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It's blowing in the wind: New insights into thunderstorm-related asthma
Reviews and feature articles
Editorials It’s blowing in the wind: New insights into thunderstorm-related asthma Guy B. Marks, MBBS, PhD,a and Robert K. Bush, MDb Sydney, Australia, and Madison, Wis
Epidemics of asthma (clusters of patients requiring emergency treatment for asthma) have occurred for a number of years. A variety of causes have been implicated including exposure to allergens from industrial sources,1 outdoor pollens,2 meteorologic parameters,3 and viral illnesses.4 In the current issue of the Journal, Pulimood et al5 report that exposure to the fungus Alternaria in sensitized individuals might also play an important role in thunderstorm-related asthma exacerbations. Sensitivity to fungi, especially Alternaria, is known to be linked with the onset of asthma and its persistence and severity.6 Epidemics of near-fatal asthma7 and asthma deaths may also be associated with exposure to fungal spores.8 Beginning in the early 1950s, reports of environmental factors involved in epidemics of asthma began to surface— eg, outbreaks in the Yokohama area of Japan—were attributed to air pollution.9 Subsequently, air pollution as a cause for hospital admissions for asthma in various locales throughout the world have been reported.3 In the early 1960s, epidemics of acute asthma occurring in New Orleans were initially felt to be due to meteorologic conditions as well as exposure to fungal spores.10 Epidemic asthma in Barcelona, Spain, was ultimately linked to offloading of soybeans from ships in the harbor.11-13 In the New Orleans and Barcelona outbreaks, both fungal spores and soybean allergens may have been involved.14 Several reports have indicated increased acute asthma episodes occurring during thunderstorms.8,12,15 In many
From athe Woolcock Institute of Medical Research, Sydney; and bthe University of Wisconsin–Madison and Wm. S. Middleton VA Hospital, Madison. Disclosure of potential conflict of interest: G. B. Marks has received an allocation of grant funding from Woolcock Institute by GlaxoSmithKline, AstraZeneca, Pfizer, Boehringer Ingelheim, and Ait Liguide Healthcare and for seminars given on the Woolcock has received payments from GlaxoSmithKline; has received grant educational support from GlaxoSmithKline to attend the American Thoracic Society international scientific meeting; and has been funded by AstraZeneca to attend a scientific leadership symposium in Lund, Sweden. R. K. Bush has consulting arrangements with Gentel Biosciences and has received grant support from the National Institutes of Health, the University of Nebraska, Amgen Inc, and Greer Laboratories. Received for publication July 9, 2007; accepted for publication July 11, 2007. Reprint requests: Robert K. Bush, MD, 2500 Overlook Terrace, Madison, WI 53705. E-mail: [email protected]. J Allergy Clin Immunol 2007;120:530-2. 0091-6749/$32.00 Ó 2007 American Academy of Allergy, Asthma & Immunology doi:10.1016/j.jaci.2007.07.012
530
instances, there were large numbers of fungal spores such as Didymella, a sporobolomycete, in the air at the time of the episodes, although a direct causal effect was not proven.8 Subsequent studies indicated that grass pollen sensitivity and exposure to the pollen is an important cause of thunderstorm-related asthma.15 The article by Pulimood et al5 in this issue of the Journal was a study of an epidemic of asthma admissions associated with a thunderstorm outflow in the United Kingdom. Evaluation of the affected individuals demonstrated that the majority were sensitized to Alternaria (23 of 26). The odds ratio of developing thunderstorm-related asthma attacks if sensitive to Alternaria and Cladosporium was 9.31 (95% CI, 2.3-37.6) and 63.96 (95% CI, 3.571143.9). Analysis of the atmosphere indicated that high levels of Didymella, Alternaria, and Cladosporium spores were present and that broken Alternaria spores in the air were highly correlated with the admission rate for acute asthma. The authors conclude that Alternaria sensitivity is a compelling risk factor for epidemic asthma in patients with seasonal asthma with coexisting grass pollen sensitivity, and Alternaria exposure is another important factor in thunderstorm-related asthma. The present study does have methodologic flaws, particularly in the selection of the control population, who were from the outpatient clinic, whereas cases were selected from hospitalized patients. In addition, less than half of the thunderstorm-related cases had skin prick tests performed, further raising the possibility of selection bias. Further studies investigating controls who are hospitalized in the absence of a thunderstorm would be necessary to provide proof that Alternaria sensitivity and exposure were indeed responsible for the phenomenon. Despite these limitations, the present study adds further evidence that Alternaria sensitivity is an important factor in asthma and its severity. Population studies in the North America6 and Australia16 have shown that sensitization to Alternaria is associated with an increased risk of having asthma. In Europe, sensitization to Alternaria has been linked to the presence of severe asthma as opposed to asthma of mild to moderate severity.17 The association with very severe episodes of asthma resulting in respiratory arrest7 or admission to intensive care18 has been demonstrated on 2 continents. The link with sensitization implies a causal role of exposure to Alternaria. However, the evidence for this has been more limited. Previous studies in rural New South Wales, Australia, have shown that the severity of
nonspecific airway hyperresponsiveness and the frequency of wheeze and bronchodilator use correlated with ambient levels of Alternaria spores among children who were sensitized to Alternaria but not among children sensitized to other allergens.19 In London, daily counts of presentations with exacerbations of asthma were correlated with ambient levels of fungal spores, including Alternaria.20 The current study adds further weight to the conclusion that Alternaria has a particular propensity to cause severe attacks of asthma. The present study is the first to demonstrate that thunderstorms may be an important trigger for Alternariarelated exacerbations of asthma. The mechanism remains uncertain. The link with sensitization implicates an allergen-IgE–mediated pathway. However, nonallergic pathways may also be involved. In addition to its effects through IgE-mediated mechanisms, fungal spores, particularly those that may be germinating, can liberate proteases that can have direct effects on epithelial cells, leading to increased airway inflammation. Germination also increases the release of allergen from Alternaria spores.21 Hence, meteorologic conditions favoring germination of Alternaria spores would be expected to enhance both allergic and nonallergic adverse effects of exposure to Alternaria. It seems plausible that thunderstorms or some of the meteorologic conditions associated with them might promote germination, and this may explain the observed adverse effect of thunderstorms in Alternaria-sensitized individuals when airborne levels of Alternaria are high. There has been recent interest in the role of smaller fungal fragments and hyphae, in addition to the conidia, as contributors to total fungal exposure. These small particles may be released under different circumstances, remain airborne for longer, be deposited more deeply in the lung, and have been described as being associated with Alternaria.22 In the present study, only 7 of 26 thunderstorm cases who were assessed were taking inhaled corticosteroids. Girgis et al23 also found that patients presenting with asthma during the thunderstorm were much less likely than patients presenting at other times to be taking inhaled corticosteroids. This implies, but does not prove, that inhaled corticosteroids may protect at-risk individuals against severe attacks of asthma during thunderstorms. In sum, a combination of sensitivity to grass pollen and fungi (particularly Alternaria and Cladosporium) along with exposure to high levels of these allergens may account for the epidemics of acute asthma occurring during or in proximity to thunderstorms. The evidence points to a common set of circumstances that underlie the diverse reports of thunderstorm-related epidemics. The following conditions appear necessary for an epidemic to occur: 1. An abundance of potentially allergenic biologic material, specifically grass pollen and fungi; 2. A thunderstorm outflow14 sweeping up the grass pollen and/or fungi and concentrating the material near ground level in a population centre;
3. Formation of respirable particles (<10 mm), eg, by the action of water in rupturing pollen grains to release starch granules15 or germinating fungal spores; 4. Exposure of individuals who are sensitized to the relevant allergen and have a propensity for airway narrowing, ie, untreated airway hyperresponsiveness, to an air mass containing a high concentration of respirable allergenic particles. In effect, individuals in the path of this air mass receive a high-dose allergen challenge. Those who are susceptible have a predictable severe asthmatic response.18 Allergen-mediated epidemics may occur without thunderstorms, as evidenced by the soybean-related episodes in Barcelona.1 Thunderstorm outflows are not required when abundant respirable-size allergen particles are generated in high concentration near population centers by another means. However, this seems to be a relatively rare occurrence in nature, and most focal severe epidemics are reported in association with thunderstorms. Indeed, an analysis of data for 6 rural towns in New South Wales demonstrated that, during late spring and summer, nearly 50% of days with excessive emergency attendances for asthma coincided with the passage of thunderstorm outflows over those towns.14 Thunderstorm-related epidemics of asthma are alarming. They affect patients, health care workers, and health system administrators in a dramatic way. Understanding these epidemics not only enhances knowledge about the mechanisms of severe asthma and the role of allergen exposure in its etiology, but it also may help predict the events, prepare health authorities for their impact, and possibly even facilitate and provide health advice for atrisk individuals. The report by Pulimood et al5 fills in another piece of the puzzle: demonstrating the role of fungal spores, in particular Alternaria, as the triggering allergen in some episodes of thunderstorm-related asthma. In regions where thunderstorm-related epidemics are known to occur, health authorities should identify the specific conditions preceding the events and, when these conditions are met and a thunderstorm outflow is forecast, they should alert emergency departments and primary care doctors to prepare for the epidemic of exacerbations of asthma. Further research is required to identify what advice, if any, may be helpful for the individuals and communities at risk. REFERENCES 1. Mendes E, Cintra AU. Collective asthma, simulating an epidemic, provoked by castor-bean dust. J Allergy 1954;25:253-9. 2. Pollart SM, Reid MJ, Fling JA, Chapman MD, Platts-Mills TA. Epidemiology of emergency room asthma in northern California: association with IgE antibody to ryegrass pollen. J Allergy Clin Immunol 1988;82: 224-30. 3. Piccolo MC, Perillo GM, Ramon CG, DiDio V. Outbreaks of asthma attacks and meteorologic parameters in Bahia Blanca, Argentina. Ann Allergy 1988;60:107-10. 4. Johnston NW, Johnston SL, Norman GR, Dai J, Sears MR. The September epidemic of asthma hospitalization: school children as disease vectors. J Allergy Clin Immunol 2006;117:557-62.
Reviews and feature articles
Marks and Bush 531
J ALLERGY CLIN IMMUNOL VOLUME 120, NUMBER 3
532 Marks and Bush
Reviews and feature articles
5. Pulimood TB, Corden JM, Bryden C, Sharples L, Nasser SM. Epidemic asthma and the role of fungal mold, Alternaria alternata. J Allergy Clin Immunol 2007;120:610-7. 6. Bush RK, Prochnau JJ. Alternaria-induced asthma. J Allergy Clin Immunol 2004;113:227-34. 7. O’Hollaren MT, Yunginger JW, Offord KP, Somers MJ, O’Connell EJ, Ballard DJ, et al. Exposure to an aeroallergen as a possible precipitating factor in respiratory arrest in young patients with asthma. N Engl J Med 1991;324:359-63. 8. Ackroyd JF, Fry JS. Hyaline ascospores as a cause of the epidemic of asthma deaths in the 1960s. Clin Allergy 1983;13:287-90. 9. Redfearn PL, Karakawa JA. Etiology of Yokohama asthma: a preliminary report. Med Bull US 1953;1:108-10. 10. Salvaggio JE, Klein RC. New Orleans asthma. I. Characterization of individuals involved in epidemics. J Allergy 1967;39:227-33. 11. Anto JM, Sunyer J, Rodriguez-Roisin R, Suarez-Cervera M, Vazquez L. Community outbreaks of asthma associated with inhalation of soybean dust. Toxicoepidemiological Committee. N Engl J Med 1989;320:1097-102. 12. Codina R, Lockey RF. Possible role of molds as secondary etiologic agents of the asthma epidemics in Barcelona. Spain. J Allergy Clin Immunol 1998;102:318-20. 13. Packe GE, Ayres JG. Asthma outbreak during a thunderstorm. Lancet 1985;2:199-204. 14. Marks GB, Colquhoun JR, Girgis ST, Koski MH, Treloar AB, Hansen P, et al. Thunderstorm outflows preceding epidemics of asthma during spring and summer. Thorax 2001;56:468-71.
J ALLERGY CLIN IMMUNOL SEPTEMBER 2007
15. Suphioglu C, Singh MB, Taylor P, Bellomo R, Holmes P, Puy R, et al. Mechanism of grass-pollen-induced asthma. Lancet 1992;339:569-72. 16. Peat JK, Tovey E, Mellis CM, Leeder SR, Woolcock AJ. Importance of house dust mite and Alternaria allergens in childhood asthma: an epidemiological study in two climatic regions of Australia. Clin Exp Allergy 1993;23:812-20. 17. Zureik M, Neukirch C, Leynaert B, Liard R, Bousquet J, Neukirch F. Sensitisation to airborne moulds and severity of asthma: cross sectional study from European Community respiratory health survey. BMJ 2002; 325:411-4. 18. Black PN, Udy AA, Brodie SM. Sensitivity to fungal allergens is a risk factor for life-threatening asthma. Allergy 2000;55:501-4. 19. Downs SH, Mitakakis TZ, Marks GB, Car NG, Belousova EG, Leuppi JD, et al. Clinical importance of Alternaria exposure in children. Am J Respir Crit Care Med 2001;164:455-9. 20. 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. 21. Mitakakis TZ, Barnes C, Tovey ER. Spore germination increases allergen release from Alternaria. J Allergy Clin Immunol 2001;107:388-90. 22. Green BJ, Schmechel D, Tovey ER. Detection of aerosolized Alternaria alternata conidia, hyphae, and fragments by using a novel double-immunostaining technique. Clin Diagn Lab Immunol 2005;12:1114-6. 23. Girgis ST, Marks GB, Downs SH, Kolbe A, Car GN, Paton R. Thunderstorm-associated asthma in an inland town in south-eastern Australia. Who is at risk? Eur Respir J 2000;16:3-8.
Correction With regard to the July 2007 editorial entitled ‘‘Anaphylaxis and vitamin D: A role for the sunshine hormone?’’ (2007;120:128-30): In the 7th paragraph (p 129), the unit of measure given for UVB solar radiation is incorrect. The relevant portion sentence should read ‘‘.in the range of 290 to 320 nm.’’ Please note that this error appears only in the print version of this editorial.
Editorials It’s blowing in the wind: New insights into thunderstorm-related asthma Guy B. Marks, MBBS, PhD,a and Robert K. Bush, MDb Sydney, Australia, and Madison, Wis
Epidemics of asthma (clusters of patients requiring emergency treatment for asthma) have occurred for a number of years. A variety of causes have been implicated including exposure to allergens from industrial sources,1 outdoor pollens,2 meteorologic parameters,3 and viral illnesses.4 In the current issue of the Journal, Pulimood et al5 report that exposure to the fungus Alternaria in sensitized individuals might also play an important role in thunderstorm-related asthma exacerbations. Sensitivity to fungi, especially Alternaria, is known to be linked with the onset of asthma and its persistence and severity.6 Epidemics of near-fatal asthma7 and asthma deaths may also be associated with exposure to fungal spores.8 Beginning in the early 1950s, reports of environmental factors involved in epidemics of asthma began to surface— eg, outbreaks in the Yokohama area of Japan—were attributed to air pollution.9 Subsequently, air pollution as a cause for hospital admissions for asthma in various locales throughout the world have been reported.3 In the early 1960s, epidemics of acute asthma occurring in New Orleans were initially felt to be due to meteorologic conditions as well as exposure to fungal spores.10 Epidemic asthma in Barcelona, Spain, was ultimately linked to offloading of soybeans from ships in the harbor.11-13 In the New Orleans and Barcelona outbreaks, both fungal spores and soybean allergens may have been involved.14 Several reports have indicated increased acute asthma episodes occurring during thunderstorms.8,12,15 In many
From athe Woolcock Institute of Medical Research, Sydney; and bthe University of Wisconsin–Madison and Wm. S. Middleton VA Hospital, Madison. Disclosure of potential conflict of interest: G. B. Marks has received an allocation of grant funding from Woolcock Institute by GlaxoSmithKline, AstraZeneca, Pfizer, Boehringer Ingelheim, and Ait Liguide Healthcare and for seminars given on the Woolcock has received payments from GlaxoSmithKline; has received grant educational support from GlaxoSmithKline to attend the American Thoracic Society international scientific meeting; and has been funded by AstraZeneca to attend a scientific leadership symposium in Lund, Sweden. R. K. Bush has consulting arrangements with Gentel Biosciences and has received grant support from the National Institutes of Health, the University of Nebraska, Amgen Inc, and Greer Laboratories. Received for publication July 9, 2007; accepted for publication July 11, 2007. Reprint requests: Robert K. Bush, MD, 2500 Overlook Terrace, Madison, WI 53705. E-mail: [email protected]. J Allergy Clin Immunol 2007;120:530-2. 0091-6749/$32.00 Ó 2007 American Academy of Allergy, Asthma & Immunology doi:10.1016/j.jaci.2007.07.012
530
instances, there were large numbers of fungal spores such as Didymella, a sporobolomycete, in the air at the time of the episodes, although a direct causal effect was not proven.8 Subsequent studies indicated that grass pollen sensitivity and exposure to the pollen is an important cause of thunderstorm-related asthma.15 The article by Pulimood et al5 in this issue of the Journal was a study of an epidemic of asthma admissions associated with a thunderstorm outflow in the United Kingdom. Evaluation of the affected individuals demonstrated that the majority were sensitized to Alternaria (23 of 26). The odds ratio of developing thunderstorm-related asthma attacks if sensitive to Alternaria and Cladosporium was 9.31 (95% CI, 2.3-37.6) and 63.96 (95% CI, 3.571143.9). Analysis of the atmosphere indicated that high levels of Didymella, Alternaria, and Cladosporium spores were present and that broken Alternaria spores in the air were highly correlated with the admission rate for acute asthma. The authors conclude that Alternaria sensitivity is a compelling risk factor for epidemic asthma in patients with seasonal asthma with coexisting grass pollen sensitivity, and Alternaria exposure is another important factor in thunderstorm-related asthma. The present study does have methodologic flaws, particularly in the selection of the control population, who were from the outpatient clinic, whereas cases were selected from hospitalized patients. In addition, less than half of the thunderstorm-related cases had skin prick tests performed, further raising the possibility of selection bias. Further studies investigating controls who are hospitalized in the absence of a thunderstorm would be necessary to provide proof that Alternaria sensitivity and exposure were indeed responsible for the phenomenon. Despite these limitations, the present study adds further evidence that Alternaria sensitivity is an important factor in asthma and its severity. Population studies in the North America6 and Australia16 have shown that sensitization to Alternaria is associated with an increased risk of having asthma. In Europe, sensitization to Alternaria has been linked to the presence of severe asthma as opposed to asthma of mild to moderate severity.17 The association with very severe episodes of asthma resulting in respiratory arrest7 or admission to intensive care18 has been demonstrated on 2 continents. The link with sensitization implies a causal role of exposure to Alternaria. However, the evidence for this has been more limited. Previous studies in rural New South Wales, Australia, have shown that the severity of
nonspecific airway hyperresponsiveness and the frequency of wheeze and bronchodilator use correlated with ambient levels of Alternaria spores among children who were sensitized to Alternaria but not among children sensitized to other allergens.19 In London, daily counts of presentations with exacerbations of asthma were correlated with ambient levels of fungal spores, including Alternaria.20 The current study adds further weight to the conclusion that Alternaria has a particular propensity to cause severe attacks of asthma. The present study is the first to demonstrate that thunderstorms may be an important trigger for Alternariarelated exacerbations of asthma. The mechanism remains uncertain. The link with sensitization implicates an allergen-IgE–mediated pathway. However, nonallergic pathways may also be involved. In addition to its effects through IgE-mediated mechanisms, fungal spores, particularly those that may be germinating, can liberate proteases that can have direct effects on epithelial cells, leading to increased airway inflammation. Germination also increases the release of allergen from Alternaria spores.21 Hence, meteorologic conditions favoring germination of Alternaria spores would be expected to enhance both allergic and nonallergic adverse effects of exposure to Alternaria. It seems plausible that thunderstorms or some of the meteorologic conditions associated with them might promote germination, and this may explain the observed adverse effect of thunderstorms in Alternaria-sensitized individuals when airborne levels of Alternaria are high. There has been recent interest in the role of smaller fungal fragments and hyphae, in addition to the conidia, as contributors to total fungal exposure. These small particles may be released under different circumstances, remain airborne for longer, be deposited more deeply in the lung, and have been described as being associated with Alternaria.22 In the present study, only 7 of 26 thunderstorm cases who were assessed were taking inhaled corticosteroids. Girgis et al23 also found that patients presenting with asthma during the thunderstorm were much less likely than patients presenting at other times to be taking inhaled corticosteroids. This implies, but does not prove, that inhaled corticosteroids may protect at-risk individuals against severe attacks of asthma during thunderstorms. In sum, a combination of sensitivity to grass pollen and fungi (particularly Alternaria and Cladosporium) along with exposure to high levels of these allergens may account for the epidemics of acute asthma occurring during or in proximity to thunderstorms. The evidence points to a common set of circumstances that underlie the diverse reports of thunderstorm-related epidemics. The following conditions appear necessary for an epidemic to occur: 1. An abundance of potentially allergenic biologic material, specifically grass pollen and fungi; 2. A thunderstorm outflow14 sweeping up the grass pollen and/or fungi and concentrating the material near ground level in a population centre;
3. Formation of respirable particles (<10 mm), eg, by the action of water in rupturing pollen grains to release starch granules15 or germinating fungal spores; 4. Exposure of individuals who are sensitized to the relevant allergen and have a propensity for airway narrowing, ie, untreated airway hyperresponsiveness, to an air mass containing a high concentration of respirable allergenic particles. In effect, individuals in the path of this air mass receive a high-dose allergen challenge. Those who are susceptible have a predictable severe asthmatic response.18 Allergen-mediated epidemics may occur without thunderstorms, as evidenced by the soybean-related episodes in Barcelona.1 Thunderstorm outflows are not required when abundant respirable-size allergen particles are generated in high concentration near population centers by another means. However, this seems to be a relatively rare occurrence in nature, and most focal severe epidemics are reported in association with thunderstorms. Indeed, an analysis of data for 6 rural towns in New South Wales demonstrated that, during late spring and summer, nearly 50% of days with excessive emergency attendances for asthma coincided with the passage of thunderstorm outflows over those towns.14 Thunderstorm-related epidemics of asthma are alarming. They affect patients, health care workers, and health system administrators in a dramatic way. Understanding these epidemics not only enhances knowledge about the mechanisms of severe asthma and the role of allergen exposure in its etiology, but it also may help predict the events, prepare health authorities for their impact, and possibly even facilitate and provide health advice for atrisk individuals. The report by Pulimood et al5 fills in another piece of the puzzle: demonstrating the role of fungal spores, in particular Alternaria, as the triggering allergen in some episodes of thunderstorm-related asthma. In regions where thunderstorm-related epidemics are known to occur, health authorities should identify the specific conditions preceding the events and, when these conditions are met and a thunderstorm outflow is forecast, they should alert emergency departments and primary care doctors to prepare for the epidemic of exacerbations of asthma. Further research is required to identify what advice, if any, may be helpful for the individuals and communities at risk. REFERENCES 1. Mendes E, Cintra AU. Collective asthma, simulating an epidemic, provoked by castor-bean dust. J Allergy 1954;25:253-9. 2. Pollart SM, Reid MJ, Fling JA, Chapman MD, Platts-Mills TA. Epidemiology of emergency room asthma in northern California: association with IgE antibody to ryegrass pollen. J Allergy Clin Immunol 1988;82: 224-30. 3. Piccolo MC, Perillo GM, Ramon CG, DiDio V. Outbreaks of asthma attacks and meteorologic parameters in Bahia Blanca, Argentina. Ann Allergy 1988;60:107-10. 4. Johnston NW, Johnston SL, Norman GR, Dai J, Sears MR. The September epidemic of asthma hospitalization: school children as disease vectors. J Allergy Clin Immunol 2006;117:557-62.
Reviews and feature articles
Marks and Bush 531
J ALLERGY CLIN IMMUNOL VOLUME 120, NUMBER 3
532 Marks and Bush
Reviews and feature articles
5. Pulimood TB, Corden JM, Bryden C, Sharples L, Nasser SM. Epidemic asthma and the role of fungal mold, Alternaria alternata. J Allergy Clin Immunol 2007;120:610-7. 6. Bush RK, Prochnau JJ. Alternaria-induced asthma. J Allergy Clin Immunol 2004;113:227-34. 7. O’Hollaren MT, Yunginger JW, Offord KP, Somers MJ, O’Connell EJ, Ballard DJ, et al. Exposure to an aeroallergen as a possible precipitating factor in respiratory arrest in young patients with asthma. N Engl J Med 1991;324:359-63. 8. Ackroyd JF, Fry JS. Hyaline ascospores as a cause of the epidemic of asthma deaths in the 1960s. Clin Allergy 1983;13:287-90. 9. Redfearn PL, Karakawa JA. Etiology of Yokohama asthma: a preliminary report. Med Bull US 1953;1:108-10. 10. Salvaggio JE, Klein RC. New Orleans asthma. I. Characterization of individuals involved in epidemics. J Allergy 1967;39:227-33. 11. Anto JM, Sunyer J, Rodriguez-Roisin R, Suarez-Cervera M, Vazquez L. Community outbreaks of asthma associated with inhalation of soybean dust. Toxicoepidemiological Committee. N Engl J Med 1989;320:1097-102. 12. Codina R, Lockey RF. Possible role of molds as secondary etiologic agents of the asthma epidemics in Barcelona. Spain. J Allergy Clin Immunol 1998;102:318-20. 13. Packe GE, Ayres JG. Asthma outbreak during a thunderstorm. Lancet 1985;2:199-204. 14. Marks GB, Colquhoun JR, Girgis ST, Koski MH, Treloar AB, Hansen P, et al. Thunderstorm outflows preceding epidemics of asthma during spring and summer. Thorax 2001;56:468-71.
J ALLERGY CLIN IMMUNOL SEPTEMBER 2007
15. Suphioglu C, Singh MB, Taylor P, Bellomo R, Holmes P, Puy R, et al. Mechanism of grass-pollen-induced asthma. Lancet 1992;339:569-72. 16. Peat JK, Tovey E, Mellis CM, Leeder SR, Woolcock AJ. Importance of house dust mite and Alternaria allergens in childhood asthma: an epidemiological study in two climatic regions of Australia. Clin Exp Allergy 1993;23:812-20. 17. Zureik M, Neukirch C, Leynaert B, Liard R, Bousquet J, Neukirch F. Sensitisation to airborne moulds and severity of asthma: cross sectional study from European Community respiratory health survey. BMJ 2002; 325:411-4. 18. Black PN, Udy AA, Brodie SM. Sensitivity to fungal allergens is a risk factor for life-threatening asthma. Allergy 2000;55:501-4. 19. Downs SH, Mitakakis TZ, Marks GB, Car NG, Belousova EG, Leuppi JD, et al. Clinical importance of Alternaria exposure in children. Am J Respir Crit Care Med 2001;164:455-9. 20. 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. 21. Mitakakis TZ, Barnes C, Tovey ER. Spore germination increases allergen release from Alternaria. J Allergy Clin Immunol 2001;107:388-90. 22. Green BJ, Schmechel D, Tovey ER. Detection of aerosolized Alternaria alternata conidia, hyphae, and fragments by using a novel double-immunostaining technique. Clin Diagn Lab Immunol 2005;12:1114-6. 23. Girgis ST, Marks GB, Downs SH, Kolbe A, Car GN, Paton R. Thunderstorm-associated asthma in an inland town in south-eastern Australia. Who is at risk? Eur Respir J 2000;16:3-8.
Correction With regard to the July 2007 editorial entitled ‘‘Anaphylaxis and vitamin D: A role for the sunshine hormone?’’ (2007;120:128-30): In the 7th paragraph (p 129), the unit of measure given for UVB solar radiation is incorrect. The relevant portion sentence should read ‘‘.in the range of 290 to 320 nm.’’ Please note that this error appears only in the print version of this editorial.