TY - JOUR
T1 - Lack of association of Aspergillus colonization with the development of bronchiolitis obliterans syndrome in lung transplant recipients
T2 - An international cohort study
AU - Law, Nancy
AU - Hamandi, Bassem
AU - Fegbeutel, Christine
AU - Silveira, Fernanda P.
AU - Verschuuren, Erik A.
AU - Ussetti, Piedad
AU - Chin-Hong, Peter V.
AU - Sole, Amparo
AU - Holmes-Liew, Chien Li
AU - Billaud, Eliane M.
AU - Grossi, Paolo A.
AU - Manuel, Oriol
AU - Levine, Deborah J.
AU - Barbers, Richard G.
AU - Hadjiliadis, Denis
AU - Younus, Muhammad
AU - Aram, Jay
AU - Chaparro, Cecilia
AU - Singer, Lianne G.
AU - Husain, Shahid
N1 - Funding Information:
This study was funded by Pfizer. Pfizer did not have any input in the manuscript preparation and conclusion. Dr Shahid Husain has received research grants from Merck and Pfizer, educational grant from Astellas, and consultancy fees from Cidara. F.P.S. has received research support from Pfizer, Gilead, Shire, CSL Behring, Qiagen, Ansun Biopharma, and Whiscon. Drs Jay Aram and Muhammad Younus are employees of Pfizer Inc, New York, USA. L.G.S. has received research support from Gilead, and Pfizer, New York. All other authors have nothing report.
Publisher Copyright:
© 2019 International Society for Heart and Lung Transplantation
PY - 2019/9
Y1 - 2019/9
N2 - 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.
AB - 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.
KW - BOS
KW - aspergillus
KW - colonization
KW - lung transplantation
KW - risk factors
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U2 - 10.1016/j.healun.2019.06.007
DO - 10.1016/j.healun.2019.06.007
M3 - Article
C2 - 31300191
AN - SCOPUS:85068437818
VL - 38
SP - 963
EP - 971
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
SN - 1053-2498
IS - 9
ER -