Correspondence

Asthma and the Hygiene Hypothesis

N Engl J Med 2001; 344:1643-1644May 24, 2001

Article

To the Editor:

With reference to the review article by Busse and Lemanske on asthma (Feb. 1 issue),1 we would like to raise the following points. Figure 4 fails to make it clear that several serious diseases, including type 1 diabetes,2 are mediated by a type 1 helper-T-cell (Th1) response; for this reason, any immunotherapy aimed at manipulating the helper-T-cell response in favor of a Th1 response may have unwanted effects, such as the development of Th1-mediated diseases. Type 1 diabetes, like atopy, commonly presents early in life, is also rising in incidence in Europe, and is most common in first-born children and children whose families are well off.3-5 Thus, the epidemiologic features of type 1 diabetes have much in common with those of atopic disease. This evidence contradicts the hypothesis that a change in the balance between Th1 and type 2 helper-T-cell responses is occurring in children.

Wendy J.A. Anderson, M.R.C.P.
Antrim Hospital, Antrim BT41 2RL, Northern Ireland

Lorna Watson, M.R.C.P.
Lothian Health, Edinburgh EH8 6RE, Scotland

5 References

1. 1

   Busse WW, Lemanske RF Jr. Asthma. N Engl J Med 2001;344:350-362
   Full Text | Web of Science | Medline

2. 2

   Liblau RS, Singer SM, McDevitt HO. Th1 and Th2 CD4+ T cells in the pathogenesis of organ-specific autoimmune diseases. Immunol Today 1995;16:34-38
   CrossRef | Medline

3. 3

   Patterson CC, Carson DJ, Hadden DR. Epidemiology of childhood IDDM in Northern Ireland 1989-1994: low incidence in areas with highest population density and most household crowding. Diabetologia 1996;39:1063-1069
   CrossRef | Web of Science | Medline

4. 4

   Bingley PJ, Douek IF, Rogers CA, Gale EA. Influence of maternal age at delivery and birth order on risk of type 1 diabetes in childhood: prospective population based family study. BMJ 2000;321:420-424
   CrossRef | Web of Science | Medline

5. 5

   Green A, Gale EA, Patterson CC. Incidence of childhood-onset insulin-dependent diabetes mellitus: the EURODIAB ACE Study. Lancet 1992;339:905-909
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: We greatly appreciate the comments of Anderson and Watson regarding the “hygiene hypothesis” and the parallel increases in incidence noted for atopic asthma and type 1 diabetes. The contribution of the hygiene hypothesis to our understanding of allergic diseases and asthma continues to be both supported and challenged by epidemiologic data and in vitro observations. The figure depicting this hypothesis in our review article was purposely drawn to emphasize the importance of a balance between Th1 and Th2 cytokine responses. We agree entirely that early interventions aimed at stimulating the immune response to be dominated by Th1 cells might create more problems than they would solve.

With regard to type 1 diabetes in children, recent studies have shown that preschool day-care attendance, a proxy measure for infectious disease in childhood, is inversely associated with the incidence of type 1 diabetes.1 Similar correlations have been noted for childhood asthma.2 These parallel trends do not necessarily contradict the hypothesis that a change in the balance between Th1 and Th2 responses is occurring in children. The explanation for these findings according to the hygiene hypothesis would be that frequent childhood infections may stimulate Th1 responses in a way that corrects any underlying imbalance between Th1 and Th2 in children destined for atopy, without “pushing” the immune system too far in the opposite direction, thereby leading to the preferential Th1 response of diabetes.3,4 It will require further study to resolve this debate, but the hygiene hypothesis provides a new perspective on mechanisms of asthma and allergic diseases, as well as potential treatments.

Robert F. Lemanske, Jr., M.D.
William W. Busse, M.D.
University of Wisconsin–Madison Medical School, Madison, WI 53792

4 References

1. 1

   EURODIAB Substudy 2 Study Group. Infections and vaccinations as risk factors for childhood type I (insulin-dependent) diabetes mellitus: a multicentre case-control investigation. Diabetologia 2000;43:47-53
   CrossRef | Web of Science | Medline

2. 2

   Ball TM, Castro-Rodriguez JA, Griffith KA, Holberg CJ, Martinez FD, Wright AL. Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. N Engl J Med 2000;343:538-543
   Full Text | Web of Science | Medline

3. 3

   Bottini N, Fontana L. Asthma and diabetes. Lancet 1999;354:515-516
   CrossRef | Web of Science | Medline

4. 4

   Azar ST, Tamim H, Beyhum HN, Habbal MZ, Almawi WY. Type I (insulin-dependent) diabetes is a Th1- and Th2-mediated autoimmune disease. Clin Diagn Lab Immunol 1999;6:306-310
   Medline

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