Risk factors for bronchiolitis obliterans: a systematic review of recent publications.
BACKGROUND
Obliterative bronchiolitis remains the major limitation to long-term survival after lung transplantation. A thorough understanding of the factors that confer high risk of developing obliterative bronchiolitis or its physiologic surrogate bronchiolitis obliterans syndrome is important to help define therapeutic strategies.


METHODS
We performed a systematic review of studies published since the beginning of 1990. The review excluded non-human studies, publications before 1990, small (less than 25 patients) studies that were predominantly concerned with investigating the pathogenesis of obliterative bronchiolitis, studies solely concerned with diagnosis or treatment of obliterative bronchiolitis, and overlapping studies from the same center. Onset of bronchiolitis obliterans syndrome or obliterative bronchiolitis was the outcome of interest.


RESULTS
Acute rejection plays an important role in obliterative bronchiolitis and bronchiolitis obliterans syndrome onset, and late rejection is a significant risk factor. Lymphocytic bronchitis/bronchiolitis is also a risk factor, with some evidence that late onset is associated with greater risk. The effects of cytomegalovirus, other infectious organisms, and human leukocyte antigen matching are less clear and require further confirmation. There is little evidence that recipient and donor characteristics play a major role.


CONCLUSIONS
This systematic review supports the view that obliterative bronchiolitis arises from alloimmunologic injury marked by clinically apparent acute rejection episodes and that inflammatory conditions, including viral infections or ischemic injury, may also play a role. Implications for therapy are discussed.
Sharples
Linda D
LD
Medical Research Council (MRC) Biostatistics Unit, University Forvie Site, Papworth Everard, Cambridge, United Kingdom. linda.sharples@mrc-bsu.cam.ac.uk
McNeil
Keith
K
Stewart
Susan
S
Wallwork
John
J
D001989:Bronchiolitis Obliterans / Q000150:complications / Q000401:mortality* / Q000601:surgery; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000150:complications; D006084:Graft Rejection / Q000209:etiology; D006681:HLA-D Antigens / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use; D016040:Lung Transplantation; D016239:MEDLINE; D012307:Risk Factors; D016019:Survival Analysis; D014019:Tissue Donors
D006681:HLA-D Antigens; D007166:Immunosuppressive Agents; D016572:Cyclosporine