Respiratory Mycoses in COPD and Bronchiectasis.
Aspergillus
Fungi
ITS sequencing
Mycobiome
Respiratory mycoses
Journal
Mycopathologia
ISSN: 1573-0832
Titre abrégé: Mycopathologia
Pays: Netherlands
ID NLM: 7505689
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
received:
18
12
2020
accepted:
22
02
2021
pubmed:
13
3
2021
medline:
27
10
2021
entrez:
12
3
2021
Statut:
ppublish
Résumé
Chronic obstructive pulmonary disease (COPD) and bronchiectasis represent chronic airway diseases associated with significant morbidity and mortality. Bacteria and viruses are commonly implicated in acute exacerbations; however the significance of fungi in these airways remains poorly defined. While COPD and bronchiectasis remain recognized risk factors for the occurrence of Aspergillus-associated disease including chronic and invasive aspergillosis, underlying mechanisms that lead to the progression from colonization to invasive disease remain uncertain. Nonetheless, advances in molecular technologies have improved our detection, identification and understanding of resident fungi characterizing these airways. Mycobiome sequencing has revealed the complex varied and myriad profile of airway fungi in COPD and bronchiectasis, including their association with disease presentation, progression, and mortality. In this review, we outline the emerging evidence for the clinical importance of fungi in COPD and bronchiectasis, available diagnostic modalities, mycobiome sequencing approaches and association with clinical outcomes.
Identifiants
pubmed: 33709335
doi: 10.1007/s11046-021-00539-z
pii: 10.1007/s11046-021-00539-z
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
623-638Subventions
Organisme : National Medical Research Council Singapore
ID : NMRC/Fellowship/0049/2017
Organisme : National Medical Research Council Singapore
ID : MOH-000141
Organisme : NTU Integrated Medical, Biological and Environmental Life Sciences (NIMBELS)
ID : NIM/03/2018
Organisme : British Lung Foundation
ID : British Lung Foundation through the GSK/British Lung Foundation Chair of Respiratory Research
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Chandrasekaran R, Mac Aogáin M, Chalmers JD, Elborn SJ, Chotirmall SH. Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis. BMC Pulm Med. 2018;18(1):83. https://doi.org/10.1186/s12890-018-0638-0 .
doi: 10.1186/s12890-018-0638-0
pubmed: 29788932
pmcid: 5964678
Polverino E, Goeminne PC, McDonnell MJ, Aliberti S, Marshall SE, Loebinger MR, et al. European respiratory society guidelines for the management of adult bronchiectasis. Eur Respir J. 2017. https://doi.org/10.1183/13993003.00629-2017 .
doi: 10.1183/13993003.00629-2017
pubmed: 29242262
GOLD. Global strategy for the diagnosis, management and prevention of COPD, global initiative for chronic obstructive lung disease (GOLD) 2018. ( http://goldcopd.org/ ); 2018.
Chalmers JD, Chang AB, Chotirmall SH, Dhar R, McShane PJ. Bronchiectasis. Nat Rev Dis Primers. 2018;4(1):45. https://doi.org/10.1038/s41572-018-0042-3 .
doi: 10.1038/s41572-018-0042-3
pubmed: 30442957
Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3(11):e442. https://doi.org/10.1371/journal.pmed.0030442 .
doi: 10.1371/journal.pmed.0030442
pubmed: 17132052
pmcid: 1664601
Sin S, Yun SY, Kim JM, Park CM, Cho J, Choi SM, et al. Mortality risk and causes of death in patients with non-cystic fibrosis bronchiectasis. Respir Res. 2019;20(1):271. https://doi.org/10.1186/s12931-019-1243-3 .
doi: 10.1186/s12931-019-1243-3
pubmed: 31796019
pmcid: 6889428
Snell N, Gibson J, Jarrold I, Quint JK. Epidemiology of bronchiectasis in the UK: findings from the British lung foundation’s “Respiratory health of the nation” project. Respir Med. 2019;158:21–3. https://doi.org/10.1016/j.rmed.2019.09.012 .
doi: 10.1016/j.rmed.2019.09.012
pubmed: 31550642
Leung JM, Tiew PY, Mac Aogain M, Budden KF, Yong VF, Thomas SS, et al. The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD. Respirology. 2017;22(4):634–50. https://doi.org/10.1111/resp.13032 .
doi: 10.1111/resp.13032
pubmed: 28342288
pmcid: 7169176
Chotirmall SH, Al-Alawi M, Mirkovic B, Lavelle G, Logan PM, Greene CM, et al. Aspergillus-associated airway disease, inflammation, and the innate immune response. Biomed Res Int. 2013;2013:723129. https://doi.org/10.1155/2013/723129 .
doi: 10.1155/2013/723129
pubmed: 23971044
pmcid: 3736487
Chotirmall SH, Martin-Gomez MT. Aspergillus species in bronchiectasis: challenges in the cystic fibrosis and non-cystic fibrosis airways. Mycopathologia. 2018;183(1):45–59. https://doi.org/10.1007/s11046-017-0143-7 .
doi: 10.1007/s11046-017-0143-7
pubmed: 28516246
Yii AC, Koh MS, Lapperre TS, Tan GL, Chotirmall SH. The emergence of Aspergillus species in chronic respiratory disease. Front Biosci (Schol Ed). 2017;9:127–38. https://doi.org/10.2741/s477 .
doi: 10.2741/s477
Bulpa P, Dive A, Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Respir J. 2007;30(4):782–800. https://doi.org/10.1183/09031936.00062206 .
doi: 10.1183/09031936.00062206
pubmed: 17906086
Huerta A, Soler N, Esperatti M, Guerrero M, Menendez R, Gimeno A, et al. Importance of Aspergillus spp. isolation in Acute exacerbations of severe COPD: prevalence factors and follow-up: the FUNGI-COPD study. Respir Res. 2014;15:17. https://doi.org/10.1186/1465-9921-15-17 .
doi: 10.1186/1465-9921-15-17
pubmed: 24517318
pmcid: 3996133
Bafadhel M, McKenna S, Agbetile J, Fairs A, Desai D, Mistry V, et al. Aspergillus fumigatus during stable state and exacerbations of COPD. Eur Respir J. 2014;43(1):64–71. https://doi.org/10.1183/09031936.00162912 .
doi: 10.1183/09031936.00162912
pubmed: 23598955
Pashley CH, Fairs A, Morley JP, Tailor S, Agbetile J, Bafadhel M, et al. Routine processing procedures for isolating filamentous fungi from respiratory sputum samples may underestimate fungal prevalence. Med Mycol. 2012;50(4):433–8. https://doi.org/10.3109/13693786.2011.615762 .
doi: 10.3109/13693786.2011.615762
pubmed: 21961802
Waqas S, Dunne K, Talento AF, Wilson G, Martin-Loeches I, Keane J, et al. Prospective observational study of respiratory Aspergillus colonization or disease in patients with various stages of chronic obstructive pulmonary disease utilizing culture versus nonculture techniques. Med Mycol. 2020. https://doi.org/10.1093/mmy/myaa077 .
doi: 10.1093/mmy/myaa077
pubmed: 32926151
Tong X, Cheng A, Xu H, Jin J, Yang Y, Zhu S, et al. Aspergillus fumigatus during COPD exacerbation: a pair-matched retrospective study. BMC Pulm Med. 2018;18(1):55. https://doi.org/10.1186/s12890-018-0611-y .
doi: 10.1186/s12890-018-0611-y
pubmed: 29615101
pmcid: 5883425
Barberan J, Garcia-Perez FJ, Villena V, Fernandez-Villar A, Malmierca E, Salas C, et al. Development of Aspergillosis in a cohort of non-neutropenic, non-transplant patients colonised by Aspergillus spp. BMC Infect Dis. 2017;17(1):34. https://doi.org/10.1186/s12879-016-2143-5 .
doi: 10.1186/s12879-016-2143-5
pubmed: 28056830
pmcid: 5217298
Guinea J, Torres-Narbona M, Gijon P, Munoz P, Pozo F, Pelaez T, et al. Pulmonary Aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome. Clin Microbiol Infect. 2010;16(7):870–7. https://doi.org/10.1111/j.1469-0691.2009.03015.x .
doi: 10.1111/j.1469-0691.2009.03015.x
pubmed: 19906275
Mirkovic B, Lavelle GM, Azim AA, Helma K, Gargoum FS, Molloy K, et al. The basophil surface marker CD203c identifies Aspergillus species sensitization in patients with cystic fibrosis. J Allergy Clin Immunol. 2016;137(2):436-43e9. https://doi.org/10.1016/j.jaci.2015.07.045 .
doi: 10.1016/j.jaci.2015.07.045
pubmed: 26388311
Maes T, Provoost S, Lanckacker EA, Cataldo DD, Vanoirbeek JA, Nemery B, et al. Mouse models to unravel the role of inhaled pollutants on allergic sensitization and airway inflammation. Respir Res. 2010;11:7. https://doi.org/10.1186/1465-9921-11-7 .
doi: 10.1186/1465-9921-11-7
pubmed: 20092634
pmcid: 2831838
Hammond EE, McDonald CS, Vestbo J, Denning DW. The global impact of Aspergillus infection on COPD. BMC Pulm Med. 2020;20(1):241. https://doi.org/10.1186/s12890-020-01259-8 .
doi: 10.1186/s12890-020-01259-8
pubmed: 32912168
pmcid: 7488557
Jin J, Liu X, Sun Y. The prevalence of increased serum IgE and Aspergillus sensitization in patients with COPD and their association with symptoms and lung function. Respir Res. 2014;15:130. https://doi.org/10.1186/s12931-014-0130-1 .
doi: 10.1186/s12931-014-0130-1
pubmed: 25359094
pmcid: 4216660
Agarwal R, Hazarika B, Gupta D, Aggarwal AN, Chakrabarti A, Jindal SK. Aspergillus hypersensitivity in patients with chronic obstructive pulmonary disease: COPD as a risk factor for ABPA? Med Mycol. 2010;48(7):988–94. https://doi.org/10.3109/13693781003743148 .
doi: 10.3109/13693781003743148
pubmed: 20370368
Everaerts S, Lagrou K, Dubbeldam A, Lorent N, Vermeersch K, Van Hoeyveld E, et al. Sensitization to Aspergillus fumigatus as a risk factor for bronchiectasis in COPD. Int J Chron Obstruct Pulmon Dis. 2017;12:2629–38. https://doi.org/10.2147/COPD.S141695 .
doi: 10.2147/COPD.S141695
pubmed: 28919731
pmcid: 5587018
Agarwal R, Aggarwal AN, Gupta D, Jindal SK. Aspergillus hypersensitivity and allergic bronchopulmonary aspergillosis in patients with bronchial asthma: systematic review and meta-analysis. Int J Tuberc Lung Dis. 2009;13(8):936–44.
pubmed: 19723372
Tiew PY, Ko FWS, Pang SL, Matta SA, Sio YY, Poh ME, et al. Environmental fungal sensitisation associates with poorer clinical outcomes in COPD. Eur Respir J. 2020. https://doi.org/10.1183/13993003.00418-2020 .
doi: 10.1183/13993003.00418-2020
pubmed: 32341102
pmcid: 7453645
Mac Aogain M, Tiew PY, Lim AYH, Low TB, Tan GL, Hassan T, et al. Distinct “Immunoallertypes” of disease and high frequencies of sensitization in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2019;199(7):842–53. https://doi.org/10.1164/rccm.201807-1355OC .
doi: 10.1164/rccm.201807-1355OC
pubmed: 30265843
Chotirmall SH, Branagan P, Gunaratnam C, McElvaney NG. Aspergillus/allergic bronchopulmonary aspergillosis in an Irish cystic fibrosis population: a diagnostically challenging entity. Respir Care. 2008;53(8):1035–41.
pubmed: 18655741
Gernez Y, Waters J, Mirkovic B, Lavelle GM, Dunn CE, Davies ZA, et al. Blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis. Eur Respir J. 2016;47(1):177–85. https://doi.org/10.1183/13993003.01068-2015 .
doi: 10.1183/13993003.01068-2015
pubmed: 26585435
Coughlan CA, Chotirmall SH, Renwick J, Hassan T, Low TB, Bergsson G, et al. The effect of Aspergillus fumigatus infection on vitamin D receptor expression in cystic fibrosis. Am J Respir Crit Care Med. 2012;186(10):999–1007. https://doi.org/10.1164/rccm.201203-0478OC .
doi: 10.1164/rccm.201203-0478OC
pubmed: 22904183
Shah A, Panjabi C. Allergic aspergillosis of the respiratory tract. Eur Respir Rev. 2014;23(131):8–29. https://doi.org/10.1183/09059180.00007413 .
doi: 10.1183/09059180.00007413
pubmed: 24591658
Wark PA, Gibson PG. Allergic bronchopulmonary aspergillosis: new concepts of pathogenesis and treatment. Respirology. 2001;6(1):1–7. https://doi.org/10.1046/j.1440-1843.2001.00289.x .
doi: 10.1046/j.1440-1843.2001.00289.x
pubmed: 11264756
Poh TY, Mac Aogain M, Chan AK, Yii AC, Yong VF, Tiew PY, et al. Understanding COPD-overlap syndromes. Expert Rev Respir Med. 2017;11(4):285–98. https://doi.org/10.1080/17476348.2017.1305895 .
doi: 10.1080/17476348.2017.1305895
pubmed: 28282995
Denning DW, Cadranel J, Beigelman-Aubry C, Ader F, Chakrabarti A, Blot S, et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J. 2016;47(1):45–68. https://doi.org/10.1183/13993003.00583-2015 .
doi: 10.1183/13993003.00583-2015
pubmed: 26699723
Smith NL, Denning DW. Underlying conditions in chronic pulmonary aspergillosis including simple aspergilloma. Eur Respir J. 2011;37(4):865–72. https://doi.org/10.1183/09031936.00054810 .
doi: 10.1183/09031936.00054810
pubmed: 20595150
Aguilar-Company J, Martin MT, Goterris-Bonet L, Martinez-Marti A, Sampol J, Roldan E, et al. Chronic pulmonary aspergillosis in a tertiary care centre in Spain: a retrospective, observational study. Mycoses. 2019;62(9):765–72. https://doi.org/10.1111/myc.12950 .
doi: 10.1111/myc.12950
pubmed: 31162731
Camara B, Reymond E, Saint-Raymond C, Roth H, Brenier-Pinchart MP, Pinel C, et al. Characteristics and outcomes of chronic pulmonary aspergillosis: a retrospective analysis of a tertiary hospital registry. Clin Respir J. 2015;9(1):65–73. https://doi.org/10.1111/crj.12105 .
doi: 10.1111/crj.12105
pubmed: 24406138
Koyama K, Ohshima N, Suzuki J, Kawashima M, Okuda K, Sato R, et al. Evaluation of clinical characteristics and prognosis of chronic pulmonary aspergillosis depending on the underlying lung diseases: Emphysema vs prior tuberculosis. J Infect Chemother. 2015;21(11):795–801. https://doi.org/10.1016/j.jiac.2015.08.006 .
doi: 10.1016/j.jiac.2015.08.006
pubmed: 26410549
Lowes D, Al-Shair K, Newton PJ, Morris J, Harris C, Rautemaa-Richardson R, et al. Predictors of mortality in chronic pulmonary aspergillosis. Eur Respir J. 2017. https://doi.org/10.1183/13993003.01062-2016 .
doi: 10.1183/13993003.01062-2016
pubmed: 28179437
Xu H, Li L, Huang WJ, Wang LX, Li WF, Yuan WF. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: a case control study from China. Clin Microbiol Infect. 2012;18(4):403–8. https://doi.org/10.1111/j.1469-0691.2011.03503.x .
doi: 10.1111/j.1469-0691.2011.03503.x
pubmed: 22023558
Gao X, Chen L, Hu G, Mei H. Invasive pulmonary aspergillosis in acute exacerbation of chronic obstructive pulmonary disease and the diagnostic value of combined serological tests. Ann Saudi Med. 2010;30(3):193–7. https://doi.org/10.4103/0256-4947.62828 .
doi: 10.4103/0256-4947.62828
pubmed: 20427934
pmcid: 2886868
Garnacho-Montero J, Amaya-Villar R, Ortiz-Leyba C, Leon C, Alvarez-Lerma F, Nolla-Salas J, et al. Isolation of Aspergillus spp. from the respiratory tract in critically ill patients: risk factors clinical presentation and outcome. Crit Care. 2005;9(3):R191-9. https://doi.org/10.1186/cc3488 .
doi: 10.1186/cc3488
pubmed: 15987390
pmcid: 1175876
Ader F, Nseir S, Le Berre R, Leroy S, Tillie-Leblond I, Marquette CH, et al. Invasive pulmonary aspergillosis in chronic obstructive pulmonary disease: an emerging fungal pathogen. Clin Microbiol Infect. 2005;11(6):427–9. https://doi.org/10.1111/j.1469-0691.2005.01143.x .
doi: 10.1111/j.1469-0691.2005.01143.x
pubmed: 15882191
Barberan J, Sanz F, Hernandez JL, Merlos S, Malmierca E, Garcia-Perez FJ, et al. Clinical features of invasive pulmonary aspergillosis vs. colonization in COPD patients distributed by gold stage. J Infect. 2012;65(5):447–52. https://doi.org/10.1016/j.jinf.2012.07.006 .
doi: 10.1016/j.jinf.2012.07.006
pubmed: 22863904
Meersseman W, Vandecasteele SJ, Wilmer A, Verbeken E, Peetermans WE, Van Wijngaerden E. Invasive aspergillosis in critically ill patients without malignancy. Am J Respir Crit Care Med. 2004;170(6):621–5. https://doi.org/10.1164/rccm.200401-093OC .
doi: 10.1164/rccm.200401-093OC
pubmed: 15229094
Bulpa PA, Dive AM, Garrino MG, Delos MA, Gonzalez MR, Evrard PA, et al. Chronic obstructive pulmonary disease patients with invasive pulmonary aspergillosis: benefits of intensive care? Intensive Care Med. 2001;27(1):59–67. https://doi.org/10.1007/s001340000768 .
doi: 10.1007/s001340000768
pubmed: 11280674
Morris A, Sciurba FC, Lebedeva IP, Githaiga A, Elliott WM, Hogg JC, et al. Association of chronic obstructive pulmonary disease severity and Pneumocystis colonization. Am J Respir Crit Care Med. 2004;170(4):408–13. https://doi.org/10.1164/rccm.200401-094OC .
doi: 10.1164/rccm.200401-094OC
pubmed: 15117741
Xue T, Ma Z, Liu F, Du W, He L, Wang J, et al. Pneumocystis jirovecii colonization and its association with pulmonary diseases: a multicenter study based on a modified loop-mediated isothermal amplification assay. BMC Pulm Med. 2020;20(1):70. https://doi.org/10.1186/s12890-020-1111-4 .
doi: 10.1186/s12890-020-1111-4
pubmed: 32197601
pmcid: 7085144
Cui L, Lucht L, Tipton L, Rogers MB, Fitch A, Kessinger C, et al. Topographic diversity of the respiratory tract mycobiome and alteration in HIV and lung disease. Am J Respir Crit Care Med. 2015;191(8):932–42. https://doi.org/10.1164/rccm.201409-1583OC .
doi: 10.1164/rccm.201409-1583OC
pubmed: 25603113
pmcid: 4435454
Fitzpatrick ME, Tedrow JR, Hillenbrand ME, Lucht L, Richards T, Norris KA, et al. Pneumocystis jirovecii colonization is associated with enhanced Th1 inflammatory gene expression in lungs of humans with chronic obstructive pulmonary disease. Microbiol Immunol. 2014;58(3):202–11. https://doi.org/10.1111/1348-0421.12135 .
doi: 10.1111/1348-0421.12135
pubmed: 24438206
pmcid: 4106795
Calderon EJ, Rivero L, Respaldiza N, Morilla R, Montes-Cano MA, Friaza V, et al. Systemic inflammation in patients with chronic obstructive pulmonary disease who are colonized with Pneumocystis jiroveci. Clin Infect Dis. 2007;45(2):e17–9. https://doi.org/10.1086/518989 .
doi: 10.1086/518989
pubmed: 17578770
Agarwal K, Gaur SN, Chowdhary A. The role of fungal sensitisation in clinical presentation in patients with chronic obstructive pulmonary disease. Mycoses. 2015;58(9):531–5. https://doi.org/10.1111/myc.12352 .
doi: 10.1111/myc.12352
pubmed: 26201384
Latge JP. Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev. 1999;12(2):310–50.
doi: 10.1128/CMR.12.2.310
van de Veerdonk FL, Gresnigt MS, Romani L, Netea MG, Latge JP. Aspergillus fumigatus morphology and dynamic host interactions. Nat Rev Microbiol. 2017;15(11):661–74. https://doi.org/10.1038/nrmicro.2017.90 .
doi: 10.1038/nrmicro.2017.90
pubmed: 28919635
Chotirmall SH, Mirkovic B, Lavelle GM, McElvaney NG. Immunoevasive Aspergillus virulence factors. Mycopathologia. 2014;178(5–6):363–70. https://doi.org/10.1007/s11046-014-9768-y .
doi: 10.1007/s11046-014-9768-y
pubmed: 24972669
Knutsen AP, Bush RK, Demain JG, Denning DW, Dixit A, Fairs A, et al. Fungi and allergic lower respiratory tract diseases. J Allergy Clin Immunol. 2012. https://doi.org/10.1016/j.jaci.2011.12.970 .
doi: 10.1016/j.jaci.2011.12.970
pubmed: 22284927
McMahon MA, Chotirmall SH, McCullagh B, Branagan P, McElvaney NG, Logan PM. Radiological abnormalities associated with Aspergillus colonization in a cystic fibrosis population. Eur J Radiol. 2012;81(3):e197-202. https://doi.org/10.1016/j.ejrad.2011.01.114 .
doi: 10.1016/j.ejrad.2011.01.114
pubmed: 21349668
Mac Aogain M, Chandrasekaran R, Lim AYH, Low TB, Tan GL, Hassan T, et al. Immunological corollary of the pulmonary mycobiome in bronchiectasis: the CAMEB study. Eur Respir J. 2018. https://doi.org/10.1183/13993003.00766-2018 .
doi: 10.1183/13993003.00766-2018
pubmed: 29880655
pmcid: 6092680
Poh TY, Tiew PY, Lim AYH, Thng KX, Binte Mohamed Ali NA, Narayana JK, et al. Increased chitotriosidase is associated with Aspergillus and frequent exacerbations in South-East Asian patients with bronchiectasis. Chest. 2020;158(2):512–22. https://doi.org/10.1016/j.chest.2020.02.048 .
doi: 10.1016/j.chest.2020.02.048
pubmed: 32184111
Hector A, Chotirmall SH, Lavelle GM, Mirkovic B, Horan D, Eichler L, et al. Chitinase activation in patients with fungus-associated cystic fibrosis lung disease. J Allergy Clin Immunol. 2016;138(4):1183-9e4. https://doi.org/10.1016/j.jaci.2016.01.031 .
doi: 10.1016/j.jaci.2016.01.031
pubmed: 27056270
de Vrankrijker AM, van der Ent CK, van Berkhout FT, Stellato RK, Willems RJ, Bonten MJ, et al. Aspergillus fumigatus colonization in cystic fibrosis: implications for lung function? Clin Microbiol Infect. 2011;17(9):1381–6. https://doi.org/10.1111/j.1469-0691.2010.03429.x .
doi: 10.1111/j.1469-0691.2010.03429.x
pubmed: 21087348
Romani L. Immunity to fungal infections. Nat Rev Immunol. 2011;11(4):275–88. https://doi.org/10.1038/nri2939 .
doi: 10.1038/nri2939
pubmed: 21394104
Máiz L, Vendrell M, Olveira C, Girón R, Nieto R, Martínez-García M. Prevalence and factors associated with isolation of Aspergillus and Candida from sputum in patients with non-cystic fibrosis bronchiectasis. Respiration. 2015;89(5):396–403. https://doi.org/10.1159/000381289 .
doi: 10.1159/000381289
pubmed: 25924628
Chalmers JD, Moffitt KL, Suarez-Cuartin G, Sibila O, Finch S, Furrie E, et al. Neutrophil elastase activity is associated with exacerbations and lung function decline in bronchiectasis. Am J Respir Crit Care Med. 2017;195(10):1384–93. https://doi.org/10.1164/rccm.201605-1027OC .
doi: 10.1164/rccm.201605-1027OC
pubmed: 27911604
pmcid: 5443898
Angrill J, Agustí C, De Celis R, Filella X, Rañó A, Elena M, et al. Bronchial inflammation and colonization in patients with clinically stable bronchiectasis. Am J Respir Crit Care Med. 2001;164(9):1628–32. https://doi.org/10.1164/ajrccm.164.9.2105083 .
doi: 10.1164/ajrccm.164.9.2105083
pubmed: 11719301
Taylor SL, Rogers GB, Chen AC, Burr LD, McGuckin MA, Serisier DJ. Matrix metalloproteinases vary with airway microbiota composition and lung function in non-cystic fibrosis bronchiectasis. Ann Am Thorac Soc. 2015;12(5):701–7. https://doi.org/10.1513/AnnalsATS.201411-513OC .
doi: 10.1513/AnnalsATS.201411-513OC
pubmed: 25679336
Noverr MC, Noggle RM, Toews GB, Huffnagle GB. Role of antibiotics and fungal microbiota in driving pulmonary allergic responses. Infect Immun. 2004;72(9):4996–5003. https://doi.org/10.1128/iai.72.9.4996-5003.2004 .
doi: 10.1128/iai.72.9.4996-5003.2004
pubmed: 15321991
pmcid: 517468
Bacher P, Hohnstein T, Beerbaum E, Rocker M, Blango MG, Kaufmann S, et al. Human anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans. Cell. 2019;176(6):1340-5515e15.
doi: 10.1016/j.cell.2019.01.041
Goh KJ, Yii ACA, Lapperre TS, Chan AK, Chew FT, Chotirmall SH, et al. Sensitization to Aspergillus species is associated with frequent exacerbations in severe asthma. J Asthma Allergy. 2017;10:131–40. https://doi.org/10.2147/JAA.S130459 .
doi: 10.2147/JAA.S130459
pubmed: 28461762
pmcid: 5407445
Chotirmall SH, McElvaney NG. Fungi in the cystic fibrosis lung: bystanders or pathogens? Int J Biochem Cell Biol. 2014;52:161–73. https://doi.org/10.1016/j.biocel.2014.03.001 .
doi: 10.1016/j.biocel.2014.03.001
pubmed: 24625547
Baxter CG, Moore CB, Jones AM, Webb AK, Denning DW. IgE-mediated immune responses and airway detection of Aspergillus and Candida in adult cystic fibrosis. Chest. 2013;143(5):1351–7. https://doi.org/10.1378/chest.12-1363 .
doi: 10.1378/chest.12-1363
pubmed: 23139075
Amin R, Dupuis A, Aaron SD, Ratjen F. The effect of chronic infection with Aspergillus fumigatus on lung function and hospitalization in patients with cystic fibrosis. Chest. 2010;137(1):171–6. https://doi.org/10.1378/chest.09-1103 .
doi: 10.1378/chest.09-1103
pubmed: 19567494
Murphy MB, Reen DJ, Fitzgerald MX. Atopy, immunological changes, and respiratory function in bronchiectasis. Thorax. 1984;39(3):179–84.
doi: 10.1136/thx.39.3.179
De Soyza A, Aliberti S. Bronchiectasis and Aspergillus: how are they linked? Med Mycol. 2017;55(1):69–81. https://doi.org/10.1093/mmy/myw109 .
doi: 10.1093/mmy/myw109
pubmed: 27794529
Schafer J, Griese M, Chandrasekaran R, Chotirmall SH, Hartl D. Pathogenesis, imaging and clinical characteristics of CF and non-CF bronchiectasis. BMC Pulm Med. 2018;18(1):79. https://doi.org/10.1186/s12890-018-0630-8 .
doi: 10.1186/s12890-018-0630-8
pubmed: 29788954
pmcid: 5964733
Chotirmall SH, Chalmers JD. Bronchiectasis: an emerging global epidemic. BMC Pulm Med. 2018;18(1):76. https://doi.org/10.1186/s12890-018-0629-1 .
doi: 10.1186/s12890-018-0629-1
pubmed: 29788944
pmcid: 5963022
Aksamit TR, O’Donnell AE, Barker A, Olivier KN, Winthrop KL, Daniels MLA, et al. Adult Patients With Bronchiectasis: A First Look at the US Bronchiectasis Research Registry. Chest. 2017;151(5):982–92. https://doi.org/10.1016/j.chest.2016.10.055 .
doi: 10.1016/j.chest.2016.10.055
pubmed: 27889361
Lim AYH, Chotirmall SH, Fok ETK, Verma A, De PP, Goh SK, et al. Profiling non-tuberculous mycobacteria in an Asian setting: characteristics and clinical outcomes of hospitalized patients in Singapore. BMC Pulm Med. 2018;18(1):85. https://doi.org/10.1186/s12890-018-0637-1 .
doi: 10.1186/s12890-018-0637-1
pubmed: 29788943
pmcid: 5964916
Kunst H, Wickremasinghe M, Wells A, Wilson R. Nontuberculous mycobacterial disease and Aspergillus-related lung disease in bronchiectasis. Eur Respir J. 2006;28(2):352–7. https://doi.org/10.1183/09031936.06.00139005 .
doi: 10.1183/09031936.06.00139005
pubmed: 16611651
Kosmidis C, Denning DW. The clinical spectrum of pulmonary aspergillosis. Thorax. 2015;70(3):270–7. https://doi.org/10.1136/thoraxjnl-2014-206291 .
doi: 10.1136/thoraxjnl-2014-206291
pubmed: 25354514
Lowes D, Chishimba L, Greaves M, Denning DW. Development of chronic pulmonary aspergillosis in adult asthmatics with ABPA. Respir Med. 2015;109(12):1509–15. https://doi.org/10.1016/j.rmed.2015.09.007 .
doi: 10.1016/j.rmed.2015.09.007
pubmed: 26507434
McShane PJ, Naureckas ET, Tino G, Strek ME. Non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2013;188(6):647–56. https://doi.org/10.1164/rccm.201303-0411CI .
doi: 10.1164/rccm.201303-0411CI
pubmed: 23898922
Chotirmall SH, McShane PJ. Time to acknowledge, address, and take action against bronchiectasis. Lancet Glob Health. 2019;7(9):e1162–3. https://doi.org/10.1016/S2214-109X(19)30311-0 .
doi: 10.1016/S2214-109X(19)30311-0
pubmed: 31401993
Severiche-Bueno D, Gamboa E, Reyes LF, Chotirmall SH. Hot topics and current controversies in non-cystic fibrosis bronchiectasis. Breathe (Sheff). 2019;15(4):286–95. https://doi.org/10.1183/20734735.0261-2019 .
doi: 10.1183/20734735.0261-2019
Boaventura R, Sibila O, Agusti A, Chalmers JD. Treatable traits in bronchiectasis. Eur Respir J. 2018. https://doi.org/10.1183/13993003.01269-2018 .
doi: 10.1183/13993003.01269-2018
pubmed: 30190263
Chalmers JD, Chotirmall SH. Bronchiectasis: new therapies and new perspectives. Lancet Respir Med. 2018;6(9):715–26. https://doi.org/10.1016/S2213-2600(18)30053-5 .
doi: 10.1016/S2213-2600(18)30053-5
pubmed: 29478908
Vinh DC, Sugui JA, Hsu AP, Freeman AF, Holland SM. Invasive fungal disease in autosomal-dominant hyper-IgE syndrome. J Allergy Clin Immunol. 2010;125(6):1389–90. https://doi.org/10.1016/j.jaci.2010.01.047 .
doi: 10.1016/j.jaci.2010.01.047
pubmed: 20392475
pmcid: 2879472
Kröner C, Neumann J, Ley-Zaporozhan J, Hagl B, Meixner I, Spielberger BD, et al. Lung disease in STAT3 hyper-IgE syndrome requires intense therapy. Allergy. 2019;74(9):1691–702. https://doi.org/10.1111/all.13753 .
doi: 10.1111/all.13753
pubmed: 30793327
Chotirmall SH, O’Donoghue E, Bennett K, Gunaratnam C, O’Neill SJ, McElvaney NG. Sputum Candida albicans presages FEV(1) decline and hospital-treated exacerbations in cystic fibrosis. Chest. 2010;138(5):1186–95. https://doi.org/10.1378/chest.09-2996 .
doi: 10.1378/chest.09-2996
pubmed: 20472859
Máiz L, Nieto R, Cantón R, de la Pedrosa Gómez G, E, Martinez-García M. . Fungi in Bronchiectasis: A Concise Review. Int J Mol Sci. 2018. https://doi.org/10.3390/ijms19010142 .
doi: 10.3390/ijms19010142
pubmed: 29300314
pmcid: 5796091
Chmiel JF, Aksamit TR, Chotirmall SH, Dasenbrook EC, Elborn JS, LiPuma JJ, et al. Antibiotic management of lung infections in cystic fibrosis .II. Nontuberculous mycobacteria, anaerobic bacteria, and fungi. Ann Am Thorac Soc. 2014;11(8):1298–306. https://doi.org/10.1513/AnnalsATS.201405-203AS .
doi: 10.1513/AnnalsATS.201405-203AS
pubmed: 25167882
pmcid: 5469357
Chotirmall SH, Greene CM, McElvaney NG. Candida species in cystic fibrosis: A road less travelled. Med Mycol. 2010;48(Suppl 1):S114–24. https://doi.org/10.3109/13693786.2010.503320 .
doi: 10.3109/13693786.2010.503320
pubmed: 21067323
Chotirmall SH. Candida albicans in cystic fibrosis: “Opening statements presented, let the trial begin.” Pediatr Pulmonol. 2016;51(5):445–6. https://doi.org/10.1002/ppul.23315 .
doi: 10.1002/ppul.23315
pubmed: 26418834
Layeghifard M, Hwang DM, Guttman DS. Disentangling Interactions in the Microbiome: A Network Perspective. Trends Microbiol. 2017;25(3):217–28. https://doi.org/10.1016/j.tim.2016.11.008 .
doi: 10.1016/j.tim.2016.11.008
pubmed: 27916383
Budden KF, Shukla SD, Rehman SF, Bowerman KL, Keely S, Hugenholtz P, et al. Functional effects of the microbiota in chronic respiratory disease. Lancet Respir Med. 2019. https://doi.org/10.1016/s2213-2600(18)30510-1 .
doi: 10.1016/s2213-2600(18)30510-1
pubmed: 30975495
Tiew PY, Mac Aogain M, Ali N, Thng KX, Goh K, Lau KJX, et al. The Mycobiome in Health and Disease: Emerging Concepts. Methodologies and Challenges Mycopathologia. 2020;185(2):207–31. https://doi.org/10.1007/s11046-019-00413-z .
doi: 10.1007/s11046-019-00413-z
pubmed: 31894501
Kozel TR, Wickes B. Fungal diagnostics. Cold Spring Harbor perspectives in medicine. 2014;4(4):a019299. https://doi.org/10.1101/cshperspect.a019299 .
doi: 10.1101/cshperspect.a019299
pubmed: 24692193
pmcid: 3968782
Consortium O, Gabaldon T. Recent trends in molecular diagnostics of yeast infections: from PCR to NGS. FEMS Microbiol Rev. 2019;43(5):517–47. https://doi.org/10.1093/femsre/fuz015 .
doi: 10.1093/femsre/fuz015
Ullmann AJ, Aguado JM, Arikan-Akdagli S, Denning DW, Groll AH, Lagrou K, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018;24(Suppl 1):e1–38. https://doi.org/10.1016/j.cmi.2018.01.002 .
doi: 10.1016/j.cmi.2018.01.002
pubmed: 29544767
Poh TY, Ali N, Chan LLY, Tiew PY, Chotirmall SH. Evaluation of Droplet Digital Polymerase Chain Reaction (ddPCR) for the Absolute Quantification of Aspergillus species in the Human Airway. Int J Mol Sci. 2020. https://doi.org/10.3390/ijms21093043 .
doi: 10.3390/ijms21093043
pubmed: 32443699
pmcid: 7279333
Ali N, Mac Aogain M, Morales RF, Tiew PY, Chotirmall SH. Optimisation and benchmarking of targeted amplicon sequencing for mycobiome analysis of respiratory specimens. Int J Mol Sci. 2019. https://doi.org/10.3390/ijms20204991 .
doi: 10.3390/ijms20204991
pubmed: 31835852
pmcid: 6969939
Mac Aogain M, Lau KJX, Cai Z, Kumar Narayana J, Purbojati RW, Drautz-Moses DI, et al. Metagenomics Reveals a Core Macrolide Resistome Related to Microbiota in Chronic Respiratory Disease. Am J Respir Crit Care Med. 2020;202(3):433–47. https://doi.org/10.1164/rccm.201911-2202OC .
doi: 10.1164/rccm.201911-2202OC
pubmed: 32320621
pmcid: 7397787
Otasevic S, Momcilovic S, Stojanovic NM, Skvarc M, Rajkovic K, Arsic-Arsenijevic V. Non-culture based assays for the detection of fungal pathogens. Journal de mycologie medicale. 2018;28(2):236–48. https://doi.org/10.1016/j.mycmed.2018.03.001 .
doi: 10.1016/j.mycmed.2018.03.001
pubmed: 29605542
pmcid: 7110445
Hage CA, Carmona EM, Epelbaum O, Evans SE, Gabe LM, Haydour Q, et al. Microbiological Laboratory Testing in the Diagnosis of Fungal Infections in Pulmonary and Critical Care Practice. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2019;200(5):535–50.
doi: 10.1164/rccm.201906-1185ST
Yeo SF, Wong B. Current status of nonculture methods for diagnosis of invasive fungal infections. Clin Microbiol Rev. 2002;15(3):465–84. https://doi.org/10.1128/cmr.15.3.465-484.2002 .
doi: 10.1128/cmr.15.3.465-484.2002
pubmed: 12097252
pmcid: 118074
Richardson M, Page I. Role of Serological Tests in the Diagnosis of Mold Infections. Curr Fungal Infect Rep. 2018;12(3):127–36. https://doi.org/10.1007/s12281-018-0321-1 .
doi: 10.1007/s12281-018-0321-1
pubmed: 30294405
pmcid: 6153857
Leeflang MM, Debets-Ossenkopp YJ, Wang J, Visser CE, Scholten RJ, Hooft L, et al. Galactomannan detection for invasive aspergillosis in immunocompromised patients. Cochrane Database Syst Rev. 2015;12:CD007394. https://doi.org/10.1002/14651858.CD007394.pub2 .
doi: 10.1002/14651858.CD007394.pub2
de Heer K, Gerritsen MG, Visser CE, Leeflang MM. Galactomannan detection in broncho-alveolar lavage fluid for invasive aspergillosis in immunocompromised patients. Cochrane Database Syst Rev. 2019;5:CD012399. https://doi.org/10.1002/14651858.CD012399.pub2 .
doi: 10.1002/14651858.CD012399.pub2
pubmed: 31107543
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. https://doi.org/10.1128/JCM.00345-17 .
doi: 10.1128/JCM.00345-17
pubmed: 28446576
pmcid: 5483917
Zhang XB, Chen GP, Lin QC, Lin X, Zhang HY, Wang JH. Bronchoalveolar lavage fluid galactomannan detection for diagnosis of invasive pulmonary aspergillosis in chronic obstructive pulmonary disease. Med Mycol. 2013;51(7):688–95. https://doi.org/10.3109/13693786.2013.777162 .
doi: 10.3109/13693786.2013.777162
pubmed: 23527739
Meersseman W, Lagrou K, Maertens J, Wilmer A, Hermans G, Vanderschueren S, et al. Galactomannan in bronchoalveolar lavage fluid: a tool for diagnosing aspergillosis in intensive care unit patients. Am J Respir Crit Care Med. 2008;177(1):27–34. https://doi.org/10.1164/rccm.200704-606OC .
doi: 10.1164/rccm.200704-606OC
pubmed: 17885264
pmcid: 17885264
Asano-Mori Y, Kanda Y, Oshima K, Kako S, Shinohara A, Nakasone H, et al. False-positive Aspergillus galactomannan antigenaemia after haematopoietic stem cell transplantation. J Antimicrob Chemother. 2008;61(2):411–6. https://doi.org/10.1093/jac/dkm463 .
doi: 10.1093/jac/dkm463
pubmed: 18055488
Cummings JR, Jamison GR, Boudreaux JW, Howles MJ, Walsh TJ, Hayden RT. Cross-reactivity of non-Aspergillus fungal species in the Aspergillus galactomannan enzyme immunoassay. Diagn Microbiol Infect Dis. 2007;59(1):113–5. https://doi.org/10.1016/j.diagmicrobio.2007.04.022 .
doi: 10.1016/j.diagmicrobio.2007.04.022
pubmed: 17662550
Min Z, Baddley JW, Rodriguez JM, Moser SA, Patel M. Cross-reactivity of Aspergillus galactomannan in an HIV-infected patient with histoplasmosis. Med Mycol Case Rep. 2012;1(1):119–22. https://doi.org/10.1016/j.mmcr.2012.10.009 .
doi: 10.1016/j.mmcr.2012.10.009
pubmed: 24371756
pmcid: 3854635
Croxatto A, Prod’hom G, Greub G. Applications of MALDI-TOF mass spectrometry in clinical diagnostic microbiology. FEMS Microbiol Rev. 2012;36(2):380–407. https://doi.org/10.1111/j.1574-6976.2011.00298.x .
doi: 10.1111/j.1574-6976.2011.00298.x
pubmed: 22092265
Palanivel M, Mac Aogain M, Purbojati RW, Uchida A, Aung NW, Lim SBY, et al. Whole-genome sequencing of Aspergillus terreus species complex. Mycopathologia. 2020;185(2):405–8. https://doi.org/10.1007/s11046-020-00433-0 .
doi: 10.1007/s11046-020-00433-0
pubmed: 32108289
Morton CO, White PL, Barnes RA, Klingspor L, Cuenca-Estrella M, Lagrou K, et al. Determining the analytical specificity of PCR-based assays for the diagnosis of IA: what is Aspergillus? Med Mycol. 2017;55(4):402–13. https://doi.org/10.1093/mmy/myw093 .
doi: 10.1093/mmy/myw093
pubmed: 28339744
Mac Aogain M, Chaturvedi V, Chotirmall SH. MycopathologiaGENOMES: the new “home” for the publication of fungal genomes. Mycopathologia. 2019;184(5):551–4. https://doi.org/10.1007/s11046-019-00366-3 .
doi: 10.1007/s11046-019-00366-3
pubmed: 31399887
Mac Aogain M, Lau KJX, Cai Z, Narayana JK, Purbojati RW, Drautz-Moses DI, et al. Metagenomics reveals a core macrolide resistome related to microbiota in chronic respiratory disease. Am J Respir Crit Care Med. 2020. https://doi.org/10.1164/rccm.201911-2202OC .
doi: 10.1164/rccm.201911-2202OC
pubmed: 32320621
pmcid: 7397787
Zhu H, Zhang H, Xu Y, Lassakova S, Korabecna M, Neuzil P. PCR past, present and future. Biotechniques. 2020;69(4):317–25. https://doi.org/10.2144/btn-2020-0057 .
doi: 10.2144/btn-2020-0057
pubmed: 32815744
Patterson TF, Thompson GR 3rd, Denning DW, Fishman JA, Hadley S, Herbrecht R, et al. Practice guidelines for the diagnosis and management of Aspergillosis: 2016 update by the infectious diseases society of America. Clin Infect Dis. 2016;63(4):e1–60. https://doi.org/10.1093/cid/ciw326 .
doi: 10.1093/cid/ciw326
pubmed: 27365388
pmcid: 4967602
Jenks JD, Hoenigl M. Treatment of Aspergillosis. J Fungi (Basel). 2018. https://doi.org/10.3390/jof4030098 .
doi: 10.3390/jof4030098
Fuhren J, Voskuil WS, Boel CH, Haas PJ, Hagen F, Meis JF, et al. High prevalence of azole resistance in Aspergillus fumigatus isolates from high-risk patients. J Antimicrob Chemother. 2015;70(10):2894–8. https://doi.org/10.1093/jac/dkv177 .
doi: 10.1093/jac/dkv177
pubmed: 26163402
Howard SJ, Cerar D, Anderson MJ, Albarrag A, Fisher MC, Pasqualotto AC, et al. Frequency and evolution of Azole resistance in Aspergillus fumigatus associated with treatment failure. Emerg Infect Dis. 2009;15(7):1068–76. https://doi.org/10.3201/eid1507.090043 .
doi: 10.3201/eid1507.090043
pubmed: 19624922
pmcid: 2744247
van der Linden JW, Snelders E, Kampinga GA, Rijnders BJ, Mattsson E, Debets-Ossenkopp YJ, et al. Clinical implications of azole resistance in Aspergillus fumigatus, The Netherlands, 2007–2009. Emerg Infect Dis. 2011;17(10):1846–54. https://doi.org/10.3201/eid1710.110226 .
doi: 10.3201/eid1710.110226
pubmed: 22000354
pmcid: 3311118
Schauwvlieghe A, de Jonge N, van Dijk K, Verweij PE, Bruggemann RJ, Biemond BJ, et al. The diagnosis and treatment of invasive aspergillosis in Dutch haematology units facing a rapidly increasing prevalence of azole-resistance. A nationwide survey and rationale for the DB-MSG 002 study protocol. Mycoses. 2018;61(9):656–64. https://doi.org/10.1111/myc.12788 .
doi: 10.1111/myc.12788
pubmed: 29687483
Chong GM, van der Beek MT, von dem Borne PA, Boelens J, Steel E, Kampinga GA, et al. PCR-based detection of Aspergillus fumigatus Cyp51A mutations on bronchoalveolar lavage: a multicentre validation of the AsperGenius assay(R) in 201 patients with haematological disease suspected for invasive aspergillosis. J Antimicrob Chemother. 2016;71(12):3528–35. https://doi.org/10.1093/jac/dkw323 .
doi: 10.1093/jac/dkw323
pubmed: 27530755
Chotirmall SH, Gellatly SL, Budden KF, Mac Aogain M, Shukla SD, Wood DL, et al. Microbiomes in respiratory health and disease: an Asia-Pacific perspective. Respirology. 2017;22(2):240–50. https://doi.org/10.1111/resp.12971 .
doi: 10.1111/resp.12971
pubmed: 28102970
Tiew PY, Dicker AJ, Keir HR, Poh ME, Pang SL, Mac Aogain M, et al. A high-risk airway mycobiome is associated with frequent exacerbation and mortality in COPD. Eur Respir J. 2020. https://doi.org/10.1183/13993003.02050-2020 .
doi: 10.1183/13993003.02050-2020
pubmed: 32341102
pmcid: 7453645
Tiew PY, Jaggi TK, Chan LLY, Chotirmall SH. The airway microbiome in COPD, bronchiectasis and bronchiectasis-COPD overlap. Clin Respir J. 2020. https://doi.org/10.1111/crj.13294 .
doi: 10.1111/crj.13294
pubmed: 33063421
Binte Mohamed Ali NA, Ivan FX, Aogain MM, Narayana JK, Lee SY, Lim CL, et al. The healthy airway mycobiome in individuals of Asian descent. Chest. 2020. https://doi.org/10.1016/j.chest.2020.09.072 .
doi: 10.1016/j.chest.2020.09.072
pubmed: 32184111
Chotirmall SH, Chang AB. Twenty-five years of respirology: advances in bronchiectasis. Respirology. 2020;25(1):14–6. https://doi.org/10.1111/resp.13738 .
doi: 10.1111/resp.13738
pubmed: 31840891
Su J, Liu HY, Tan XL, Ji Y, Jiang YX, Prabhakar M, et al. Sputum bacterial and fungal dynamics during exacerbations of severe COPD. PLoS ONE. 2015;10(7):e0130736. https://doi.org/10.1371/journal.pone.0130736 .
doi: 10.1371/journal.pone.0130736
pubmed: 26147303
pmcid: 4493005