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. 2001 Dec;56(12):941–946. doi: 10.1136/thorax.56.12.941

Alveolar macrophage activity and the pulmonary complications of haematopoietic stem cell transplantation

A Whittle 1, M Davis 1, C Shovlin 1, P Ganly 1, C Haslett 1, A Greening 1
PMCID: PMC1745976  PMID: 11713357

Abstract

BACKGROUND—The success of haematopoietic (bone marrow or peripheral blood) stem cell transplantation (SCT) is compromised by pulmonary complications. We hypothesised that a proinflammatory alveolar microenvironment, reflected in alveolar macrophage (AM) cytokine production, would predispose to such complications.
METHODS—AM were isolated from adult SCT recipients by bronchoalveolar lavage before SCT (n=32) and during post-transplant pancytopenia (n=23). Concentrations of tumour necrosis factor (TNF)α, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin (IL)-1β, IL-6, and IL-8 in 24 hour AM culture medium were measured by enzyme linked immunosorbent assay and compared with both the occurrence of post-SCT lung disease and with subjects' previous respiratory histories.
RESULTS—Eleven subjects developed lung disease within 6 months of SCT. These subjects had higher median pre-transplant AM TNFα (8(IQR 1-8) v 2 (1-5) ng/106AM, p=0.01, median difference (D) = 3, 95% CI 0.1 to 7), GM-CSF (5 (0.7-8) v 0.2 (0.1-0.8), p=0.006, D = 4, 95% CI 0.5 to 7), and IL-6 (0.5 (0.1-1) v 0.1 (0.02-0.3), p=0.049, D = 0.3, 95% CI 0.0002 to 1) production than remaining subjects; IL-1β and IL-8 did not differ. During pancytopenia high AM GM-CSF production again predicted later lung disease (1 (0.7-9) v 0.1 (0.06-0.3), p=0.01, D = 1, 95% CI 0.1 to 6). A history of recent chest disease was associated with high AM TNFα and GM-CSF production and with post-SCT lung disease. Pre-SCT lung function was unrelated to post-SCT lung disease.
CONCLUSIONS—Recent respiratory disease and persistent proinflammatory AM behaviour detectable before transplantation are associated with lung disease following SCT. These associations may prove useful in pre-transplant risk assessment.



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Selected References

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  1. Bilyk N., Holt P. G. Inhibition of the immunosuppressive activity of resident pulmonary alveolar macrophages by granulocyte/macrophage colony-stimulating factor. J Exp Med. 1993 Jun 1;177(6):1773–1777. doi: 10.1084/jem.177.6.1773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brockstein B. E., Smiley C., Al-Sadir J., Williams S. F. Cardiac and pulmonary toxicity in patients undergoing high-dose chemotherapy for lymphoma and breast cancer: prognostic factors. Bone Marrow Transplant. 2000 Apr;25(8):885–894. doi: 10.1038/sj.bmt.1702234. [DOI] [PubMed] [Google Scholar]
  3. Campbell M. J., Gardner M. J. Calculating confidence intervals for some non-parametric analyses. Br Med J (Clin Res Ed) 1988 May 21;296(6634):1454–1456. doi: 10.1136/bmj.296.6634.1454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carlson K., Bäcklund L., Smedmyr B., Oberg G., Simonsson B. Pulmonary function and complications subsequent to autologous bone marrow transplantation. Bone Marrow Transplant. 1994 Nov;14(5):805–811. [PubMed] [Google Scholar]
  5. Crawford S. W., Fisher L. Predictive value of pulmonary function tests before marrow transplantation. Chest. 1992 May;101(5):1257–1264. doi: 10.1378/chest.101.5.1257. [DOI] [PubMed] [Google Scholar]
  6. Donnelly S. C., Strieter R. M., Kunkel S. L., Walz A., Robertson C. R., Carter D. C., Grant I. S., Pollok A. J., Haslett C. Interleukin-8 and development of adult respiratory distress syndrome in at-risk patient groups. Lancet. 1993 Mar 13;341(8846):643–647. doi: 10.1016/0140-6736(93)90416-e. [DOI] [PubMed] [Google Scholar]
  7. Gratwohl A., Passweg J., Baldomero H., Hermans J. Blood and marrow transplantation activity in Europe 1997. European Group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 1999 Aug;24(3):231–245. doi: 10.1038/sj.bmt.1701866. [DOI] [PubMed] [Google Scholar]
  8. Horak D. A., Schmidt G. M., Zaia J. A., Niland J. C., Ahn C., Forman S. J. Pretransplant pulmonary function predicts cytomegalovirus-associated interstitial pneumonia following bone marrow transplantation. Chest. 1992 Nov;102(5):1484–1490. doi: 10.1378/chest.102.5.1484. [DOI] [PubMed] [Google Scholar]
  9. Kantrow S. P., Hackman R. C., Boeckh M., Myerson D., Crawford S. W. Idiopathic pneumonia syndrome: changing spectrum of lung injury after marrow transplantation. Transplantation. 1997 Apr 27;63(8):1079–1086. doi: 10.1097/00007890-199704270-00006. [DOI] [PubMed] [Google Scholar]
  10. Kreuzfelder E., Quabeck K., Braun M., Weber W., Westhoff U., Schaefer U. W., Bruch J., Costabel U., Grosse-Wilde H. Association of increased bronchoalveolar lavage fluid albumin and serum beta 2-microglobulin with pulmonary complications after allogeneic bone marrow transplantation. Bone Marrow Transplant. 1995 Aug;16(2):249–252. [PubMed] [Google Scholar]
  11. Krowka M. J., Rosenow E. C., 3rd, Hoagland H. C. Pulmonary complications of bone marrow transplantation. Chest. 1985 Feb;87(2):237–246. doi: 10.1378/chest.87.2.237. [DOI] [PubMed] [Google Scholar]
  12. Kunkel S. L., Lukacs N. W., Strieter R. M. The role of interleukin-8 in the infectious process. Ann N Y Acad Sci. 1994 Aug 15;730:134–143. doi: 10.1111/j.1749-6632.1994.tb44245.x. [DOI] [PubMed] [Google Scholar]
  13. Morris J. A., Gardner M. J. Calculating confidence intervals for relative risks (odds ratios) and standardised ratios and rates. Br Med J (Clin Res Ed) 1988 May 7;296(6632):1313–1316. doi: 10.1136/bmj.296.6632.1313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pittet J. F., Mackersie R. C., Martin T. R., Matthay M. A. Biological markers of acute lung injury: prognostic and pathogenetic significance. Am J Respir Crit Care Med. 1997 Apr;155(4):1187–1205. doi: 10.1164/ajrccm.155.4.9105054. [DOI] [PubMed] [Google Scholar]
  15. Schmitz N., Diehl V. Carmustine and the lungs . Lancet. 1997 Jun 14;349(9067):1712–1713. doi: 10.1016/S0140-6736(05)62951-0. [DOI] [PubMed] [Google Scholar]
  16. Seiden M. V., Elias A., Ayash L., Hunt M., Eder J. P., Schnipper L. E., Frei E., 3rd, Antman K. H. Pulmonary toxicity associated with high dose chemotherapy in the treatment of solid tumors with autologous marrow transplant: an analysis of four chemotherapy regimens. Bone Marrow Transplant. 1992 Jul;10(1):57–63. [PubMed] [Google Scholar]
  17. Thomas E. D., Ramberg R. E., Sale G. E., Sparkes R. S., Golde D. W. Direct evidence for a bone marrow origin of the alveolar macrophage in man. Science. 1976 Jun 4;192(4243):1016–1018. doi: 10.1126/science.775638. [DOI] [PubMed] [Google Scholar]
  18. Twohig K. J., Matthay R. A. Pulmonary effects of cytotoxic agents other than bleomycin. Clin Chest Med. 1990 Mar;11(1):31–54. [PubMed] [Google Scholar]
  19. Tyndall A., Gratwohl A. Blood and marrow stem cell transplants in auto-immune disease: a consensus report written on behalf of the European League against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT) Bone Marrow Transplant. 1997 Apr;19(7):643–645. doi: 10.1038/sj.bmt.1700727. [DOI] [PubMed] [Google Scholar]
  20. Whittle A. T., Davis M., Johnson P. R., Leonard R. C., Greening A. P. The safety and usefulness of routine bronchoscopy before stem cell transplantation and during neutropenia. Bone Marrow Transplant. 1999 Jul;24(1):63–67. doi: 10.1038/sj.bmt.1701818. [DOI] [PubMed] [Google Scholar]
  21. Wilczynski S. W., Erasmus J. J., Petros W. P., Vredenburgh J. J., Folz R. J. Delayed pulmonary toxicity syndrome following high-dose chemotherapy and bone marrow transplantation for breast cancer. Am J Respir Crit Care Med. 1998 Feb;157(2):565–573. doi: 10.1164/ajrccm.157.2.9705072. [DOI] [PubMed] [Google Scholar]
  22. Xing Z., Braciak T., Ohkawara Y., Sallenave J. M., Foley R., Sime P. J., Jordana M., Graham F. L., Gauldie J. Gene transfer for cytokine functional studies in the lung: the multifunctional role of GM-CSF in pulmonary inflammation. J Leukoc Biol. 1996 Apr;59(4):481–488. doi: 10.1002/jlb.59.4.481. [DOI] [PubMed] [Google Scholar]

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