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The hygiene hypothesis for allergy – conception and evolution

Perkin, Michael R, Strachan, David P·2022·Frontiers in Allergy
DOI 10.3389/falgy.2022.1051368PMC PMC9731379
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Abstract

In 1989, a short paper entitled “Hay fever, hygiene and household size” observed that British children from larger families were less likely to develop hay fever and suggested that this could be because early exposure to infection prevents allergy. This sibship size association for hay fever, since replicated many times in Britain and other affluent countries and confirmed by objective measures of atopy, prompted what has come to be known as the “hygiene hypothesis for allergy”, although that term was not specifically used in the 1989 paper. The present paper reviews the historical roots of the “hygiene hypothesis” and charts its development over more than 30 years. Initial scepticism among immunologists turned to enthusiasm in the mid-1990s as the Th1/Th2 paradigm for allergic sensitisation emerged from animal experiments and the concept of “immunological old friends” became popular from the early 2000s. From the late 1990s, observations of reduced allergy risk among children of anthroposophic families and those brought up on farms suggested that the sibship size effects formed part of a broader range of “hygiene-related” determinants of allergy. Children from large families with farming exposure have approximately sixfold reduction in prevalence of hay fever, indicating the potential strength and epidemiological importance of these environmental determinants. During the 21st century, a wide range of specific microbial, environmental and lifestyle factors have been investigated as possible underlying mechanisms, but sadly none have emerged as robust explanations for the family size and farming effects. Thus, while the “hygiene hypothesis” led to a fundamental reappraisal of our relationship with our microbial environment and to the concept that early exposure, rather than avoidance, is beneficial for developing a healthy immune system, the underlying mechanism for variations in allergy prevalence with family size remains, in Churchillian terms, “a riddle wrapped in a mystery inside an enigma”.

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Figure 1 Prevalence of hay fever and eczema by number of older children (top panel) and number of younger children (bottom panel) in the household at age 11. *Adjusted for number of younger children in household, father's social class, housing tenure and shared household amenities in childhood, breastfeeding, region of birth and cigarette smoking at 23.
Figure 1 Prevalence of hay fever and eczema by number of older children (top panel) and number of younger children (bottom panel) in the household at age 11. *Adjusted for number of younger children in household, father's social class, housing tenure and shared household amenities in childhood, breastfeeding, region of birth and cigarette smoking at 23.CC BY · PubMed Central
Figure 2 Prevalence of helminths infection and allergic disease in the Metis and white populations of Saskatchewan.
Figure 2 Prevalence of helminths infection and allergic disease in the Metis and white populations of Saskatchewan.CC BY · PubMed Central
Figure 3 Parent reported eczema and hay fever by five years of age, by number of older children (top panel) and number of younger children (bottom panel) in the household (8).
Figure 3 Parent reported eczema and hay fever by five years of age, by number of older children (top panel) and number of younger children (bottom panel) in the household (8).CC BY · PubMed Central
Figure 4 Citations to Strachan's “hygiene hypothesis” paper and papers using the term “hygiene hypothesis” in the title or abstract.
Figure 4 Citations to Strachan's “hygiene hypothesis” paper and papers using the term “hygiene hypothesis” in the title or abstract.CC BY · PubMed Central

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Research works printed but not linked: 89

  1. Strachan, 1989, Hay fever, hygiene, and household size, Br Med J, 299, 1259, 10.1136/bmj.299.6710.1259 · DOI · Paper page
  2. Emanuel, 1988, Hay fever, a post industrial revolution epidemic: a history of its growth during the 19th century, Clin Allergy, 18, 295, 10.1111/j.1365-2222.1988.tb02872.x · DOI
  3. Bostock, 1828, On the catarrhus aestivus or summer catarrh, Medico-Chir Trans, 437, 10.1177/09595287280140P204 · DOI
  4. Gerrard, 1976, Serum IgE levels in white and metis communities in Saskatchewan, Ann Allergy, 37, 91
  5. Barker, 1985, Acute appendicitis and dietary fibre: an alternative hypothesis, Br Med J (Clin Res Ed), 290, 1125, 10.1136/bmj.290.6475.1125 · DOI
  6. Morris, 1987, Diet, infection, and acute appendicitis in britain and Ireland, J Epidemiol Community Health, 41, 44, 10.1136/jech.41.1.44 · DOI
  7. Barker, 1988, Acute appendicitis and bathrooms in three samples of British children, Br Med J (Clin. Res. Ed), 296, 956, 10.1136/bmj.296.6627.956 · DOI
  8. Golding, 1986, Eczema and hay fever, 171
  9. Golding, 1986, The end of the beginning, 320
  10. Martinez, 1999, Role of microbial burden in aetiology of allergy and asthma, Lancet, 354, SII12, 10.1016/S0140-6736(99)90437-3 · DOI
  11. Openshaw, 1999, Infections prevent the development of asthma–true, false or both?, J R Soc Med, 92, 495, 10.1177/014107689909201001 · DOI
  12. Rotmagnani, 1998, The Th1/Th2 paradigm and allergic disorders, Allergy, 53, 12, 10.1111/j.1398-9995.1998.tb04951.x · DOI
  13. Romagnani, 1992, Human TH1 and TH2 subsets: regulation of differentiation and role in protection and immunopathology, Int Arch Allergy Immunol, 98, 279, 10.1159/000236199 · DOI
  14. Renz, 2002, Maturation of the immune system and development of immune responses to allergens, Eur Respir Mon, 19, 25
  15. Holt, 1997, Allergic respiratory disease: strategic targets for primary prevention during childhood, Thorax, 52, 1, 10.1136/thx.52.1.1 · DOI
  16. Romagnani, 1992, Induction of TH1 and TH2 responses: a key role for the “natural” immune response?, Immunol Today, 13, 379, 10.1016/0167-5699(92)90083-J · DOI
  17. Prescott, 1999, Development of allergen-specific T-cell memory in atopic and Normal children, Lancet, 353, 196, 10.1016/S0140-6736(98)05104-6 · DOI
  18. Sudo, 1997, The requirement of intestinal bacterial flora for the development of an IgE production system fully susceptible to oral tolerance induction, J Immunol, 159, 1739, 10.4049/jimmunol.159.4.1739 · DOI
  19. Sheikh, 2004, The hygiene theory: fact or fiction?, Curr Opin Otolaryngol Head Neck Surg, 12, 232, 10.1097/01.moo.0000122311.13359.30 · DOI
  20. Johansson, 2004, Revised nomenclature for allergy for global use: report of the nomenclature review committee of the world allergy organization, october 2003, J Allergy Clin Immunol, 113, 832, 10.1016/j.jaci.2003.12.591 · DOI · Paper page
  21. von Mutius, 1994, Skin test reactivity and number of siblings, Br Med J, 308, 692, 10.1136/bmj.308.6930.692 · DOI
  22. Strachan, 1996, Family structure, neonatal infection, and hay fever in adolescence, Arch Dis Child, 74, 422, 10.1136/adc.74.5.422 · DOI
  23. Strachan, 1997, Childhood antecedents of allergic sensitization in young British adults, J Allergy Clin Immunol, 99, 6, 10.1016/s0091-6749(97)70294-x · DOI
  24. Forastiere, 1997, Socioeconomic status, number of siblings, and respiratory infections in early life as determinants of atopy in children, Epidemiology, 8, 566, 10.1097/00001648-199709000-00015 · DOI
  25. Jarvis, 1997, The association of family size with atopy and atopic disease, Clin Exp Allergy, 27, 240, 10.1111/j.1365-2222.1997.tb00701.x · DOI
  26. Matricardi, 1998, Sibship size, birth order, and atopy in 11,371 Italian young men, J Allergy Clin Immunol, 101, 439, 10.1016/S0091-6749(98)70350-1 · DOI
  27. Svanes, 1999, Childhood environment and adult atopy: results from the European community respiratory health survey, J Allergy Clin Immunol, 103, 415, 10.1016/S0091-6749(99)70465-3 · DOI
  28. Strachan, 1997, Allergy and family size: a riddle worth solving, Clin Exp Allergy, 27, 235, 10.1111/j.1365-2222.1997.tb00699.x · DOI
  29. Strachan, 1995, Epidemiology of hay fever: towards a community diagnosis, Clin Exp Allergy, 25, 296, 10.1111/j.1365-2222.1995.tb01046.x · DOI
  30. Strachan, 2015, Siblings, asthma, rhinoconjunctivitis and eczema: a worldwide perspective from the international study of asthma and allergies in childhood, Clin Exp Allergy, 45, 126, 10.1111/cea.12349 · DOI · Paper page
  31. Bråbäck, 1994, Atopic sensitization and respiratory symptoms among Polish and Swedish school children, Clin Exp Allergy, 24, 826, 10.1111/j.1365-2222.1994.tb01805.x · DOI
  32. Backman, 1984, Do infections in infancy affect sensitization to airborne allergens and development of atopic disease?, Allergy, 39, 309, 10.1111/j.1398-9995.1984.tb00867.x · DOI
  33. Krämer, 1999, Age of entry to day nursery and allergy in later childhood, Lancet, 353, 450, 10.1016/S0140-6736(98)06329-6 · DOI
  34. Busse, 1989, The relationship between viral infections and onset of allergic diseases and asthma, Clin Exp Allergy, 19, 1, 10.1111/j.1365-2222.1989.tb02336.x · DOI
  35. Rook, 1998, Give us this day our daily germs, Immunol Today, 19, 113, 10.1016/S0167-5699(98)80008-X · DOI
  36. Shaheen, 1996, Measles and atopy in Guinea-Bissau, Lancet, 347, 1792, 10.1016/S0140-6736(96)91617-7 · DOI
  37. Bodner, 1998, Family size, childhood infections and atopic diseases. The Aberdeen WHEASE group, Thorax, 53, 28, 10.1136/thx.53.1.28 · DOI
  38. Matricardi, 1997, Cross sectional retrospective study of prevalence of atopy among Italian military students with antibodies against hepatitis A virus, Br Med J, 314, 999, 10.1136/bmj.314.7086.999 · DOI
  39. Lionetti, 2014, Helicobacter pylori infection and atopic diseases: is there a relationship? A systematic review and meta-analysis, World J Gastroenterol, 20, 17635, 10.3748/wjg.v20.i46.17635 · DOI
  40. Matricardi, 2000, Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study, Br Med J, 320, 412, 10.1136/bmj.320.7232.412 · DOI
  41. von Mutius, 2001, The increase in asthma can be ascribed to cleanliness, Am J Respir Crit Care Med, 164, 1106, 10.1164/ajrccm.164.7.2107130a · DOI
  42. Farooqi, 1998, Early childhood infection and atopic disorder, Thorax, 53, 927, 10.1136/thx.53.11.927 · DOI
  43. Martinez, 1994, Role of viral infections in the inception of asthma and allergies during childhood: could they be protective?, Thorax, 49, 1189, 10.1136/thx.49.12.1189 · DOI
  44. Bjorksten, 1999, The intestinal microflora in allergic Estonian and Swedish 2-year-old children, Clin Exp Allergy, 29, 342, 10.1046/j.1365-2222.1999.00560.x · DOI
  45. Matricardi, 2000, High microbial turnover rate preventing atopy: a solution to inconsistencies impinging on the hygiene hypothesis?, Clin Exp Allergy, 30, 1506, 10.1046/j.1365-2222.2000.00994.x · DOI
  46. Alm, 1999, Atopy in children of families with an anthroposophic lifestyle, Lancet, 353, 1485, 10.1016/S0140-6736(98)09344-1 · DOI
  47. Alfvén, 2006, Allergic diseases and atopic sensitization in children related to farming and anthroposophic lifestyle - the PARSIFAL study, Allergy, 61, 414, 10.1111/j.1398-9995.2005.00939.x · DOI
  48. Flöistrup, 2006, Allergic disease and sensitization in steiner school children, J Allergy Clin Immunol, 117, 59, 10.1016/j.jaci.2005.09.039 · DOI
  49. Blackley, 1873, Experimental researches on the causes and nature of catarrhus aestivus (hay-fever or hay-asthma)
  50. Genuneit, 2012, Exposure to farming environments in childhood and asthma and wheeze in rural populations: a systematic review with meta-analysis, Pediatr Allergy Immunol, 23, 509, 10.1111/j.1399-3038.2012.01312.x · DOI
  51. Campbell, 2015, Exposure to “farming” and objective markers of atopy: a systematic review and meta-analysis, Clin Exp Allergy, 45, 744, 10.1111/cea.12429 · DOI · Paper page
  52. von Mutius, 2000, Exposure to endotoxin or other bacterial components might protect against the development of atopy, Clin Exp Allergy, 30, 1230, 10.1046/j.1365-2222.2000.00959.x · DOI
  53. Perkin, 2006, Which aspects of the farming lifestyle explain the inverse association with childhood allergy?, J Allergy Clin Immunol, 117, 1374, 10.1016/j.jaci.2006.03.008 · DOI
  54. Genuneit, 2013, The combined effects of family size and farm exposure on childhood hay fever and atopy, Pediatr Allergy Immunol, 24, 293, 10.1111/pai.12053 · DOI
  55. Heinrich, 2001, Pets and vermin are associated with high endotoxin levels in house dust, Clin Exp Allergy, 31, 1839, 10.1046/j.1365-2222.2001.01220.x · DOI
  56. Hesselmar, 1999, Does early exposure to cat or dog protect against later allergy development?, Clin Exp Allergy, 29, 611, 10.1046/j.1365-2222.1999.00534.x · DOI
  57. Lodge, 2012, Perinatal cat and dog exposure and the risk of asthma and allergy in the urban environment: a systematic review of longitudinal studies, Clin Dev Immunol, 2012, 176484, 10.1155/2012/176484 · DOI · Paper page
  58. Bloomfield, 2016, Time to abandon the hygiene hypothesis: new perspectives on allergic disease, the human microbiome, infectious disease prevention and the role of targeted hygiene, Perspect Public Health, 136, 213, 10.1177/1757913916650225 · DOI
  59. Adlerberth, 2007, Gut microbiota and development of atopic eczema in 3 European birth cohorts, J Allergy Clin Immunol, 120, 343, 10.1016/j.jaci.2007.05.018 · DOI
  60. Wang, 2008, Reduced diversity in the early fecal microbiota of infants with atopic eczema, J Allergy Clin Immunol, 121, 129, 10.1016/j.jaci.2007.09.011 · DOI
  61. Cooper, 2003, Reduced risk of atopy among school-age children infected with geohelminth parasites in a rural area of the tropics, J Allergy Clin Immunol, 111, 995, 10.1067/mai.2003.1348 · DOI
  62. Cooper, 2016, Effects of maternal geohelminth infections on allergy in early childhood, J Allergy Clin Immunol, 137, 899, 10.1016/j.jaci.2015.07.044 · DOI · Paper page
  63. Cooper, 2018, Effect of early-life geohelminth infections on the development of wheezing at 5 years of age, Am J Respir Crit Care Med, 197, 364, 10.1164/rccm.201706-1222OC · DOI
  64. Flohr, 2006, Poor sanitation and helminth infection protect against skin sensitization in Vietnamese children: a cross-sectional study, J Allergy Clin Immunol, 118, 1305, 10.1016/j.jaci.2006.08.035 · DOI
  65. Flohr, 2010, Reduced helminth burden increases allergen skin sensitization but not clinical allergy: a randomized, double-blind, placebo-controlled trial in Vietnam, Clin Exp Allergy, 40, 131, 10.1111/j.1365-2222.2009.03346.x · DOI · Paper page
  66. Karmaus, 2002, Does a higher number of siblings protect against the development of allergy and asthma? A review, J Epidemiol Community Health, 56, 209, 10.1136/jech.56.3.209 · DOI · Paper page
  67. Lisik, 2021, Sibship size, birth order and risk of asthma and allergy: protocol for a systematic review and meta-analysis, BMJ Open, 11, e045795, 10.1136/bmjopen-2020-045795 · DOI
  68. Strachan, 1997, Sibship size and self-reported inhalant allergy among adult women, Clin Exp Allergy, 27, 151, 10.1111/j.1365-2222.1997.tb00686.x · DOI
  69. von Hertzen, 2007, Microbial content of drinking water in Finnish and Russian Karelia - implications for atopy prevalence, Allergy, 62, 288, 10.1111/j.1398-9995.2006.01281.x · DOI
  70. Hanski, 2012, Environmental biodiversity, human microbiota, and allergy are interrelated, Proc Natl Acad Sci U S A, 109, 8334, 10.1073/pnas.1205624109 · DOI · Paper page
  71. Sherriff, 2002, Factors associated with different hygiene practices in the homes of 15 month old infants, Arch Dis Child, 87, 30, 10.1136/adc.87.1.30 · DOI
  72. Sherriff, 2002, Hygiene levels in a contemporary population cohort are associated with wheezing and atopic eczema in preschool infants, Arch Dis Child, 87, 26, 10.1136/adc.87.1.26 · DOI
  73. Soriano, 2021, Infant pacifier sanitization and risk of challenge-proven food allergy: a cohort study, J Allergy Clin Immunol, 147, 1823, 10.1016/j.jaci.2021.01.032 · DOI
  74. Bloomfield, 2006, Too clean, or not too clean: the hygiene hypothesis and home hygiene, Clin Exp Allergy, 36, 402, 10.1111/j.1365-2222.2006.02463.x · DOI
  75. Wickens, 1999, The magnitude of the effect of smaller family sizes on the increase in the prevalence of asthma and hay fever in the United Kingdom and New Zealand, J Allergy Clin Immunol, 104, 554, 10.1016/S0091-6749(99)70323-4 · DOI
  76. Okada, 2010, The “hygiene hypothesis” for autoimmune and allergic diseases: an update, Clin Exp Immunol, 160, 1, 10.1111/j.1365-2249.2010.04139.x · DOI
  77. Ponsonby, 2005, Exposure to infant siblings during early life and risk of multiple sclerosis, JAMA, 293, 463, 10.1001/jama.293.4.463 · DOI
  78. Patterson, 1996, Epidemiology of childhood IDDM in Northern Ireland 1989–1994: low incidence in areas with highest population density and most household crowding, Diabetologia, 39, 1063, 10.1007/BF00400655 · DOI
  79. Greaves, 2018, A causal mechanism for childhood acute lymphoblastic leukaemia, Nat Rev Cancer, 18, 471, 10.1038/s41568-018-0015-6 · DOI
  80. Dekker, 1999, Risk factors for preeclampsia, Clin Obstet Gynecol, 42, 422, 10.1097/00003081-199909000-00002 · DOI
  81. Karmaus, 2001, Does the sibling effect have its origin in utero? Investigating birth order, cord blood immunoglobulin E concentration, and allergic sensitization at age 4 years, Am J Epidemiol, 154, 909, 10.1093/aje/154.10.909 · DOI
  82. Woodcock, 2004, Early life environmental control, Am J Respir Crit Care Med, 170, 433, 10.1164/rccm.200401-083OC · DOI
  83. Haahtela, 2017, The finnish allergy programme 2008–2018 works, Eur Respir J, 49, 1700470, 10.1183/13993003.00470-2017 · DOI
  84. 2000, Hypoallergenic infant formulas, Pediatrics, 106, 346, 10.1542/peds.106.2.346 · DOI
  85. Perkin, 2016, Randomized trial of introduction of allergenic foods in breast-fed infants, N Engl J Med, 374, 1733, 10.1056/NEJMoa1514210 · DOI
  86. Du Toit, 2015, Randomized trial of peanut consumption in infants at risk for peanut allergy, N Engl J Med, 372, 803, 10.1056/NEJMoa1414850 · DOI · Paper page
  87. Rook, 2010, 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: darwinian medicine and the “hygiene” or “old friends” hypothesis, Clin Exp Immunol, 160, 70, 10.1111/j.1365-2249.2010.04133.x · DOI · Paper page
  88. Björkstén, 2012, Diverse microbial exposure – consequences for vaccine development, Vaccine, 30, 4336, 10.1016/j.vaccine.2011.10.074 · DOI
  89. Haahtela, 2019, A biodiversity hypothesis, Allergy, 74, 1445, 10.1111/all.13763 · DOI · Paper page

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Metadata

Authors
Perkin, M. R., & Strachan, D. P.
Venue
Frontiers in Allergy
Publisher
Frontiers Media SA
Published
2022-11-24
Volume
3
ISSN
2673-6101
DOI
10.3389/falgy.2022.1051368
PMC
PMC9731379
Cited by
64
References
5
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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