Alternaria Alternata Sensitization in Asthma: A Cross-sectional Study of Prevalence and Demographic Risk Factors
-
Seyed Hesamodin Nabavizadeh
,
Aida Askarisarvestani
,
Elham Amini
,
Fardin Karbakhsh Ravari
,
Golnoosh Karimi
Abstract
Alternaria alternata is one of the most potent fungal allergens associated with allergic respiratory diseases, particularly asthma. Sensitization to A alternata has been linked to poor asthma control and increased morbidity, yet its prevalence varies widely across populations due to environmental and methodological differences. This study aimed to determine the prevalence and demographic predictors of A alternata sensitization among patients with moderate to severe asthma.
A cross-sectional study was conducted from March to September 2024 among 80 patients with physician-diagnosed moderate or severe asthma in Shiraz, Iran. Participants underwent skin prick testing (SPT) for A. alternata. Demographic and clinical data were collected and analyzed using descriptive statistics, χ2 tests, and logistic regression.
Among the 80 patients (mean age 29.03 ± 20.45 years; 53.8% male), 28.8% tested positive for Alternaria sensitization. Sensitization was significantly more prevalent in patients younger than 18 years (44.1%) compared to adults (17.4%). No significant difference was observed based on sex. Although sensitization was more frequent in patients with severe asthma (40.6%) than moderate asthma (20.8%), this trend was not statistically significant. Logistic regression identified younger age as the only independent predictor of sensitization.
Alternaria alternata sensitization is common among individuals with moderate to severe asthma, particularly in younger patients. These findings underscore the importance of routine fungal allergen screening in asthmatics, especially children, to inform targeted management strategies and potentially reduce asthma-related morbidity.
1. Damialis A, Kaimakamis E, Konoglou M, Akritidis I, Traidl-Hoffmann C, Gioulekas D. Estimating the abundance of airborne pollen and fungal spores at variable elevations using an aircraft: how high can they fly? Sci Rep. 2017;7:44535.
2. Rick EM, Woolnough K, Pashley CH, Wardlaw AJ. Allergic Fungal Airway Disease. J Investig Allergol Clin Immunol. 2016;26(6):344-54.
3. Al-Ahmad M, Jusufovic E, Arifhodzic N, Rodriguez T, Nurkic J. Association of molds and metrological parameters to frequency of severe asthma exacerbation. Allergy Asthma Clin Immunol. 2019;15:29.
4. Agnihotri NT, Saltoun C. Acute severe asthma (status asthmaticus). Allergy Asthma Proc. 2019;40(6):406-9.
5. Gabriel MF, Postigo I, Tomaz CT, Martínez J. Alternaria alternata allergens: Markers of exposure, phylogeny and risk of fungi-induced respiratory allergy. Environ Int. 2016;89-90:71-80.
6. Sachdeva K, Do DC, Zhang Y, Hu X, Chen J, Gao P. Environmental Exposures and Asthma Development: Autophagy, Mitophagy, and Cellular Senescence. Front Immunol. 2019;10:2787.
7. Bousquet PJ, Chinn S, Janson C, Kogevinas M, Burney P, Jarvis D. Geographical variation in the prevalence of positive skin tests to environmental aeroallergens in the European Community Respiratory Health Survey I. Allergy. 2007;62(3):301-9.
8. Borna E, Nwaru BI, Bjerg A, Mincheva R, Rådinger M, Lundbäck B, et al. Changes in the prevalence of asthma and respiratory symptoms in western Sweden between 2008 and 2016. Allergy. 2019;74(9):1703-15.
9. Mahboubi Oskouei Y, Farid Hosseini R, Ahanchian H, Jarahi L, Ariaee N, Jabbari Azad F. Report of Common Aeroallergens among Allergic Patients in Northeastern Iran. Iran J Otorhinolaryngol. 2017;29(91):89-94.
10. Swed S, Sawaf B, Al-Obeidat F, Hafez W, Rakab A, Alibrahim H, et al. Asthma prevalence among United States population insights from NHANES data analysis. Sci Rep. 2024;14(1):8059.
11. Moore WC, Bleecker ER, Curran-Everett D, Erzurum SC, Ameredes BT, Bacharier L, et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program. J Allergy Clin Immunol. 2007;119(2):405-13.
12. Antonicelli L, Bucca C, Neri M, De Benedetto F, Sabbatani P, Bonifazi F, et al. Asthma severity and medical resource utilisation. Eur Respir J. 2004;23(5):723-9.
13. Levy BD, Noel PJ, Freemer MM, Cloutier MM, Georas SN, Jarjour NN, et al. Future Research Directions in Asthma. An NHLBI Working Group Report. Am J Respir Crit Care Med. 2015;192(11):1366-72.
14. Denning DW, O'Driscoll BR, Hogaboam CM, Bowyer P, Niven RM. The link between fungi and severe asthma: a summary of the evidence. Eur Respir J. 2006;27(3):615-26.
15. Sporik R, Holgate ST, Platts-Mills TA, Cogswell JJ. Exposure to house-dust mite allergen (Der p I) and the development of asthma in childhood. A prospective study. N Engl J Med. 1990;323(8):502-7.
16. Rosenstreich DL, Eggleston P, Kattan M, Baker D, Slavin RG, Gergen P, et al. The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma. N Engl J Med. 1997;336(19):1356-63.
17. Tanaka A, Fujiwara A, Uchida Y, Yamaguchi M, Ohta S, Homma T, et al. Evaluation of the association between sensitization to common inhalant fungi and poor asthma control. Ann Allergy Asthma Immunol. 2016;117(2):163-8.e1.
18. O'Driscoll BR, Hopkinson LC, Denning DW. Mold sensitization is common amongst patients with severe asthma requiring multiple hospital admissions. BMC Pulm Med. 2005;5:4.
19. Cloutier MM, Baptist AP, Blake KV, Brooks EG, Bryant-Stephens T, DiMango E, et al. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020;146(6):1217-70.
20. Lehmann S, Sprünken A, Wagner N, Tenbrock K, Ott H. Clinical relevance of IgE-mediated sensitization against the mould Alternaria alternata in children with asthma. Ther Adv Respir Dis. 2017;11(1):30-9.
21. Hernandez-Ramirez G, Barber D, Tome-Amat J, Garrido-Arandia M, Diaz-Perales A. Alternaria as an Inducer of Allergic Sensitization. J Fungi (Basel). 2021;7(10).
22. Bousquet PJ, Hooper R, Kogevinas M, Jarvis D, Burney P. Number of allergens to be tested to assess allergenic sensitization in epidemiologic studies: results of the European Community Respiratory Health Survey I. Clin Exp Allergy. 2007;37(5):780-7.
23. Guan K, Zhu W, Sha L, Liu C, Zhao J, Yin J, et al. Prevalence of Sensitization to Aeroallergens in Greater Beijing Region Children With Respiratory Allergy. Front Pediatr. 2022;10:848357.
24. Loghmani A, Raoofi R, Ownagh A, Delirezh N. Alternaria alternata acts on human Monocyte-derived Dendritic cells to mediate Th2/Th17 polarisation. Allergol Immunopathol (Madr). 2017;45(2):175-82.
25. Yabuhara A, Macaubas C, Prescott SL, Venaille TJ, Holt BJ, Habre W, et al. TH2-polarized immunological memory to inhalant allergens in atopics is established during infancy and early childhood. Clin Exp Allergy. 1997;27(11):1261-9.
26. Forkel S, Beutner C, Schröder SS, Bader O, Gupta S, Fuchs T, et al. Sensitization against Fungi in Patients with Airway Allergies over 20 Years in Germany. Int Arch Allergy Immunol. 2021;182(6):515-23.
27. Ohn J, Paik SH, Doh EJ, Park HS, Yoon HS, Cho S. Allergen Sensitization Pattern by Sex: A Cluster Analysis in Korea. Ann Dermatol. 2017;29(6):735-41.
28. Schaefer AL, Ceesay M, Leier JA, Tesch J, Wisenden BD, Pandey S. Factors Contributing to Sex Differences in Mice Inhaling Aspergillus fumigatus. Int J Environ Res Public Health. 2020;17(23).
29. Lombardi C, Savi E, Ridolo E, Passalacqua G, Canonica GW. Is allergic sensitization relevant in severe asthma? Which allergens may be culprit? World Allergy Organ J. 2017;10(1):2.
30. Fergeson JE, Patel SS, Lockey RF. Acute asthma, prognosis, and treatment. J Allergy Clin Immunol. 2017;139(2):438-47.
31. Lyons TW, Wakefield DB, Cloutier MM. Mold and Alternaria skin test reactivity and asthma in children in Connecticut. Ann Allergy Asthma Immunol. 2011;106(4):301-7.
32. 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.
33. Halonen M, Stern DA, Wright AL, Taussig LM, Martinez FD. Alternaria as a major allergen for asthma in children raised in a desert environment. Am J Respir Crit Care Med. 1997;155(4):1356-61.
34. Perzanowski MS, Sporik R, Squillace SP, Gelber LE, Call R, Carter M, et al. Association of sensitization to Alternaria allergens with asthma among school-age children. J Allergy Clin Immunol. 1998;101(5):626-32.
35. Salo PM, Arbes SJ, Jr., Sever M, Jaramillo R, Cohn RD, London SJ, et al. Exposure to Alternaria alternata in US homes is associated with asthma symptoms. J Allergy Clin Immunol. 2006;118(4):892-8.
36. Wiesner DL, Klein BS. Lung epithelium: barrier immunity to inhaled fungi and driver of fungal-associated allergic asthma. Curr Opin Microbiol. 2017;40:8-13.
37. Bartemes KR, Kita H. Innate and adaptive immune responses to fungi in the airway. J Allergy Clin Immunol. 2018;142(2):353-63.
38. Garrido-Arandia M, Silva-Navas J, Ramírez-Castillejo C, Cubells-Baeza N, Gómez-Casado C, Barber D, et al. Characterisation of a flavonoid ligand of the fungal protein Alt a 1. Sci Rep. 2016;6:33468.
39. Hernández-Ramírez G, Pazos-Castro D, Gómez Torrijos E, Yuste Montalvo A, Romero-Sahagun A, González-Klein Z, et al. Group 1 allergens, transported by mold spores, induce asthma exacerbation in a mouse model. Allergy. 2020;75(9):2388-91.
40. Gómez-Casado C, Murua-García A, Garrido-Arandia M, González-Melendi P, Sánchez-Monge R, Barber D, et al. Alt a 1 from Alternaria interacts with PR5 thaumatin-like proteins. FEBS Lett. 2014;588(9):1501-8.
41. Nolte M, Barber D, Maloney J, Li Z, Kaur A, Galan A, et al. Timothy specific IgE levels are associated with efficacy and safety of timothy grass sublingual immunotherapy tablet. Ann Allergy Asthma Immunol. 2015;115(6):509-15.e2.
42. Kobayashi T, Iijima K, Radhakrishnan S, Mehta V, Vassallo R, Lawrence CB, et al. Asthma-related environmental fungus, Alternaria, activates dendritic cells and produces potent Th2 adjuvant activity. J Immunol. 2009;182(4):2502-10.
2. Rick EM, Woolnough K, Pashley CH, Wardlaw AJ. Allergic Fungal Airway Disease. J Investig Allergol Clin Immunol. 2016;26(6):344-54.
3. Al-Ahmad M, Jusufovic E, Arifhodzic N, Rodriguez T, Nurkic J. Association of molds and metrological parameters to frequency of severe asthma exacerbation. Allergy Asthma Clin Immunol. 2019;15:29.
4. Agnihotri NT, Saltoun C. Acute severe asthma (status asthmaticus). Allergy Asthma Proc. 2019;40(6):406-9.
5. Gabriel MF, Postigo I, Tomaz CT, Martínez J. Alternaria alternata allergens: Markers of exposure, phylogeny and risk of fungi-induced respiratory allergy. Environ Int. 2016;89-90:71-80.
6. Sachdeva K, Do DC, Zhang Y, Hu X, Chen J, Gao P. Environmental Exposures and Asthma Development: Autophagy, Mitophagy, and Cellular Senescence. Front Immunol. 2019;10:2787.
7. Bousquet PJ, Chinn S, Janson C, Kogevinas M, Burney P, Jarvis D. Geographical variation in the prevalence of positive skin tests to environmental aeroallergens in the European Community Respiratory Health Survey I. Allergy. 2007;62(3):301-9.
8. Borna E, Nwaru BI, Bjerg A, Mincheva R, Rådinger M, Lundbäck B, et al. Changes in the prevalence of asthma and respiratory symptoms in western Sweden between 2008 and 2016. Allergy. 2019;74(9):1703-15.
9. Mahboubi Oskouei Y, Farid Hosseini R, Ahanchian H, Jarahi L, Ariaee N, Jabbari Azad F. Report of Common Aeroallergens among Allergic Patients in Northeastern Iran. Iran J Otorhinolaryngol. 2017;29(91):89-94.
10. Swed S, Sawaf B, Al-Obeidat F, Hafez W, Rakab A, Alibrahim H, et al. Asthma prevalence among United States population insights from NHANES data analysis. Sci Rep. 2024;14(1):8059.
11. Moore WC, Bleecker ER, Curran-Everett D, Erzurum SC, Ameredes BT, Bacharier L, et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program. J Allergy Clin Immunol. 2007;119(2):405-13.
12. Antonicelli L, Bucca C, Neri M, De Benedetto F, Sabbatani P, Bonifazi F, et al. Asthma severity and medical resource utilisation. Eur Respir J. 2004;23(5):723-9.
13. Levy BD, Noel PJ, Freemer MM, Cloutier MM, Georas SN, Jarjour NN, et al. Future Research Directions in Asthma. An NHLBI Working Group Report. Am J Respir Crit Care Med. 2015;192(11):1366-72.
14. Denning DW, O'Driscoll BR, Hogaboam CM, Bowyer P, Niven RM. The link between fungi and severe asthma: a summary of the evidence. Eur Respir J. 2006;27(3):615-26.
15. Sporik R, Holgate ST, Platts-Mills TA, Cogswell JJ. Exposure to house-dust mite allergen (Der p I) and the development of asthma in childhood. A prospective study. N Engl J Med. 1990;323(8):502-7.
16. Rosenstreich DL, Eggleston P, Kattan M, Baker D, Slavin RG, Gergen P, et al. The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma. N Engl J Med. 1997;336(19):1356-63.
17. Tanaka A, Fujiwara A, Uchida Y, Yamaguchi M, Ohta S, Homma T, et al. Evaluation of the association between sensitization to common inhalant fungi and poor asthma control. Ann Allergy Asthma Immunol. 2016;117(2):163-8.e1.
18. O'Driscoll BR, Hopkinson LC, Denning DW. Mold sensitization is common amongst patients with severe asthma requiring multiple hospital admissions. BMC Pulm Med. 2005;5:4.
19. Cloutier MM, Baptist AP, Blake KV, Brooks EG, Bryant-Stephens T, DiMango E, et al. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020;146(6):1217-70.
20. Lehmann S, Sprünken A, Wagner N, Tenbrock K, Ott H. Clinical relevance of IgE-mediated sensitization against the mould Alternaria alternata in children with asthma. Ther Adv Respir Dis. 2017;11(1):30-9.
21. Hernandez-Ramirez G, Barber D, Tome-Amat J, Garrido-Arandia M, Diaz-Perales A. Alternaria as an Inducer of Allergic Sensitization. J Fungi (Basel). 2021;7(10).
22. Bousquet PJ, Hooper R, Kogevinas M, Jarvis D, Burney P. Number of allergens to be tested to assess allergenic sensitization in epidemiologic studies: results of the European Community Respiratory Health Survey I. Clin Exp Allergy. 2007;37(5):780-7.
23. Guan K, Zhu W, Sha L, Liu C, Zhao J, Yin J, et al. Prevalence of Sensitization to Aeroallergens in Greater Beijing Region Children With Respiratory Allergy. Front Pediatr. 2022;10:848357.
24. Loghmani A, Raoofi R, Ownagh A, Delirezh N. Alternaria alternata acts on human Monocyte-derived Dendritic cells to mediate Th2/Th17 polarisation. Allergol Immunopathol (Madr). 2017;45(2):175-82.
25. Yabuhara A, Macaubas C, Prescott SL, Venaille TJ, Holt BJ, Habre W, et al. TH2-polarized immunological memory to inhalant allergens in atopics is established during infancy and early childhood. Clin Exp Allergy. 1997;27(11):1261-9.
26. Forkel S, Beutner C, Schröder SS, Bader O, Gupta S, Fuchs T, et al. Sensitization against Fungi in Patients with Airway Allergies over 20 Years in Germany. Int Arch Allergy Immunol. 2021;182(6):515-23.
27. Ohn J, Paik SH, Doh EJ, Park HS, Yoon HS, Cho S. Allergen Sensitization Pattern by Sex: A Cluster Analysis in Korea. Ann Dermatol. 2017;29(6):735-41.
28. Schaefer AL, Ceesay M, Leier JA, Tesch J, Wisenden BD, Pandey S. Factors Contributing to Sex Differences in Mice Inhaling Aspergillus fumigatus. Int J Environ Res Public Health. 2020;17(23).
29. Lombardi C, Savi E, Ridolo E, Passalacqua G, Canonica GW. Is allergic sensitization relevant in severe asthma? Which allergens may be culprit? World Allergy Organ J. 2017;10(1):2.
30. Fergeson JE, Patel SS, Lockey RF. Acute asthma, prognosis, and treatment. J Allergy Clin Immunol. 2017;139(2):438-47.
31. Lyons TW, Wakefield DB, Cloutier MM. Mold and Alternaria skin test reactivity and asthma in children in Connecticut. Ann Allergy Asthma Immunol. 2011;106(4):301-7.
32. 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.
33. Halonen M, Stern DA, Wright AL, Taussig LM, Martinez FD. Alternaria as a major allergen for asthma in children raised in a desert environment. Am J Respir Crit Care Med. 1997;155(4):1356-61.
34. Perzanowski MS, Sporik R, Squillace SP, Gelber LE, Call R, Carter M, et al. Association of sensitization to Alternaria allergens with asthma among school-age children. J Allergy Clin Immunol. 1998;101(5):626-32.
35. Salo PM, Arbes SJ, Jr., Sever M, Jaramillo R, Cohn RD, London SJ, et al. Exposure to Alternaria alternata in US homes is associated with asthma symptoms. J Allergy Clin Immunol. 2006;118(4):892-8.
36. Wiesner DL, Klein BS. Lung epithelium: barrier immunity to inhaled fungi and driver of fungal-associated allergic asthma. Curr Opin Microbiol. 2017;40:8-13.
37. Bartemes KR, Kita H. Innate and adaptive immune responses to fungi in the airway. J Allergy Clin Immunol. 2018;142(2):353-63.
38. Garrido-Arandia M, Silva-Navas J, Ramírez-Castillejo C, Cubells-Baeza N, Gómez-Casado C, Barber D, et al. Characterisation of a flavonoid ligand of the fungal protein Alt a 1. Sci Rep. 2016;6:33468.
39. Hernández-Ramírez G, Pazos-Castro D, Gómez Torrijos E, Yuste Montalvo A, Romero-Sahagun A, González-Klein Z, et al. Group 1 allergens, transported by mold spores, induce asthma exacerbation in a mouse model. Allergy. 2020;75(9):2388-91.
40. Gómez-Casado C, Murua-García A, Garrido-Arandia M, González-Melendi P, Sánchez-Monge R, Barber D, et al. Alt a 1 from Alternaria interacts with PR5 thaumatin-like proteins. FEBS Lett. 2014;588(9):1501-8.
41. Nolte M, Barber D, Maloney J, Li Z, Kaur A, Galan A, et al. Timothy specific IgE levels are associated with efficacy and safety of timothy grass sublingual immunotherapy tablet. Ann Allergy Asthma Immunol. 2015;115(6):509-15.e2.
42. Kobayashi T, Iijima K, Radhakrishnan S, Mehta V, Vassallo R, Lawrence CB, et al. Asthma-related environmental fungus, Alternaria, activates dendritic cells and produces potent Th2 adjuvant activity. J Immunol. 2009;182(4):2502-10.
| Files | ||
| Issue | Articles in Press | |
| Section | Original Article(s) | |
| Keywords | ||
| Age Alternaria Asthma Fungal sensitization Skin test | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Nabavizadeh SH, Askarisarvestani A, Amini E, Karbakhsh Ravari F, Karimi G. Alternaria Alternata Sensitization in Asthma: A Cross-sectional Study of Prevalence and Demographic Risk Factors. Iran J Allergy Asthma Immunol. 2025;:1-7.
