Allergic Bronchopulmonary Aspergillosis in Children with Cystic Fibrosis: An Update on the Newest Diagnostic Tools and Therapeutic Approaches
Abstract
:1. Background
2. Epidemiology of Aspergillus fumigatus in Patients with CF
3. Risk Factors for Aspergillus Colonization and Infection in Patients with CF
4. Pathogenesis of Aspergillus fumigatus Infection in Patients with CF
5. Clinical Features of ABPA in Patients with CF
6. ABPA and Lung Function
7. Diagnosis of ABPA in Patients with CF
8. Treatment of ABPA in Patients with CF
9. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Eickmeier, O.; Rieber, N.; Eckrich, J.; Hector, A.; Graeppler-Mainka, U.; Hartl, D. Immune response, diagnosis and treatment of allergic bronchopulmonary aspergillosis in cystic fibrosis lung disease. Curr. Pharm. Des. 2013, 19, 3669–3678. [Google Scholar] [CrossRef]
- Zemanick, E.T.; Hoffman, L.R. Cystic fibrosis: Microbiology and host response. Pediatr. Clin. 2016, 63, 617–636. [Google Scholar]
- Amin, R.; Dupuis, A.; Aaron, S.D.; Ratjen, F. The effect of chronic infection with Aspergillus fumigatus on lung function and hospitalization in patients with cystic fibrosis. Chest 2010, 137, 171–176. [Google Scholar] [CrossRef] [PubMed]
- Valenza, G.; Tappe, D.; Turnwald, D.; Frosch, M.; König, C.; Hebestreit, H.; Abele-Horn, M. Prevalence and antimicrobial susceptibility of microorganisms isolated from sputa of patients with cystic fibrosis. J. Cyst. Fibros. 2008, 7, 123–127. [Google Scholar] [CrossRef] [PubMed]
- Tracy, M.C.; Moss, R.B. The myriad challenges of respiratory fungal infection in cystic fibrosis. Pediatr Pneumol 2018, 53 (Suppl. S3), S75–S85. [Google Scholar] [CrossRef] [Green Version]
- Reece, E.; McClean, S.; Greally, P.; Renwick, J. The prevalence of Aspergillus fumigatus in early cystic fibrosis disease is underestimated by culture-based diagnostic methods. J. Microbiol. Methods 2019, 164, 105683. [Google Scholar] [CrossRef]
- Jones, A.M.; Horsley, A.; Denning, D.W. What is the importance of classifying Aspergillus disease in cystic fibrosis patients? Expert Rev. Respir. Med. 2014, 8, 389–392. [Google Scholar] [CrossRef] [Green Version]
- Saunders, R.V.; Modha, D.E.; Claydon, A.; Gaillard, E.A. Chronic Aspergillus fumigatus colonization of the pediatric cystic fibrosis airway is common and may be associated with a more rapid decline in ling function. Sabouraudia 2016, 54, 537–543. [Google Scholar] [CrossRef] [Green Version]
- Breuer, O.; Schultz, A.; Turkovic, L.; De Klerk, N.; Keil, A.D.; Brennan, S.; Harrison, J.; Robertson, C.; Robinson, P.J.; Sly, P.D.; et al. Changing prevalence of lower airway infections in young children with cystic fibrosis. Am. J. Respir. Crit. Care Med. 2019, 200, 590–599. [Google Scholar] [CrossRef]
- Sisodia, J.; Bajaj, T. Allergic Bronchopulmonary Aspergillosis (ABPA). In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2020. [Google Scholar]
- Keown, K.; Abbott, S.; Kuzeljevic, B.; Rayment, J.H.; Chilvers, M.A.; Yang, C.L. An investigation into biomarkers for the diagnosis of ABPA and Aspergillus disease in cystic fibrosis. Pediatr. Pulmonol. 2019, 54, 1787–1793. [Google Scholar] [CrossRef] [PubMed]
- Agarwal, R.; Sehgal, I.S.; Dhooria, S.; Aggarwal, A.N. Developments in the diagnosis and treatment of allergic bronchopulmonary aspergillosis. Expert Rev. Respir. Med. 2016, 10, 1317–1334. [Google Scholar] [CrossRef] [PubMed]
- Denning, D.W.; Pleuvry, A.; Cole, D.C. Global burden of allergic bronchopulmonary aspergillosis with asthma and its complications chronic pulmonary aspergillosis in adults. Med. Mycol. 2013, 51, 361–370. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stevens, D.A.; Moss, R.B.; Kurup, V.P.; Knutsen, A.P.; Greenberger, P.; Judson, M.A.; Denning, D.W.; Crameri, R.; Brody, A.S.; Light, M.; et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin. Infect. Dis. 2003, 37 (Suppl. 3), S225–S264. [Google Scholar] [CrossRef] [PubMed]
- Gothe, F.; Kappler, M.; Griese, M. Increasing Total Serum IgE, Allergic Bronchopulmonary Aspergillosis, and Lung Function in Cystic Fibrosis. J. Allergy Clin. Immunol. Pract. 2017, 5, 1591–1598. [Google Scholar] [CrossRef]
- Agarwal, R.; Chakrabarti, A.; Shah, A.; Gupta, D.; Guleria, R.; Moss, R.; Denning, D.W. Allergic bronchopulmonary aspergillosis: Review of literature and proposed of new diagnostic and classification criteria. Clin. Exp. Allergy 2013, 43, 850–873. [Google Scholar] [CrossRef]
- Hong, G.; Psoter, K.J.; Jennings, M.T.; Merlo, C.A.; Boyle, M.P.; Hadjiliadis, D.; Kawut, S.M.; Lechtzin, N. Risk factors for persistent Aspergillus respiratory isolation in cystic fibrosis. J. Cyst. Fibros. 2018, 17, 624–630. [Google Scholar] [CrossRef]
- Jubin, V.; Ranque, S.; Stremler Le Bel, N.; Sarles, J.; Dubus, J.C. Risk factors for Aspergillus colonization and Allergic Bronchopulmonary Aspergillosis in children with cystic fibrosis. Pediatr. Pulmonol. 2010, 45, 764–771. [Google Scholar] [CrossRef]
- Thompson, J.M.; Wesley, A.; Bymes, C.A.; Nixon, G.M. Pulse intravenous metilprednisolone for resistant allergic bronchipulmonary aspergillosis in cystic fibrosis. Pediatr. Pulmonol. 2006, 41, 164–170. [Google Scholar] [CrossRef]
- Knutsen, A.P.; Kariuki, B.; Santiago, L.A.; Slvin, R.G.; Wofford, J.D.; Bellone, C.; Shah, M.R. HLADR, IL-4RA, and IL-10: Genetic risk factors in allergic bronchopulmonary aspergillosis. Pediatr. Asthma Allergy Immunol. 2008, 21, 185–190. [Google Scholar] [CrossRef]
- Brouard, J.; Knauer, N.; Boelle, P.-Y.; Corvol, H.; Henrion-Caude, A.; Flamant, C.; Brémont, F.; Delaisi, B.; Duhamel, J.; Marguet, C.; et al. Influence of interleukin-10 on Aspergillus fumigatus infection in patients with cystic fibrosis. J. Infect. Dis. 2005, 191, 1988–1991. [Google Scholar] [CrossRef] [Green Version]
- Overton, N.L.; Denning, D.W.; Bowyer, P.; Simpson, A. Genetic susceptibility to allergic bronchopulmonary aspergillosis in asthma: A genetic association study. Allergy Asthma Clin. Immunol. 2016, 12, 47. [Google Scholar] [CrossRef] [Green Version]
- Kolwijck, E.; van de Veerdonk, F.L. The potential impact of the pulmonary microbiome on immunopathogenesis of Aspergillus-related lung disease. Eur. J. Immunol. 2014, 44, 3156–3165. [Google Scholar] [CrossRef] [PubMed]
- Noverr, M.C.; Noggle, R.M.; Toews, G.B.; Huffnagle, G.B. Role of antibiotics and fungal microbiota in driving pulmonary allergic responses. Infect. Immun. 2004, 72, 4996–5003. [Google Scholar] [CrossRef] [Green Version]
- Moss, R.B. Pathophysiology and immunology of allergic bronchopulmonary aspergillosis. Med. Mycol. 2005, 43 (Suppl. 1), S203–S206. [Google Scholar] [CrossRef] [PubMed]
- Agarwal, R. Allergic bronchopulmonary aspergillosis. Chest 2009, 135, 805–826. [Google Scholar] [CrossRef] [PubMed]
- Wiesner, D.L.; Klein, B.S. Lung epithelium: Barrier immunity to inhaled fungi and driver of fungal-associated allergic asthma. Curr. Opin. Microbiol. 2017, 40, 8–13. [Google Scholar] [CrossRef] [Green Version]
- Mueller, C.; Braag, S.A.; Keeler, A.; Hodges, C.; Drumm, M.; Flotte, T.R. Lack of cystic fibrosis transmembrane conductance regulator in CD3+ lymphocytes leads to aberrant cytokine secretion and hyperinflammatory adaptive immune responses. Am. J. Respir. Cell Mol. Boil. 2011, 44, 922–929. [Google Scholar] [CrossRef] [Green Version]
- Millien, V.O.; Lu, W.; Shaw, J.; Yuan, X.; Mak, G.; Roberts, L.; Song, L.-Z.; Knight, J.M.; Creighton, C.J.; Luong, A.; et al. Cleavage of fibrinogen by proteinases elicits allergic responses through Toll-like receptor 4. Science 2013, 341, 792–796. [Google Scholar] [CrossRef] [Green Version]
- Cunha, C.; Romani, L.; Carvalho, A. Cracking the Toll-like receptor code in fungal infections. Expert Rev. Anti-Infect. Ther. 2010, 8, 1121–1137. [Google Scholar] [CrossRef] [Green Version]
- Bellocchio, S.; Moretti, S.; Perruccio, K.; Fallarino, F.; Bozza, S.; Montagnoli, C.; Mosci, P.; Lipford, G.B.; Pitzurra, L.; Romani, L. TLRs govern neutrophil activity in aspergillosis. J. Immunol. 2004, 173, 7406–7415. [Google Scholar] [CrossRef]
- Knutsen, A.P.; Hutchinson, P.S.; Albers, G.M.; Consolino, J.; Smick, J.; Kurup, V.P. Increased sensitivity to IL-4 in cystic fibrosis patients with allergic bronchopulmonary aspergillosis. Allergy 2004, 59, 81–87. [Google Scholar] [CrossRef] [PubMed]
- Dietschmann, A.; Schruefer, S.; Krappmann, S.; Voehringer, D. Th2 cells promote eosinophil independent pathology in a murine model of allergic bronchopulmonary aspergillosis. [published online ahead of print, 28 February 2020]. Eur. J. Immunol. 2020. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gago, S.; Denning, D.W.; Bowyer, P. Pathophysiological aspects of Aspergillus colonization in disease. Med. Mycol. 2019, 57 (Suppl. 2), S219–S227. [Google Scholar] [CrossRef] [PubMed]
- Kosmidis, C.; Denning, D.W. The clinical spectrum of pulmonary aspergillosis. Thorax 2015, 70, 270–277. [Google Scholar] [CrossRef] [Green Version]
- Brandt, C.; Roehmel, J.; Rickerts, V.; Melichar, V.; Niemann, N.; Schwarz, C. Aspergillus Bronchitis in Patients with Cystic Fibrosis. Mycopathologia 2018, 183, 61–69. [Google Scholar] [CrossRef]
- Patel, A.R.; Singh, S.; Khawaja, I. Diagnosing allergic bronchopulmonary aspergillosis: A review. Cureus 2019, 11, e4550. [Google Scholar] [CrossRef] [Green Version]
- Kaditis, A.G.; Miligkos, M.; Bossi, A.; Colombo, C.; Hatziagorou, E.; Kashirskaya, N.; De Monestrol, I.; Thomas, M.; Mei-Zahav, M.; Chrousos, G.; et al. Effect of allergic bronchopulmonary aspergillosis on FEV1 in children and adolescents with cystic fibrosis: A European Cystic Fibrosis Society Patient Registry analysis. Arch. Dis. Child. 2017, 102, 742–747. [Google Scholar] [CrossRef]
- De Baets, F.; De Keyzer, L.; Van Daele, S.; Schelstraete, P.; Van Biervliet, S.; Van Braeckel, E.; Thomas, M.; Wanyama, S.S. Risk factors and impact of allergic bronchopulmonary aspergillosis in Pseudomonas aeruginosa-negative CF patients. Pediatr. Allergy Immunol. 2018, 29, 726–731. [Google Scholar] [CrossRef]
- Harun, S.N.; Wainwright, C.E.; Grimwood, K.; Henning, S. Aspergillus and progression of lung disease in children with cystic fibrosis. Thorax 2018, 74, 125–131. [Google Scholar] [CrossRef]
- Breuer, O.; Schultz, A.; Garratt, L.W.; Turkovic, L.; Rosenow, T.; Murray, C.P.; Karpievitch, Y.V.; Akesson, L.; Dalton, S.; Sly, P.D.; et al. Aspergillus Infections and Progression of Structural Lung Disease in Children with Cystic Fibrosis. Am. J. Respir. Crit. Care Med. 2020, 201, 688–696. [Google Scholar] [CrossRef]
- Noni, M.; Katelari, A.; Dimopoulos, G.; Doudounakis, S.E.; Tzoumaka-Bakoula, C.; Spoulou, V. Aspergillus fumigatus chronic colonization and lung function decline in cystic fibrosis may have a two-way relationship. Eur. J. Clin. Microbiol. Infect. Dis. 2015, 34, 2235–2241. [Google Scholar] [CrossRef] [PubMed]
- Beswick, E.; Amich, J.; Gago, S. Factoring in the Complexity of the Cystic Fibrosis Lung to Understand Aspergillus fumigatus and Pseudomonas aeruginosa Interactions. Pathogens 2020, 9, 639. [Google Scholar] [CrossRef] [PubMed]
- Shah, A.; Panjabi, C. Allergic bronchopulmonary aspergillosis: A perplexing clinical entity. Allergy Asthma Immunol. Res. 2016, 8, 282–297. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maleki, M.; Mortezaee, V.; Hassanzad, H.; Mahdaviani, S.; Poorabdollah, M.; Mehrian, P.; Behnampour, N.; Mirenayat, M.; Abastabar, M.; Tavakoli, M.; et al. Prevalence of allergic bronchopulmonary aspergillosis in cystic fibrosis patients using two different diagnostic criteria. Eur. Ann. Allergy Clin. Immunol. 2020, 52, 104–111. [Google Scholar] [CrossRef]
- Denning, D.W.; Pashley, C.; Hartl, D.; Wardlaw, A.; Godet, C.; Del Giacco, S.; Delhaes, L.; Sergejeva, S. Fungal allergy in asthma-state of the art and research needs. Clin. Transl. Allergy 2014, 4, 14. [Google Scholar] [CrossRef] [Green Version]
- Baxter, C.G.; Dunn, G.; Jones, A.M.; Webb, K.; Gore, R.; Richardson, M.D.; Denning, D.W. Novel immunologic classification of aspergillosis in adult cystic fibrosis. J. Allergy Clin. Immunol. 2013, 132, 560–566.e10. [Google Scholar] [CrossRef]
- Knutsen, A.P.; Bush, R.K.; Demain, J.G.; Denning, D.W.; Dixit, A.; Fairs, A.; Greenberger, P.A.; Kariuki, B.; Kita, H.; Kurup, V.P.; et al. Fungi and allergic lower respiratory tract diseases. J. Allergy Clin. Immunol. 2012, 129, 280–291. [Google Scholar] [CrossRef]
- Agarwal, R.; Garg, M.; Aggarwal, A.N.; Saikia, B.; Gupta, D.; Chakrabarti, A. Serologic allergic bronchopulmonary aspergillosis (ABPA-S): Long term outcomes. Respir. Med. 2012, 106, 942–947. [Google Scholar] [CrossRef] [Green Version]
- Lu, H.W.; Mao, B.; Wei, P.; Jiang, S.; Wang, H.; Li, C.W.; Ji, X.B.; Gu, S.Y.; Yang, J.W.; Liang, S.; et al. The clinical characteristics and prognosis of ABPA are closely related to the mucus plugs in central bronchiectasis. Clin. Respir. J. 2020, 14, 140–147. [Google Scholar] [CrossRef] [Green Version]
- Peccini, L.; Pennoni, S.; Mencarini, V.; Saponara, M.; Palladino, N.; Principi, N.; Pennoni, G.; Esposito, S. A peculiar case of pneumonia due to Mycoplasma pneumoniae in a child with cystic fibrosis and sensibilization to Aspergillus fumigatus. Pathogens 2019, 9, 15. [Google Scholar] [CrossRef] [Green Version]
- Michel, M.; Gomez, C.; Sereme, Y.; Gouitaa, M.; Chartier, C.; Blanchard, P.; Pinchemel, S.; Cassagne, C.; Ranque, S.; Mege, J.L.; et al. Evaluation of Cellular Responses for the Diagnosis of Allergic Bronchopulmonary Mycosis: A Preliminary Study in Cystic Fibrosis Patients. Front. Immunol. 2020, 10, 3149. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hemmings, O.; Kwok, M.; McKendry, R.; Santos, A.F. Correction to: Basophil Activation Test: Old and New Applications in Allergy. Curr. Allergy Asthma Rep. 2019, 19, 58. [Google Scholar] [CrossRef] [Green Version]
- Patel, A.R.; Singh, S.; Khawaja, I. Treating allergic bronchopulmonary aspergillosis: A review. Cureus 2019, 11, e4538. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ohn, M.; Robinson, P.; Selvadurai, H.; Fitzgerald, D.A. Question 11: How should allergic bronchopulmonary aspergillosis (ABPA) be managed in cystic fibrosis? Paediatr. Respir. Rev. 2017, 24, 35–38. [Google Scholar] [CrossRef] [PubMed]
- Natarajan, S.; Subramanian, P. Allergic bronchopulmonary aspergillosis: A clinical review of 24 patients: Are we right in frequent serologic monitoring? Ann. Thorac. Med. 2014, 9, 216. [Google Scholar] [CrossRef]
- Agarwal, R.; Dhooria, S.; Sehgal, I.S.; Aggarwal, A.N.; Garg, M.; Saikia, B.; Behera, D.; Chakrabarti, A. A randomized trial of Itraconazole vs Prednisolone in acute-stage allergic bronchopulmonary aspergillosis complicating asthma. Chest 2018, 153, 656–664. [Google Scholar] [CrossRef] [PubMed]
- Agarwal, R. What is the current place of azoles in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Expert Rev. Respir. Med. 2012, 6, 363–371. [Google Scholar] [CrossRef]
- Elphick, H.E.; Southern, K.W. Antifungal therapies for allergic bronchopulmonaryaspergillosis in people with cystic fibrosis. Cochrane Database Syst. Rev. 2016, 11. [Google Scholar] [CrossRef]
- Denning, D.W.; O’Driscoll, B.R.; Powell, G.; Chew, F.; Atherton, G.T.; Vyas, A.; Miles, J.; Morris, J.; Niven, R.M. Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization: The Fungal Asthma Sensitization Trial (FAST) study. Am. J. Respir. Crit. Care Med. 2009, 179, 11–18. [Google Scholar] [CrossRef] [Green Version]
- Sheu, J.; Hawryluk, E.B.; Guo, D.; London, W.B.; Huang, J.T. Voriconazole phototoxicity in children: A retrospective review. J. Am. Acad. Dermatol. 2015, 72, 314–320. [Google Scholar] [CrossRef]
- El-Baba, F.; Gao, Y.; Soubani, A.O. Pulmonary Aspergillosis: What the Generalist Needs to Know. Am. J. Med. 2020, 133, 668–674. [Google Scholar] [CrossRef] [PubMed]
- Clancy, C.J.; Nguyen, M.H. Long-term voriconazole and skin cancer: Is there cause for concern? Curr. Infect. Dis. Rep. 2011, 13, 536–543. [Google Scholar] [CrossRef] [PubMed]
- Rivero-Menendez, O.; Alastruey-Izquierdo, A.; Mellado, E.; Cuenca-Estrella, M. Triazole resistance in Aspergillus spp.: A worldwide problem? J. Fungi 2016, 2, 21. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Periselneris, J.; Nwankwo, L.; Schelenz, S.; Shah, A.; Armstrong-James, D. Posaconazole for the treatment of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. J. Antimicrob. Chemother. 2019, 74, 1701–1703. [Google Scholar] [CrossRef] [PubMed]
- Patel, D.; Popple, S.; Claydon, A.; Modha, D.E.; Gaillard, E.A. Posaconazole therapy in children with cystic fibrosis and Aspergillus-related lung disease. Med. Mycol. 2019, 58, 11–21. [Google Scholar] [CrossRef]
- Jacobs, S.E.; Saez-Lacy, D.; Wynkoop, W.; Walsh, T.J. Successful Treatment of Allergic Bronchopulmonary Aspergillosis with Isavuconazole: Case Report and Review of the Literature. In Open Forum Infectious Diseases; Oxford University Press: Oxford, UK, 2017; Volume 4. [Google Scholar]
- Voskamp, A.L.; Gillman, A.; Symons, K.; Sandrini, A.; Rolland, J.M.; O’Heir, R.E.; Douglass, J.A. Clinical efficacy and immunologic effects of Omalizumab in allergic bronchopulmonary aspergillosis. J. Allergy Clin. Immunol. Pr. 2015, 3, 192–199. [Google Scholar] [CrossRef]
- Koutsokera, A.; Corriveau, S.; Sykes, J.; Coriati, A.; Cortes, D.; Vadas, P.; Chaparro, C.; Mclntyre, K.; Tullis, E.; Stephenson, A.L. Omalizumab for asthma and allergic bronchopulmonary aspergillosis in adults with cystic fibrosis. J. Cyst. Fibros. 2020, 19, 119–124. [Google Scholar] [CrossRef] [Green Version]
- Perisson, C.; Destruys, L.; Grenet, D.; Bassinet, L.; Derelle, J.; Sermet-Gaudelus, I.; Thumerelle, C.; Prevotat, A.; Rosner, V.; Clement, A.; et al. Omalizumab treatment for allergic bronchopulmonary aspergillosis in young patients with cystic fibrosis. Respir. Med. 2017, 133, 12–15. [Google Scholar] [CrossRef] [Green Version]
- Zhang, L.; Borish, L.; Smith, A.; Somerville, L.; Albon, D. Use of mepolizumab in adult patients with cystic fibrosis and an eosinophilic phenotype: Case series. Allergy Asthma Clin. Immunol. 2020, 16, 3. [Google Scholar] [CrossRef]
- Kreindler, J.L.; Steele, C.; Nguyen, N.; Chan, Y.R.; Pilewski, J.M.; Alcorn, J.F.; Vyas, Y.M.; Aujla, S.J.; Finelli, P.; Blanchard, M.; et al. Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis. J. Clin. Investig. 2010, 120, 3242–3254. [Google Scholar] [CrossRef] [Green Version]
- Nguyen, N.L.H.; Pilewski, J.M.; Celedón, J.C.; Mandalapu, S.; Blanchard, M.L.; De Ricco, A.; Hartigan, E.; Alcorn, J.F.; Kolls, J.K. Vitamin D supplementation decreases Aspergillus fumigatus specific Th2 responses in CF patients with aspergillus sensitization: A phase one open-label study. Asthma Res. Pr. 2015, 1, 3. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Frost, F.J.; Nazareth, D.S.; Charman, S.C.; Winstanley, C.; Walshaw, M.J. Ivacaftor Is Associated with Reduced Lung Infection by Key Cystic Fibrosis Pathogens. A Cohort Study Using National Registry Data. Ann. Am. Thorac. Soc. 2019, 16, 1375–1382. [Google Scholar] [CrossRef] [PubMed]
Stage |
---|
Stage I, acute The patient is diagnosed with all typical features (Aspergillus-specific IgE, radiological abnormalities, peripheral blood eosinophilia, Aspergillus-specific serum precipitins) |
Stage II, remission Asymptomatic patient, no new radiological infiltrates, no rise in total IgE for at least 6 months |
Stage III, exacerbation New pulmonary infiltrates on chest X-ray with peripheral blood eosinophilia and double the remission IgE level |
Stage IV, corticosteroid-dependent asthma Inability to taper off from corticosteroid treatment |
Stage V, fibrotic lung disease Irreversible fibrosis and chronic cavitation at X-ray and CT scan |
Diagnostic Criteria |
---|
Major Asthma Presence of transient pulmonary infiltrates (fleeting shadows Immediate cutaneous reactivity to A. fumigatus Elevated total serum IgE Precipitating antibodies against A. fumigatus Peripheral blood eosinophilia Elevated serum IgE and IgG to A. fumigatus Central/proximal bronchiectasis with normal tapering of distal bronchi |
Minor Expectoration of golden-brownish sputum plugs Positive sputum culture for Aspergillus species Late (Arthus-type) skin reactivity to A. fumigatus |
Diagnostic Criteria |
---|
Cystic fibrosis with acute or subacute clinical deterioration Serum total IgE concentration >1000 IU/mL unless the patient is receiving systemic corticosteroids Positive serum-specific IgE (>0.35 kUA/L) or immediate skin test Precipitating antibodies to A. fumigatus or serum IgG antibodies to A. fumigatus by an in vitro test New or recent infiltrates (or mucus plugging) on chest radiography or CT that do not respond to antibiotics and standard physiotherapy |
Diagnostic Criteria |
---|
Obligatory (both needed) Type 1 Aspergillus skin test positive or elevated IgE against A. fumigatus Elevated total IgE levels (>1000 IU/mL unless all other criteria are met) |
Other (≥2 out of 3): Presence of IgG antibodies against A. fumigatus or precipitating antibodies Presence of fleeting or fixed pulmonary opacities on chest X-ray Eosinophil count >500 cells/µL in steroid-naïve patients |
Proposed Definition | |
---|---|
Fungal colonization |
|
Fungal sensitization | Aspergillus skin test positive or elevated IgE against A. fumigatus without inflammation or lung damage |
ABPA |
|
Regimen |
---|
Weeks 0–2 Prednisolone 1 mg/kg/day (max 50 mg/die) |
Weeks 2–4 Prednisolone 0.5 mg/kg/day |
Weeks 4–6 Prednisolone 0.5 mg/kg 3 times per week |
Weeks 6–8 Prednisolone 0.5 mg/kg 3 times per week |
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Lattanzi, C.; Messina, G.; Fainardi, V.; Tripodi, M.C.; Pisi, G.; Esposito, S. Allergic Bronchopulmonary Aspergillosis in Children with Cystic Fibrosis: An Update on the Newest Diagnostic Tools and Therapeutic Approaches. Pathogens 2020, 9, 716. https://doi.org/10.3390/pathogens9090716
Lattanzi C, Messina G, Fainardi V, Tripodi MC, Pisi G, Esposito S. Allergic Bronchopulmonary Aspergillosis in Children with Cystic Fibrosis: An Update on the Newest Diagnostic Tools and Therapeutic Approaches. Pathogens. 2020; 9(9):716. https://doi.org/10.3390/pathogens9090716
Chicago/Turabian StyleLattanzi, Claudia, Giulia Messina, Valentina Fainardi, Maria Candida Tripodi, Giovanna Pisi, and Susanna Esposito. 2020. "Allergic Bronchopulmonary Aspergillosis in Children with Cystic Fibrosis: An Update on the Newest Diagnostic Tools and Therapeutic Approaches" Pathogens 9, no. 9: 716. https://doi.org/10.3390/pathogens9090716
APA StyleLattanzi, C., Messina, G., Fainardi, V., Tripodi, M. C., Pisi, G., & Esposito, S. (2020). Allergic Bronchopulmonary Aspergillosis in Children with Cystic Fibrosis: An Update on the Newest Diagnostic Tools and Therapeutic Approaches. Pathogens, 9(9), 716. https://doi.org/10.3390/pathogens9090716