{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:09:22Z","timestamp":1788368962430,"version":"build-2803163510"},"reference-count":131,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Singapore General Hospital Grant","award":["SRG-OPN-06-2021"],"award-info":[{"award-number":["SRG-OPN-06-2021"]}]},{"name":"Singapore General Hospital Grant","award":["MOH-000710"],"award-info":[{"award-number":["MOH-000710"]}]},{"DOI":"10.13039\/501100001349","name":"Singapore Ministry of Health\u2019s National Medical Research Council","doi-asserted-by":"publisher","award":["SRG-OPN-06-2021"],"award-info":[{"award-number":["SRG-OPN-06-2021"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"Singapore Ministry of Health\u2019s National Medical Research Council","doi-asserted-by":"publisher","award":["MOH-000710"],"award-info":[{"award-number":["MOH-000710"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Pulmonary mycoses remain a global threat, causing significant morbidity and mortality. Patients with airways disease, including COPD and bronchiectasis, are at increased risks of pulmonary mycoses and its associated complications. Frequent use of antibiotics and corticosteroids coupled with impaired host defenses predispose patients to fungal colonization and airway persistence, which are associated with negative clinical consequences. Notably, Aspergillus species remain the best-studied fungal pathogen and induce a broad spectrum of clinical manifestations in COPD and bronchiectasis ranging from colonization and sensitization to more invasive disease. Next-generation sequencing (NGS) has gained prominence in the field of respiratory infection, and in some cases is beginning to act as a viable alternative to traditional culture. NGS has revolutionized our understanding of airway microbiota and in particular fungi. In this context, it permits the identification of the previously unculturable, fungal composition, and dynamic change within microbial communities of the airway, including potential roles in chronic respiratory disease. Furthermore, inter-kingdom microbial interactions, including fungi, in conjunction with host immunity have recently been shown to have important clinical roles in COPD and bronchiectasis. In this review, we provide an overview of clinical Aspergillus signatures in COPD and bronchiectasis and cover the current advances in the understanding of the mycobiome in these disease states. The challenges and limitations of NGS will be addressed.<\/jats:p>","DOI":"10.3390\/jof8050480","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T02:46:39Z","timestamp":1651805199000},"page":"480","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Clinical Aspergillus Signatures in COPD and Bronchiectasis"],"prefix":"10.3390","volume":"8","author":[{"given":"Pei Yee","family":"Tiew","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore 168753, Singapore"},{"name":"Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai Xian","family":"Thng","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0417-7607","authenticated-orcid":false,"given":"Sanjay H.","family":"Chotirmall","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore"},{"name":"Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41572-018-0042-3","article-title":"Bronchiectasis","volume":"4","author":"Chalmers","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1111\/resp.13032","article-title":"The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD","volume":"22","author":"Leung","year":"2017","journal-title":"Respirology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1183\/09031936.00081409","article-title":"Infection as a comorbidity of COPD","volume":"35","author":"Sethi","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2147\/JAA.S130459","article-title":"Sensitization to Aspergillus species is associated with frequent exacerbations in severe asthma","volume":"10","author":"Goh","year":"2017","journal-title":"J. Asthma Allergy"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s11046-021-00539-z","article-title":"Respiratory Mycoses in COPD and Bronchiectasis","volume":"186","author":"Tiew","year":"2021","journal-title":"Mycopathologia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1055\/s-0041-1730947","article-title":"Aspergillus-Associated Endophenotypes in Bronchiectasis","volume":"42","author":"Jaggi","year":"2021","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3389\/fmicb.2015.00089","article-title":"The lung mycobiome: An emerging field of the human respiratory microbiome","volume":"6","author":"Nguyen","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1800766","DOI":"10.1183\/13993003.00766-2018","article-title":"Immunological corollary of the pulmonary mycobiome in bronchiectasis: The CAMEB study","volume":"52","author":"Chandrasekaran","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/s41591-021-01289-7","article-title":"Integrative microbiomics in bronchiectasis exacerbations","volume":"27","author":"Narayana","year":"2021","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20020502002050","DOI":"10.1183\/13993003.02050-2020","article-title":"A high-risk airway mycobiome is associated with frequent exacerbation and mortality in COPD","volume":"57","author":"Tiew","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1183\/13993003.01888-2015","article-title":"Research priorities in bronchiectasis: A consensus statement from the EMBARC Clinical Research Collaboration","volume":"48","author":"Aliberti","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s11046-021-00589-3","article-title":"Respiratory Mycoses: A Call to Action to Recognize, Educate and Invest","volume":"186","author":"Shah","year":"2021","journal-title":"Mycopathologia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/2045-7022-4-14","article-title":"Fungal allergy in asthma-state of the art and research needs","volume":"4","author":"Denning","year":"2014","journal-title":"Clin. Transl. Allergy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S207","DOI":"10.1080\/13693780600857348","article-title":"Fungal pneumonia, chronic respiratory diseases and glucocorticoids","volume":"44","author":"Agusti","year":"2006","journal-title":"Med. Mycol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"832510","DOI":"10.3389\/fmed.2022.832510","article-title":"Recent Advances in Fungal Infections: From Lung Ecology to Therapeutic Strategies With a Focus on Aspergillus spp.","volume":"9","author":"Palmieri","year":"2022","journal-title":"Front. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s11046-017-0143-7","article-title":"Aspergillus Species in Bronchiectasis: Challenges in the Cystic Fibrosis and Non-cystic Fibrosis Airways","volume":"183","author":"Chotirmall","year":"2018","journal-title":"Mycopathologia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"723129","DOI":"10.1155\/2013\/723129","article-title":"Aspergillus-associated airway disease, inflammation, and the innate immune response","volume":"2013","author":"Chotirmall","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"23299","DOI":"10.1073\/pnas.1908493116","article-title":"Microbial communities in the tropical air ecosystem follow a precise diel cycle","volume":"116","author":"Gusareva","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/MCP.0000000000000850","article-title":"The current understanding and future directions for sputum microbiome profiling in chronic obstructive pulmonary disease","volume":"28","author":"Tiew","year":"2022","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"127","DOI":"10.2741\/s477","article-title":"The emergence of Aspergillus species in chronic respiratory disease","volume":"9","author":"Yii","year":"2017","journal-title":"Front. Biosci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Chandrasekaran, R., Mac Aogain, M., Chalmers, J.D., Elborn, S.J., and Chotirmall, S.H. (2018). Geographic variation in the aetiology, epidemiology and microbiology of bronchiectasis. BMC Pulm. Med., 18.","DOI":"10.1186\/s12890-018-0638-0"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1080\/00016480410018133","article-title":"Comparison between polymerase chain reaction and fungal culture for the detection of fungi in patients with chronic sinusitis and normal controls","volume":"125","author":"Kim","year":"2005","journal-title":"Acta Otolaryngol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.trsl.2012.02.005","article-title":"The microbiome of the lung","volume":"160","author":"Beck","year":"2012","journal-title":"Transl. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/S2213-2600(18)30510-1","article-title":"Functional effects of the microbiota in chronic respiratory disease","volume":"7","author":"Budden","year":"2019","journal-title":"Lancet Respir. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/crj.13294","article-title":"The airway microbiome in COPD, bronchiectasis and bronchiectasis-COPD overlap","volume":"15","author":"Tiew","year":"2021","journal-title":"Clin. Respir. J."},{"key":"ref_26","first-page":"207","article-title":"The Mycobiome in Health and Disease: Emerging Concepts, Methodologies and Challenges","volume":"185","author":"Tiew","year":"2020","journal-title":"Mycopathologia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1164\/rccm.201409-1583OC","article-title":"Topographic diversity of the respiratory tract mycobiome and alteration in HIV and lung disease","volume":"191","author":"Cui","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Su, J., Liu, H.-Y., Tan, X.-L., Ji, Y., Jiang, Y.-X., Prabhakar, M., Rong, Z.-H., Zhou, H.-W., and Zhang, G.-X. (2015). Sputum Bacterial and Fungal Dynamics during Exacerbations of Severe COPD. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130736"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.3389\/fmicb.2017.01163","article-title":"Oropharyngeal and Sputum Microbiomes Are Similar Following Exacerbation of Chronic Obstructive Pulmonary Disease","volume":"8","author":"Liu","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s11046-014-9768-y","article-title":"Immunoevasive Aspergillus virulence factors","volume":"178","author":"Chotirmall","year":"2014","journal-title":"Mycopathologia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1164\/rccm.201203-0478OC","article-title":"The effect of Aspergillus fumigatus infection on vitamin D receptor expression in cystic fibrosis","volume":"186","author":"Coughlan","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e197","DOI":"10.1016\/j.ejrad.2011.01.114","article-title":"Radiological abnormalities associated with Aspergillus colonization in a cystic fibrosis population","volume":"81","author":"McMahon","year":"2012","journal-title":"Eur. J. Radiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1111\/resp.12971","article-title":"Microbiomes in respiratory health and disease: An Asia-Pacific perspective","volume":"22","author":"Chotirmall","year":"2017","journal-title":"Respirology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/S2213-2600(18)30053-5","article-title":"Bronchiectasis: New therapies and new perspectives","volume":"6","author":"Chalmers","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.chest.2020.09.072","article-title":"The Healthy Airway Mycobiome in Individuals of Asian Descent","volume":"159","author":"Ali","year":"2021","journal-title":"Chest"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2000418","DOI":"10.1183\/13993003.00418-2020","article-title":"Environmental fungal sensitisation associates with poorer clinical outcomes in COPD","volume":"56","author":"Tiew","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1164\/rccm.201807-1355OC","article-title":"Distinct \u201cImmunoallertypes\u201d of Disease and High Frequencies of Sensitization in Non-Cystic Fibrosis Bronchiectasis","volume":"199","author":"Tiew","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1702444","DOI":"10.1183\/13993003.02444-2017","article-title":"RESPIRE: Breathing new life into bronchiectasis","volume":"51","author":"Chotirmall","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1183\/13993003.01068-2015","article-title":"Blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis","volume":"47","author":"Gernez","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.jaci.2015.07.045","article-title":"The basophil surface marker CD203c identifies Aspergillus species sensitization in patients with cystic fibrosis","volume":"137","author":"Mirkovic","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/j.jaci.2016.01.031","article-title":"Chitinase activation in patients with fungus-associated cystic fibrosis lung disease","volume":"138","author":"Hector","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.chest.2020.02.048","article-title":"Increased Chitotriosidase Is Associated with Aspergillus and Frequent Exacerbations in South-East Asians with Bronchiectasis","volume":"158","author":"Poh","year":"2020","journal-title":"Chest"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ccm.2021.11.002","article-title":"Microbiology and the Microbiome in Bronchiectasis","volume":"43","author":"Chotirmall","year":"2022","journal-title":"Clin. Chest Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1080\/17476348.2017.1305895","article-title":"Understanding COPD-overlap syndromes","volume":"11","author":"Poh","year":"2017","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.chest.2021.07.2165","article-title":"High Frequency of Allergic Bronchopulmonary Aspergillosis in Bronchiectasis-COPD Overlap","volume":"161","author":"Tiew","year":"2022","journal-title":"Chest"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.arbres.2021.08.003","article-title":"The Airway Microbiome: Present and Future Applications","volume":"58","author":"Aogain","year":"2022","journal-title":"Arch Bronconeumol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2101016","DOI":"10.1183\/13993003.01016-2021","article-title":"Similarity network fusion for the integration of multi-omics and microbiomes in respiratory disease","volume":"58","author":"Narayana","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6272","DOI":"10.1016\/j.csbj.2021.11.029","article-title":"Mathematical-based microbiome analytics for clinical translation","volume":"19","author":"Narayana","year":"2021","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"a019299","DOI":"10.1101\/cshperspect.a019299","article-title":"Fungal diagnostics","volume":"4","author":"Kozel","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.cmi.2018.01.002","article-title":"Diagnosis and management of Aspergillus diseases: Executive summary of the 2017 ESCMID-ECMM-ERS guideline","volume":"24","author":"Ullmann","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1128\/JCM.00345-17","article-title":"Diagnostic Value of Galactomannan Antigen Test in Serum and Bronchoalveolar Lavage Fluid Samples from Patients with Nonneutropenic Invasive Pulmonary Aspergillosis","volume":"55","author":"Zhou","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"688","DOI":"10.3109\/13693786.2013.777162","article-title":"Bronchoalveolar lavage fluid galactomannan detection for diagnosis of invasive pulmonary aspergillosis in chronic obstructive pulmonary disease","volume":"51","author":"Zhang","year":"2013","journal-title":"Med. Mycol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1164\/rccm.200704-606OC","article-title":"Galactomannan in bronchoalveolar lavage fluid: A tool for diagnosing aspergillosis in intensive care unit patients","volume":"177","author":"Meersseman","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s12281-018-0321-1","article-title":"Role of Serological Tests in the Diagnosis of Mold Infections","volume":"12","author":"Richardson","year":"2018","journal-title":"Curr. Fungal Infect. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.mycmed.2018.03.001","article-title":"Non-culture based assays for the detection of fungal pathogens","volume":"28","author":"Otasevic","year":"2018","journal-title":"J. Mycol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1309\/EXBVYAUPENBM285Y","article-title":"Diagnosis of invasive septate mold infections. A correlation of microbiological culture and histologic or cytologic examination","volume":"119","author":"Tarrand","year":"2003","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1093\/femsre\/fuz015","article-title":"Recent trends in molecular diagnostics of yeast infections: From PCR to NGS","volume":"43","year":"2019","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/j.1574-6976.2011.00298.x","article-title":"Applications of MALDI-TOF mass spectrometry in clinical diagnostic microbiology","volume":"36","author":"Croxatto","year":"2012","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s11046-020-00433-0","article-title":"Whole-Genome Sequencing of Aspergillus terreus Species Complex","volume":"185","author":"Palanivel","year":"2020","journal-title":"Mycopathologia"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Tsang, C.-C., Teng, J.L.L., Lau, S.K.P., and Woo, P.C.Y. (2021). Rapid Genomic Diagnosis of Fungal Infections in the Age of Next-Generation Sequencing. J. Fungi, 7.","DOI":"10.3390\/jof7080636"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41579-018-0116-y","article-title":"Mycobiome diversity: High-throughput sequencing and identification of fungi","volume":"17","author":"Nilsson","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1093\/femsre\/fuw047","article-title":"Forgotten fungi\u2014the gut mycobiome in human health and disease","volume":"41","author":"Huseyin","year":"2017","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1128\/AEM.03870-12","article-title":"Improved selection of internal transcribed spacer-specific primers enables quantitative, ultra-high-throughput profiling of fungal communities","volume":"79","author":"Bokulich","year":"2013","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6241","DOI":"10.1073\/pnas.1117018109","article-title":"Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi","volume":"109","author":"Schoch","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00253-010-2585-4","article-title":"Current state and perspectives of fungal DNA barcoding and rapid identification procedures","volume":"87","author":"Begerow","year":"2010","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Bellemain, E., Carlsen, T., Brochmann, C., Coissac, E., Taberlet, P., and Kauserud, H. (2010). ITS as an environmental DNA barcode for fungi: An in silico approach reveals potential PCR biases. BMC Microbiol., 10.","DOI":"10.1186\/1471-2180-10-189"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Ali, N., Mac Aogain, M., Morales, R.F., Tiew, P.Y., and Chotirmall, S.H. (2019). Optimisation and Benchmarking of Targeted Amplicon Sequencing for Mycobiome Analysis of Respiratory Specimens. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20204991"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Angebault, C., Payen, M., Woerther, P.L., Rodriguez, C., and Botterel, F. (2020). Combined bacterial and fungal targeted amplicon sequencing of respiratory samples: Does the DNA extraction method matter?. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232215"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Op De Beeck, M., Lievens, B., Busschaert, P., Declerck, S., Vangronsveld, J., and Colpaert, J.V. (2014). Comparison and validation of some ITS primer pairs useful for fungal metabarcoding studies. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097629"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1111\/1758-2229.12438","article-title":"Fungal identification biases in microbiome projects","volume":"8","author":"Tedersoo","year":"2016","journal-title":"Environ. Microbiol. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1111\/j.1574-6941.2012.01437.x","article-title":"New primers to amplify the fungal ITS2 region\u2014Evaluation by 454-sequencing of artificial and natural communities","volume":"82","author":"Ihrmark","year":"2012","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"S231","DOI":"10.1093\/cid\/ciy693","article-title":"Microbiological Diagnostic Performance of Metagenomic Next-generation Sequencing When Applied to Clinical Practice","volume":"67","author":"Miao","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Wang, J., Han, Y., and Feng, J. (2019). Metagenomic next-generation sequencing for mixed pulmonary infection diagnosis. BMC Pulm. Med., 19.","DOI":"10.1186\/s12890-019-1022-4"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Diao, Z., Han, D., Zhang, R., and Li, J. (2021). Metagenomics next-generation sequencing tests take the stage in the diagnosis of lower respiratory tract infections. J. Adv. Res., in press.","DOI":"10.1016\/j.jare.2021.09.012"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A Novel Coronavirus from Patients with Pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"567","DOI":"10.2147\/IDR.S235182","article-title":"Metagenomic Next-Generation Sequencing versus Traditional Pathogen Detection in the Diagnosis of Peripheral Pulmonary Infectious Lesions","volume":"13","author":"Huang","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nature08821","article-title":"A human gut microbial gene catalogue established by metagenomic sequencing","volume":"464","author":"Qin","year":"2010","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/nbt.3935","article-title":"Shotgun metagenomics, from sampling to analysis","volume":"35","author":"Quince","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/s40168-017-0373-4","article-title":"The gut mycobiome of the Human Microbiome Project healthy cohort","volume":"5","author":"Nash","year":"2017","journal-title":"Microbiome"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1002\/bies.20441","article-title":"The structure and synthesis of the fungal cell wall","volume":"28","author":"Bowman","year":"2006","journal-title":"Bioessays"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s12223-011-0069-2","article-title":"Comparative study of fungal cell disruption--scope and limitations of the methods","volume":"56","author":"Lejczak","year":"2011","journal-title":"Folia Microbiol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Angebault, C., Ghozlane, A., Volant, S., Botterel, F., d\u2019Enfert, C., and Bougnoux, M.-E. (2018). Combined bacterial and fungal intestinal microbiota analyses: Impact of storage conditions and DNA extraction protocols. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201174"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1038\/s41598-018-38049-6","article-title":"Evaluation of Oral Cavity DNA Extraction Methods on Bacterial and Fungal Microbiota","volume":"9","author":"Rosenbaum","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1080\/21505594.2016.1235671","article-title":"The lung mycobiome in the next-generation sequencing era","volume":"8","author":"Tipton","year":"2017","journal-title":"Virulence"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1186\/s13059-014-0487-y","article-title":"Improved characterization of medically relevant fungi in the human respiratory tract using next-generation sequencing","volume":"15","author":"Bittinger","year":"2014","journal-title":"Genome Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e150473","DOI":"10.1172\/JCI150473","article-title":"The lung microbiome: Progress and promise","volume":"131","author":"Whiteside","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.3389\/fmicb.2017.01432","article-title":"The Fungal Frontier: A Comparative Analysis of Methods Used in the Study of the Human Gut Mycobiome","volume":"8","author":"Huseyin","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1046\/j.1365-280X.1998.00161.x","article-title":"Comparison of six extraction techniques for isolation of DNA from filamentous fungi","volume":"36","author":"Schreckhise","year":"1998","journal-title":"Med. Mycol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Goig, G.A., Blanco, S., Garcia-Basteiro, A.L., and Comas, I. (2020). Contaminant DNA in bacterial sequencing experiments is a major source of false genetic variability. BMC Biol., 18.","DOI":"10.1186\/s12915-020-0748-z"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s13059-020-1935-5","article-title":"Opportunities and challenges in long-read sequencing data analysis","volume":"21","author":"Amarasinghe","year":"2020","journal-title":"Genome Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1128\/CMR.00056-16","article-title":"Navigating Microbiological Food Safety in the Era of Whole-Genome Sequencing","volume":"29","author":"Ronholm","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s11046-019-00366-3","article-title":"MycopathologiaGENOMES: The New \u2018Home\u2019 for the Publication of Fungal Genomes","volume":"184","author":"Chaturvedi","year":"2019","journal-title":"Mycopathologia"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.funeco.2015.01.006","article-title":"Fungi inhabiting the healthy human gastrointestinal tract: A diverse and dynamic community","volume":"15","author":"Kachman","year":"2015","journal-title":"Fungal Ecol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.simyco.2018.05.001","article-title":"Large-scale generation and analysis of filamentous fungal DNA barcodes boosts coverage for kingdom fungi and reveals thresholds for fungal species and higher taxon delimitation","volume":"92","author":"Vu","year":"2019","journal-title":"Stud. Mycol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Donovan, P.D., Gonzalez, G., Higgins, D.G., Butler, G., and Ito, K. (2018). Identification of fungi in shotgun metagenomics datasets. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192898"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Hilty, M., Burke, C., Pedro, H., Cardenas, P., Bush, A., Bossley, C., Davies, J., Ervine, A., Poulter, L., and Pachter, L. (2010). Disordered microbial communities in asthmatic airways. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008578"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1111\/cea.13722","article-title":"The airway fungal microbiome in asthma","volume":"50","author":"Rick","year":"2020","journal-title":"Clin. Exp. Allergy"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1164\/rccm.201204-0693OC","article-title":"Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant","volume":"186","author":"Charlson","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12879-019-3718-8","article-title":"A survey of fungal microbiota in airways of healthy volunteer subjects from Puglia (Apulia), Italy","volume":"19","author":"Carpagnano","year":"2019","journal-title":"BMC Infect. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Ghannoum, M.A., Jurevic, R.J., Mukherjee, P.K., Cui, F., Sikaroodi, M., Naqvi, A., and Gillevet, P.M. (2010). Characterization of the oral fungal microbiome (mycobiome) in healthy individuals. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000713"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Krause, R., Halwachs, B., Thallinger, G.G., Klymiuk, I., Gorkiewicz, G., Hoenigl, M., Prattes, J., Valentin, T., Heidrich, K., and Buzina, W. (2016). Characterisation of Candida within the mycobiome\/microbiome of the lower respiratory tract of ICU patients. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155033"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1056\/NEJMra0800353","article-title":"Infection in the pathogenesis and course of chronic obstructive pulmonary disease","volume":"359","author":"Sethi","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1183\/09031936.00162912","article-title":"Aspergillus fumigatus during stable state and exacerbations of COPD","volume":"43","author":"Bafadhel","year":"2014","journal-title":"Eur. Respir. J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1111\/j.1469-0691.2009.03015.x","article-title":"Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: Incidence, risk factors, and outcome","volume":"16","author":"Guinea","year":"2010","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2002223","DOI":"10.1183\/13993003.02223-2020","article-title":"The contribution of Aspergillus fumigatus to COPD exacerbations: A \u201csensitive\u201d topic","volume":"56","author":"Connell","year":"2020","journal-title":"Eur. Respiratory Soc."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Martinsen, E.M., Eagan, T.M., Leiten, E.O., Haaland, I., Huseb\u00f8, G.R., Knudsen, K.S., Drengenes, C., Sanseverino, W., Paytuv\u00ed-Gallart, A., and Nielsen, R. (2021). The pulmonary mycobiome\u2014A study of subjects with and without chronic obstructive pulmonary disease. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0248967"},{"key":"ref_107","first-page":"2177884","article-title":"Different Airway Inflammatory Phenotypes Correlate with Specific Fungal and Bacterial Microbiota in Asthma and Chronic Obstructive Pulmonary Disease","volume":"2022","author":"Yang","year":"2022","journal-title":"J. Immunol. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/S0140-6736(18)31767-7","article-title":"Advances in bronchiectasis: Endotyping, genetics, microbiome, and disease heterogeneity","volume":"392","author":"Flume","year":"2018","journal-title":"Lancet"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Chotirmall, S.H., and Chalmers, J.D. (2018). Bronchiectasis: An emerging global epidemic. BMC Pulm. Med., 18.","DOI":"10.1186\/s12890-018-0629-1"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"190048","DOI":"10.1183\/16000617.0048-2019","article-title":"The microbiome in bronchiectasis","volume":"28","author":"Richardson","year":"2019","journal-title":"Eur. Respir. Rev."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/S2213-2600(20)30557-9","article-title":"The sputum microbiome and clinical outcomes in patients with bronchiectasis: A prospective observational study","volume":"9","author":"Dicker","year":"2021","journal-title":"Lancet Respir. Med."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Al Shakirchi, M., Sorjonen, K., Klingspor, L., Bergman, P., Hjelte, L., and de Monestrol, I. (2021). The Effects of Aspergillus fumigatus Colonization on Lung Function in Patients with Cystic Fibrosis. J. Fungi, 7.","DOI":"10.3390\/jof7110944"},{"key":"ref_113","first-page":"1035","article-title":"Aspergillus\/allergic bronchopulmonary aspergillosis in an Irish cystic fibrosis population: A diagnostically challenging entity","volume":"53","author":"Chotirmall","year":"2008","journal-title":"Respir. Care"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/ppul.23315","article-title":"Candida albicans in cystic fibrosis: \u201cOpening statements presented, let the trial begin\u201d","volume":"51","author":"Chotirmall","year":"2016","journal-title":"Pediatr. Pulmonol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.biocel.2014.03.001","article-title":"Fungi in the cystic fibrosis lung: Bystanders or pathogens?","volume":"52","author":"Chotirmall","year":"2014","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jcf.2020.05.013","article-title":"The fungal airway microbiome in cystic fibrosis and non-cystic fibrosis bronchiectasis","volume":"20","author":"Cuthbertson","year":"2021","journal-title":"J. Cyst. Fibros."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature05746","article-title":"Chitin induces accumulation in tissue of innate immune cells associated with allergy","volume":"447","author":"Reese","year":"2007","journal-title":"Nature"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"5499","DOI":"10.4049\/jimmunol.168.11.5499","article-title":"A rational strategy to design multiepitope immunogens based on multiple Th lymphocyte epitopes","volume":"168","author":"Livingston","year":"2002","journal-title":"J. Immunol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1165\/rcmb.2011-0054OC","article-title":"Fungal allergen \u03b2-glucans trigger p38 mitogen-activated protein kinase\u2013mediated IL-6 translation in lung epithelial cells","volume":"45","author":"Neveu","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3266","DOI":"10.1128\/iai.63.9.3266-3271.1995","article-title":"Purification and characterization of factors produced by Aspergillus fumigatus which affect human ciliated respiratory epithelium","volume":"63","author":"Amitani","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.4049\/jimmunol.1300748","article-title":"The rodA hydrophobin on Aspergillus fumigatus spores masks dectin-1\u2013and dectin-2\u2013dependent responses and enhances fungal survival in vivo","volume":"191","author":"Leal","year":"2013","journal-title":"J. Immunol."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Oosthuizen, J.L., Gomez, P., Ruan, J., Hackett, T.L., Moore, M.M., Knight, D.A., and Tebbutt, S.J. (2011). Dual organism transcriptomics of airway epithelial cells interacting with conidia of Aspergillus fumigatus. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020527"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"M\u00e1iz, L., Nieto, R., Cant\u00f3n, R., G\u00f3mez, G., and Martinez-Garc\u00eda, M.\u00c1. (2018). Fungi in bronchiectasis: A concise review. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010142"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Poh, T.Y., Ali, N., Chan, L.L.Y., Tiew, P.Y., and Chotirmall, S.H. (2020). Evaluation of Droplet Digital Polymerase Chain Reaction (ddPCR) for the Absolute Quantification of Aspergillus species in the Human Airway. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093043"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1513\/AnnalsATS.201310-335OC","article-title":"A novel microbiota stratification system predicts future exacerbations in bronchiectasis","volume":"11","author":"Rogers","year":"2014","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1164\/rccm.201210-1937OC","article-title":"Lung microbiota and bacterial abundance in patients with bronchiectasis when clinically stable and during exacerbation","volume":"187","author":"Tunney","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1136\/thoraxjnl-2012-203105","article-title":"Clinical measures of disease in adult non-CF bronchiectasis correlate with airway microbiota composition","volume":"68","author":"Rogers","year":"2013","journal-title":"Thorax"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1159\/000381289","article-title":"Prevalence and factors associated with isolation of Aspergillus and Candida from sputum in patients with non-cystic fibrosis bronchiectasis","volume":"89","author":"Maiz","year":"2015","journal-title":"Respiration"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Skalski, J.H., Limon, J.J., Sharma, P., Gargus, M.D., Nguyen, C., Tang, J., Coelho, A.L., Hogaboam, C.M., Crother, T.R., and Underhill, D.M. (2018). Expansion of commensal fungus Wallemia mellicola in the gastrointestinal mycobiota enhances the severity of allergic airway disease in mice. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007260"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.chom.2018.11.003","article-title":"Response to Fungal Dysbiosis by Gut-Resident CX3CR1(+) Mononuclear Phagocytes Aggravates Allergic Airway Disease","volume":"24","author":"Li","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"4996","DOI":"10.1128\/IAI.72.9.4996-5003.2004","article-title":"Role of antibiotics and fungal microbiota in driving pulmonary allergic responses","volume":"72","author":"Noverr","year":"2004","journal-title":"Infect. Immun."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/8\/5\/480\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:06:43Z","timestamp":1760137603000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/8\/5\/480"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,5]]},"references-count":131,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["jof8050480"],"URL":"https:\/\/doi.org\/10.3390\/jof8050480","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,5]]}}}