Functional and computed tomographic evolution and survival of restrictive allograft syndrome after lung transplantation

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Background

Restrictive allograft syndrome (RAS) has recently been defined as a novel phenotype of chronic lung allograft dysfunction (CLAD) after lung transplantation. The goal was to describe computed tomographic (CT) changes of RAS patients and to correlate this with spirometry and survival.

Methods

All 24 established RAS patients at our center were retrospectively included. CT scans from pre-CLAD, CLAD, post-CLAD and late-CLAD subjects were systematically evaluated by a blinded observer using a semi-quantitative scoring system. Changes in CT patterns were correlated with spirometry and survival.

Results

The most prominent CT features at diagnosis of CLAD as compared with pre-CLAD were appearance of central (p = 0.020) and peripheral ground glass opacities (p = 0.052), as well as septal and non-septal lines (p = 0.020). Survival after diagnosis of CLAD was only associated with the absolute value of forced vital capacity (FVC) at diagnosis (R = 0.46 and p = 0.021), and not with any CT alterations. Evolution of CT abnormalities after diagnosis of CLAD included significant increases in (traction) bronchiectasis (p < 0.0001), central (p = 0.051) and peripheral (p = 0.0002) consolidation, architectural deformation (p = 0.0002), volume loss (p = 0.0004) and hilus retraction (p = 0.0036). The absolute FVC decrease post-CLAD diagnosis correlated with CT alterations.

Conclusions

In the early stages of RAS, central and peripheral ground glass opacities are the most prominent feature on CT, whereas, in later stages, bronchiectasis, traction, central and peripheral consolidation, architectural deformation, volume loss and hilus retraction are more pronounced. CT changes, however, could not predict survival, whereas FVC at diagnosis of CLAD seems to be the best predictor of survival.

Section snippets

Patients’ characteristics

Patients who underwent double-lung or heart–lung transplantation between 2001 and 2012 were retrospectively recruited. All patients provided written informed consent before transplantation. CLAD was defined as a persistent FEV1 decline of ≥ 20% compared with the mean of the two best post-operative values. Subsequently, irreversible CLAD was defined as a lack of improvement in FEV1 after azithromycin therapy. Within the CLAD patient group, RAS was diagnosed in cases of restrictive pulmonary

Patients’ characteristics

Detailed characteristics of patients are presented in Table 1. Twenty-four of the patients were ultimately diagnosed with RAS. At the end of the study period, 5 patients were alive and did not undergo retransplantation, 10 underwent retransplantation, and 9 died. Mean time of developing CLAD after transplantation was 1,194 ± 206 days. Mean time of follow-up after diagnosis of CLAD was 584 ± 111 days (182 to 3,521 days). Fifty percent graft loss after CLAD diagnosis occurred at 501 days. At

Discussion

In 24 patients who ultimately fulfilled the RAS criteria, we evaluated changes in CT patterns from pre-CLAD to end-stage CLAD in relation to pulmonary function and survival. The most prominent features at diagnosis of CLAD compared with the last pre-CLAD CT were appearance of central and peripheral ground glass and septal and non-septal lines. Survival after diagnosis of CLAD was only associated with FVC at the moment of CLAD diagnosis, but not with any CT alterations. When comparing the

Disclosure statement

The authors have no conflicts of interest to disclose.

G.M.V. is holder of the GSK chair in respiratory pharmacology at the KU Leuven and is supported by the Research Foundation Flanders (FWO) (G.0723.10, G.0705.12 and G.0679.12) and Onderzoeksfonds KU Leuven (OT/10/050). B.M.V. and D.E.v.R. are senior research fellows of the FWO. S.E.V. is supported by the KU Leuven Research Fund. RV is partially funded by Klinisch Onderzoeksfonds UZ Leuven.

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