Clinical risk factors for invasive aspergillosis in lung transplant recipients: Results of an international cohort study

Claire A. Aguilar, Bassem Hamandi, Christine Fegbeutel, Fernand P. Silveira, Eric A. Verschuuren, Pietat Ussetti, Peter V. Chin-Hong, Amparo Sole, C. Holmes-Liew, Eliane M. Billaud, Paolo A. Grossi, Oriol Manuel, Deborah J Levine, Richard G. Barbers, Denis Hadjiliadis, Lianne G. Singer, Shahid Husain

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

BACKGROUND: Invasive aspergillosis (IA) is a frequent complication in lung transplant recipients (LTRs). Clinical risk factors for IA have not been fully characterized, especially in the era of extensive anti-fungal prophylaxis. The primary objective of this study was to evaluate the clinical risk factors associated with IA in LTRs. The secondary objective was to assess the mortality in LTRs who had at least 1 episode of IA compared with LTRs who never had experienced IA. METHODS: We conducted an international, multicenter, retrospective cohort study of 900 consecutive adults who received lung transplants between 2005 and 2008 with 4 years of follow-up. Risk factors associated with IA were identified using univariate and multiple regression Cox proportional hazards models. RESULTS: Anti-fungal prophylaxis was administered to 61.7% (555 of 900) of patients, and 79 patients developed 115 episodes of IA. The rate to development of the first episode was 29.6 per 1,000 person-years. Aspergillus fumigatus was the most common species isolated (63% [72 of 115 episodes]). Through multivariate analysis, significant risk factors identified for IA development were single lung transplant (hazard ratio, 1.84; 95% confidence interval, 1.09–3.10; p = 0.02,) and colonization with Aspergillus at 1 year post-transplantation (hazard ratio, 2.11; 95% confidence interval, 1.28–3.49; p = 0.003,). Cystic fibrosis, pre-transplant colonization with Aspergillus spp, and use of anti-fungal prophylaxis were not significantly associated with the development of IA. Time-dependent analysis showed IA was associated with higher mortality rates. CONCLUSION: Incidence of IA remains high in LTRs. Single-lung transplant and airway colonization with Aspergillus spp. within 1 year post-transplant were significantly associated with IA.

Original languageEnglish (US)
JournalJournal of Heart and Lung Transplantation
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Pulmonary Aspergillosis
Aspergillosis
Cohort Studies
Lung
Transplants
Aspergillus
Transplant Recipients
Confidence Intervals
Aspergillus fumigatus
Mortality
Proportional Hazards Models
Cystic Fibrosis
Multivariate Analysis
Retrospective Studies

Keywords

  • anti-fungal prophylaxis
  • Aspergillus spp
  • invasive aspergillosis
  • lung transplant recipient
  • single-lung transplant

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

Cite this

Clinical risk factors for invasive aspergillosis in lung transplant recipients : Results of an international cohort study. / Aguilar, Claire A.; Hamandi, Bassem; Fegbeutel, Christine; Silveira, Fernand P.; Verschuuren, Eric A.; Ussetti, Pietat; Chin-Hong, Peter V.; Sole, Amparo; Holmes-Liew, C.; Billaud, Eliane M.; Grossi, Paolo A.; Manuel, Oriol; Levine, Deborah J; Barbers, Richard G.; Hadjiliadis, Denis; Singer, Lianne G.; Husain, Shahid.

In: Journal of Heart and Lung Transplantation, 01.01.2018.

Research output: Contribution to journalArticle

Aguilar, CA, Hamandi, B, Fegbeutel, C, Silveira, FP, Verschuuren, EA, Ussetti, P, Chin-Hong, PV, Sole, A, Holmes-Liew, C, Billaud, EM, Grossi, PA, Manuel, O, Levine, DJ, Barbers, RG, Hadjiliadis, D, Singer, LG & Husain, S 2018, 'Clinical risk factors for invasive aspergillosis in lung transplant recipients: Results of an international cohort study', Journal of Heart and Lung Transplantation. https://doi.org/10.1016/j.healun.2018.06.008
Aguilar, Claire A. ; Hamandi, Bassem ; Fegbeutel, Christine ; Silveira, Fernand P. ; Verschuuren, Eric A. ; Ussetti, Pietat ; Chin-Hong, Peter V. ; Sole, Amparo ; Holmes-Liew, C. ; Billaud, Eliane M. ; Grossi, Paolo A. ; Manuel, Oriol ; Levine, Deborah J ; Barbers, Richard G. ; Hadjiliadis, Denis ; Singer, Lianne G. ; Husain, Shahid. / Clinical risk factors for invasive aspergillosis in lung transplant recipients : Results of an international cohort study. In: Journal of Heart and Lung Transplantation. 2018.
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abstract = "BACKGROUND: Invasive aspergillosis (IA) is a frequent complication in lung transplant recipients (LTRs). Clinical risk factors for IA have not been fully characterized, especially in the era of extensive anti-fungal prophylaxis. The primary objective of this study was to evaluate the clinical risk factors associated with IA in LTRs. The secondary objective was to assess the mortality in LTRs who had at least 1 episode of IA compared with LTRs who never had experienced IA. METHODS: We conducted an international, multicenter, retrospective cohort study of 900 consecutive adults who received lung transplants between 2005 and 2008 with 4 years of follow-up. Risk factors associated with IA were identified using univariate and multiple regression Cox proportional hazards models. RESULTS: Anti-fungal prophylaxis was administered to 61.7{\%} (555 of 900) of patients, and 79 patients developed 115 episodes of IA. The rate to development of the first episode was 29.6 per 1,000 person-years. Aspergillus fumigatus was the most common species isolated (63{\%} [72 of 115 episodes]). Through multivariate analysis, significant risk factors identified for IA development were single lung transplant (hazard ratio, 1.84; 95{\%} confidence interval, 1.09–3.10; p = 0.02,) and colonization with Aspergillus at 1 year post-transplantation (hazard ratio, 2.11; 95{\%} confidence interval, 1.28–3.49; p = 0.003,). Cystic fibrosis, pre-transplant colonization with Aspergillus spp, and use of anti-fungal prophylaxis were not significantly associated with the development of IA. Time-dependent analysis showed IA was associated with higher mortality rates. CONCLUSION: Incidence of IA remains high in LTRs. Single-lung transplant and airway colonization with Aspergillus spp. within 1 year post-transplant were significantly associated with IA.",
keywords = "anti-fungal prophylaxis, Aspergillus spp, invasive aspergillosis, lung transplant recipient, single-lung transplant",
author = "Aguilar, {Claire A.} and Bassem Hamandi and Christine Fegbeutel and Silveira, {Fernand P.} and Verschuuren, {Eric A.} and Pietat Ussetti and Chin-Hong, {Peter V.} and Amparo Sole and C. Holmes-Liew and Billaud, {Eliane M.} and Grossi, {Paolo A.} and Oriol Manuel and Levine, {Deborah J} and Barbers, {Richard G.} and Denis Hadjiliadis and Singer, {Lianne G.} and Shahid Husain",
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T1 - Clinical risk factors for invasive aspergillosis in lung transplant recipients

T2 - Results of an international cohort study

AU - Aguilar, Claire A.

AU - Hamandi, Bassem

AU - Fegbeutel, Christine

AU - Silveira, Fernand P.

AU - Verschuuren, Eric A.

AU - Ussetti, Pietat

AU - Chin-Hong, Peter V.

AU - Sole, Amparo

AU - Holmes-Liew, C.

AU - Billaud, Eliane M.

AU - Grossi, Paolo A.

AU - Manuel, Oriol

AU - Levine, Deborah J

AU - Barbers, Richard G.

AU - Hadjiliadis, Denis

AU - Singer, Lianne G.

AU - Husain, Shahid

PY - 2018/1/1

Y1 - 2018/1/1

N2 - BACKGROUND: Invasive aspergillosis (IA) is a frequent complication in lung transplant recipients (LTRs). Clinical risk factors for IA have not been fully characterized, especially in the era of extensive anti-fungal prophylaxis. The primary objective of this study was to evaluate the clinical risk factors associated with IA in LTRs. The secondary objective was to assess the mortality in LTRs who had at least 1 episode of IA compared with LTRs who never had experienced IA. METHODS: We conducted an international, multicenter, retrospective cohort study of 900 consecutive adults who received lung transplants between 2005 and 2008 with 4 years of follow-up. Risk factors associated with IA were identified using univariate and multiple regression Cox proportional hazards models. RESULTS: Anti-fungal prophylaxis was administered to 61.7% (555 of 900) of patients, and 79 patients developed 115 episodes of IA. The rate to development of the first episode was 29.6 per 1,000 person-years. Aspergillus fumigatus was the most common species isolated (63% [72 of 115 episodes]). Through multivariate analysis, significant risk factors identified for IA development were single lung transplant (hazard ratio, 1.84; 95% confidence interval, 1.09–3.10; p = 0.02,) and colonization with Aspergillus at 1 year post-transplantation (hazard ratio, 2.11; 95% confidence interval, 1.28–3.49; p = 0.003,). Cystic fibrosis, pre-transplant colonization with Aspergillus spp, and use of anti-fungal prophylaxis were not significantly associated with the development of IA. Time-dependent analysis showed IA was associated with higher mortality rates. CONCLUSION: Incidence of IA remains high in LTRs. Single-lung transplant and airway colonization with Aspergillus spp. within 1 year post-transplant were significantly associated with IA.

AB - BACKGROUND: Invasive aspergillosis (IA) is a frequent complication in lung transplant recipients (LTRs). Clinical risk factors for IA have not been fully characterized, especially in the era of extensive anti-fungal prophylaxis. The primary objective of this study was to evaluate the clinical risk factors associated with IA in LTRs. The secondary objective was to assess the mortality in LTRs who had at least 1 episode of IA compared with LTRs who never had experienced IA. METHODS: We conducted an international, multicenter, retrospective cohort study of 900 consecutive adults who received lung transplants between 2005 and 2008 with 4 years of follow-up. Risk factors associated with IA were identified using univariate and multiple regression Cox proportional hazards models. RESULTS: Anti-fungal prophylaxis was administered to 61.7% (555 of 900) of patients, and 79 patients developed 115 episodes of IA. The rate to development of the first episode was 29.6 per 1,000 person-years. Aspergillus fumigatus was the most common species isolated (63% [72 of 115 episodes]). Through multivariate analysis, significant risk factors identified for IA development were single lung transplant (hazard ratio, 1.84; 95% confidence interval, 1.09–3.10; p = 0.02,) and colonization with Aspergillus at 1 year post-transplantation (hazard ratio, 2.11; 95% confidence interval, 1.28–3.49; p = 0.003,). Cystic fibrosis, pre-transplant colonization with Aspergillus spp, and use of anti-fungal prophylaxis were not significantly associated with the development of IA. Time-dependent analysis showed IA was associated with higher mortality rates. CONCLUSION: Incidence of IA remains high in LTRs. Single-lung transplant and airway colonization with Aspergillus spp. within 1 year post-transplant were significantly associated with IA.

KW - anti-fungal prophylaxis

KW - Aspergillus spp

KW - invasive aspergillosis

KW - lung transplant recipient

KW - single-lung transplant

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