Claire A Aguilar1, Bassem Hamandi2, Christine Fegbeutel3, Fernand P Silveira4, Eric A Verschuuren5, Pietat Ussetti6, Peter V Chin-Hong7, Amparo Sole8, C Holmes-Liew9, Eliane M Billaud10, Paolo A Grossi11, Oriol Manuel12, Deborah J Levine13, Richard G Barbers14, Denis Hadjiliadis15, Lianne G Singer16, Shahid Husain17. 1. Multi-Organ Transplant Program, Division of Infectious Diseases, University Health Network, Toronto, Ontario, Canada. 2. Department of Pharmacy, University Health Network, Toronto, Ontario, Canada and Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada. 3. Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany. 4. Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania. 5. Department of Pulmonology and Tuberculosis, University Medical Center Groningen, University of Groningen, Groningen, Netherlands. 6. Department of Pneumology, University Hospital Clínica Puerta del Hierro-Majadahonda, Madrid, Spain. 7. Division of Infectious Diseases Department of Medicine, University of California, San Francisco, San Francisco, California. 8. Lung Transplant Unit, University and Polytechnic Hospital La Fe, Universidad de Valencia, Valencia, Spain. 9. South Australian Lung Transplant Unit, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia and Faculty of Health Sciences, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia. 10. Service de Pharmacologie, Hôpital Européen Georges Pompidou, AP-HP and Université Paris Descartes, Paris, France and Assistance Publique Hopitaux de Paris, Hopital Europeen Georges-Pompidou, Paris, France. 11. Division of Infectious Diseases, University of Insubria, Varese, Italy. 12. Infectious Disease Service, University Hospital of Lausanne, Lausanne, Switzerland. 13. Division of Pulmonary and Critical Care Medicine and CT Surgery, University of Texas Health Science Center San Antonio, San Antonio, Texas. 14. Division of Pulmonary and Critical Care, Keck Medical Center of University of Southern California, Los Angeles, California. 15. Division of Pulmonary and Critical Care Medicine, University of Pennsylvania, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. 16. Toronto Lung Transplant Program, University Health Network, Toronto, Ontario, Canada. 17. Multi-Organ Transplant Program, Division of Infectious Diseases, University Health Network, Toronto, Ontario, Canada. Electronic address: shahid.husain@uhn.ca.
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 4years 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.
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 4years 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.