Background
Respiratory viral infections (RVI) are associated with chronic lung allograft dysfunction
(CLAD) and mortality in lung transplant recipients (LTRs). However, the prevalence
and impact of secondary invasive fungal infections (IFIs) post RVIs in LTRs have not
been investigated.
Methods
We performed a single center retrospective study including LTRs diagnosed with 5 different
respiratory viral pathogens between January 2010 to May 2021 and evaluated their clinical
outcomes in 1 year. The risk factors of IFIs were evaluated by logistic regression.
The impact of IFIs on CLAD stage progression/death was examined by Cox regression.
Results
A total of 202 RVI episodes (50 influenza, 31 severe acute respiratory syndrome coronavirus-2,
30 metapneumovirus, 44 parainfluenza, and 47 respiratory syncytial virus) in 132 patients
was included for analysis. Thirty-one episodes (15%) were associated with secondary
IFIs, and 27 occurred in LTRs with lower respiratory tract infection (LRTI; 28% from
96 LRTI episodes). Aspergillosis was the most common IFI (80%). LTRs with IFIs had
higher disease severity during RVI episodes. In multivariable analysis, RVI with LTRI
was associated with IFI (adjusted odds ratio [95% confidence interval (CI)] of 7.85
(2.48-24.9). Secondary IFIs were associated with CLAD stage progression/death after
accounting for LRTI, pre-existing CLAD, intensive care unit admission, secondary bacterial
pneumonia and underlying lung diseases pre-transplant with adjusted hazard ratio (95%CI)
of 2.45 (1.29-4.64).
Conclusions
This cohort demonstrated 15% secondary IFI prevalence in LTRs with RVIs. Importantly,
secondary IFIs were associated with CLAD stage progression/death, underscoring the
importance of screening for fungal infections in this setting.
KEYWORDS
Abbreviations:
ACR (acute cellular rejection), AMR (acute antibody mediated rejection), ANC (absolute neutrophil count), BAL (bronchoalveolar lavage), BMI (body mass index), CAPA (COVID-19 associated pulmonary aspergillosis), CLAD (chronic lung allograft dysfunction), CMV (cytomegalovirus), COVID-19 (coronavirus disease 2019), CT (computed tomography), DSA (donor-specific antibodies), FEV1 (forced expiratory volume in one second percent), FCV (forced vital capacity), HLA (human anti-leukocyte antibody), HMPV (human metapneumovirus), HRs (hazard ratios), IAPA (influenza associated pulmonary aspergillosis), ICU (intensive care unit), IFI (invasive fungal infections), ISHLT (International Society for Heart and Lung Transplantation), LRTI (lower respiratory tract infection), LTRs (lung transplant recipients), OR (odds ratio), PCR (polymerase chain reaction), PIV (parainfluenza virus), RSV (respiratory syncytial virus), RVI (respiratory viral infections), SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), SD (standard deviation), SOT (solid organ transplant recipients), URTI (upper respiratory tract infection)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The Journal of Heart and Lung TransplantationAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Therapy options for chronic lung allograft dysfunction-bronchiolitis obliterans syndrome following first-line immunosuppressive strategies: A systematic review.J Heart Lung Transplant. 2017; 36: 921-933https://doi.org/10.1016/j.healun.2017.05.030
- The registry of the international society for heart and lung transplantation: thirty-second official adult lung and heart-lung transplantation report–2015; focus theme: early graft failure.J Heart Lung Transplant. 2015; 34: 1264-1277https://doi.org/10.1016/j.healun.2015.08.014
- Community-acquired respiratory viruses are a risk factor for chronic lung allograft dysfunction.Clin Infect Dis. 2019; 69: 1192-1197https://doi.org/10.1093/cid/ciy1047
- Symptomatic respiratory virus infection and chronic lung allograft dysfunction.Clin Infect Dis. 2016; 62: 313-319https://doi.org/10.1093/cid/civ871
- Oral and inhaled ribavirin treatment for respiratory syncytial virus infection in lung transplant recipients.Transplantation. 2020; 104: 1280-1286https://doi.org/10.1097/TP.0000000000002985
- Host-pathogen interactions and chronic lung allograft dysfunction.Ann Am Thorac Soc. 2017; 14: S242-S246https://doi.org/10.1513/AnnalsATS.201606-464MG
- Colonization with small conidia Aspergillus species is associated with bronchiolitis obliterans syndrome: a two-center validation study.Am J Transplant. 2013; 13: 919-927https://doi.org/10.1111/ajt.12131
- Aspergillus colonization of the lung allograft is a risk factor for bronchiolitis obliterans syndrome.Am J Transplant. 2009; 9: 1903-1911https://doi.org/10.1111/j.1600-6143.2009.02635.x
- High rates of influenza-associated invasive pulmonary aspergillosis may not be universal: a retrospective cohort study from Alberta.Clin Infect Dis. 2020; 71 (Canada.): 1760-1763https://doi.org/10.1093/cid/ciaa007
- Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study.Lancet Respir Med. 2018; 6: 782-792https://doi.org/10.1016/S2213-2600(18)30274-1
- Invasive pulmonary aspergillosis is a frequent complication of critically ill H1N1 patients: a retrospective study.Intensive Care Med. 2012; 38: 1761-1768https://doi.org/10.1007/s00134-012-2673-2
- Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion.Intensive Care Med. 2020; 46: 1524-1535https://doi.org/10.1007/s00134-020-06091-6
- Coronavirus disease 2019-associated pulmonary aspergillosis in mechanically ventilated patients.Clin Infect Dis. 2022; 74: 83-91https://doi.org/10.1093/cid/ciab223
- Aspergillosis complicating severe coronavirus disease.Emerg Infect Dis. 2020; 27: 18-25https://doi.org/10.3201/eid2701.202896
- A national strategy to diagnose COVID-19 associated invasive fungal disease in the ICU.Clin Infect Dis. 2020; 29: e1634-e1644https://doi.org/10.1093/cid/ciaa1298
- Prevalence of putative invasive pulmonary aspergillosis in critically ill patients with COVID-19.Lancet Respir Med. 2020; 8: e48-e49https://doi.org/10.1016/S2213-2600(20)30237-X
- COVID-19-associated invasive pulmonary aspergillosis.Ann Intensive Care. 2020; 10: 1706-1708https://doi.org/10.1186/s13613-020-00686-4
- Incidence of invasive pulmonary aspergillosis among critically ill COVID-19 patients.Clin Microbiol Infect. 2020; 10https://doi.org/10.1016/j.cmi.2020.07.010
- Impact of COVID-19 on lung allograft and clinical outcomes in lung transplant recipients: a case-control study.Transplantation. 2021; 105: 2072-2079https://doi.org/10.1097/TP.0000000000003839
- A 2010 working formulation for the standardization of definitions of infections in cardiothoracic transplant recipients.J Heart Lung Transplant. 2011; 30: 361-374https://doi.org/10.1016/j.healun.2011.01.701
- Human metapneumovirus and parainfluenza virus infections in lung transplant recipients: the effects on lung allograft and clinical outcomes.Transplantation. 2021; 105: 2625-2631https://doi.org/10.1097/TP.0000000000003645
- Update on COVID-19 therapeutics for solid organ transplant recipients, including the omicron surge.Transplantation. 2022; 24: 1528-1537https://doi.org/10.1097/TP.0000000000004200
- Short-term outcomes in a nurse coordinator-led and nurse practitioner-led sotrovimab initiative for solid organ transplant recipients during the omicron surge.Transplantation. 2022; 106: e424-e425https://doi.org/10.1097/TP.0000000000004217
- Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection.J Heart Lung Transplant. 2007; 26: 1229-1242https://doi.org/10.1016/j.healun.2007.10.017
- Antibody-mediated rejection of the lung: a consensus report of the International Society for Heart and Lung Transplantation.J Heart Lung Transplant. 2016; 35: 397-406https://doi.org/10.1016/j.healun.2016.01.1223
- Chronic lung allograft dysfunction: definition, diagnostic criteria, and approaches to treatment-A consensus report from the Pulmonary Council of the ISHLT.J Heart Lung Transplant. 2019; 38: 493-503https://doi.org/10.1016/j.healun.2019.03.009
- Elevated cell free DNA in respiratory viral infection and associated lung allograft dysfunction.Am J Transplant. 2022; 22: 2560-2570https://doi.org/10.1111/ajt.17125
- Higher mortality of severe influenza patients with probable aspergillosis than those with and without other coinfections.J Formos Med Assoc. 2017; 116: 660-670https://doi.org/10.1016/j.jfma.2017.06.002
- Epidemiology of invasive pulmonary aspergillosis among COVID-19 intubated patients: a prospective study.Clin Infect Dis. 2020; 73: e3606-e3614https://doi.org/10.1093/cid/ciaa1065
- Modifications of lung clearance mechanisms by acute influenza A infection.J Lab Clin Med. 1985; 106: 428-432
- Invasive pulmonary aspergillosis complicating noninfluenza respiratory viral infections in solid organ transplant recipients.Open Forum Infect Dis. 2021; 8: ofab478https://doi.org/10.1093/ofid/ofab478
Article info
Publication history
Published online: February 19, 2023
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 International Society for Heart and Lung Transplantation. All rights reserved.
