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Bronchiolitis obliterans syndrome: incidence, natural history, prognosis, and risk factors
D Heng1, L D Sharples, K McNeil
1Papworth Hospital NHS Trust, Papworth Everard, MRC Biostatistics Unit, Institute of Public Health, Cambridge, United Kingdom.
Background:
In lung transplantation, obliterative bronchiolitis is the major factor limiting long-term survival. Bronchiolitis obliterans syndrome (BOS), defined as staged decline in pulmonary function has proved a reproducible and sensitive marker of obliterative bronchiolitis.
Methods:
The incidence of, and risk factors for, BOS were investigated in 230 lung transplant recipients who underwent transplantation from April 1984 to December 1995 and who survived at least 3 months after operation. Progression 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 (hazard ratio [HR], 5.96; 95% confidence interval [CI], 3.61, 9.83). Donor and recipient characteristics such as sex, age, underlying disease, type of transplant, and graft ischemic time did not affect BOS onset, progression, or prognosis. Cytomegalovirus serologic status and early acute rejection were risk factors for BOS onset in multivariate modeling. In univariate analysis, other risk factors were lung infection, cytomegalovirus episodes, organizing pneumonia, and human leukocyte antigen mismatch. Later transplantation era (1991 to 1995) was associated with decreased risk of BOS (HR, 0.64; 95% 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 transplantation, with a high incidence, rapid progression, and poor survival. It affects all modes of lung transplantation, regardless of sex, age, or underlying diagnosis. Acute rejection is a major prognostic factor. Lung infections after BOS onset worsen survival rates.