) of the transplanted patient. A decrease in FEV1 not associated with other potential causes such as airway infection can indicate the onset of bronchiolitis obliterans syndrome (BOS). Early detection of BOS might increase the probability of successful treatment of the patient with a potential therapeutic agent. Previous studies have shown that traditional high resolution CT scans may be useful in the management of post-transplant patients, but lack in sensitivity for early detection of BOS changes. In this study we used a novel imaging method called Functional Respiratory Imaging (FRI) to assess the post LTx changes in lung structure and function. We aimed to see which lung zones are key drivers for the decline in FEV1. Identifying key areas in the lung affected in early BOS and having tools to describe these areas in more detail could lead to earlier diagnosis of BOS and improved outcomes using potential treatments. Paired inspiratory-expiratory CT scans of 29 Ltxp patients were analyzed retrospectively. All patients had received either single or double LTx and experienced a reduction in FEV1 > 10% compared to the baseline value (BOS 0-p). The number of follow up paired HRCT scans ranged from 2 to 8. FRI yielded regional parameters related to lung volumes (iVlobe) and airway volumes (iVaw), airway resistance (iRaw), all reported on a lobar level. Airway volumes and resistance were made specific by correcting for the lung volume (siVaw and siRaw respectively). Multiple regression modeling was performed to determine the most relevant image metrics for FEV1 decline in this cohort. The FEV1 decline in this patient cohort could be accurately described with a conditional R2 of 0.9. Key drivers for the decline were changes in iVlobe (p < 0.001) and siVaw (p < 0.001) as derived from the expiratory HRCT scans and changes in iRaw (p < 0.05), iVlobe (p < 0.001) and siVaw (p < 0.01) based on the inspiratory HRCT scans. FRI parameters, based on inspiratory and expiratory scans, can determine with great accuracy the regional key drivers for FEV1 decline in transplanted patients. These results illustrate the potential of FRI as a diagnostic tool for BOS.