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Increasing prevalence of asthma and allergic rhinitis and the role of environmental factors

Authors
Thomas A E Platts-Mills, MD, PhD
Scott P Commins, MD, PhD
Section Editor
Bruce S Bochner, MD
Deputy Editor
Elizabeth TePas, MD, MS

INTRODUCTION

Allergic rhinitis and asthma are both common chronic diseases that affect the quality of life of patients and have a significant economic impact. The prevalence of allergic rhinitis increased in Westernized countries from the 1870s through the 1950s. The rate of asthma subsequently increased in these countries beginning in the 1960s. Asthma and allergic rhinitis prevalence began increasing in many developing countries in the late 1980s to early 1990s.

Changes in genetic factors are unlikely to be the underlying cause of the rise in allergic diseases, since the increases in allergic rhinitis and asthma occurred relatively rapidly. Instead, multiple environmental factors may have played a role. These include improvements in hygiene, eradication of most parasitic worm infections, changes in home heating and ventilation, and a decline in physical activity and alterations in diet due to lifestyle changes. Although we lack a complete understanding of the possible role of epigenetic changes in the rise of allergic diseases, there is increasing literature on potential mechanisms by which environmental exposures associated with specific epigenetic changes could lead to allergic phenotypes [1].

This topic discusses the increase in rates of allergic rhinitis and asthma and the environmental changes that may have led to their alterations in prevalence. Risk factors for the development of asthma, including atopy and allergen sensitization, and the relationship between allergic rhinitis and asthma are discussed separately. (See "Risk factors for asthma" and "Relationships between rhinosinusitis and asthma".)

The rising prevalence of food allergy and the factors that may play a role in this increase are also reviewed in detail separately. (See "Food allergy in children: Prevalence, natural history, and monitoring for resolution", section on 'Prevalence of childhood food allergy' and "Pathogenesis of food allergy", section on 'Prevalence'.)

EPIDEMIOLOGIC HISTORY

Seasonal allergic rhinitis was first described in the United States in 1872 (autumnal catarrh or ragweed hay fever) [2] and in England in 1873 (catarrhus aestivus) [3]. The disease was well recognized in England and Germany by 1900 and in the United States by 1920. The island of Heligoland in the North Sea was established as a summer refuge for hay fever patients by 1910, and, during the early part of the 20th century, it became common for sufferers in New England to retreat to resorts in the mountains to escape the pollen. The first paper on immunotherapy against pollen "toxin" was published in 1911 [4]. At that time, hay fever was considered to be a disease of the affluent and was rarely reported among working-class people, especially farmers.

              

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References
Top
  1. Bégin P, Nadeau KC. Epigenetic regulation of asthma and allergic disease. Allergy Asthma Clin Immunol 2014; 10:27.
  2. Wyman M. Autumnal catarrh (hay fever), Huro & Houghton, Cambridge, MA 1872.
  3. Blackley CH. Experiments and researches on the causes and nature of catarrhus aestivas, Balliere, London 1873.
  4. Noon L. Prophylactic inoculation for hay fever. Lancet 1911; i:1572.
  5. "4000 acres that breed sneezes, target in city's hay fever war." New York Times, June 3, 1949.
  6. RATNER B, SILBERMAN DE. Critical analysis of the hereditary concept of allergy. J Allergy 1953; 24:371.
  7. WALZER M, SIEGEL BB. The effectiveness of the ragweed eradication campaigns in New York City; a 9-year study; 1946-1954. J Allergy 1956; 27:113.
  8. Broder I, Higgins MW, Mathews KP, Keller JB. Epidemiology of asthma and allergic rhinitis in a total community, Tecumseh, Michigan. IV. Natural history. J Allergy Clin Immunol 1974; 54:100.
  9. Nathan R, Meltzer E, Selner J, Storms W. Prevalence of allergic rhinitis in the United States. J Allergy Clin Immunol 1997; 99:S808 (Abstract).
  10. Björkstén B, Clayton T, Ellwood P, et al. Worldwide time trends for symptoms of rhinitis and conjunctivitis: Phase III of the International Study of Asthma and Allergies in Childhood. Pediatr Allergy Immunol 2008; 19:110.
  11. Smith JM, Disney ME, Williams JD, Goels ZA. Clinical significance of skin reactions to mite extracts in children with asthma. Br Med J 1969; 2:723.
  12. Miyamoto T, Johansson SG, Ito K, Horiuchi Y. Atopic allergy in Japanese subjects: studies primarily with radioallergosorbent test. J Allergy Clin Immunol 1974; 53:9.
  13. 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.
  14. Sears MR, Herbison GP, Holdaway MD, 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.
  15. Chapman MD, Platts-Mills TA. Purification and characterization of the major allergen from Dermatophagoides pteronyssinus-antigen P1. J Immunol 1980; 125:587.
  16. Platts-Mills TA, Tovey ER, Mitchell EB, et al. Reduction of bronchial hyperreactivity during prolonged allergen avoidance. Lancet 1982; 2:675.
  17. Platts-Mills TA, Tovey ER, Chapman MD, Wilkins SR. Airborne allergen exposure, allergen avoidance and bronchial hyperractivity. In: Asthma: Physiology, immunopharmacology and treatment: Third International Symposium, Kay AB, Austen KF, Lichtenstein LM (Eds), Academic Press, London 1984. p.297.
  18. Magnus P, Jaakkola JJ. Secular trend in the occurrence of asthma among children and young adults: critical appraisal of repeated cross sectional surveys. BMJ 1997; 314:1795.
  19. Beasley R, Pearce N, Crane J. International trends in asthma mortality. Ciba Found Symp 1997; 206:140.
  20. Burney PG. Asthma mortality in England and Wales: evidence for a further increase, 1974-84. Lancet 1986; 2:323.
  21. Crater DD, Heise S, Perzanowski M, et al. Asthma hospitalization trends in Charleston, South Carolina, 1956 to 1997: twenty-fold increase among black children during a 30-year period. Pediatrics 2001; 108:E97.
  22. Weiss KB, Gergen PJ, Wagener DK. Breathing better or wheezing worse? The changing epidemiology of asthma morbidity and mortality. Annu Rev Public Health 1993; 14:491.
  23. Haahtela T, Lindholm H, Björkstén F, et al. Prevalence of asthma in Finnish young men. BMJ 1990; 301:266.
  24. Beasley R, Crane J, Lai CK, Pearce N. Prevalence and etiology of asthma. J Allergy Clin Immunol 2000; 105:S466.
  25. Eder W, Ege MJ, von Mutius E. The asthma epidemic. N Engl J Med 2006; 355:2226.
  26. Pearce N, Aït-Khaled N, Beasley R, et al. Worldwide trends in the prevalence of asthma symptoms: phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax 2007; 62:758.
  27. Kalyoncu AF, Selçuk ZT, Enünlü T, et al. Prevalence of asthma and allergic diseases in primary school children in Ankara, Turkey: two cross-sectional studies, five years apart. Pediatr Allergy Immunol 1999; 10:261.
  28. Ronchetti R, Villa MP, Barreto M, et al. Is the increase in childhood asthma coming to an end? Findings from three surveys of schoolchildren in Rome, Italy. Eur Respir J 2001; 17:881.
  29. Senthilselvan A, Lawson J, Rennie DC, Dosman JA. Stabilization of an increasing trend in physician-diagnosed asthma prevalence in Saskatchewan, 1991 to 1998. Chest 2003; 124:438.
  30. Braun-Fahrländer C, Gassner M, Grize L, et al. No further increase in asthma, hay fever and atopic sensitisation in adolescents living in Switzerland. Eur Respir J 2004; 23:407.
  31. Nowak D, Suppli Ulrik C, von Mutius E. Asthma and atopy: has peak prevalence been reached? Eur Respir J 2004; 23:359.
  32. Toelle BG, Ng K, Belousova E, et al. Prevalence of asthma and allergy in schoolchildren in Belmont, Australia: three cross sectional surveys over 20 years. BMJ 2004; 328:386.
  33. Chinn S, Jarvis D, Burney P, et al. Increase in diagnosed asthma but not in symptoms in the European Community Respiratory Health Survey. Thorax 2004; 59:646.
  34. Mommers M, Gielkens-Sijstermans C, Swaen GM, van Schayck CP. Trends in the prevalence of respiratory symptoms and treatment in Dutch children over a 12 year period: results of the fourth consecutive survey. Thorax 2005; 60:97.
  35. Bollag U, Capkun G, Caesar J, Low N. Trends in primary care consultations for asthma in Switzerland, 1989-2002. Int J Epidemiol 2005; 34:1012.
  36. Rönmark E, Bjerg A, Perzanowski M, et al. Major increase in allergic sensitization in schoolchildren from 1996 to 2006 in northern Sweden. J Allergy Clin Immunol 2009; 124:357.
  37. Yemaneberhan H, Bekele Z, Venn A, et al. Prevalence of wheeze and asthma and relation to atopy in urban and rural Ethiopia. Lancet 1997; 350:85.
  38. Perzanowski MS, Ng'ang'a LW, Carter MC, et al. Atopy, asthma, and antibodies to Ascaris among rural and urban children in Kenya. J Pediatr 2002; 140:582.
  39. Addo-Yobo EO, Woodcock A, Allotey A, et al. Exercise-induced bronchospasm and atopy in Ghana: two surveys ten years apart. PLoS Med 2007; 4:e70.
  40. Anderson HR. The epidemiological and allergic features of asthma in the New Guinea Highlands. Clin Allergy 1974; 4:171.
  41. Keeley DJ, Neill P, Gallivan S. Comparison of the prevalence of reversible airways obstruction in rural and urban Zimbabwean children. Thorax 1991; 46:549.
  42. Ma Y, Zhao J, Han ZR, et al. Very low prevalence of asthma and allergies in schoolchildren from rural Beijing, China. Pediatr Pulmonol 2009; 44:793.
  43. Hirvonen A. Gene-environment interactions in chronic pulmonary diseases. Mutat Res 2009; 667:132.
  44. Douwes J, Pearce N. Asthma and the westernization 'package'. Int J Epidemiol 2002; 31:1098.
  45. Schwartz DA. Gene-environment interactions and airway disease in children. Pediatrics 2009; 123 Suppl 3:S151.
  46. Kobayashi Y, Bossley C, Gupta A, et al. Passive smoking impairs histone deacetylase-2 in children with severe asthma. Chest 2014; 145:305.
  47. Winkler AR, Nocka KN, Williams CM. Smoke exposure of human macrophages reduces HDAC3 activity, resulting in enhanced inflammatory cytokine production. Pulm Pharmacol Ther 2012; 25:286.
  48. Liu F, Killian JK, Yang M, et al. Epigenomic alterations and gene expression profiles in respiratory epithelia exposed to cigarette smoke condensate. Oncogene 2010; 29:3650.
  49. Emanuel MB. Hay fever, a post industrial revolution epidemic: a history of its growth during the 19th century. Clin Allergy 1988; 18:295.
  50. Armstrong GL, Conn LA, Pinner RW. Trends in infectious disease mortality in the United States during the 20th century. JAMA 1999; 281:61.
  51. Platts-Mills TA. Asthma severity and prevalence: an ongoing interaction between exposure, hygiene, and lifestyle. PLoS Med 2005; 2:e34.
  52. Platts-Mills T, Vaughan J, Squillace S, et al. Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study. Lancet 2001; 357:752.
  53. Platts-Mills TA, Perzanowski M, Woodfolk JA, Lundback B. Relevance of early or current pet ownership to the prevalence of allergic disease. Clin Exp Allergy 2002; 32:335.
  54. Okada H, Kuhn C, Feillet H, Bach JF. The 'hygiene hypothesis' for autoimmune and allergic diseases: an update. Clin Exp Immunol 2010; 160:1.
  55. Fishbein AB, Fuleihan RL. The hygiene hypothesis revisited: does exposure to infectious agents protect us from allergy? Curr Opin Pediatr 2012; 24:98.
  56. Strachan DP. Hay fever, hygiene, and household size. BMJ 1989; 299:1259.
  57. Martinez FD. Role of viral infections in the inception of asthma and allergies during childhood: could they be protective? Thorax 1994; 49:1189.
  58. 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.
  59. Bisgaard H, Hermansen MN, Buchvald F, et al. Childhood asthma after bacterial colonization of the airway in neonates. N Engl J Med 2007; 357:1487.
  60. Gurka MJ, Blackman JA, Heymann PW. Risk of childhood asthma in relation to the timing of early child care exposures. J Pediatr 2009; 155:781.
  61. Shirakawa T, Enomoto T, Shimazu S, Hopkin JM. The inverse association between tuberculin responses and atopic disorder. Science 1997; 275:77.
  62. Walker C, Sawicka E, Rook GA. Immunotherapy with mycobacteria. Curr Opin Allergy Clin Immunol 2003; 3:481.
  63. Brothers S, Asher MI, Jaksic M, Stewart AW. Effect of a Mycobacterium vaccae derivative on paediatric atopic dermatitis: a randomized, controlled trial. Clin Exp Dermatol 2009; 34:770.
  64. Matricardi PM, Rosmini F, Ferrigno L, et al. Cross sectional retrospective study of prevalence of atopy among Italian military students with antibodies against hepatitis A virus. BMJ 1997; 314:999.
  65. Matricardi PM, Rosmini F, Panetta V, et al. Hay fever and asthma in relation to markers of infection in the United States. J Allergy Clin Immunol 2002; 110:381.
  66. Umetsu DT, Umetsu SE, Freeman GJ, DeKruyff RH. TIM gene family and their role in atopic diseases. Curr Top Microbiol Immunol 2008; 321:201.
  67. Dienstag JL. Acute viral hepatitis. In: Harrison's principles of internal medicine, 17th ed, Fauci AS, Braunwald E, Kasper DL, et al (Eds), McGraw-Hill, Madrid 2008. p.1932.
  68. Hesselmar B, Sjöberg F, Saalman R, et al. Pacifier cleaning practices and risk of allergy development. Pediatrics 2013; 131:e1829.
  69. Hesselmar B, Hicke-Roberts A, Wennergren G. Allergy in children in hand versus machine dishwashing. Pediatrics 2015; 135:e590.
  70. Penders J, Thijs C, van den Brandt PA, et al. Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. Gut 2007; 56:661.
  71. Arrieta MC, Stiemsma LT, Dimitriu PA, et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci Transl Med 2015; 7:307ra152.
  72. Fujimura KE, Sitarik AR, Havstad S, et al. Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat Med 2016; 22:1187.
  73. Johnson CC, Ownby DR, Alford SH, et al. Antibiotic exposure in early infancy and risk for childhood atopy. J Allergy Clin Immunol 2005; 115:1218.
  74. Platts-Mills TA. How environment affects patients with allergic disease: indoor allergens and asthma. Ann Allergy 1994; 72:381.
  75. Tovey ER, Chapman MD, Wells CW, Platts-Mills TA. The distribution of dust mite allergen in the houses of patients with asthma. Am Rev Respir Dis 1981; 124:630.
  76. 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; 323:502.
  77. Rosenstreich DL, Eggleston P, Kattan M, 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; 336:1356.
  78. Call RS, Smith TF, Morris E, et al. Risk factors for asthma in inner city children. J Pediatr 1992; 121:862.
  79. Sporik R, Ingram JM, 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.
  80. Luczynska CM, Li Y, Chapman MD, Platts-Mills TA. Airborne concentrations and particle size distribution of allergen derived from domestic cats (Felis domesticus). Measurements using cascade impactor, liquid impinger, and a two-site monoclonal antibody assay for Fel d I. Am Rev Respir Dis 1990; 141:361.
  81. Hesselmar B, Aberg N, Aberg B, et al. Does early exposure to cat or dog protect against later allergy development? Clin Exp Allergy 1999; 29:611.
  82. Ownby DR, Johnson CC, Peterson EL. Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. JAMA 2002; 288:963.
  83. Aalberse R, University of Amsterdam, personal communication, 2008.
  84. Spieksmah F, Leiden University, personal communication, 2007.
  85. Gortmaker SL, Must A, Sobol AM, et al. Television viewing as a cause of increasing obesity among children in the United States, 1986-1990. Arch Pediatr Adolesc Med 1996; 150:356.
  86. Dennison BA, Erb TA, Jenkins PL. Television viewing and television in bedroom associated with overweight risk among low-income preschool children. Pediatrics 2002; 109:1028.
  87. Peterson B, Saxon A. Global increases in allergic respiratory disease: the possible role of diesel exhaust particles. Ann Allergy Asthma Immunol 1996; 77:263.
  88. Lang DM, Polansky M. Patterns of asthma mortality in Philadelphia from 1969 to 1991. N Engl J Med 1994; 331:1542.
  89. Platts-Mills TA, Sporik RB, Chapman MD, Heymann PW. The role of domestic allergens. Ciba Found Symp 1997; 206:173.
  90. Sherriff A, Maitra A, Ness AR, et al. Association of duration of television viewing in early childhood with the subsequent development of asthma. Thorax 2009; 64:321.
  91. Skloot G, Permutt S, Togias A. Airway hyperresponsiveness in asthma: a problem of limited smooth muscle relaxation with inspiration. J Clin Invest 1995; 96:2393.
  92. Fish JE, Ankin MG, Kelly JF, Peterman VI. Regulation of bronchomotor tone by lung inflation in asthmatic and nonasthmatic subjects. J Appl Physiol Respir Environ Exerc Physiol 1981; 50:1079.
  93. Hark WT, Thompson WM, McLaughlin TE, et al. Spontaneous sigh rates during sedentary activity: watching television vs reading. Ann Allergy Asthma Immunol 2005; 94:247.
  94. Fredberg JJ, Inouye D, Miller B, et al. Airway smooth muscle, tidal stretches, and dynamically determined contractile states. Am J Respir Crit Care Med 1997; 156:1752.
  95. Fredberg JJ. Airway smooth muscle in asthma: flirting with disaster. Eur Respir J 1998; 12:1252.
  96. McConnell R, Berhane K, Gilliland F, et al. Asthma in exercising children exposed to ozone: a cohort study. Lancet 2002; 359:386.
  97. Lucas SR, Platts-Mills TA. Physical activity and exercise in asthma: relevance to etiology and treatment. J Allergy Clin Immunol 2005; 115:928.
  98. Platts-Mills TA. The allergy epidemics: 1870-2010. J Allergy Clin Immunol 2015; 136:3.
  99. Brehm JM, Celedón JC, Soto-Quiros ME, et al. Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica. Am J Respir Crit Care Med 2009; 179:765.
  100. Camargo CA Jr, Rifas-Shiman SL, Litonjua AA, et al. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J Clin Nutr 2007; 85:788.
  101. Peat JK, Li J. Reversing the trend: reducing the prevalence of asthma. J Allergy Clin Immunol 1999; 103:1.
  102. Patel S, Murray CS, Woodcock A, et al. Dietary antioxidant intake, allergic sensitization and allergic diseases in young children. Allergy 2009; 64:1766.
  103. Braun-Fahrländer C, Riedler J, Herz U, et al. Environmental exposure to endotoxin and its relation to asthma in school-age children. N Engl J Med 2002; 347:869.
  104. Illi S, Depner M, Genuneit J, et al. Protection from childhood asthma and allergy in Alpine farm environments-the GABRIEL Advanced Studies. J Allergy Clin Immunol 2012; 129:1470.
  105. Genuneit J. Exposure to farming environments in childhood and asthma and wheeze in rural populations: a systematic review with meta-analysis. Pediatr Allergy Immunol 2012; 23:509.
  106. Sozańska B, Błaszczyk M, Pearce N, Cullinan P. Atopy and allergic respiratory disease in rural Poland before and after accession to the European Union. J Allergy Clin Immunol 2014; 133:1347.
  107. Fall T, Lundholm C, Örtqvist AK, et al. Early Exposure to Dogs and Farm Animals and the Risk of Childhood Asthma. JAMA Pediatr 2015; 169:e153219.
  108. Ege MJ, Mayer M, Normand AC, et al. Exposure to environmental microorganisms and childhood asthma. N Engl J Med 2011; 364:701.
  109. Stein MM, Hrusch CL, Gozdz J, et al. Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children. N Engl J Med 2016; 375:411.
  110. Godfrey RC, Gradidge CF. Allergic sensitisation of human lung fragments prevented by saturation of IgE binding sites. Nature 1976; 259:484.
  111. Chung CH, Mirakhur B, Chan E, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med 2008; 358:1109.
  112. Grönlund H, Adédoyin J, Commins SP, et al. The carbohydrate galactose-alpha-1,3-galactose is a major IgE-binding epitope on cat IgA. J Allergy Clin Immunol 2009; 123:1189.
  113. Steinke JW, Platts-Mills TA, Commins SP. The alpha-gal story: lessons learned from connecting the dots. J Allergy Clin Immunol 2015; 135:589.
  114. Commins SP, Satinover SM, Hosen J, et al. Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. J Allergy Clin Immunol 2009; 123:426.
  115. van den Biggelaar AH, van Ree R, Rodrigues LC, et al. Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Lancet 2000; 356:1723.
  116. Silverberg JI, Braunstein M, Lee-Wong M. Association between climate factors, pollen counts, and childhood hay fever prevalence in the United States. J Allergy Clin Immunol 2015; 135:463.
  117. Kim J, Lim Y, Kim H. Outdoor temperature changes and emergency department visits for asthma in Seoul, Korea: A time-series study. Environ Res 2014; 135:15.
  118. Beck I, Jochner S, Gilles S, et al. High environmental ozone levels lead to enhanced allergenicity of birch pollen. PLoS One 2013; 8:e80147.
  119. Clayton EM, Todd M, Dowd JB, Aiello AE. The impact of bisphenol A and triclosan on immune parameters in the U.S. population, NHANES 2003-2006. Environ Health Perspect 2011; 119:390.
  120. Savage JH, Matsui EC, Wood RA, Keet CA. Urinary levels of triclosan and parabens are associated with aeroallergen and food sensitization. J Allergy Clin Immunol 2012; 130:453.
  121. Bertelsen RJ, Longnecker MP, Løvik M, et al. Triclosan exposure and allergic sensitization in Norwegian children. Allergy 2013; 68:84.
  122. Anderson SE, Franko J, Kashon ML, et al. Exposure to triclosan augments the allergic response to ovalbumin in a mouse model of asthma. Toxicol Sci 2013; 132:96.
  123. Gascon M, Casas M, Morales E, et al. Prenatal exposure to bisphenol A and phthalates and childhood respiratory tract infections and allergy. J Allergy Clin Immunol 2015; 135:370.