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Published in: BMC Pulmonary Medicine 1/2020

Open Access 01-12-2020 | Aspergillosis | Research article

Invasive pulmonary aspergillosis in immunocompetent patients hospitalised with influenza A-related pneumonia: a multicenter retrospective study

Authors: Liang Chen, Xiudi Han, Yanli Li, Chunxiao Zhang, Xiqian Xing

Published in: BMC Pulmonary Medicine | Issue 1/2020

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Abstract

Background

Increasing cases of pulmonary aspergillosis (IPA) in immunocompetent patients with severe influenza have been reported. Howevere, the risk factors for occurence and death are largely unknown.

Methods

Data of hospitalised patients with influenza A-related pneumonia (FluA-p) obtained from five teaching hospitals from 2031 to 2018, were reviewed. Univariate and multivariate logistical regression analyses were performed to determine the risk factors involved in the acquisition and 60-day mortality in IPA patients.

Results

Of the 693 FluA-p patients included in the study, 3.0% (21/693) were IPA patients with a 60-day mortality of 42.9% (9/21). Adjusted for confounders, a Cox proportional hazard model showed that IPA was associated with increased risk for 60-day mortality [hazard ratio (HR) 4.336, 95% confidence interval (CI) 1.191–15.784, p = 0.026] in FluA-p patients. A multivariate logistic regression model confirmed that age (odd ratio (OR) 1.147, 95% CI 1.048–1.225, p = 0.003), systemic corticosteroids use before IPA diagnosis (OR 33.773, 95% CI 5.681–76.764, p <  0.001), leukocytes > 10 × 109/L (OR 1.988, 95% CI 1.028–6.454, p = 0.029) and lymphocytes < 0.8 × 109/L on admission (OR 34.813, 95% CI 1.676–73.006, p = 0.022), were related with the acquisition of IPA. Early neuraminidase inhibitor use (OR 0.290, 95% CI 0.002–0.584, p = 0.021) was associated with a decreased risk for a 60-day mortality in IPA patients.

Conclusions

Our results showed that IPA worsen the clinical outcomes of FluA-p patients. The risk factors for the acquisition and death were helpful for the clinicians in preventing and treating IPA.
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Literature
1.
go back to reference Peteranderl C, Herold S, Schmoldt C. Human influenza virus infections. Semin Respir Crit Care Med. 2006;37(4):487–500.CrossRef Peteranderl C, Herold S, Schmoldt C. Human influenza virus infections. Semin Respir Crit Care Med. 2006;37(4):487–500.CrossRef
2.
go back to reference Neuzil KM, Bresee JS, de la Hoz F, Johansen K, Karron RA, Krishnan A, et al. Data and product needs for influenza immunization programs in low- and middle-income countries: rationale and main conclusions of the WHO preferred product characteristics for next-generation influenza vaccines. Vaccine. 2017;35(43):5734–7.PubMedCrossRef Neuzil KM, Bresee JS, de la Hoz F, Johansen K, Karron RA, Krishnan A, et al. Data and product needs for influenza immunization programs in low- and middle-income countries: rationale and main conclusions of the WHO preferred product characteristics for next-generation influenza vaccines. Vaccine. 2017;35(43):5734–7.PubMedCrossRef
3.
go back to reference Dahal S, Jenner M, Dinh L, Mizumoto K, Viboud C, Chowell G. Excess mortality patterns during 1918-1921 influenza pandemic in the state of Arizona, USA. Ann Epidemiol. 2016;28(5):273–80.CrossRef Dahal S, Jenner M, Dinh L, Mizumoto K, Viboud C, Chowell G. Excess mortality patterns during 1918-1921 influenza pandemic in the state of Arizona, USA. Ann Epidemiol. 2016;28(5):273–80.CrossRef
5.
go back to reference Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analfor the global burden of disease study 2010. Lancet. 2012;380(9859):2095–128.PubMedCrossRef Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analfor the global burden of disease study 2010. Lancet. 2012;380(9859):2095–128.PubMedCrossRef
6.
go back to reference Li M, Bolker BM, Dushoff J, Ma J, Earn DJD. Patterns of seasonal and pandemic influenza-associated health care and mortality in Ontario, Canada. BMC Public Health. 2019;19(1):1237.PubMedPubMedCentralCrossRef Li M, Bolker BM, Dushoff J, Ma J, Earn DJD. Patterns of seasonal and pandemic influenza-associated health care and mortality in Ontario, Canada. BMC Public Health. 2019;19(1):1237.PubMedPubMedCentralCrossRef
7.
go back to reference Klein EY, Monteforte B, Gupta A, Jiang W, May L, Hsieh YH, Dugas A. The frequency of influenza and bacterial coinfection: a systematic review and meta-analysis. Influenza Other Respir Viruses. 2016;10(5):394–403.PubMedPubMedCentralCrossRef Klein EY, Monteforte B, Gupta A, Jiang W, May L, Hsieh YH, Dugas A. The frequency of influenza and bacterial coinfection: a systematic review and meta-analysis. Influenza Other Respir Viruses. 2016;10(5):394–403.PubMedPubMedCentralCrossRef
8.
go back to reference Kylla H, Dutta TK, Roychoudhury P, Subudhi PK. Coinfection of diarrheagenic bacterial and viral pathogens in piglets of northeast region of India. Vet World. 2019;12(2):224–30.PubMedPubMedCentralCrossRef Kylla H, Dutta TK, Roychoudhury P, Subudhi PK. Coinfection of diarrheagenic bacterial and viral pathogens in piglets of northeast region of India. Vet World. 2019;12(2):224–30.PubMedPubMedCentralCrossRef
9.
go back to reference Brundage JF. Interactions between influenza and bacterial respiratory pathogens: implications for pandemic preparedness. Lancet Infect Dis. 2016;6(5):303–12.CrossRef Brundage JF. Interactions between influenza and bacterial respiratory pathogens: implications for pandemic preparedness. Lancet Infect Dis. 2016;6(5):303–12.CrossRef
10.
go back to reference Harper SA, Bradley JS, Englund JA, File TM, Gravenstein S, Hayden FG, et al. Seasonal influenza in adults and children--diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2019;48(8):1003–32.CrossRef Harper SA, Bradley JS, Englund JA, File TM, Gravenstein S, Hayden FG, et al. Seasonal influenza in adults and children--diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2019;48(8):1003–32.CrossRef
11.
go back to reference Cao B, Huang Y, She DY, Cheng QJ, Fan H, Tian XL, et al. Diagnosis and treatment of community-acquired pneumonia in adults: 2016 clinical practice guidelines by the Chinese thoracic society, Chinese Medical Association. Clin Respir J. 2018;12(4):1320–60.PubMedCrossRef Cao B, Huang Y, She DY, Cheng QJ, Fan H, Tian XL, et al. Diagnosis and treatment of community-acquired pneumonia in adults: 2016 clinical practice guidelines by the Chinese thoracic society, Chinese Medical Association. Clin Respir J. 2018;12(4):1320–60.PubMedCrossRef
12.
go back to reference Cadena J, Thompson GR 3rd, Patterson TF. Invasive Aspergillosis: current strategies for diagnosis and management. Infect Dis Clin N Am. 2016;30(1):125–42.CrossRef Cadena J, Thompson GR 3rd, Patterson TF. Invasive Aspergillosis: current strategies for diagnosis and management. Infect Dis Clin N Am. 2016;30(1):125–42.CrossRef
13.
go back to reference Solano C, Vázquez L. Invasive aspergillosis in the patient with oncohematologic disease. Rev Iberoam Micol. 2018;35(4):198–205.PubMedCrossRef Solano C, Vázquez L. Invasive aspergillosis in the patient with oncohematologic disease. Rev Iberoam Micol. 2018;35(4):198–205.PubMedCrossRef
14.
go back to reference Alshabani K, Haq A, Miyakawa R, Palla M, Soubani AO. Invasive pulmonary aspergillosis in patients with influenza infection: report of two cases and systematic review of the literature. Expert Rev Respir Med. 2015;9(1):89–96.PubMedCrossRef Alshabani K, Haq A, Miyakawa R, Palla M, Soubani AO. Invasive pulmonary aspergillosis in patients with influenza infection: report of two cases and systematic review of the literature. Expert Rev Respir Med. 2015;9(1):89–96.PubMedCrossRef
15.
go back to reference Kim SH, Kim MN, Lee SO, Choi SH, Kim YS, Woo JH, et al. Fatal pandemic influenza A/H1N1 infection complicated by probable invasive pulmonary aspergillosis. Mycoses. 2012;55(2):189–92.PubMed Kim SH, Kim MN, Lee SO, Choi SH, Kim YS, Woo JH, et al. Fatal pandemic influenza A/H1N1 infection complicated by probable invasive pulmonary aspergillosis. Mycoses. 2012;55(2):189–92.PubMed
16.
17.
go back to reference Chen L, Zhou F, Li H, Xing X, Han X, Wang Y, et al. Disease characteristics and management of hospitalised adolescents and adults with community-acquired pneumonia in China: a retrospective multicentre survey. BMJ Open. 2018;8(2):e018709.PubMedPubMedCentralCrossRef Chen L, Zhou F, Li H, Xing X, Han X, Wang Y, et al. Disease characteristics and management of hospitalised adolescents and adults with community-acquired pneumonia in China: a retrospective multicentre survey. BMJ Open. 2018;8(2):e018709.PubMedPubMedCentralCrossRef
18.
go back to reference Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, et al. Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis. 2019;ciz1008. Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, et al. Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis. 2019;ciz1008.
19.
go back to reference Ku YH, Chan KS, Yang CC, Tan CK, Chuang YC, Yu WL, et al. Higher mortality of severe influenza patients with probable aspergillosis than those with and without other coinfections. J Formos Med Assoc. 2017;116(9):660–70.PubMedCrossRef Ku YH, Chan KS, Yang CC, Tan CK, Chuang YC, Yu WL, et al. Higher mortality of severe influenza patients with probable aspergillosis than those with and without other coinfections. J Formos Med Assoc. 2017;116(9):660–70.PubMedCrossRef
20.
go back to reference Rice TW, Rubinson L, Uyeki TM, Vaughn FL, John BB, Miller RR 3rd, et al. Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States. Crit Care Med. 2012;40(5):1487–98.PubMedPubMedCentralCrossRef Rice TW, Rubinson L, Uyeki TM, Vaughn FL, John BB, Miller RR 3rd, et al. Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States. Crit Care Med. 2012;40(5):1487–98.PubMedPubMedCentralCrossRef
21.
go back to reference Martin-Loeches I, Schultz JM, Vincent JL, Alvarez-Lerma F, Bos LD, Solé-Violán J, et al. Increased incidence of co-infection in critically ill patients with influenza. Intensive Care Med. 2017;43(1):48–58.PubMedCrossRef Martin-Loeches I, Schultz JM, Vincent JL, Alvarez-Lerma F, Bos LD, Solé-Violán J, et al. Increased incidence of co-infection in critically ill patients with influenza. Intensive Care Med. 2017;43(1):48–58.PubMedCrossRef
22.
go back to reference Schauwvlieghe AFAD, Rijnders BJA, Philips N, Verwijs R, Vanderbeke L, Van Tienen C, et al. Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study. Lancet Respir Med. 2018;6(10):782–92.PubMedCrossRef Schauwvlieghe AFAD, Rijnders BJA, Philips N, Verwijs R, Vanderbeke L, Van Tienen C, et al. Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study. Lancet Respir Med. 2018;6(10):782–92.PubMedCrossRef
23.
go back to reference Cattaneo C, Gramegna D, Malagola M, Pagani C, Borlenghi E, Cerqui E, et al. Invasive pulmonary aspergillosis in acute leukemia: a still frequent condition with a negative impact on the overall treatment outcome. Leuk Lymphoma. 2019;60(12):3044–50.PubMedCrossRef Cattaneo C, Gramegna D, Malagola M, Pagani C, Borlenghi E, Cerqui E, et al. Invasive pulmonary aspergillosis in acute leukemia: a still frequent condition with a negative impact on the overall treatment outcome. Leuk Lymphoma. 2019;60(12):3044–50.PubMedCrossRef
24.
go back to reference Huang L, Zhang N, Huang X, Xiong S, Feng Y, Zhang Y, et al. Invasive pulmonary aspergillosis in patients with influenza infection: A retrospective study and review of the literature. Clin Respir J. 2019;13(4):202–11.PubMedCrossRef Huang L, Zhang N, Huang X, Xiong S, Feng Y, Zhang Y, et al. Invasive pulmonary aspergillosis in patients with influenza infection: A retrospective study and review of the literature. Clin Respir J. 2019;13(4):202–11.PubMedCrossRef
25.
go back to reference Vandewoude KH, Blot SI, Depuydt P, Benoit D, Temmerman W, Colardyn F, Vogelaers D. Clinical relevance of Aspergillus isolation from respiratory tract samples in critically ill patients. Crit Care. 2006;10(1):R31.PubMedPubMedCentralCrossRef Vandewoude KH, Blot SI, Depuydt P, Benoit D, Temmerman W, Colardyn F, Vogelaers D. Clinical relevance of Aspergillus isolation from respiratory tract samples in critically ill patients. Crit Care. 2006;10(1):R31.PubMedPubMedCentralCrossRef
26.
go back to reference Park SY, Lim C, Lee SO, Choi SH, Kim YS, et al. Computed tomography findings in invasive pulmonary aspergillosis in non-neutropenic transplant recipients and neutropenic patients, and their prognostic value. J Inf Secur. 2011;63(6):447–56. Park SY, Lim C, Lee SO, Choi SH, Kim YS, et al. Computed tomography findings in invasive pulmonary aspergillosis in non-neutropenic transplant recipients and neutropenic patients, and their prognostic value. J Inf Secur. 2011;63(6):447–56.
28.
go back to reference Rosano A, Bella A, Gesualdo F, Acampora A, Pezzotti P, Marchetti S, et al. Investigating the impact of influenza on excess mortality in all ages in Italy during recent seasons (2013/14-2016/17 seasons). Int J Infect Dis. 2019;88:127–34.PubMedCrossRef Rosano A, Bella A, Gesualdo F, Acampora A, Pezzotti P, Marchetti S, et al. Investigating the impact of influenza on excess mortality in all ages in Italy during recent seasons (2013/14-2016/17 seasons). Int J Infect Dis. 2019;88:127–34.PubMedCrossRef
29.
go back to reference Choi JJ, McCarthy MW. Novel applications for serum procalcitonin testing in clinical practice. Expert Rev Mol Diagn. 2018;18(1):27–34.PubMedCrossRef Choi JJ, McCarthy MW. Novel applications for serum procalcitonin testing in clinical practice. Expert Rev Mol Diagn. 2018;18(1):27–34.PubMedCrossRef
30.
go back to reference Lionakis MS, Kontoyiannis DP. Glucocorticoids and invasive fungal infections. Lancet. 2003;362(9398):1828–38.PubMedCrossRef Lionakis MS, Kontoyiannis DP. Glucocorticoids and invasive fungal infections. Lancet. 2003;362(9398):1828–38.PubMedCrossRef
31.
go back to reference Karthaus M, Buchheidt D. Invasive aspergillosis: new insights into disease, diagnostic and treatment. Curr Pharm Des. 2013;19(20):3569–94.PubMedCrossRef Karthaus M, Buchheidt D. Invasive aspergillosis: new insights into disease, diagnostic and treatment. Curr Pharm Des. 2013;19(20):3569–94.PubMedCrossRef
32.
go back to reference Ni YN, Chen G, Sun J, Liang BM, Liang ZA. The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis. Crit Care. 2019;23(1):99.PubMedPubMedCentralCrossRef Ni YN, Chen G, Sun J, Liang BM, Liang ZA. The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis. Crit Care. 2019;23(1):99.PubMedPubMedCentralCrossRef
33.
go back to reference Li H, Yang SG, Gu L, Zhang Y, Yan XX, Liang ZA, et al. Effect of low-to-moderate-dose corticosteroids on mortality of hospitalised adolescents and adults with influenza A(H1N1)pdm09 viral pneumonia. Influenza Other Respir Viruses. 2017;11(4):345–54.PubMedPubMedCentralCrossRef Li H, Yang SG, Gu L, Zhang Y, Yan XX, Liang ZA, et al. Effect of low-to-moderate-dose corticosteroids on mortality of hospitalised adolescents and adults with influenza A(H1N1)pdm09 viral pneumonia. Influenza Other Respir Viruses. 2017;11(4):345–54.PubMedPubMedCentralCrossRef
34.
go back to reference Ghoneim HE, McCullers JA. Adjunctive corticosteroid therapy improves lung immunopathology and survival during severe secondary pneumococcal pneumonia in mice. J Infect Dis. 2014;209(9):1459–68.PubMedCrossRef Ghoneim HE, McCullers JA. Adjunctive corticosteroid therapy improves lung immunopathology and survival during severe secondary pneumococcal pneumonia in mice. J Infect Dis. 2014;209(9):1459–68.PubMedCrossRef
35.
go back to reference Osthoff M, Erb S. Neuraminidase inhibitors and influenza infection. JAMA Intern Med. 2016;176(3):415.PubMedCrossRef Osthoff M, Erb S. Neuraminidase inhibitors and influenza infection. JAMA Intern Med. 2016;176(3):415.PubMedCrossRef
36.
go back to reference Muthuri SG, Venkatesan S, Myles PR, Leonardi-Bee J, Lim WS, Al Mamun A, et al. Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an individual participant data meta-analysis. Influenza Other Respir Viruses. 2016;10(3):192–204.PubMedPubMedCentralCrossRef Muthuri SG, Venkatesan S, Myles PR, Leonardi-Bee J, Lim WS, Al Mamun A, et al. Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an individual participant data meta-analysis. Influenza Other Respir Viruses. 2016;10(3):192–204.PubMedPubMedCentralCrossRef
37.
go back to reference Zhou W, Li H, Zhang Y, Huang M, He Q, Li P, et al. Diagnostic value of Galactomannan antigen test in serum and Bronchoalveolar lavage fluid samples from patients with Nonneutropenic invasive pulmonary Aspergillosis. J Clin Microbiol. 2017;55(7):2153–61.PubMedPubMedCentralCrossRef Zhou W, Li H, Zhang Y, Huang M, He Q, Li P, et al. Diagnostic value of Galactomannan antigen test in serum and Bronchoalveolar lavage fluid samples from patients with Nonneutropenic invasive pulmonary Aspergillosis. J Clin Microbiol. 2017;55(7):2153–61.PubMedPubMedCentralCrossRef
38.
go back to reference van de Groep K, Verboom DM, van de Veerdonk FL, Haas P-JA, van der Poll T, Schultz MJ, et al. Detection of invasive Aspergillosis in critically ill patients with influenza: the role of plasma Galactomannan. Am J Respir Crit Care Med. 2019;200(5):636–8.PubMedCrossRef van de Groep K, Verboom DM, van de Veerdonk FL, Haas P-JA, van der Poll T, Schultz MJ, et al. Detection of invasive Aspergillosis in critically ill patients with influenza: the role of plasma Galactomannan. Am J Respir Crit Care Med. 2019;200(5):636–8.PubMedCrossRef
Metadata
Title
Invasive pulmonary aspergillosis in immunocompetent patients hospitalised with influenza A-related pneumonia: a multicenter retrospective study
Authors
Liang Chen
Xiudi Han
Yanli Li
Chunxiao Zhang
Xiqian Xing
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2020
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-020-01257-w

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