Elsevier

Transplantation Proceedings

Volume 52, Issue 1, January–February 2020, Pages 309-314
Transplantation Proceedings

Progress in Transplantation
Lung transplantation
Safety and Efficacy of Steroid Pulse Therapy for Acute Loss of FEV1 in Lung Transplant Recipients After Exclusion of Acute Cellular Rejection

https://doi.org/10.1016/j.transproceed.2019.10.013Get rights and content

Abstract

Background

The standard treatment of acute cellular rejection after lung transplantation (LTx) is a high-dose steroid pulse therapy. In our center, this therapy is also the standard of care for LTx recipients with acute loss of forced expiratory volume in 1 second (FEV1), after excluding specific causes such as acute rejection on biopsy. The aim of this retrospective study was to evaluate the safety and efficacy of steroid pulse therapy.

Methods

From 2015 to 2018, 33 consecutive patients (17 male patients, mean age ± SD, 50.5 ± 12.5 years) were included. All patients underwent routine examinations to exclude acute cellular rejection and other specific causes. FEV1 was routinely measured after 5 days, and 1, 3, and 6 months. Positive response to steroid pulse therapy was defined by increase of FEV1 > 10%.

Results

The mean decrease ± SD from baseline in FEV1 at the start of steroid pulse therapy was 380 ± 630 mL (P = .02). FEV1 changed after 5 days by 170 ± 180 mL (P = .0007), and after 1 month by 140 ± 230 mL (P = .70), 3 months by −60 ± 240 mL (P = .15), and 6 months by −80 ± 290 mL (P = .73). A positive response was observed in 21% of patients after 3 months and 12% after 6 months. High bronchoalveolar lavage (BAL) eosinophil count correlated with a higher FEV1 after steroid pulse therapy. Serious complications were observed in 4 out of 33 patients (12%) with 1 fatal event (pneumonia).

Conclusions

Only a minority of patients after LTx with loss of FEV1 after exclusion of acute cellular rejection benefit from steroid pulse therapy. Patients with BAL eosinophilia are more likely to respond. However, severe complications were observed.

Section snippets

Patient Population and Standard of Care

We retrospectively included consecutive patients who had a LTx between 2015 and 2018 and who experienced loss of FEV1 from baseline of more than 10%.

Criteria for inclusion were absence of all causes that could explain loss of FEV1, including acute cellular rejection (A ≥ 1 according to ISHLT), humoral rejection (C4d positivity or donor-specific human leukocyte antigen antibodies), infections, bronchial stenosis and other specific causes such as persistent acute rejection, anastomotic stricture,

Patient Cohort

A total of 33 patients (51.5% male) were included in this study, 87.9% of whom had a bilateral LTx (BLTx) (Table 1). Mean age ± SD at the time of loss of FEV1 was 50.5 ± 12.5 years.

The mean time ± SD of observation after LTx with available pulmonary function data until loss of FEV1 and treatment with prednisolone pulse was 46.5 ± 35.7 months (range, 4-129), with a total mean follow-up time ± SD after pulse therapy of 176.4 ± 38.9 days. The mean number of available lung function tests ± SD

Discussion

The absence of an effective treatment for decline of lung function and BOS still limits survival in LTx recipients. Treatment with azithromycin, switching cyclosporine to tacrolimus, and managing gastroesophageal reflux have shown positive effects on lung function [[3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14]]. Retransplantation should be considered in select patients with end-stage BOS [[15], [16], [17]].

We clearly recognize the limitations of our study, given the

Conclusions

Given the lack of data and limited therapeutic options to treat loss of FEV1 and CLAD in LTx recipients, our study adds important data to the field. We show that a subgroup of patients has a sustained benefit from steroid pulse therapy, while this approach may be associated with severe complications. Patients with BAL eosinophilia are more likely to respond. Steroid pulse therapy has a higher value for this subgroup. Further investigations are necessary to guide the treatment of patients after

References (23)

  • K.C. Meyer et al.

    An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome

    Eur Respir J

    (2014)
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    The first 2 authors contributed equally to this work.

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