Bronchiolitis obliterans syndrome (BOS) remains a major complication after lung transplantation. Air trapping and mosaic attenuation are typical radiological features of BOS, however quantitative evaluation remains troublesome. We evaluated parametric response mapping (PRM, voxel-to-voxel comparison of inspiratory and expiratory CT scans) in lung transplant recipients diagnosed with BOS (n=20) and time-matched stable lung transplant recipients (n=20). Serial PRM measurements were performed pre-diagnosis, at time of BOS diagnosis and post-diagnosis (Tpre, T0 and Tpost respectively); or at a post-operatively matched time in stable patients. PRM results were correlated with pulmonary function and confirmed by microCT analysis of end-stage explanted lung tissue. We observed by PRM an increase in functional small airway disease (fSAD), from Tpre to T0 (p=0.006) and a concurrent decrease in healthy parenchyma (p=0.02) in the BOS group. This change in PRM continued to Tpost, which was significantly different compared to the stable patients (p=0.0002). At BOS diagnosis, the increase in fSAD was strongly associated with a decrease in FEV1 (p=0.011). MicroCT confirmed the presence of airway obliteration in a sample of a BOS patient identified with 67% fSAD by PRM. We demonstrated the use of PRM as an adequate readout to monitor BOS progression in lung transplant recipients.

No abstract

BackgroundLong-term survival after lung transplantation (LTx) is hampered by development of chronic lung allograft dysfunction (CLAD). Pseudomonas aeruginosa (PA) is an established risk factor for CLAD. Therefore, we investigated the effect of PA eradication on CLAD-free and graft survival.MethodsPatients who underwent first LTx between 07/1991–02/2016 and were free from CLAD, were retrospectively classified according to PA presence in respiratory samples between 09/2011 and 09/2016. PA positive patients were subsequently stratified according to success of PA eradication following targeted antibiotic treatment. CLAD-free and graft survival were compared between PA positive and PA negative patients; and between patients with or without successful PA eradication. In addition, pulmonary function was assessed during the first year following PA isolation in both groups.ResultsCLAD-free survival of PA negative patients (n=443) was longer compared to PA positive patients (n=95) (p=0.045). Graft survival of PA negative patients (n=443, 82%) was better compared to PA positive patients (n=95, 18%) (p<0.0001). Similarly, PA eradicated patients demonstrated longer CLAD-free survival compared to patients with persistent PA (p=0.018). Pulmonary function was higher in successfully PA eradicated patients compared to unsuccessfully eradicated patients (p=0.035).ConclusionPA eradication after LTx improves CLAD-free and graft survival and maintains pulmonary function. Therefore, early PA detection and eradication should be pursued.

No abstract

Pirfenidone may attenuate the decline of pulmonary function in restrictive allograft syndrome (RAS) after lung transplantation. We retrospectively assessed all lung transplant recipients with RAS who were treated with pirfenidone for at least 3 months (n = 11) in our lung transplant center and report on their long-term outcomes following initiation of pirfenidone. Main outcome parameters included evolution of pulmonary function and overall survival. Pirfenidone appears to attenuate the decline in forced vital capacity and forced expiratory volume in 1 second. Notably, 3 patients were bridged to redo-transplantation with pirfenidone for 11 (5-12) months and are currently alive, while 3 other patients demonstrate long-term stabilization of pulmonary function after 26.6 (range 18.4-46.6) months of treatment. Median overall 3-year survival after RAS diagnosis was 54.5%. Subjective intolerance, mainly anorexia and nausea, necessitating pirfenidone dose de-escalation in 55% of patients, as well as calcineurin dose increase requirements with about 20% are important complications during pirfenidone treatment after lung transplantation. Our findings provide further evidence that pirfenidone appears to be safe and may attenuate the rate of decline in lung function in patients with RAS, but the actual clinical benefit cannot be assessed in the context of this study design and requires further investigation in a larger randomized trial.