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Low Levels of Exhaled Surfactant Protein A Associated With BOS After Lung Transplantation

Ericson, Petrea A. MD1; Mirgorodskaya, Ekaterina PhD2; Hammar, Oscar S. PhD2; Viklund, Emilia A. PhD2; Almstrand, Ann-Charlotte R. PhD2; Larsson, Per J-W. MSc2; Riise, Gerdt C. MD, PhD1; Olin, Anna-Carin MD, PhD2

doi: 10.1097/TXD.0000000000000615
Lung Transplantation

Background There is no clinically available marker for early detection or monitoring of chronic rejection in the form of bronchiolitis obliterans syndrome (BOS), the main long-term complication after lung transplantation. Sampling and analysis of particles in exhaled air is a valid, noninvasive method for monitoring surfactant protein A (SP-A) and albumin in the distal airways.

Methods We asked whether differences in composition of exhaled particles can be detected when comparing stable lung transplant recipients (LTRs) (n = 26) with LTRs who develop BOS (n = 7). A comparison between LTRs and a matching group of healthy controls (n = 33) was also conducted. Using a system developed in-house, particles were collected from exhaled air by the principal of inertial impaction before chemical analysis by immunoassays.

Results Surfactant protein A in exhaled particles and the SP-A/albumin ratio were lower (P = 0.002 and P = 0.0001 respectively) in the BOS group compared to the BOS-free group. LTRs exhaled higher amount of particles (P < 0.0001) and had lower albumin content (P < 0.0001) than healthy controls.

Conclusions We conclude that low levels of SP-A in exhaled particles are associated with increased risk of BOS in LTRs. The possibility that this noninvasive method can be used to predict BOS onset deserves further study with prospective and longitudinal approaches.

1 Department of Respiratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.

2 Department of Occupational and Environmental Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Published online 26 August 2016.

Received 15 June 2016.

Accepted 8 July 2016.

This study was supported by the Swedish Heart-Lung Foundation (diary no. 20070471) and Gothenburg Medical Society (diary no. 14/407181). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Ekaterina Mirgorodskaya, Emilia Viklund, Ann-Charlotte Almstrand, Per Larsson and Anna-Carin Olin are shareholders in (PExA) AB ( that sells a commercial instrument similar to the one used in the present study. Anna-Carin Olin is a board member of PExA AB. Petrea Ericson and Gerdt Riise declare no conflicts of interest.

These senior authors contributed equally to this study (G.C.R., A.-C.O.).

All authors participated in data interpretation, reviewed, and approved the final article. P.E. wrote the main text of the article and prepared all figures. G.R., A.-C.O., A.-C.A., E.M., and P.E. conceived and designed the experiments. A.-C.A. and E.V. performed the clinical examinations including sampling of PEx. O.H., P.E., G.R., E.M., and E.V. analyzed the data. P.L. and E.M. set up the immunodetection assays and analyzed all samples. A.-C.O., A.-C.A., and P.L. developed the sampling technique. O.H. was responsible for the statistical evaluation.

Correspondence: Petrea Ericson, MD, Department of Respiratory Medicine, Sahlgrenska University Hospital, SE-41345 Gothenburg, Sweden. (

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

© 2016 The Authors. Published by Wolters Kluwer Health, Inc.