Lack of association of Aspergillus colonization with the development of bronchiolitis obliterans syndrome in lung transplant recipients: An international cohort study

Nancy Law; Bassem Hamandi; Christine Fegbeutel; Fernanda P Silveira; Erik A Verschuuren; Piedad Ussetti; Peter V Chin-Hong; Amparo Sole; Chien-Li Holmes-Liew; Eliane M Billaud; Paolo A Grossi; Oriol Manuel; Deborah J Levine; Richard G Barbers; Denis Hadjiliadis; Muhammad Younus; Jay Aram; Cecilia Chaparro; Lianne G Singer; Shahid Husain

doi:10.1016/j.healun.2019.06.007

Lack of association of Aspergillus colonization with the development of bronchiolitis obliterans syndrome in lung transplant recipients: An international cohort study

J Heart Lung Transplant. 2019 Sep;38(9):963-971. doi: 10.1016/j.healun.2019.06.007. Epub 2019 Jun 19.

Authors

Nancy Law¹, Bassem Hamandi², Christine Fegbeutel³, Fernanda P Silveira⁴, Erik A Verschuuren⁵, Piedad Ussetti⁶, Peter V Chin-Hong⁷, Amparo Sole⁸, Chien-Li Holmes-Liew⁹, Eliane M Billaud¹⁰, Paolo A Grossi¹¹, Oriol Manuel¹², Deborah J Levine¹³, Richard G Barbers¹⁴, Denis Hadjiliadis¹⁵, Muhammad Younus¹⁶, Jay Aram¹⁶, Cecilia Chaparro¹⁷, Lianne G Singer¹⁷, Shahid Husain¹⁸

Affiliations

¹ Division of Infectious Diseases, Multi-Organ Transplant Program, University of Toronto, University Health Network, Toronto, Ontario, Canada.
² Department of Pharmacy, University Health Network, Toronto, Ontario, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
³ Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Lower Saxony, Germany.
⁴ Division of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
⁵ Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, Groningen, The Netherlands.
⁶ Respiratory Department, Hospital Puerta di Hierro, Madrid, Spain.
⁷ Department of Medicine, University of California, San Francisco, California, USA.
⁸ Respiratory Department, University and Polytechnic Hospital La Fe, Universidad de Valencia, Valencia, Spain.
⁹ Lung Research, Hanson Institute and Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
¹⁰ Service de Pharmacologie, AP-HP, Hôpital Européen Georges-Pompidou, Paris, France.
¹¹ Department of Infectious Diseases, University of Insubria, Varese, Italy.
¹² Transplantation Center and Infectious Diseases Service, University Hospital of Lausanne, Lausanne, Switzerland.
¹³ Division of Pulmonary and Critical Care Medicine, University of Texas Health Science Center, San Antonio, Texas, USA.
¹⁴ Division of Pulmonary and Critical Care, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
¹⁵ Department of Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁶ Pfizer Incorporated, New York, New York, USA.
¹⁷ Toronto Lung Transplant Program, University Health Network, Toronto, Ontario, Canada.
¹⁸ Division of Infectious Diseases, Multi-Organ Transplant Program, University of Toronto, University Health Network, Toronto, Ontario, Canada. Electronic address: shahid.husain@uhn.ca.

PMID: 31300191
DOI: 10.1016/j.healun.2019.06.007

Abstract

Background: Bronchiolitis obliterans syndrome (BOS) is a major limitation in the long-term survival of lung transplant recipients (LTRs). However, the risk factors in the development of BOS remain undetermined. We conducted an international cohort study of LTRs to assess whether Aspergillus colonization with large or small conidia is a risk factor for the development of BOS.

Methods: Consecutive LTRs from January 2005 to December 2008 were evaluated. Rates of BOS and associated risk factors were recorded at 4 years. International Society of Heart and Lung Transplantation criteria were used to define fungal and other infections. A Cox proportional-hazards-model was constructed to assess the association between Aspergillus colonization and the development of BOS controlling for confounders.

Results: A total of 747 LTRs were included. The cumulative incidence of BOS at 4 years after transplant was 33% (250 of 747). Additionally, 22% of LTRs experienced Aspergillus colonization after transplantation. Aspergillus colonization with either large (hazard ratio [HR] = 0.6, 95% confidence interval [CI] = 0.3-1.2, p = 0.12) or small conidia (HR = 0.9, 95% CI = 0.6-1.4, p = 0.74) was not associated with the development of BOS. Factors associated with increased risk of development of BOS were the male gender (HR = 1.4, 95% CI = 1.1-1.8, p = 0.02) and episodes of acute rejection (1-2 episodes, HR = 1.5, 95% CI = 1.1-2.1, p = 0.014; 3-4 episodes, HR = 1.6, 95% CI = 1.0-2.6, p = 0.036; >4 episodes, HR = 2.2, 95% CI = 1.1-4.3, p = 0.02), whereas tacrolimus use was associated with reduced risk of BOS (HR = 0.6, 95% CI = 0.5-0.9, p = 0.007).

Conclusions: We conclude from this large multicenter cohort of lung transplant patients, that Aspergillus colonization with large or small conidia did not show an association with the development of BOS.

Keywords: BOS; aspergillus; colonization; lung transplantation; risk factors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aspergillus / isolation & purification*
Bronchiolitis Obliterans / epidemiology
Bronchiolitis Obliterans / microbiology*
Cohort Studies
Female
Humans
International Cooperation
Lung Transplantation*
Male
Middle Aged
Postoperative Complications / epidemiology
Postoperative Complications / microbiology*
Risk Factors
Young Adult