A novel charcoal-induced model of obliterative bronchiolitis-like lesions: implications of chronic nonspecific airway inflammation in the development of posttransplantation obliterative bronchiolitis.

OBJECTIVES

In this study, we describe the development of a nonallogeneic animal model of obliterative bronchiolitis-like lesions. Furthermore, we examined whether chronic rejection alone can lead to the development of obliterative bronchiolitis or whether additional nonspecific airway inflammation is required.

METHODS

Part I: Rats were intratracheally injected with 0.2 ml of activated charcoal or sorbitol solution (carrier for charcoal control). Animals were put to death beginning at 2 weeks up to 20 weeks. Part II: Animals were divided into three groups: group I, underimmunosuppressed Brown Norway to Lewis lung allografts; group II, charcoal-treated underimmunosuppressed allografts; and group III, charcoal-treated rats. Animals were put to death at 3 months after transplantation.

RESULTS

Part I: In charcoal-laden bronchioles, subacute nonspecific airway inflammation was detected at 2 weeks. Slow, subclinical fibroproliferation ensued during the following weeks. Obliterative bronchiolitis-like lesions were observed in 80% of charcoal-treated animals at 12 weeks. Part II: Allografts developed extensive vascular lesions consistent with acute and chronic vascular rejection. Obliterative bronchiolitis-like lesions were scarcely detected. Charcoal-treated allografts demonstrated evidence of diffuse and severe obliterative bronchiolitis-like lesions.

CONCLUSIONS

Transtracheal injection of activated charcoal into native lungs results in slowly progressive airway injury and inflammation leading to obliterative airway lesions. Inadequate immunosuppression primarily results in chronic vascular rejection but not obliterative bronchiolitis. Underimmunosuppressed allografts subjected to nonspecific airway inflammation develop obliterative airway lesions that are more prominent than in native lungs. This suggests that a cofactor to chronic rejection is likely necessary for the development of lung transplant obliterative bronchiolitis.