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

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 lavag e before SCT (n=32) and during posttransplant pancytopenia (n=23). Concentr ations of tumour necrosis factor (TNF)alpha granulocyte-macrophage colony s timulating factor (GM-CSF), interleukin (IL)-1 beta, IL-6, and IL-8 in 24 h our AM culture medium were measured by enzyme linked immunosorbent assay an d compared with both the occurrence of post-SCT lung disease and with subje cts' previous respiratory histories. Results-Eleven subjects developed lung disease within 6 months of SCT. Thes e subjects had higher median pretransplant AM TNF alpha (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% Cl 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% Cl 0.0002 to 1) production than remaining subjects; IL-1 beta and IL-8 did not differ. During pancyto penia 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% Cl 0.1 to 6). A history of recent c hest disease was associated with high AM TNF alpha and GM-CSF production an d with post-SCT lung disease. Pre-SCT lung function was unrelated to post-S CT lung disease. Conclusions-Recent respiratory disease and persistent proinflammatory AM be haviour detectable before transplantation are associated with lung disease following SCT. These associations may prove useful in pre-transplant risk a ssessment.