Bronchiolitis obliterans and lung transplantation: evidence for an infectious etiology.

Bronchiolitis obliterans (OB) or bronchiolitis obliterans syndrome (BOS) remains a major hurdle in the long-term survival of lung transplant recipients. The pathogenesis of OB or BOS remains to be fully discerned, but it is hypothesized that allogenic or nonallogenic insults result in the release of chemokines and T lymphocytes propagating the injury and ultimately recruiting fibroblasts culminating in intraluminal proliferation. Infectious agents, with or without other exogenous factors, have been proposed to have a contributory role in the development of OB or BOS. Cytomegalovirus (CMV) is an immunomodulating virus that may lead to persistent stimulation of T cells with the release of chemokines that may promote OB. Animal studies have correlated the development of OB with CMV infection. However, assessment of CMV as a risk factor for the development of OB or BOS in clinical studies has yielded conflicting results. CMV infection was noted to have a hazard ratio of 1.62 in one study, whereas CMV pneumonitis was associated with relative risk of 2.3. Additional studies did not find a higher risk for developing OB or BOS with CMV. Other viruses including respiratory syncytial virus and parainfluenza viruses can promote epithelial damage and act synergistically with chronic rejection in the development of OB. A higher (47%) incidence of BOS has been noted during the respiratory virus season. The evidence of Pneumocystis carinii pneumonia or other infectious episodes causing OB is lacking. Thus, although the role of infectious agents in the development of OB or BOS is biologically plausible, an incontrovertible association between infection and OB or BOS has not been documented. This is a US government work. There are no restrictions on its use.