The prevalence of asthma in the United States is estimated to be 5% to 8%.1 Asthma is responsible for approximately 5000 deaths annually in this country. It is a leading cause of emergency department (ED) visits, hospitalizations, and school and work absenteeism. The total estimated direct cost of the disease in the United States was $12.7 billion in 1998.2
Asthma is a multifactorial disease with complex genetic and environmental components. It can be exacerbated by exercise, laughter, exposure to allergens and environ- mental tobacco smoke, cold air, viral infections, nitrogen dioxide, sulfur dioxide, ozone, endotoxins, sulfites, and b-blockers.
In this article, we discuss the most important natural and man-made pollutants (other than those associated with occupational asthma) that cause or exacerbate asthma and the most appropriate preventive measures. These contaminants can be classified as either causal pollutants (inhaled allergens) or contributing pollutants (such as tobacco smoke, air pollution, and endotoxins, which irritate the airways). According to the World Health Organization (WHO) estimations, asthma is allergic in more than 50% of adults and in 80% of affected children.3
1. What is responsible for the increase in the prevalence of asthma?
The estimated prevalence of atopic diseases in some developed countries exceeds 30%.1,4 A variety of factors may account for this.5-7
Longer and more concentrated exposure to indoor allergens. Table 1 provides a summary of the most important indoor and outdoor contaminants. Many studies suggest that exposure to indoor allergens is an important factor in the increased incidence and prevalence of allergic diseases. The average person in developed countries spends more than 90% of his or her time indoors; exposure to indoor allergens is therefore more prolonged than it is to outdoor seasonal allergens, and the concentration of most indoor allergens is greater. This exposure of genetically predisposed persons to various allergens, especially indoor allergens during infancy, sensitizes them.8-10
Viral respiratory tract infections, as well as passive exposure to cigarette smoke and other contaminants, can enhance the airway response to inhaled allergens in atopic persons.11,12
More outdoor air pollutants. Epidemiologic studies demonstrate that outdoor levels of air pollutants--including nitrogen dioxide, sulfur dioxide, ozone, and respirable diesel exhaust particles--associated with the use of fossil fuels have progressively increased during the past decade.13,14
In the United States, the National Ambient Air Quality Standards (NAAQs) offer specific standards for air quality, including ozone, particulate matter (both particulate matter 10 [PM10] and particulate matter 2.5 [PM2.5]), sulfur dioxide, nitrogen dioxide, lead, and carbon monoxide. The NAAQs have been recently revised for both ozone and particulate matter based on data that suggested health risks at levels below those established in previous standards.15
Several outcome variables have been used in different studies to investigate a potential association between air pollution and asthma. A comparative study performed in 4 European cities reported an association between levels of nitrogen and sulfur dioxide and ED admissions for asthma in both children and adults.16 An association between nitrogen dioxide and ozone levels and asthma deaths has also been suggested.17 Nitrogen dioxide and PM10 levels have also been associated with lower forced vital capacity and forced expiratory volume in 1 second in children.18
Although an association between air pollution and asthma morbidity seems to be consistent, the possible effects of air pollution on the increased prevalence of asthma in developed countries remain controversial. Studies that compared the former East and West Germany suggested that the prevalence of asthma was greater in West Germany than in East Germany, where air pollution is more severe.19 Another study performed in Australia and New Zealand also indicated that the prevalence of asthma among children in these countries was greater than in countries with much higher levels of air pollution.20
Because traffic exhaust is one of the most important sources of air pollution in developed countries, a number of studies are being conducted to investigate the effects of this type of pollution on asthma. A study of children in the Netherlands reported a significant correlation between physician-diagnosed asthma during the first year of life and several traffic-related pollutants, such as PM2.5, soot, and nitrogen dioxide.21
Altered immune response (the hygiene hypothesis). The hygiene hypothesis suggests that the reduced microbial exposure of children--as a result of westernized lifestyles--is primarily responsible for the increased prevalence of allergic diseases during the past decades in developed countries.
Two main theories have been suggested to explain the hygiene hypothesis. The initial theory suggests that a lack of shifting from helper T cell 2 (TH2) dominance to T-helper T cell 1 (TH1) dominance--which is induced by exposure to immune stimulants, such as viruses, bacteria, and endotoxins, especially during the prenatal period and first years of life--is responsible for the increased prevalence of allergic diseases.22,23 TH1 cells produce interleukin (IL)-2, interferon g (IFN-g), and tumor necrosis factor b (TNF-b); TH2 cells produce IL-4, IL-5, IL-6, IL-10, and IL-13. IL-4, IL-13, and IL-5 promote the production of IgE in response to allergens, and IFN-g suppresses this IgE production. Bacterial and viral infections enhance IL-12 synthesis. IL-12, produced mainly by monocytes and macrophages, induces IFN-g synthesis by TH1 cells, resulting in a suppressed TH2 response.2 A more recent theory emphasizes the role of reduced activity of T regulatory cells (immune suppression) in the increased prevalence of allergic diseases.24
The results of several types of epidemiologic studies support the hygiene hypothesis. The factors that have been studied include parasitic and other infections, exposure to microbial products and cats and dogs, and breast-feeding.
Parasitic infections. The high prevalence of parasitic infections in developing countries protects against allergic diseases.25 Like allergic tissue responses, immune defenses against parasites involve IgE, mast cells, eosinophils, and TH2 lymphocytes. IgE responses are, therefore, immunoprotective against parasites and are not restricted to allergic diseases. This is illustrated by epidemiologic studies in Africa, South America, and Asia that indicate an increased prevalence of asthma associated with population shifts from rural to urban environments. Other studies investigating the effectiveness of anthelmintic treatment on allergic reactivity have demonstrated a decrease of total IgE levels accompanied by an increase in skin reactivity after treatment.
Childhood infections. Infections associated with siblings, day-care attendance, and household crowding protect against allergies and asthma.26-28 The frequency of several allergic diseases has been found to be inversely associated with the number of childhood infections and with the number of siblings and age of day-care attendance, as a measure of exposure to infections. Siblings and day-care attendance promote cross-infections and, thus, the stimulation of TH1 lymphocytes.
Microbial products. Exposure to microbial products associated with farming protects against allergies and asthma.29 It has been suggested that growing up on a farm protects against allergic sensitization in early life. High concentrations of endotoxins (lipopolysaccharide fragments that coat the outer membrane of Gram-negative bacteria) have been reported in farming environments. Endotoxins regulate various processes in the immune system, such as production of IL-12 and IFN-g.
Exposure to cats and dogs. Exposure to these animals in early life may protect against allergies.30 The presence of pets in the home may be associated with increased exposure to endotoxins and other microbial products and, thus, the immune system is indirectly affected.
Breast-feeding. The role of breast-feeding in the development of allergic sensitization is controversial.31 Some epidemiologic studies suggest a protective role of breast-feeding,32,33 and it has been hypothesized that the immunologic components of milk, such as secretory IgA, may account for this protective effect. However, other studies indicate an increased risk of allergy and asthma associated with breast-feeding.34,35
The mechanisms by which breast-feeding may increase allergies and asthma in children have been studied. Exclusively breast-fed infants may have lower levels of Gram-negative enterobacteria in their GI tract than nonbreast-fed infants. In addition, breast-feeding protects against infections.
The majority of studies that support the hygiene hypothesis are cross-sectional and cohort studies, not randomized controlled-intervention studies. Therefore, nonreported confounding factors may partially account for the observation of positive results. Moreover, many observations contradict the hygiene hypothesis and negative findings are less likely to be published than positive findings. The effects of a number of confounding factors on the hygiene hypothesis have been discussed elsewhere.36,37
Dietary influences. Other investigations indicate that dietary changes--such as a decrease in the consumption of fatty fish--may partially account for the increase in asthma.38,39 Epidemiologic studies suggest that omega-3 fatty acids, which are abundant in fish and have anti- inflammatory effects, may decrease symptoms of asthma.40 However, the effectiveness of dietary supplementation with omega-3 fatty acids in the primary prevention of asthma has not been thoroughly investigated.
1. O'Connell EJ. The burden of atopy and asthma in children. Allergy. 2004;59:7-11.
2. Weiss KB, Sullivan SD. The health economics of asthma and rhinitis, I: assessing the economic impact. J Allergy Clin Immunol. 2001;107:3-8.
3. Prevention of Allergy and Allergic Asthma. Gene-va: World Health Organization; 2003.
4. Gupta R, Sheikh A, Strachan DP, Anderson HR. Burden of allergic disease in the UK: secondary analyses of national databases. Clin Exp Allergy. 2004;34:520-526.
5. Wright AL. The epidemiology of the atopic child: who is at risk for what? J Allergy Clin Immunol. 2004;113:S2-S7.
6. Frew AJ. Advances in environmental and occupational diseases, 2003. J Allergy Clin Immunol. 2004; 113:1161-1166.
7. von Mutius E. Influences in allergy: epidemiology and the environment. J Allergy Clin Immunol. 2004;113:373-379.
8. Johnson CC, Ownby DR, Havstad SL. Family history, dust mite exposure in early childhood, and risk for pediatric atopy and asthma. J Allergy Clin Immunol. 2004;114:105-110.
9. Camara AA, Silva JM, Ferriani VPL, et al. Risk factors for wheezing in a subtropical environment: role of respiratory viruses and allergen sensitization. J Allergy Clin Immunol. 2004;113: 551-557.
10. Finn PW, Boudreau JO, He H, et al. Children at risk for asthma: home allergen levels, lymphocyte proliferation, and wheeze. J Allergy Clin Immunol. 2000;105:933-942.
11. Peebles RS. Viral infections, atopy, and asthma: is there a causal relationship? J Allergy Clin Immunol. 2004;113:S15-S18.
12. Rance F, de Blic J, Scheinmann P. Prevention of asthma and allergic diseases in children [in French]. Arch Pediatr. 2003;10:232-237.
13. Wong GW, Lai CK. Outdoor air pollution and asthma. Curr Opin Pulm Med. 2004;10:62-66.
14. D'Amato G, Liccardi G, D'Amato M, Cazzola M. Respiratory allergic diseases indiced by outdoor air pollution in urban areas. Monaldi Arch Chest Dis. 2002;57:161-163.
15. Graham LM. All I need is the air that I breathe: outdoor air quality and asthma. Paediatr Respir Rev. 2004;(suppl A):S59-S64.
16. Sunyer J, Spix C, Quenel P, et al. Urban air pollution and emergency admissions for asthma in European cities: the APHEA project. Thorax. 1997;52: 760-765.
17. Sunyer J, Basagana X, Belmonte J, Anto JM. Effect of nitrogen dioxide and ozone on the risk of dying in patients with severe asthma. Thorax. 2002; 57:687-693.
18. Peters JM, Avol E, Gauderman WJ, et al. A study of twelve Southern California communities with differing levels and types of air pollution. Am J Respir Crit Care Med. 1999;159:768-775.
19. Weiland SK, von Mutius E, Hirsch T, et al. Prevalence of respiratory and atopic disorders among children in the East and West of Germany five years after unification. Eur Respir J. 1999;14:862-870.
20. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Worldwide variations in the prevalence of asthma symptoms: the International Study of Asthma and Allergies in Childhood (ISAAC). Eur Respir J. 1998;12:315-335.
21. Brauer M, Hoek G, Van Vliet P, et al. Air pollution from traffic and the development of respiratory infections and asthmatic and allergic symptoms in children. Am J Respir Crit Care Med. 2002;166: 1092-1098.
22. Okudaira H. Why atopic diseases prevail in developed countries. Allergy Clin Immunol Int. 1998;10: 110-115.
23. Holt P, Cacaubas C, Sly P. Strategic targets for primary prevention of allergic disease in childhood. Allergy. 1998;53:72-76.
24. Romagnani S. The increased prevalence of allergy and the hygiene hypothesis: missing immune deviation, reduced immune suppression, or both? Immunology. 2004;112:352-363.
25. Ndiaye M, Bousquet J. Allergies and parasitoses in sub-Saharan Africa. Clin Rev Allergy Immunol. 2004;26:105-113.
26. Ball TM, Castro-Rodriguez JA, Griffith KA, et al. Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. N Engl J Med. 2000;343:538-543.
27. Kramer U, Heinrich J, Wjst M, Wichmann HE. Age of entry to day nursery and allergy in later childhood. Lancet. 1999;353:450-454.
28. Alves Cardoso MR, Cousens SN, Fernando de Goes Siqueira L, et al. Crowding: risk factor or protective factor for lower respiratory disease in young children? BMC Public Health. 2004; 4:19.
29. Riedler J, Braun-Hahrlander C, Eder W, et al. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet. 2001;358:1129-1133.
30. Hesselmar B, Abewrg N, Eriksson B, Bjorsten B. Does early exposure to cat or dog protect against later allergy development? Clin Exp Allergy. 1999;29: 611-617.
31. Oddy WH, Peat JK. Breastfeeding, asthma, and atopic disease: an epidemiological review of the literature. J Hum Lact. 2003;19:250-261.
32. Romieu J, Werneck G, Velasco SR, et al. Breastfeeding and asthma among Brazilian children. J Asthma. 2000;37:575-583.
33. Oddy WH, Holt PG, Sly PD, et al. Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study. BMJ. 1999;319:815-819.
34. Wright AL, Holberg CJ, Taussig LM, Martinez FD. Factors influencing the relation of infant feedin to asthma and recurrent wheeze in childhood. Tho-rax. 2001;56:192-197.
35. Sears MR, Greene JM, Willan AR, et al. Long--term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Lancet. 2002;360: 901-907.
36. van Schayck CP, Knottnerus JA. Can the "hygiene hypothesis" be explained by confounding behavior? J Clin Epidemiol. 2004;57:435-437.
37. Sheikh A, Strachan DP. The hygiene theory: fact or fiction? Curr Opin Otolaryngol Head Neck Surg. 2004;12:232-236.
38. Peat J, Li J. Reversing the trend: reducing the prevalence of asthma. J Allergy Clin Immunol. 1999; 103:1-10.
39. Black PN, Sharpe S. Dietary fat and asthma: is there a connection? Eur Respir J. 1997;10:6-12.
40. Oddy WH, de Klerk NH, Kendall GE, et al. Ratio of omega-6 to omega-3 fatty acids and childhood asthma. J Asthma. 2004;41:319-326.
41. Matsui EC, Wood RA, Rand C, et al. Cockroach allergen exposure and sensitization in suburban middle-class children with asthma. J Allergy Clin Immunol. 2003;112:87-92.
42. Matsui EC, Wood RA, Rand C, et al. Mouse allergen exposure and mouse skin test sensitivity in suburban, middle-class children with asthma. J Al-lergy Clin Immunol. 2004;113:910-915.
43. Perry T, Matsui E, Merriman B, et al. The prevalence of rat allergen in inner-city homes and its relationship to sensitization and asthma morbidity. J Allergy Clin Immunol. 2003;346-352.
44. Matsui E, Simons E, Rand C, et al. Airborne mouse allergen in the homes of inner-city children with asthma. J Allergy Clin Immunol. 2005;115: 358-363.
45. Sporik R, Ingram J, Price W, et al. Association of asthma with serum IgE and skin test reactivity to allergens among children living at high altitude: tickling the dragon's breath. Am J Respir Crit Care Med. 1995;151:1388-1392.
46. Munir A, Bjorksten B, Einarsson R, et al. Cat (Fel dI), dog (Can fI) and cockroach allergens in homes of asthmatic children from three climatic zones in Sweden. Allergy. 1994;49:508-516.
47. Arbes SJ, Cohn RD, Yin M, et al. Dog allergen (Can f1) and cat allergen (Fel d1) in US homes: results from the National Survey of Lead and Allergens in Housing. J Allergy Clin Immunol. 2004;114: 111-117.
48. Peat JK, Tovey E, Mellis CM, et al. 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: 812-820.
49. Halonen M, Stern D, Wright A, et al. Alternaria as a major allergen for asthma in a desert environment. Am J Respir Crit Care Med. 1997;155:1356-1361.
50. Nelson R, DiNicolo R, Fernandez-Caldas E, et al. Allergen-specific IgE levels and mite allergen exposure in children with acute asthma first seen in an emergency department and in nonasthmatic control subjects. J Allergy Clin Immunol. 1996;98:258-263.
51. Peat JK, Tovey E, Gray EJ, et al. Asthma severity and morbidity in a population sample of Sydney schoolchildren, II: importance of house dust mite allergen. Aust N Z J Med. 1994;24:270-276.
52. Neukirch C, Henry C, Leynaert B, et al. Is sensitization to Alternaria alternata a risk factor for severe asthma? A population-based study. J Allergy Clin Immunol. 1999;103:709-711.
53. Black PN, Udy AA, Brodie SM. Sensitivity to fungal allergens is a risk factor for life-threatening asthma. Allergy. 2000;55:501-504.
54. Targonski P, Persky V, Ramekrishnan V. Effect of environmental molds on risk of death from asth-ma during the pollen season. J Allergy Clin Immu-nol. 1995,95:955-961.
55. Rosa I, McCartney H, Payne R. Analysis of the relationship between environmental factors (aeroal-lergens, air pollution, and weather) and asthma emergency admissions to a hospital in Mexico City. Allergy. 1998;53:394-401.
56. Cakmak S, Dales RE, Burnett RT, et al. Effect of airborne allergens on emergency visits by children for conjunctivitis and rhinitis. Lancet. 2002;359: 947-948.
57. Horner WE, Helbling A, Lehrer SB. Basidiomycete allergens. Allergy. 1998;53:1114-1121.
58. Salvaggio J, Seabury J, Schoenhardt E. New Orleans asthma, V: Relationship between charity hospital asthma admission rates, semiquantitative pollen and fungal spore counts, and total particulate aerometric sampling data. J Allergy Clin Immunol. 1971;48:96-114.
59. Frankland A, Gregory P. Allergenic and agricultural implication of airborne Ascospore concentrations from a fungus, Didymella exitialis. Nature. 1973;245: 336-337.
60. Codina R, Lockey RF. Possible role of molds as secondary etiologic agents of the asthma epidemics in Barcelona, Spain. J Allergy Clin Immunol 1998; 102:318-320.
61. Gelber L, Seltzer L, Bouzoukis J, et al. Sensiti-zation and exposure to indoor allergens as risk factors for asthma among patients presenting to hospital. Am Rev Respir Dis. 1993;147:573-578.
62. Holgate S. Asthma and allergy, disorders of civilization? Q J Med. 1998;91:171-184.
63. Sears M, Hervison G, Holdaway M, et al. The relative risks of sensitivity to grass pollen, house dust mite, and cat dander in the development of childhood asthma. Clin Exp Allergy. 1989;19:419-424.
64. Platts-Mills TA, Vervloet D, Thomas WR, et al. Indoor allergens and asthma: report of the third international workshop. J Allergy Clin Immunol. 1997; 100:S2-S24.
65. Platts-Mills TA, Woodfolk JA, Erwin EA, Aalberse R. Mechanisms of tolerance to inhalant allergens: the relevance of a modified Th2 response to allergens from domestic animals. Springer Semin Immun. 2004;25:271-279.
66. Reefer AJ, Carneiro RM, Custis NJ, et al. A role for IL-10 mediated HLA-DR7-restricted T cell-dependent events in development of the modified Th2 response to cat allergen. J Immunol. 2004;172: 2763-2772.
67. Busch RK, Eggleston PA. Guidelines for control of indoor allergen exposure. J Allergy Clin Immunol. 2001;107:S403-S430.
68.Codina R, Lockey RF, Diwadkar R, et al. Disodium octaborate tetrahydrate (DOT) application and vacuum cleaning, a combined strategy to control house dust mites. Allergy. 2003;58:318-324.
69. Woodcock A, Forster L, Matthews E, et al. Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma. N Engl J Med. 2003;349:225-236.
70. Terreehorst I, Hak E, Oosting AJ, et al. Evaluation of impermeable covers for bedding in patients with allergic rhinitis. N Engl J Med. 2003;349: 237-246.
71. Vaughan J, McLaughlin T, Perzanowski M, Platts-Mills T. Evaluation of materials used for bedding encasement: effect of pore size in blocking cat and dust mite allergens. J Allergy Clin Immunol. 1999;103:227-231.
72. Harving H, Hansen L, Korsgard J, et al. House dust allergy and antimite measures in the indoor environment. Allergy. 1991;46:33-38.
73. Chandra S, Beal D, Downing A, et al. Mites, mite allergens and interior environmental conditions. Proceedings of a workshop on mites, asthma, and domestic design. Wellington School of Medi-cine, New Zealand; November 1997:26.
74. American Lung Association, supplement 1997. Residential air cleaning devices: types, effectiveness, and health impact. Available at: http://www.lungusa.org/pub. Accessed April 15, 2005.
75. Bardana E Jr, Bascom R, Burge H, et al. Achieving healthy indoor air. Report of the ATS Workshop: Santa Fe, New Mexico; November 16-19, 1995. Am J Respir Crit Care Med. 1997;156:S33-S64.
76. Chinchilla M, Guerrero O, Castro A, Sabah J. Cockroaches as transport hosts of the protozoan Toxoplasma gondii. Rev Biol Trop. 1994;42:329-331.
77. Vythilingam I, Jeffery J, Oothuman P, et al. Cockroaches from urban human dwellings: isolation of bacterial pathogens and control. Southeast Asian J Trop Med Public Health. 1997:218-222.
78. Brenner R, Focks D, Arbogast R, et al. Practical use of spatial analysis in precision targeting for integrated pest management. Am Entomologist. 1998; summer:79-101.
79. Sarpong S, Corey J. Assessment of the indoor environment in respiratory allergy. Nose Throat J. 1998;77:960-964.
80. Peat JK. Can asthma be prevented? Evidence from epidemiological studies of children in Australia and New Zealand in the last decade. Clin Exp Allergy. 1998;28:261-265.
81. Chaudhari R, Livingston E, McMahon AD, et al. Cigarrette smoking impairs the therapeutic response to oral corticosteroids in chronic asthma. Am J Crit Care Med. 2003;168:1308-1311.
82. Department of Environment expert panel on air quality standards. Report: Particles. London: HMSO; 1995.
83. Bulin G, Hedenstirna G, Lindual T, Sundin B. Ambient nitrogen dioxide concentrations increase bronchial responsiveness in subjects with mild asthma. Eur Respir J. 1998;1:606-612.
84. Jorres R, Magnussen H. Airways response of asthmatics after a 30 minute exposure, at resting ventilation, to 0.25 ppm NO2 or 0.5 ppm SO2. Eur Respir J. 1990;3:132-137.
85. Koening J, Covert D, Hanley Q, et al. Prior exposure to ozone potentiates subsequent response to sulphur dioxide in adolescent asthmatic subjects. Am Rev Respir Dis. 1990;141:377-380.
86. Department of Health advisory group on the medical aspects of air pollution episodes. First report: Ozone. London: HMSO; 1991.
87. Molfino NA, Wright SC, Katz I, et al. Effect of low concentrations of ozone on inhaled allergen responses in asthmatic subjects. Lancet. 1991;338: 199-203.
88. Jorres R, Nowak D, Magnussen H. Effect of ozone exposure on allergen responsiveness in subjects with asthma or rhinitis. Am J Respir Crit Care Med. 1996;153:56-64.
89. Michel O, Kips J, Duchateau J, et al. Severity of asthma is related to endotoxin in house dust. Am J Respir Crit Care Med. 1996;154:1641-1646.
90. Singh J, Schwartz DA. Endotoxin and the lung: insight into the host-environment interaction. J Allergy Clin Immunol. 2005;115:1130-1133.
91. Gehring U, Bischof W, Schlenvoigt G, et al. Exposure to house dust endotoxin and allergic sensitization in adults. Allergy. 2004;59:946-952.