Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Endothelial cell damage in idiopathic pneumonia syndrome

Bone Marrow Transplantation volume 53, pages 515–518 (2018)Cite this article

Subjects

Idiopathic pneumonia syndrome is a rare complication following hematopoietic stem cell transplantation (HSCT), defined by diffuse lung injury with no identified etiology, with an incidence of 2–12% [1]. It accounts for approximately 12% of paediatric post-HSCT pulmonary complications and most patients rapidly succumb to the disease [1]. Idiopathic pneumonia syndrome is a diagnosis of exclusion; bronchoalveolar lavage and ideally lung biopsy should be performed to rule out bacterial, viral, fungal, or non-infectious causes. Clinical presentation is variable but includes respiratory distress, non-productive cough and hypoxemia [1]. Currently, no effective treatment exists, although disease severity is reduced in patients receiving cyclosporine and intravenous immunoglobulin as graft- vs. host disease (GvHD) prophylaxis [2].

The pathogenesis is multi-factorial, with toxic bystander-effects of conditioning, GvHD and occult infection implicated as risk factors [1]. In murine models, endothelial cell activation and injury is a factor in the development of idiopathic pneumonia syndrome [3], and can be demonstrated histologically by endothelial leak of fibrin, endothelial apoptosis, veno-occlusive disease, venous embolization, and fibrin deposition and evidence of pulmonary hypertension, including pulmonary vascular intimal hyper-proliferation [3,4,5,6].

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

References

  1. Yanik GA, Grupp SA, Pulsipher MA, Levine JE, Schultz KR, Wall DA, et al. TNF-receptor inhibitor therapy for the treatment of children with idiopathic pneumonia syndrome. A joint Pediatric Blood and Marrow Transplant Consortium and Children’s Oncology Group Study (ASCT0521). Biol Blood Marrow Transplant. 2015;21:67–73.

    Article  CAS  Google Scholar 

  2. Khurshid I, Anderson LC. Non-infectious pulmonary complications after bone marrow transplantation. Postgrad Med J. 2002;78:257–62.

    Article  CAS  Google Scholar 

  3. Cooke KR, Jannin A, Ho V. The contribution of endothelial activation and injury to end-organ toxicity following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2008;14:23–32.

    Article  Google Scholar 

  4. Budhiraja R, Tuder RM, Hassoun PM. Endothelial dysfunction in pulmonary hypertension. Circulation. 2004;109:159–65.

    Article  Google Scholar 

  5. Zeilhofer U, Ashworth M, Amrolia P, Rao A, Chiesa R, Veys P, et al. Pulmonary hypertension following haematopoietic stem cell transplantation for primary haemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2013;60:521–3.

    Article  Google Scholar 

  6. Panoskaltsis-Mortari A, Griese M, Madtes DK, Belperio JA, Haddad IY, Folz RJ, et al. An official American Thoracic Society research statement: noninfectious lung injury after hematopoietic stem cell transplantation: idiopathic pneumonia syndrome. Am J Respir Crit Care Med. 2011;183:1262–79.

    Article  Google Scholar 

  7. Pober JS, Sessa WC. Evolving functions of endothelial cells in inflammation. Nat Rev Immunol. 2007;7:803–15.

    Article  CAS  Google Scholar 

  8. Szmitko PE, Wang CH, Weisel RD, Jeffries GA, Anderson TJ, Verma S. New markers of inflammation and endothelial cell activation: part I. Circulation. 2003;108:1917–23.

    Article  Google Scholar 

  9. Yeates L, Slatter MA, Bonanomi S, Lim WIFL, Ong SY, Dalissier A, et al. Use of defibrotide to treat transplant-associated thrombotic microangiopathy—a retrospective study of the paediatric diseases and inborn errors working parties of the european society of blood and marrow transplantation. Bone Marrow Transplant. 2017;52:762–64.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We acknowledge support for this work by the MRC/ESPRC Newcastle Molecular Pathology Node.

Author contributions

TA collected the data, performed the analysis and interpretation of the data and the writing of the manuscript. JS collected the data and contributed to manuscript writing, MAS, CO’B, AC, MT, MB contributed equally to the conceptualization of the research, manuscript writing and critical review, AS performed the analysis and interpretation of the data, manuscript writing and critical review and ARG designed and conceptualized the research project, analysis and interpretation of the data, manuscript writing and critical review at every level of the research stages.

Author information

Authors and Affiliations

  1. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK

    Thomas Altmann, James Slack, Mary A. Slatter, Andrew Cant, Malcolm Brodlie & Andrew R. Gennery

  2. Great North Children’s Hospital, Royal Victoria Infirmary, Clinical Resource Building, Floor 4, Block 2, Queen Victoria Road, Newcastle Upon Tyne, NE1 4LP, UK

    Christopher O’Brien, Matthew Thomas, Srinivas Annavarapu & Andrew R. Gennery

Authors
  1. Thomas Altmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James Slack
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mary A. Slatter
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christopher O’Brien
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrew Cant
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Matthew Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Malcolm Brodlie
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Srinivas Annavarapu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andrew R. Gennery
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrew R. Gennery.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Altmann, T., Slack, J., Slatter, M. et al. Endothelial cell damage in idiopathic pneumonia syndrome. Bone Marrow Transplant 53, 515–518 (2018). https://doi.org/10.1038/s41409-017-0042-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-017-0042-z

This article is cited by

Search

Advanced search

Quick links