Lung rejection
Acute and chronic onset of bronchiolitis obliterans syndrome (BOS): are they different entities?

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Abstract

Background

Bronchiolitis obliterans syndrome (BOS), defined as an irreversible, staged decline in forced expiratory volume in 1 second (FEV1), is an established marker of obliterative bronchiolitis. Potential causes of BOS include sub-clinical chronic rejection and/or exaggerated healing response following acute injury. BOS may thus result from two or more distinct processes, both acute and chronic.

Methods

A total of 5,916 measurements of FEV1 from 204 lung transplant recipients surviving at least 6 months after transplantation were analyzed. Follow-up ranged from 6 months to 13 years. By adjusting for the acute effects of rejection, pulmonary infection and measurement variation on FEV1 trace, patients either had a linear decline characterized by a single acute drop in FEV1 of >15% at BOS onset, or a chronic linear decline in FEV1. The fraction having acute onset was estimated. Acute events occurring within the first 6 months were assessed as risk factors for acute onset BOS.

Results

Of the 204 patients, 8% died before BOS onset and 18% were BOS-free at analysis. For 18% of patients, BOS onset followed a chronic linear decline in FEV1 of 3.7% per year, with a median time of BOS onset >99 months. For 56% of patients, BOS onset followed an acute drop in FEV1 of median 33.8% (95% CI 19.1% to 39.7%), with median onset time of 52 months. During the first 6 months, acute rejection was significantly and independently associated with acute onset of BOS (relative risk = 1.15 per episode, 95% CI [1.03 to 1.29], p = 0.01), whereas pulmonary infection and cytomegalovirus (CMV) infection were not. Acute BOS onset followed a documented acute event in the previous 6 months in 38 of 114 (33%) of cases.

Conclusions

BOS likely reflects more than one process. Compared with those who had a slow linear decline in lung function, acute BOS onset was associated with acute rejection in the first 6 months, was often triggered by an acute event and had poor prognosis, with obliterative bronchiolitis (OB) the main cause of death.

Section snippets

Patients and methods

The study population consisted of 230 consecutive patients having undergone lung transplantation between April 1984 and December 1995, and who survived at least 6 months after transplantation, and thus at risk for the development of BOS. Of these, 26 patients were excluded because either a baseline or BOS onset could not be established from the available data.5 Thus, the study cohort consisted of 204 patients that included 143 heart–lung (HLTx), 9 double-lung (DLTx) and 52 single-lung (SLTx)

Study cohort

The 204 patients were between 11 and 69 years of age at the time of transplantation, with a mean age of 38 (SD 13) years. There were 110 (54%) males and 94 (46%) females. The study cohort consisted of 143 heart–lung (HLTx), 9 double-lung (DLTx) and 52 single-lung (SLTx) transplants. The main indications for HLTx were cystic fibrosis (n = 53), Eisenmenger syndrome (n = 27), primary pulmonary hypertension (n = 17) and bronchiectasis (n = 13). The main indications for SLTx were emphysema (n = 36)

Discussion

The impact of OB in lung transplant recipients is very significant and has shown a prevalence of around 65% at 5 years.7, 8, 9 An understanding of the natural history of the disease can give important insights into its pathogenesis and suggest strategies for treatment development.

The adoption of FEV1 as a physiologic surrogate marker for OB has proved successful in describing the pattern of functional decline and the identification of the main risk factors for BOS. In addition, it is a

References (11)

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