Bronchiolitis obliterans syndrome: Incidence, natural history, prognosis, and risk factors

Background: In lung transplantation, obliterative bronchiolitis is the majo r factor limiting long-term survival. Bronchiolitis obliterans syndrome (BO S), defined as staged decline in pulmonary function has proved a reproducib le and sensitive marker of obliterative bronchiolitis. Methods: The incidence of, and risk factors for, BOS were investigated in 2 30 lung transplant recipients who underwent transplantation from April 1984 to December 1995 and who survived at least 3 months after operation. Progr ession and prognosis was investigated in the 109 cases with development of BOS. Results: Actuarial BOS-free probability at 5 years was 36%. Post-BOS onset survival was 51% at 3 years. BOS onset conferred increased risk of death (h azard ratio [HR], 5.96; 95% confidence interval [CI], 3.61, 9.83). Donor an d recipient characteristics such as sex, age, underlying disease, type of t ransplant, and graft ischemic time did not affect BOS onset, progression, o r prognosis. Cytomegalovirus serologic status and early acute rejection wer e risk factors for BOS onset in multivariate modeling. In univariate analys is, other risk factors were lung infection, cytomegalovirus episodes, organ izing pneumonia, and human leukocyte antigen mismatch. Later transplantatio n era (1991 to 1995) was associated with decreased risk of BOS (HR, 0.64; 9 5% CI, 0.44, 0.92). Acute rejection affected post-BOS progression (HR, 1.28 /episode; 95% CI, 1.12, 1.45) and survival (HR, 1.20/episode; 95% CI, 1.05, 1.37). Post-BOS lung infection was an independent prognostic factor (HR, 1 .12/episode; 95% CI, 1.01, 1.24). BOS onset in the later half of the series (1992 to 1997) was associated with decreased risk of progression (HR, 0.52 ; 95% CI, 0.33, 0.82). Conclusions: This study confirms that BOS is a major problem in lung transp lantation, with a high incidence, rapid progression, and poor survival. It affects all modes of lung transplantation, regardless of sex, age, or under lying diagnosis. Acute rejection is a major prognostic factor. Lung infecti ons after BOS onset worsen survival rates.