Med Hypotheses. 2012 Sep;79(3):363-4.

Hygiene hypothesis: why south/north geographical differences in prevalence of asthma and sarcoidosis?

Kurata A.

Department of Molecular Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan. akurata@tokyo-med.ac.jp

 

Abstract

Although asthma is multi-factorial and generally worsens during winter, prevalence of asthma tends to be higher in warm regions. By contrast, sarcoidosis, which like asthma results from immunological abnormalities that disturb the lower respiratory tracts and unlike asthma is characterized by T helper (Th) 1 response, occurs predominantly in colder regions. The hygiene hypothesis proposes that infection by intracellular pathogens such as early childhood viruses promotes Th1 immune phenotype and decreases susceptibility to later occurrence of Th2-associated asthma, since Th1 and Th2 cells are mutually inhibitory. As respiratory viral infections are generally more common under colder conditions, it is hypothesized that more respiratory viral infections in colder climates than one’s natural environment during early childhood may promote subsequent occurrence of sarcoidosis, while less infections in warmer environments may promote subsequent occurrence of asthma.

Copyright © 2012 Elsevier Ltd.

PMID: 22704943

 

Supplement:

This article presents an explanation for the geographical and ethnic differences in the prevalence of asthma and sarcoidosis. Table 1 is an excerpt from an article published in 1992 (1), with the addition of colored circles by this supplement’s author. Data shown in Table 1 appear to be reliable except with regard to Finland, where the prevalence of sarcoidosis was reported to be 28.2 per 100,000 (2).

 Table 1Table 1. Prevalence of intrathoracic sarcoidosis per 100,000 of population according to figures reported at World Conferences on Sarcoidosis.

 

In the regions marked by the same colored circles in Table 1, the prevalence of sarcoidosis is higher in the people whose ancestral land is warmer.

In Cape Town: African descent > Multiracial > Caucasian

In New York: African descent > Puerto Ricans (multiracial) > Hispanic > Caucasian

On the island of Ireland: Eire (Celt) > Northern Ireland (Anglo-Saxon)

It was speculated that the higher prevalence of sarcoidosis in former West Germany than in former East Germany was due to the fact that a larger number of immigrants whose ancestral land is warmer, such as Turkey, lived in the former region. Further, comparison of people with the same ethnic background who lived in different regions indicated that the prevalence of sarcoidosis is higher in colder regions (e.g. African descendents in New York vs. Cape Town). However, even in cold regions, the prevalence of sarcoidosis is not higher in people whose ancestral land is cold, such as Poland and USSR. Taken together, the prevalence of sarcoidosis seems to be reflected by racial migrations (Figure 1).

 Fig. 1Figure 1. Representative racial migrations in Europe. Blue arrows indicate people with higher prevalence of sarcoidosis.

 

In contrast to sarcoidosis, the prevalence of asthma tends to be higher in people who live in an environment where the temperature is warmer than that in their ancestral land. For example, the prevalence of asthma is highest in Peru and Brazil in the South American continent, which are equatorial regions and whose inhabitants had emigrated from colder regions such as Europe, while the prevalence of asthma is low in Indonesia, a region that is situated at the equator but whose inhabitants have lived there since ancient times (3). Although the occurrence of asthma may be influenced by various factors including air pollution associated with industrialization, comparison among the same rural districts demonstrated that asthma prevalence tend to be generally higher in warmer than colder districts in the United States (4).

The hygiene hypothesis can explain these geographical differences in prevalence of sarcoidosis and asthma, which proposes that exposure to infections in early childhood promotes a Th1 response, whereas lack of infections promotes a Th2 response. Indeed, repeated episodes of respiratory conditions such as a runny nose before the age of 1 year has been shown to reduce the risk of developing Th-2 associated asthma in young children up to school age (5). It is assumed that people with genetically Th1-dominant respiratory constitution survived natural selection in warm regions where respiratory viral infections are less, since people with genetically Th2-dominant respiratory constitution may have died from asthma before leaving offspring in ancient times. Likewise, people with genetically Th2-dominant respiratory constitution survived in cold regions, being free from sarcoidosis. Thus, in the present era, people with genetically Th1-dominant respiratory constitution brought up in cold regions may have more sarcoidosis, while those with genetically Th2-dominant respiratory constitution brought up in warm regions may have more asthma (Figure 2).

Fig. 2

Figure 2. Assumed innate respiratory constitutions determined by ancestral land (dotted bar), which may be modified by early childhood infections.

 

Currently, the hygiene hypothesis is not generally accepted by the academic society partly because positive correlation has been reported between the occurrence of Th1-associated type 1 diabetes and symptoms of Th2-associated asthma across various countries (6). However, type 1 diabetes is a disease attributable to the pancreas, and the condition that should be compared with asthma is one attributable to the respiratory tract such as sarcoidosis. Further, type 1 diabetes may be caused by Th2-associated autoantibodies. Thus, asthma should be compared with a condition that is definitely caused by a Th1 response such as sarcoidosis.

 

References:

1.         James DG 1992 Epidemiology of sarcoidosis. Sarcoidosis 9:79-87

2.         Pietinalho A, Hiraga Y, Hosoda Y, Löfroos AB, Yamaguchi M, Selroos O 1995 The frequency of sarcoidosis in Finland and Hokkaido, Japan. A comparative epidemiological study. Sarcoidosis 12:61-67

3.         Masoli M, Fabian D, Holt S, Beasley R; Global Initiative for Asthma (GINA) Program 2004 The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 59:469-478

4.         Akinbami LJ, Moorman JE, Garbe PL, Sondik EJ 2009 Status of childhood asthma in the United States, 1980-2007. Pediatrics 123:S131-145

5.         Illi S, von Mutius E, Lau S, Bergmann R, Niggemann B, Sommerfeld C, Wahn U; MAS Group 2001 Early childhood infectious diseases and the development of asthma up to school age: a birth cohort study. BMJ 322:390-395

6.         Stene LC, Nafstad P 2001 Relation between occurrence of type 1 diabetes and asthma. Lancet 357:607-608.

 

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