title: Alveolar macrophage activity and the pulmonary complications of haematopoietic stem cell transplantation.
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)alpha, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin (IL)-1 beta, 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 TNFalpha (8 (IQR 1-8) v 2 (1-5) ng/10(6)AM, 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-1 beta 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 TNFalpha 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.
authors.affiliation: Department of Respiratory Medicine, Royal Perth Hospital, Perth, Western Australia. Adam.Whittle@ubht.swest.nhs.uk
authors.forename: A T
authors.initials: AT
authors.lastname: Whittle
authors.forename: M
authors.initials: M
authors.lastname: Davis
authors.forename: C L
authors.initials: CL
authors.lastname: Shovlin
authors.forename: P S
authors.initials: PS
authors.lastname: Ganly
authors.forename: C
authors.initials: C
authors.lastname: Haslett
authors.forename: A P
authors.initials: AP
authors.lastname: Greening
mesh_terms: D000293:Adolescent; D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D016001:Confidence Intervals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016011:Normal Distribution; D010198:Pancytopenia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D007375:Interleukin-1; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor