Bronchiolitis Obliterans Syndrome Complicating Lung or Heart-Lung Transplantation

John A. Belperio, MD; Kathleen Lake, PharmD; Henry Tazelaar, MD; Michael P. Keane, MD; Robert M. Strieter, MD; Joseph P. Lynch, III, MD


Semin Respir Crit Care Med. 2003;24(5) 

In This Article

Clinical Course of Bronchiolitis Obliterans

The time of onset of BO is variable, ranging from 3 months to > 9 years posttransplantation.[18,22,72] Clinically, progressive airflow obstruction results in exercise limitation, recurrent lower respiratory tract infections, and, ultimately, death due to respiratory insufficiency.[9,18] Three-year mortality post-onset of BOS exceed 50%.[5,9] Importantly, 81% of patients with mild BOS (stage 1) progressed to a higher (worse) stage or died during follow-up.[9] The course of BOS is variable, however.[5,22,72] Some patients experience rapid loss of lung function and die of respiratory failure within a few months[22] (see Fig. 4E). Others experience slow progression or initial loss of lung function, followed by prolonged stability (see Figs. 4A,B).

Early onset of BOS is associated with an ominous prognosis.[72] In one retrospective study, 20 LTRs with "early onset" BOS (within the first 3 years post-LT) exhibited: greater mean decline in FEV1; greater need for oxygen (O2) dependency; and greater exercise impairment compared with nine LTRs with "late onset" BOS (i.e., > 3 years).[72] Eighteen of 20 (90%) patients with early onset BOS were O2 dependent, compared with only one of nine with late onset BOS. Importantly, graft failure (requiring retransplantation) or mortality was higher in the early onset group (90%) compared with late onset BOS (44%).

BOS may present either suddenly or insidiously.[39,73] Some investigators have suggested that acute and chronic onset of BOS may have different pathogenic mechanisms and prognosis.[22] In a cohort of 204 LTRs who survived > 6 months posttransplantation, 114 patients (56%) developed "acute onset" BOS, associated with an acute drop in FEV1, at a median of 52 months.[22] Another 37 patients (18%) developed "chronic onset" BOS, associated with a chronic linear decline in FEV1 (mean of 3.7% per year), with a median time onset of > 99 months. AR during the first 6 months was associated with acute onset BOS. Importantly, an acute event (e.g., AR or infection) was documented in the previous month in 38 of 114 patients (33%) with acute onset BOS but in only six of 37 (16%) with chronic onset BOS. Acute onset BOS was associated with a worse prognosis compared with chronic onset BOS (actuarial post-BOS survival of 29 months and 59 months, respectively). At the end of the study, 44 of 114 (39%) with acute onset BOS had died of OB; only seven of 37 (19%) with chronic OB died of OB. It is possible that these differences in clinical course and prognosis reflect differences in cellular profiles and pathogenic mechanisms in accelerated versus chronic OB.[74]


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: