S2 Thorax 2000;55(Suppl 1):S2–S10 Family size, infection and atopy: Thorax: first published as 10.1136/thorax.55.suppl_1.S2 on 1 August 2000. Downloaded from the first decade of the “hygiene hypothesis” David P Strachan Department of Public Health Sciences, St George’s Hospital Medical School, London SW17 0RE, UK Introductory article 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 K Wickens, J Crane, N Pearce, R Beasley Background. Declining family size is one factor that has been proposed to contribute to increasing asthma and hay fever prevalence, but its relative importance has not been quantified. Objective. Our purpose was to determine the change in asthma and hay fever prevalence that would be expected from the reduction in family size that has occurred in England/Wales and New Zealand over recent decades. Methods. The relative change in family size between 1961 and 1991 in England/Wales and New Zealand was determined from census data for these years. Summary weighted odds ratios were calculated for the associations among birth order, family size, and asthma and hay fever prevalence. The expected increase in the prevalence of asthma and hay fever between 1961 and 1991 resulting from changes in family size was then calculated. Results. The expected relative increase in the prevalence http://thorax.bmj.com/ of asthma between 1961 and 1991 as a result of the smaller family size was 1% and 5% for England/ Wales and New Zealand, respectively; smaller family size would be expected to increase the prevalence of hay fever prevalence in England/Wales by 4%. Conclusions. Changes in family size over the last 30 years do not appear to explain much of the reported increase in asthma or hay fever prevalence. The contribution that other risk factors have made to these increases could be assessed with use of a similar approach. (J Allergy Clin Immunol 1999;104:554–8) on September 29, 2021 by guest. Protected copyright. In 1989 I proposed a novel but speculative explanation suppressing the Th2 immune responses involved in IgE for the principal epidemiological features of hay fever mediated allergy.34 Although the Th1/Th2 paradigm and the apparent rise in the prevalence of allergic dis- may not be as clear in humans as it first appeared in eases.1 Colloquially named the “hygiene hypothesis”, rodents,5 the “hygiene hypothesis” has remained of this stated, in summary: interest to both immunologists and epidemiologists “These observations . could be explained if allergic throughout the 1990s and has been the subject of a diseases were prevented by infection in early childhood, number of editorials and review articles.6–14 transmitted by unhygienic contact with older siblings, or This commentary summarises the epidemiological acquired prenatally . Over the past century declining family evidence which has emerged during the 1990s relating size, improved household amenities and higher standards of family size, infections, and immunisations to atopy and personal cleanliness have reduced opportunities for cross- allergic diseases, and looks forward to the research infection in young families. This may have resulted in more agenda for the next decade. widespread clinical expression of atopic disease.” At first this hypothesis was received with scepticism because the prevailing immunological thinking con- Epidemiology of atopy and allergic diseases sidered infection as a potential trigger of allergic sens- itisation rather than as a protective influence.2 However, The introductory article by Wickens et al15 concentrates during the early 1990s a plausible mechanism arose on one of the most striking epidemiological features of from the distinction of Th1 and Th2 lymphocyte popu- allergy – the inverse association with family size, which lations in laboratory animals and the recognition that has been consistently found in studies of hay fever, skin “natural immunity” to bacterial and viral infections prick positivity, and specific IgE.16 Many, but not all, induces a Th1 pattern of cytokine release, potentially studies find a stronger “protective” influence for older Family size, infection and atopy: the first decade of the “hygiene hypothesis” S3 siblings than for younger siblings and, among the tendance in childhood was associated with a small, non- Thorax: first published as 10.1136/thorax.55.suppl_1.S2 on 1 August 2000. Downloaded from British and New Zealand studies summarised by Wick- significant excess of atopy.28 ens et al,15 this is the predominant pattern for hay fever, The balance of evidence does not therefore suggest although not for asthma – a point to which we return a relationship between allergy and early child contacts shortly. outside the home, which is difficult to reconcile with The “hygiene hypothesis”1 was an attempt to offer a the “hygiene hypothesis”. In retrospect, it is interesting parsimonious and coherent explanation for the current to note that Finnish investigators publishing in 198436 observations of differential hay fever risk within families had obviously set out to test the hypothesis that early and the historical evidence suggesting that hay fever infection increased,2 rather than decreased the risk of had emerged as a “post-industrial revolution epidemic” allergic symptoms. Finding no difference with respect during the 19th century17 and continued to increase in to day care attendance, they concluded that “atopy prevalence throughout the 20th century.18–20 probably cannot be prevented by protecting small chil- In 1989 the influence of family size and structure was dren from infection”. The direction of the causal hypo- apparent only for parentally reported and self-reported thesis has certainly changed in the intervening years! hay fever and eczema in two national British birth cohorts,121 and this raised the possibility of an artifactual association arising from differential awareness or label- ling of allergic diseases by parents of firstborn and Another feature of the epidemiology of allergic disease subsequent offspring. However, during the past decade for which the “hygiene hypothesis” offers an explanation this concern has been allayed by studies from several is the socioeconomic gradient, with a higher prevalence European countries showing the same inverse as- of hay fever37 38 and eczema39 among children and adults sociation of family size22–28 or, more specifically, birth from more affluent families. The variation with parental order23 25 26 with objective measures of allergic sens- socioeconomic status is independent of, and more itisation such as skin prick tests22 23 25 26 or circulating powerful than, the effect of the offsprings own socio- levels of aeroallergen specific IgE.24 27 28 economic status as an adult,31 and is also independent Large samples are required to distinguish reliably of family size and birth order.26 31 38 between the effects of older and younger siblings, but in Theoretically, some of the socioeconomic gradient in two such studies28 29 no statistically significant difference hay fever prevalence could be due to differential re- emerged, in contrast to the earlier observations on porting and labelling of symptoms,40 but this cannot British populations.12130 It is intriguing that in both the account for the similar trend in physician-diagnosed former studies28 29 a significantly stronger “protective” eczema39 and positive skin prick tests.25 26 41 42 Socio- effect emerged for brothers than for sisters. Thus, while economic variations in the prevalence of allergy an inverse association between family size and allergic are evident not only in western countries such as diseases remains a consistent feature, the possible mod- Britain,31 38 39 Italy,26 and the USA,37 41 42 but also in the ifying influences of household structure, including birth German Democratic Republic before German uni- order, sibling gender, and parental ages23 31 32 still require fication43 and in urban Ghana.44 clarification. Anecdotally, the association of allergy with affluence http://thorax.bmj.com/ A large study of specific IgE among adults from dates back to the 19th century.17 Charles Blackley, who several European countries28 has shown a statistically first demonstrated that hay fever was caused by allergy significant difference in the strength of the family size to grass pollen, described the disease as one of the urban effect between subjects with a parental history of allergy educated classes and was puzzled to find that it was and those without such a history. A protective effect of rare among farmers, despite their high exposure to siblings on atopy was evident only in the group with no pollen. Interestingly, several recent studies have reported parental allergy, suggesting that environmental in- a reduced prevalence of allergic rhinitis and/or ob- fluences on allergic sensitisation may be “overwhelmed” jectively measured atopy among children of farmers on September 29, 2021 by guest. Protected copyright. by genetic predisposition to atopy. On the other hand, compared with other children in rural com- a study of German children suggested that the effect of munities.35 45–47 The magnitude of these differences, a sibship size was concentrated among the offspring of 2–3-fold variation, is similar to the comparison of ex- atopic fathers, although the statistical significance of the tremes of parental social class or household size.31 difference between paternal and maternal atopy was not A number of explanations can be offered for this assessed.33