Lung function trajectory in bronchiolitis obliterans syndrome after allogeneic hematopoietic cell transplant

Rationale: The natural history of lung function in patients with bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplant is poorly characterized. Understanding the trajectory of lung function is necessary for prompt clinical recognition and treatment and also for the rational design of prospective studies. Objectives: To describe the longitudinal trajectory of lung function parameters, including FEV₁, in patients with BOS after hematopoietic cell transplant. Methods: Subjects withBOS defined byNational Institutes of Health consensus guidelines criteria from a recent multicenter prospective trial of combination treatment with fluticasone, azithromycin and montelukast and a retrospective cohort from Fred Hutchinson Cancer Research Center were included. Longitudinal change in FEV₁ for each patient was calculated on the basis of available pulmonary function tests in three periods: pre-BOS, from BOS diagnosis to 6 months, and 6-18 months after diagnosis. The effect of treatment on FEV₁ trajectory was analyzed by univariate and multivariate linear regression. The Kaplan-Meier method was used to estimate survival. Measurements and Main Results: The FEV₁ percent predicted value at diagnosis was 46% (interquartile range, 35-57%) for trial participants and 53% (interquartile range, 41-64%) for the retrospective cohort. There was a concomitant mild reduction in FVC, as well as amarked reduction in forced expiratory flow,midexpiratory phase, at diagnosis. While there was individual heterogeneity, the overall FEV₁ trajectory was characterized by a marked decline within 6 months prior to BOS diagnosis, followed by stability of FEV₁ early after diagnosis and a slowrate of decline beyond 6months.The effect of the trial medications on FEV₁ trajectory after BOS diagnosis was a mean rate of change of 0.92% predicted per month (95% confidence interval, -0.53 to 2.37) compared with the retrospective cohort, but this was not statistically significant. Two-year overall survival rates were 76% and 72% for the study participants and the retrospective cohort patients, respectively. Earlier time to diagnosis after hematopoietic cell transplant and severity of FVC at diagnosis were significantly associated with reduced survival. Conclusions: The FEV₁ trajectory in patients with BOS after hematopoietic cell transplant in a contemporary era of management follows a predominant pattern of rapid FEV₁ decline in the 6 months prior to diagnosis, followed by FEV₁ stabilization after diagnosis.