A challenge in diagnosis and treatment in asthma patients with allergic bronchopulmonary aspergillosis: a review
Abstract
Allergic bronchopulmonary aspergillosis (ABPA) is a common form of fungal-related asthma disease mainly caused by Aspergillus fumigatus. The increasing prevalence of asthma globally and the characteristic of Aspergillus are very easily dispersed in the air to inhale, leading to increased cases of ABPA in asthma patients. Inhalation of conidia Aspergillus spp. can trigger asthma exacerbations due to poor mucociliary clearance. However, the exact pathogenesis is still unclear. Clinical features commonly found in ABPA patients are productive cough with dark green or brown mucus or even hemoptysis. Several criteria for establishing the diagnosis of ABPA can be based on clinical features, laboratory examinations, and imaging, but none has become the gold standard. However, the primary laboratory test utilized for ABPA screening is the measurement of serum-specific IgE levels to A. fumigatus, owing to its high sensitivity. Despite the challenges in finding the most fitting universal consensus, most clinicians still follow the criteria proposed by Rosenberg et al. in 1977. The recommended ABPA treatment is prednisone and/or azole antifungal agents such as itraconazole. In addition, the potential of monoclonal antibodies in ABPA therapy is still under further research. Long-term diagnosis and treatment delays can lead to complications such as bronchiectasis and fibrosis. This review aimed to highlight ABPA in asthma patients, from etiopathogenesis to managing the disease
References
Boonpiyathad T, Sözener ZC, Satitsuksanoa P, Akdis CA. Immunologic mechanisms in asthma. Semin Immunol 2019; 46:101333.
https://doi.org/10.1016/j.smim.2019.101333
Singh M, Paul N, Singh S, Nayak GR. Asthma and fungus: role in allergic bronchopulmonary aspergillosis (abpa) and other conditions. Indian J Pediatr 2018; 85(10):899–904.
https://doi.org/10.1007/s12098-018-2646-8.
Rajagopal T V, Kant S, Verma SK, Kushwaha RAS, Kumar S, Garg R, et al. Aspergillus sensitization in bronchial asthma: A separate phenotype. Allergy Asthma Proc 2020; 41(1):e26-e32.
https://doi.org/10.2500/aap.2020.41.190008
Loftus PA, Wise SK. Epidemiology and economic burden of asthma. Int Forum Allergy Rhinol 2015; 5:S7-10.
https://doi.org/10.1002/alr.21547
Dharmage SC, Perret JL, Custovic A. Epidemiology of asthma in children and adults. Front Pediatr 2019; 7:246.
https://doi.org/10.3389/fped.2019.00246
Stern J, Pier J, Litonjua AA. Asthma epidemiology and risk factors. Semin Immunopathol 2020; 42(1):5-15.
https://doi.org/10.1007/s00281-020-00785-1
Enilari O, Sinha S. The global impact of asthma in adult populations. Ann Glob Health 2019; 85(1):2. https://doi.org/10.5334/aogh.2412
Mattiuzzi C, Lippi G. Worldwide asthma epidemiology: insights from the Global Health Data Exchange database. Int Forum Allergy Rhinol 2020; 10(1):75-80.
https://doi.org/10.1002/alr.22464
Global Initiative for Asthma. Pocket guide for asthma management and prevention for adults and children older than 5 years: a pocket guide for health professionals; 2020. [cited 2022 April 3].
https://ginasthma.org/wp-content/uploads/2020/04/Main-pocket-guide_2020_04_03-final-wms.pdf.
Sio YY, Chew FT. Risk factors of asthma in the Asian population: a systematic review and meta-analysis. J Physiol Anthropol 2021; 40(1):22.
https://doi.org/10.1186/s40101-021-00273-x.
Zhang L, He L, Gong J, Liu C. Risk factors associated with irreversible airway obstruction in asthma: a systematic review and meta-analysis. Biomed Res Int 2016; 2016:9868704.
https://doi.org/10.1155/2016/9868704
Clark VL, Gibson PG, Genn G, Hiles SA, Pavord ID, McDonald VM. Multidimensional assessment of severe asthma: A systematic review and meta-analysis. Respirology 2017; 22(7):1262-75.
https://doi.org/10.1111/resp.13134
Pakkasela J, Ilmarinen P, Honkamäki J, Tuomisto LE, Andersén H, Piirilä P, et al. Age specific incidence of allergic and non-allergic asthma. BMC Pulm Med 2020; 20(1):9.
https://doi.org/10.1186/s12890-019-1040-2
Agache I, Antolin-Amerigo D, de Blay F, Boccabella C, Caruso C, Chanez P, et al. EAACI position paper on the clinical use of the bronchial allergen challenge: Unmet needs and research priorities. Allergy Eur J Allergy Clin Immunol 2022; 77(6):1667-84.
https://doi.org/10.1111/all.15203
Masaki K, Fukunaga K, Matsusaka M, Kabata H, Tanosaki T, Mochimaru T, et al. Characteristics of severe asthma with fungal sensitization. Ann Allergy Asthma Immunol 2017; 119(3):253-7.
https://doi.org/10.1016/j.anai.2017.07.008
Kuruvilla ME, Lee FEH, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol 2019; 56(2):219-33.
https://doi.org/10.1007/s12016-018-8712-1
Namvar S, Labram B, Rowley J, Herrick S. Aspergillus fumigatus-host interactions mediating airway wall remodelling in asthma. J Fungi 2022; 8(2):159.
https://doi.org/10.3390/jof8020159
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
Tracy MC, Okorie CUA, Foley EA, Moss RB. Allergic bronchopulmonary aspergillosis. J Fungi (Basel) 2016; 2(2):17.
https://doi.org/10.3390/jof202001720
Fukutomi Y, Taniguchi M. Sensitization to fungal allergens: Resolved and unresolved issues. Allergol Int 2015; 64(4):321-31.
https://doi.org/10.1016/j.alit.2015.05.007
Rapeport WG, Ito K, Denning DW. The role of antifungals in the management of patients with severe asthma. Clin Transl Allergy 2020; 10(1):46.
https://doi.org/ 10.1186/s13601-020-00353-8
Bongomin F, Gago S, Oladele RO, Denning DW. Global and multi-national prevalence of fungal diseases-estimate precision. J Fungi (Basel) 2017; 3(4):57.
https://doi.org/10.3390/jof3040057
Denning DW, Pashley C, Hartl D, Wardlaw A, Godet C, Del Giacco S, et al. Fungal allergy in asthma-state of the art and research needs. Clin Transl Allergy 2014; 4:14.
https://doi.org/10.1186/2045-7022-4-14
Agbetile J, Fairs A, Desai D, Hargadon B, Bourne M, Mutalithas K, et al. Isolation of filamentous fungi from sputum in asthma is associated with reduced post bronchodilator FEV 1. Clin Exp Allergy 2012; 42(5):782-91.
https://doi.org/10.1111/j.1365-2222.2012.03987.x
Fairs A, Agbetile J, Hargadon B, Bourne M, Monteiro WR, Brightling CE, et al. IgE sensitization to Aspergillus fumigatus is associated with reduced lung function in asthma. Am J Respir Crit Care Med 2010; 182(11):1362-8.
https://doi.org/10.1164/rccm.201001-0087OC
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.
Hinson KFW, Moon AJ, Plummer NS. Broncho-pulmonary aspergillosis. Thorax 1952; 7(4):317-33.
https://doi.org/10.1136/thx.7.4.317
Agarwal R, Chakrabarti A, Shah A, Gupta D, Meis JF, Guleria R, et al. Allergic bronchopulmonary aspergillosis: Review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy 2013; 43(8):850-73.
https://doi.org/10.1111/cea.12141
Farrant J, Brice H, Fowler S, Niven R. Fungal sensitization in severe asthma is associated with the identification of Aspergillus fumigatus in sputum. J Asthma 2016; 53(7):732-5.
https://doi.org/10.3109/02770903.2016.1154073
Malcolm D, Richardson KB, Hope W. Aspergillus. 2th ed. China: Churchill Livingstone Elsevier, 2009. Chapter 11: Clinical Mycology; p.271-96
Agarwal R, Bansal S, Chakrabarti A. Are allergic fungal rhinosinusitis and allergic bronchopulmonary aspergillosis lifelong conditions? Med Mycol 2017; 55(1):87-95.
https://doi.org/10.1093/mmy/myw071
Fraczek MG, Chishimba L, Niven RM, Bromley M, Simpson A, Smyth L, et al. Corticosteroid treatment is associated with increased filamentous fungal burden in allergic fungal disease. J Allergy Clin Immunol 2018; 142(2):407-14.
https://doi.org/10.1016/j.jaci.2017.09.039
Tsang CC, Tang JYM, Lau SKP, Woo PCY. Taxonomy and evolution of Aspergillus, Penicillium, and Talaromyces in the omics era – Past, present and future. Comput Struct Biotechnol J 2018; 16:197-210.
https://doi.org/10.1016/j.csbj.2018.05.003
Rozaliyani A, Sedono R, Sjam R, Tugiran M, Adawiyah R, Setianingrum F, et al. Molecular typing and antifungal susceptibility study of Aspergillus spp. in intensive care unit (ICU) patients in Indonesia. J Infect Dev Ctries 2021; 15(7):1014-20.
https://doi.org/10.3855/jidc.13135
Ashton GD, Dyer PS. Culturing and mating of Aspergillus fumigatus. Curr Protoc Microbiol 2019; 54(1):e87.
https://doi.org/10.1002/cpmc.87
Zhang J, Snelders E, Zwaan BJ, Schoustra SE, Meis JF, Van Dijk K, et al. A novel environmental azole resistance mutation in Aspergillus fumigatus and a possible role of sexual reproduction in its emergence. mBio 2017; 8(3):e00791-17.
https://doi.org/10.1128/mBio.00791-17
Viegas C, Dias M, Carolino E, Sabino R. Culture media and sampling collection method for Aspergillus spp. Assessment: Tackling the gap between recommendations and the scientific evidence. Atmosphere 2021; 12(1):23.
https://doi.org/10.3390/atmos12010023
O’Gorman CM, Fuller HT, Dyer PS. Discovery of a sexual cycle in the opportunistic fungal pathogen Aspergillus fumigatus. Nature 2009; 457(7228):471-4.
https://doi.org/10.1038/nature07528
Matsuse H, Tsuchida T, Fukahori S, Kawano T, Nishino T, Fukushima C, et al. Dissociation between sensitizing and colonizing fungi in patients with allergic bronchopulmonary aspergillosis. Ann Allergy Asthma Immunol 2013; 111(3):190-3.
https://doi.org/10.1016/j.anai.2013.06.022.
Surja S, Wijaya M, Padmasutra L, Yolanda H, Joprang F, Makimian R, et al. Atlas parasitologi kedokteran. 1th ed. Jakarta: Universitas Katolik Indonesia Atma Jaya; 2019.
Garcia-Rubio R, de Oliveira HC, Rivera J, Trevijano-Contador N. The fungal cell wall: Candida, Cryptococcus, and Aspergillus species. Front Microbiol 2020; 10:2993.
https://doi.org/10.3389/fmicb.2019.02993
Aimanianda V, Bayry J, Bozza S, Kniemeyer O, Perruccio K, Elluru SR, et al. Surface hydrophobin prevents immune recognition of airborne fungal spores. Nature 2009; 460(7259):1117-21.
https://doi.org/10.1038/nature08264.
Lewington-Gower E, Chan L, Shah A. Review of current and future therapeutics in ABPA. Ther Adv Chronic Dis 2021; 12:20406223211047003.
https://doi.org/10.1177/20406223211047003
Agarwal R, Sehgal I, Dhooria S, Muthu V, Prasad K, Bal A, et al. Allergic bronchopulmonary aspergillosis. Clin Chest Med 2022; 43(1):99-125.
https://doi.org/10.1016/j.ccm.2021.12.002
Ok M, Einsele H, Loeffler J. Genetic susceptibility to Aspergillus fumigatus infections. Int J Med Microbiol 2011; 301(5):445-52.
https://doi.org/10.1016/j.ijmm.2011.04.013
Agarwal R, Dhooria S, Singh Sehgal I, Aggarwal AN, Garg M, Saikia B, et al. A randomized trial of itraconazole vs prednisolone in acute-stage allergic bronchopulmonary aspergillosis complicating asthma. Chest 2018; 153(3):656-64.
https://doi.org/10.1016/j.chest.2018.01.005
Agarwal R, Khan A, Aggarwal AN, Gupta D. Link between CFTR mutations and ABPA: A systematic review and meta-analysis. Mycoses 2012; 55(4):357-65.
https://doi.org/10.1111/j.1439-0507.2011.02130.x
Overton NLD, Denning DW, Bowyer P, Simpson A. Genetic susceptibility to allergic bronchopulmonary aspergillosis in asthma: A genetic association study. Allergy Asthma Clin Immunol 2016; 12:47.
https://doi.org/10.1186/s13223-016-0152-y
Gago S, Overton NLD, Ben-Ghazzi N, Novak-Frazer L, Read ND, Denning DW, et al. Lung colonization by Aspergillus fumigatus is controlled by ZNF77. Nat Commun 2018; 9(1):3835.
https://doi.org/10.1038/s41467-018-06148-7
Culibrk L, Croft CA, Toor A, Yang SJ, Singhera GK, Dorscheid DR, et al. Phagocytosis of Aspergillus fumigatus by human bronchial epithelial cells is mediated by the Arp2/3 complex and WIPF2. Front Cell Infect Microbiol 2019; 9:16.
https://doi.org/10.3389/fcimb.2019.00016
Croft CA, Culibrk L, Moore MM, Tebbutt SJ. Interactions of Aspergillus fumigatus conidia with airway epithelial cells: A critical review. Front Microbiol 2016; 7:472.
https://doi.org/10.3389/fmicb.2016.00472
Knutsen AP, Slavin RG. Allergic bronchopulmonary aspergillosis in asthma and cystic fibrosis. Clin Dev Immunol 2011; 2011:843763.
https://doi.org/10.1155/2011/843763.
Van De Veerdonk FL, Gresnigt MS, Romani L, Netea MG, Latgé JP. Aspergillus fumigatus morphology and dynamic host interactions. Nat Rev Microbiol 2017; 15(11):661-74.
https://doi.org/10.1038/nrmicro.2017.90
Wassano NS, Goldman GH, Damasio A. Aspergillus fumigatus. Trends Microbiol. 2020; 28(7):594-95.
https://doi.org/10.1016/j.tim.2020.02.013
Bigot J, Guillot L, Guitard J, Ruffin M, Corvol H, Balloy V, et al. Bronchial epithelial cells on the front line to fight lung infection-causing Aspergillus fumigatus. Front Immuno 2020; 11:1041.
https://doi.org/fimmu.2020.01041
Valsecchi I, Lai JI, Stephen-Victor E, Pillé A, Beaussart A, Lo V, et al. Assembly and disassembly of Aspergillus fumigatus conidial rodlets. Cell Surf 2019; 5:100023.
https://doi.org/10.1016/j.tcsw.2019.100023
Moss RB. Treatment options in severe fungal asthma and allergic bronchopulmonary aspergillosis. Eur Respir J 2014; 43(5):1487-500.
https://doi.org/10.1183/09031936.00139513
Redes JL, Basu T, Ram-Mohan S, Ghost CC, Chan EC, Sek AC, et al. Aspergillus fumigatus-secreted alkaline protease 1 mediates airways hyperresponsiveness in severe asthma. Immunohorizons 2019; 3(8):368-377.
https://doi.org/10.4049/immunohorizons.1900046
Kosmidis C, Denning DW. The clinical spectrum of pulmonary aspergillosis. Thorax 2015; 70(3):270-7.
https://doi.org/10.1136/thoraxjnl-2014-206291
Agarwal R, Sehgal IS, Dhooria S, Aggarwal AN. Developments in the diagnosis and treatment of allergic bronchopulmonary aspergillosis. Expert Rev Respir Med 2016; 10(12):1317-34.
https://doi.org/10.1080/17476348.2016.1249853
Mendelson EB, Fisher MR, Mintzer RA, Halwig JM, Greenberger PA. Roentgenographic and clinical staging of allergic bronchopulmonary aspergillosis. Chest 1985; 87(3):334-9.
https://doi.org/10.1378/chest.87.3.334
Patterson R, Greenberger PA, Radin RC, Roberts M. Allergic bronchopulmonary aspergillosis: staging as an aid to management. Ann Intern Med 1982; 96(3):286-91.
https://doi.org/10.7326/0003-4819-96-3-286
Agarwal R, Maskey D, Aggarwal AN, Saikia B, Garg M, Gupta D, et al. Diagnostic performance of various tests and criteria employed in allergic bronchopulmonary aspergillosis: a latent class analysis. PLoS One 2013; 8(4):e61105.
https://doi.org/10.1371/journal.pone.0061105
Patterson K, Strek ME. Allergic bronchopulmonary aspergillosis. Proc Am Thorac Soc 2010: 7(3):237-44.
https://doi.org/10.1513/pats.200908-086AL
Agarwal R, Dua D, Choudhary H, Aggarwal AN, Sehgal IS, Dhooria S, et al. Role of Aspergillus fumigatus-specific IgG in diagnosis and monitoring treatment response in allergic bronchopulmonary aspergillosis. Mycoses 2017; 60(1):33-39.
https://doi.org/10.1111/myc.12541
Page ID, Richardson MD, Denning DW. Comparison of six Aspergillus-specific IgG assays for the diagnosis of chronic pulmonary aspergillosis (CPA). J Infect 2016; 72(2):240-9.
https://doi.org/10.1016/j.jinf.2015.11.003
Rosenberg M, Patterson R, Mintzer R, Cooper BJ, Roberts M, Harris KE. Clinical and immunologic criteria for the diagnosis of allergic bronchopulmonary aspergillosis. Ann Intern Med 1977; 86(4):405-14.
https://doi.org/10.7326/0003-4819-86-4-405
Greenberger PA, Patterson R. Allergic bronchopulmonary aspergillosis and the evaluation of the patient with asthma. J Allergy Clin Immunol 1988; 81(4):646-50.
https://doi.org/10.1016/0091-6749(88)91034-2
Greenberger PA. Allergic bronchopulmonary aspergillosis. Clin Immunol 2002; 110(5):685-92.
https://doi.org/10.1067/mai.2002.130179
Greenberger PA. When to suspect and work up allergic bronchopulmonary aspergillosis. Ann Allergy Asthma Immunol 2013; 111(1):1-4.
https://doi.org/10.1016/j.anai.2013.04.014
Agarwal R, Saxena P, Muthu V, Sehgal IS, Dhooria S, Prasad KT, et al. Evaluation of simpler criteria for diagnosing allergic bronchopulmonary aspergillosis complicating asthma. Front Cell Infect Microbiol 2022; 12:861866.
https://doi.org/10.3389/fcimb.2022.861866
Asano K, Hebisawa A, Ishiguro T, Takayanagi N, Nakamura Y, Suzuki J, et al. New clinical diagnostic criteria for allergic bronchopulmonary aspergillosis/mycosis and its validation. J Allergy Clin Immunol 2021; 147(4):1261-8.e5.
https://doi.org/10.1016/j.jaci.2020.08.029
Saxena P, Choudhary H, Muthu V, Sehgal IS, Dhooria S, Prasad KT, et al. Which are the optimal criteria for the diagnosis of allergic bronchopulmonary aspergillosis? A latent class analysis. J Allergy Clin Immunol Pract 2021; 9(1):328-35.e1.
https://doi.org/10.1016/j.jaip.2020.08.043
Eraso IC, Sangiovanni S, Morales EI, Fernández-Trujillo L. Use of monoclonal antibodies for allergic bronchopulmonary aspergillosis in patients with asthma and cystic fibrosis: literature review. Ther Adv Respir Dis 2020; 14:1753466620961648.
https://doi.org/10.1177/1753466620961648
Sunman B, Ademhan Tural D, Ozsezen B, Emiralioglu N, Yalcin E, Özçelik U. Current approach in the diagnosis and management of allergic bronchopulmonary aspergillosis in children with cystic fibrosis. Front Pediatr 2020; 8:582964.
https://doi.org/10.3389/fped.2020.582964
Agarwal R, Aggarwal AN, Dhooria S, Sehgal IS, Garg M, Saikia B, et al. A randomised trial of glucocorticoids in acute-stage allergic bronchopulmonary aspergillosis complicating asthma. Eur Respir J 2016; 47(2):490-8.
