Editorial Allergy Asthma Immunol Res. 2016 September;8(5):389-390. http://dx.doi.org/10.4168/aair.2016.8.5.389 pISSN 2092-7355 • eISSN 2092-7363
Does Specific Fungal Allergen Really Matter? Young Yoo1,2* 1
Department of Pediatrics, Korea University Anam Hospital 2Allergy Immunology Center, Korea University, Seoul, Korea
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Exposure and sensitization to allergens can promote development and exacerbation of allergic disease. Various indoor allergens, including dust mites, animal dander, and mold have been reported to associate with allergic disease. Fungal spores and particles are widely distributed in outdoor and indoor environments and exposure to fungi has been shown to induce allergic disease and exacerbate symptoms in individuals sensitized to fungi.1 However, it is still unclear whether the total fungal spore count or specific species is more relevant to allergic responses. It should be investigated that the contribution of fungi to allergic disease is species-specific, with specific fungal species leading to allergic disease exacerbations. Many studies examining the relationships between fungal exposure and allergic disease have focused on the total fungal spore count instead of specific fungal species as an indicator of exposure.2,3 In an elementary school with indoor mold count ranging 6,000 to 50,000 spores/m3, 85% of the students and teachers reported significant allergy symptoms.2 The author concluded that the elevations of the total spore count can have clinical implications, and a building is considered unhealthy at a total spore count of >1,000 spores/m3.2 Another observational study which is conducted in a large urban population demonstrated a positive correlation between daily concentrations of fungal spores and the frequency of visits to the emergency department.4 Therefore, changes in total fungal spore concentrations appear to be associated with an increase in allergy exacerbations. A more recent study5 on fungal spores in 173 asthmatic homes and 85 non-asthmatic homes reported that the total fungal spore and specific fungal species were higher in asthmatic homes than in non-asthmatic homes. However, that study did not confirm that the differences in the total fungal spore count or the distribution of specific fungi can cause asthma symptoms. In contrast, case-control studies conducted with patients with asthma6 or allergic rhinitis7 showed no significant differences in the total spore count between cases and controls. The authors of these studies documented a potential relationship between genus-species and allergic diseases because some allergenic
fungi were significantly higher in the allergy patients’ homes, suggesting the type of mold is more important than the total spore count. In a large study of Taiwanese schoolchildren, there was no significant correlation between asthma and the total fungal spore in classrooms; however, Aspergillus/Penicillium and basidiospores spp. significantly correlated with current asthma.8 In a birth cohort study, exposure to specific fungal species in water-damaged buildings during infancy was associated with childhood asthma at 7 years.9 Thus, it could be possible that specific fungal species are more important in developing allergy symptoms rather than the total fungal spore count. This indicates that fungal species may play a different role in allergic disease. There is accumulating evidence that precise recognition of species-specific sensitization to fungal allergens is important in the management of allergic disease. In this issue of the AAIR Journal, Lin et al.10 report the importance of specific allergenic species rather than the total fungal spore count for the exacerbation of allergy symptoms in fungus sensitized patients. They measured total and specific spore concentrations in 12 allergic patients’ homes at active and inactive symptom stages. They could not find any significant association between exacerbations of allergy symptoms and the total or viable fungal spore count. Instead, they revealed that specific fungal species were more frequently found during the active stage. They also concluded the importance of specific species rather than the total fungal spore count for allergy exacerbations. However, an extreme small sample size (10 fungus-sensitized patients), heterogeneity of allergic disease, and no investigation into the effect of house dust mite (HDM) concentrations, the most important risk factor for allergy exacerbation in HDMsensitized patients, should be considered in the interpretation of their results. Correspondence to: Young Yoo, MD, PhD, Department of Pediatrics, College of Medicine, Korea University, 73 Inchon-ro, Sungbuk-gu, Seoul 02841, Korea. Tel: +82-2-920-5090; Fax: +82-2-922-7476; E-mail: [email protected] Received: May 25, 2016; Accepted: May 27, 2016 •There are no financial or other issues that might lead to conflict of interest.
© Copyright The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease
http://e-aair.org 389
Volume 8, Number 5, September 2016
Yoo Meanwhile, recent studies11,12 have demonstrated the clinical implications of a high concentration of small fungal fragments in asthma severity. Submicron fungal fragments, such as fungal hyphae and fragmented conidia, are more common than airborne spores, and these fragments may function as allergen sources. These authors found that the presence of submicron fungal fragments is positively associated with a higher prevalence of reported asthma symptoms.11,12 Researchers emphasized the importance of submicron fungal fragments rather than fungal spores as a potential risk factor for allergic disease exacerbations, because they can penetrate into the lungs and be deposited therein.12 Recent progress in gene technology has greatly contributed to the identification of species-specific allergic molecules from different allergenic fungal sources.13 However, data verifying the allergenic reactivity of fungal allergens are insufficient. Studies regarding the species-specific impact of indoor fungi on the allergen sensitized population are warranted. Identification of exact contributing factors for allergy exacerbations is crucial to evaluating the role of fungal species in fungal allergic patients.13,14 Identification of the spectrum of fungal species in allergic patients’ homes will provide information about potential intervention targets for promoting allergic disease and improving understanding of possible mechanisms involved in fungi associated allergy. It is also necessary to assess not only specific fungal species but also submicron fragments for better understanding of exact mechanisms for allergic exacerbations in fungal allergic patients.
REFERENCES 1. Twaroch TE, Curin M, Valenta R, Swoboda I. Mold allergens in respiratory allergy: from structure to therapy. Allergy Asthma Immunol Res 2015;7:205-20. 2. Santilli J, Rockwell W. Fungal contamination of elementary schools:
http://e-aair.org 390
a new environmental hazard. Ann Allergy Asthma Immunol 2003; 90:203-8. 3. Yazicioglu M, Asan A, Ones U, Vatansever U, Sen B, Ture M, et al. Indoor airborne fungal spores and home characteristics in asthmatic children from Edirne region of Turkey. Allergol Immunopathol (Madr) 2004;32:197-203. 4. Atkinson RW, Strachan DP, Anderson HR, Hajat S, Emberlin J. Temporal associations between daily counts of fungal spores and asthma exacerbations. Occup Environ Med 2006;63:580-90. 5. Meng J, Barnes CS, Rosenwasser LJ; Children’s Mercy Center for Environmental Health. Identify of the fungal species present in the homes of asthmatic children. Clin Exp Allergy 2012;42:1448-58. 6. Jones R, Recer GM, Hwang SA, Lin S. Association between indoor mold and asthma among children in Buffalo, New York. Indoor Air 2011;21:156-64. 7. Osborne M, Reponen T, Adhikari A, Cho SH, Grinshpun SA, Levin L, et al. Specific fungal exposures, allergic sensitization, and rhinitis in infants. Pediatr Allergy Immunol 2006;17:450-7. 8. Chen CH, Chao HJ, Chan CC, Chen BY, Guo YL. Current asthma in schoolchildren is related to fungal spores in classrooms. Chest 2014; 146:123-34. 9. Reponen T, Lockey J, Bernstein DI, Vesper SJ, Levin L, Khurana Hershey GK, et al. Infant origins of childhood asthma associated with specific molds. J Allergy Clin Immunol 2012;130:639-44. 10. Lin WR, Chen YH, Lee MF, Hsu LY, Tien CJ, Shih FM, et al. Does spore count matter in fungal allergy?: The role of allergenic fungal species. Allergy Asthma Immunol Res 2016;8:404-11. 11. Seo S, Choung JT, Chen BT, Lindsley WG, Kim KY. The level of submicron fungal fragments in homes with asthmatic children. Environ Res 2014;131:71-6. 12. Green BJ, Tovey ER, Sercombe JK, Blachere FM, Beezhold DH, Schmechel D. Airborne fungal fragments and allergenicity. Med Mycol 2006;44:S245-55. 13. Fukutomi Y, Taniguchi M. Sensitization to fungal allergens: Resolved and unresolved issue. Allergol Int 2015;64:321-31. 14. Hope J. A review of the mechanism of injury and treatment approaches for illness resulting from exposure to water-damaged buildings, mold, and mycotoxins. ScientificWorldJournal 2013;2013: 767482.
Allergy Asthma Immunol Res. 2016 September;8(5):389-390. http://dx.doi.org/10.4168/aair.2016.8.5.389
Does Specific Fungal Allergen Really Matter? Young Yoo1,2* 1
Department of Pediatrics, Korea University Anam Hospital 2Allergy Immunology Center, Korea University, Seoul, Korea
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Exposure and sensitization to allergens can promote development and exacerbation of allergic disease. Various indoor allergens, including dust mites, animal dander, and mold have been reported to associate with allergic disease. Fungal spores and particles are widely distributed in outdoor and indoor environments and exposure to fungi has been shown to induce allergic disease and exacerbate symptoms in individuals sensitized to fungi.1 However, it is still unclear whether the total fungal spore count or specific species is more relevant to allergic responses. It should be investigated that the contribution of fungi to allergic disease is species-specific, with specific fungal species leading to allergic disease exacerbations. Many studies examining the relationships between fungal exposure and allergic disease have focused on the total fungal spore count instead of specific fungal species as an indicator of exposure.2,3 In an elementary school with indoor mold count ranging 6,000 to 50,000 spores/m3, 85% of the students and teachers reported significant allergy symptoms.2 The author concluded that the elevations of the total spore count can have clinical implications, and a building is considered unhealthy at a total spore count of >1,000 spores/m3.2 Another observational study which is conducted in a large urban population demonstrated a positive correlation between daily concentrations of fungal spores and the frequency of visits to the emergency department.4 Therefore, changes in total fungal spore concentrations appear to be associated with an increase in allergy exacerbations. A more recent study5 on fungal spores in 173 asthmatic homes and 85 non-asthmatic homes reported that the total fungal spore and specific fungal species were higher in asthmatic homes than in non-asthmatic homes. However, that study did not confirm that the differences in the total fungal spore count or the distribution of specific fungi can cause asthma symptoms. In contrast, case-control studies conducted with patients with asthma6 or allergic rhinitis7 showed no significant differences in the total spore count between cases and controls. The authors of these studies documented a potential relationship between genus-species and allergic diseases because some allergenic
fungi were significantly higher in the allergy patients’ homes, suggesting the type of mold is more important than the total spore count. In a large study of Taiwanese schoolchildren, there was no significant correlation between asthma and the total fungal spore in classrooms; however, Aspergillus/Penicillium and basidiospores spp. significantly correlated with current asthma.8 In a birth cohort study, exposure to specific fungal species in water-damaged buildings during infancy was associated with childhood asthma at 7 years.9 Thus, it could be possible that specific fungal species are more important in developing allergy symptoms rather than the total fungal spore count. This indicates that fungal species may play a different role in allergic disease. There is accumulating evidence that precise recognition of species-specific sensitization to fungal allergens is important in the management of allergic disease. In this issue of the AAIR Journal, Lin et al.10 report the importance of specific allergenic species rather than the total fungal spore count for the exacerbation of allergy symptoms in fungus sensitized patients. They measured total and specific spore concentrations in 12 allergic patients’ homes at active and inactive symptom stages. They could not find any significant association between exacerbations of allergy symptoms and the total or viable fungal spore count. Instead, they revealed that specific fungal species were more frequently found during the active stage. They also concluded the importance of specific species rather than the total fungal spore count for allergy exacerbations. However, an extreme small sample size (10 fungus-sensitized patients), heterogeneity of allergic disease, and no investigation into the effect of house dust mite (HDM) concentrations, the most important risk factor for allergy exacerbation in HDMsensitized patients, should be considered in the interpretation of their results. Correspondence to: Young Yoo, MD, PhD, Department of Pediatrics, College of Medicine, Korea University, 73 Inchon-ro, Sungbuk-gu, Seoul 02841, Korea. Tel: +82-2-920-5090; Fax: +82-2-922-7476; E-mail: [email protected] Received: May 25, 2016; Accepted: May 27, 2016 •There are no financial or other issues that might lead to conflict of interest.
© Copyright The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease
http://e-aair.org 389
Volume 8, Number 5, September 2016
Yoo Meanwhile, recent studies11,12 have demonstrated the clinical implications of a high concentration of small fungal fragments in asthma severity. Submicron fungal fragments, such as fungal hyphae and fragmented conidia, are more common than airborne spores, and these fragments may function as allergen sources. These authors found that the presence of submicron fungal fragments is positively associated with a higher prevalence of reported asthma symptoms.11,12 Researchers emphasized the importance of submicron fungal fragments rather than fungal spores as a potential risk factor for allergic disease exacerbations, because they can penetrate into the lungs and be deposited therein.12 Recent progress in gene technology has greatly contributed to the identification of species-specific allergic molecules from different allergenic fungal sources.13 However, data verifying the allergenic reactivity of fungal allergens are insufficient. Studies regarding the species-specific impact of indoor fungi on the allergen sensitized population are warranted. Identification of exact contributing factors for allergy exacerbations is crucial to evaluating the role of fungal species in fungal allergic patients.13,14 Identification of the spectrum of fungal species in allergic patients’ homes will provide information about potential intervention targets for promoting allergic disease and improving understanding of possible mechanisms involved in fungi associated allergy. It is also necessary to assess not only specific fungal species but also submicron fragments for better understanding of exact mechanisms for allergic exacerbations in fungal allergic patients.
REFERENCES 1. Twaroch TE, Curin M, Valenta R, Swoboda I. Mold allergens in respiratory allergy: from structure to therapy. Allergy Asthma Immunol Res 2015;7:205-20. 2. Santilli J, Rockwell W. Fungal contamination of elementary schools:
http://e-aair.org 390
a new environmental hazard. Ann Allergy Asthma Immunol 2003; 90:203-8. 3. Yazicioglu M, Asan A, Ones U, Vatansever U, Sen B, Ture M, et al. Indoor airborne fungal spores and home characteristics in asthmatic children from Edirne region of Turkey. Allergol Immunopathol (Madr) 2004;32:197-203. 4. Atkinson RW, Strachan DP, Anderson HR, Hajat S, Emberlin J. Temporal associations between daily counts of fungal spores and asthma exacerbations. Occup Environ Med 2006;63:580-90. 5. Meng J, Barnes CS, Rosenwasser LJ; Children’s Mercy Center for Environmental Health. Identify of the fungal species present in the homes of asthmatic children. Clin Exp Allergy 2012;42:1448-58. 6. Jones R, Recer GM, Hwang SA, Lin S. Association between indoor mold and asthma among children in Buffalo, New York. Indoor Air 2011;21:156-64. 7. Osborne M, Reponen T, Adhikari A, Cho SH, Grinshpun SA, Levin L, et al. Specific fungal exposures, allergic sensitization, and rhinitis in infants. Pediatr Allergy Immunol 2006;17:450-7. 8. Chen CH, Chao HJ, Chan CC, Chen BY, Guo YL. Current asthma in schoolchildren is related to fungal spores in classrooms. Chest 2014; 146:123-34. 9. Reponen T, Lockey J, Bernstein DI, Vesper SJ, Levin L, Khurana Hershey GK, et al. Infant origins of childhood asthma associated with specific molds. J Allergy Clin Immunol 2012;130:639-44. 10. Lin WR, Chen YH, Lee MF, Hsu LY, Tien CJ, Shih FM, et al. Does spore count matter in fungal allergy?: The role of allergenic fungal species. Allergy Asthma Immunol Res 2016;8:404-11. 11. Seo S, Choung JT, Chen BT, Lindsley WG, Kim KY. The level of submicron fungal fragments in homes with asthmatic children. Environ Res 2014;131:71-6. 12. Green BJ, Tovey ER, Sercombe JK, Blachere FM, Beezhold DH, Schmechel D. Airborne fungal fragments and allergenicity. Med Mycol 2006;44:S245-55. 13. Fukutomi Y, Taniguchi M. Sensitization to fungal allergens: Resolved and unresolved issue. Allergol Int 2015;64:321-31. 14. Hope J. A review of the mechanism of injury and treatment approaches for illness resulting from exposure to water-damaged buildings, mold, and mycotoxins. ScientificWorldJournal 2013;2013: 767482.
Allergy Asthma Immunol Res. 2016 September;8(5):389-390. http://dx.doi.org/10.4168/aair.2016.8.5.389
