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

Guang Shing Cheng, Barry Storer, Jason W. Chien, Madan Jagasia, Jesse J. Hubbard, Linda Burns, Vincent T. Ho, Joseph Pidala, Jeanne Palmer, Laura Johnston, Sebastian Mayer, Kristina Crothers, Iskra Pusic, Stephanie J. Lee, Kirsten M. Williams

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1932-1939
Number of pages8
JournalAnnals of the American Thoracic Society
Volume13
Issue number11
DOIs
StatePublished - Nov 1 2016

Fingerprint

Bronchiolitis Obliterans
Transplants
Lung
montelukast
Azithromycin
Survival
Respiratory Function Tests
Natural History
Multicenter Studies
Early Diagnosis
Linear Models
Therapeutics
Survival Rate
Retrospective Studies
Prospective Studies
Guidelines
Confidence Intervals

Keywords

  • Bronchiolitis obliterans syndrome
  • FEV trajectory
  • Hematopoietic cell transplantation
  • Outcomes
  • Pulmonary complications

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Cheng, G. S., Storer, B., Chien, J. W., Jagasia, M., Hubbard, J. J., Burns, L., ... Williams, K. M. (2016). Lung function trajectory in bronchiolitis obliterans syndrome after allogeneic hematopoietic cell transplant. Annals of the American Thoracic Society, 13(11), 1932-1939. https://doi.org/10.1513/AnnalsATS.201604-262OC

Lung function trajectory in bronchiolitis obliterans syndrome after allogeneic hematopoietic cell transplant. / Cheng, Guang Shing; Storer, Barry; Chien, Jason W.; Jagasia, Madan; Hubbard, Jesse J.; Burns, Linda; Ho, Vincent T.; Pidala, Joseph; Palmer, Jeanne; Johnston, Laura; Mayer, Sebastian; Crothers, Kristina; Pusic, Iskra; Lee, Stephanie J.; Williams, Kirsten M.

In: Annals of the American Thoracic Society, Vol. 13, No. 11, 01.11.2016, p. 1932-1939.

Research output: Contribution to journalArticle

Cheng, GS, Storer, B, Chien, JW, Jagasia, M, Hubbard, JJ, Burns, L, Ho, VT, Pidala, J, Palmer, J, Johnston, L, Mayer, S, Crothers, K, Pusic, I, Lee, SJ & Williams, KM 2016, 'Lung function trajectory in bronchiolitis obliterans syndrome after allogeneic hematopoietic cell transplant', Annals of the American Thoracic Society, vol. 13, no. 11, pp. 1932-1939. https://doi.org/10.1513/AnnalsATS.201604-262OC
Cheng, Guang Shing ; Storer, Barry ; Chien, Jason W. ; Jagasia, Madan ; Hubbard, Jesse J. ; Burns, Linda ; Ho, Vincent T. ; Pidala, Joseph ; Palmer, Jeanne ; Johnston, Laura ; Mayer, Sebastian ; Crothers, Kristina ; Pusic, Iskra ; Lee, Stephanie J. ; Williams, Kirsten M. / Lung function trajectory in bronchiolitis obliterans syndrome after allogeneic hematopoietic cell transplant. In: Annals of the American Thoracic Society. 2016 ; Vol. 13, No. 11. pp. 1932-1939.
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abstract = "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.",
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author = "Cheng, {Guang Shing} and Barry Storer and Chien, {Jason W.} and Madan Jagasia and Hubbard, {Jesse J.} and Linda Burns and Ho, {Vincent T.} and Joseph Pidala and Jeanne Palmer and Laura Johnston and Sebastian Mayer and Kristina Crothers and Iskra Pusic and Lee, {Stephanie J.} and Williams, {Kirsten M.}",
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AU - Storer, Barry

AU - Chien, Jason W.

AU - Jagasia, Madan

AU - Hubbard, Jesse J.

AU - Burns, Linda

AU - Ho, Vincent T.

AU - Pidala, Joseph

AU - Palmer, Jeanne

AU - Johnston, Laura

AU - Mayer, Sebastian

AU - Crothers, Kristina

AU - Pusic, Iskra

AU - Lee, Stephanie J.

AU - Williams, Kirsten M.

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N2 - 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.

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KW - Bronchiolitis obliterans syndrome

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KW - Outcomes

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