Changes in atopy over a quarter of a century, based on cross sectional data at three time periods
BMJ 2005; 330 doi: https://doi.org/10.1136/bmj.38435.582975.AE (Published 19 May 2005) Cite this as: BMJ 2005;330:1187
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Respiratory allergy has been considered a disease primarily occurring
in childhood or adolescence and thereafter tending to ameliorate or
disappear during adulthood. According to this notion the lower prevalence
of allergy with increasing age has been interpreted as an effect of age.
The novel data presented by Law et al in the BMJ (1) seems to challenge
this paradigm. They present evidence that atopy (detectable serum IgE
antibodies against inhalant allergens) has increased in middle-aged men
over recent decades. Furthermore, their results support that atopy is a
reasonably stable condition, since the prevalence of atopy was similar in
two groups of persons from the same birth cohort examined at 40-50 and 55-
64 years of age. In line with this, data from a Danish prospective
population-based cohort of 15-69-year-olds has shown that hay fever is a
stable condition. Thus, the 8-year remission rate of hay fever symptoms
was 15% (2) However, remission of both symptoms and sensitisation was
rare, i.e. approximately 2%, underlining the chronic intermittent nature
of this condition. Within this prospective cohort followed over an 8-year
period (from 1990-1998), the prevalence of atopy increased among subjects
who were less than c. 30 years in 1990, i.e. subjects who were born during
the 1960s or later, while the prevalence was unchanged among subjects who
were more than c. 30 years in 1990 (3). These results support the notion
that, in Denmark, the increasing prevalence of atopy is caused by a cohort
effect, i.e. an increase associated with being born around 1960 or
thereafter. As compared to earlier generations, these "allergic
generations" may have been subjected to a more urbanized and westernized
lifestyle increasing their susceptibility to allergy. Although this cohort
effect may point towards early life risk factors, it is increasingly being
recognized that also adult persons may develop atopy, if they are exposed
to changes in risk (or protective) factors such as migration to more
urbanized areas (4).
As a consequence of the apparent chronic nature of respiratory allergy and
the aging of “the allergic generations” one would expect the prevalence of
atopic conditions such as hay fever and allergic asthma to continue its
increase among middle-aged and subsequently also start to increase in
older people in the years to come. It appears that the allergy epidemic
may be spreading to old age: “the allergic march in adulthood”.
Reference List
1. Law M, Morris JK, Wald N, Luczynska C, Burney P. Changes in atopy
over a quarter of a century, based on cross sectional data at three time
periods. BMJ 15 April 2005.
2. Bodtger U,.Linneberg A. Remission of allergic rhinitis: An 8-year
observational study. J Allergy Clin Immunol 2004;114:1384-8.
3. Linneberg A, Nielsen NH, Madsen F, Frølund L, Dirksen A, Jørgensen
T. Is the prevalence of allergic respiratory disease caused by a cohort
effect? Clin Exp Allergy 2002;32:1702-5.
4. Linneberg A. Hypothesis: urbanization and the allergy epidemic--a
reverse case of immunotherapy? Allergy 2005;60:538-9.
Competing interests:
None declared
Competing interests: No competing interests
The hypothesis that increasing intake of antioxidants is increasing
atopy is puzzling.1 High IgE levels relate to low levels of vitamin E. The
correlation between vitamin E intake, IgE levels, and the clinical
manifestations of atopy indicates that vitamin E should be an excellent
therapeutic tool for atopic dermatitis.2-4
However, deficiencies of vitamin E and vitamin C are much less common
than deficiencies of zinc and copper. These trace minerals are main
regulators of the immune system and are involved in the balance of Th1 -
type and Th 2-type immune responses. Alcohol drinking causes increased
urinary losses of zinc and magnesium, functional deficiencies of B
vitamins and deficiencies of essential fatty acids. Surely the most
obvious reason for increases in atopy in men is increases in alcohol
drinking?
As tobacco smoking has decreased, wine drinking as been promoted as
beneficial because of the epidemiological “J” curve. In reality,
individuals who are immuno-compromised tend to avoid alcohol becuase of
unpleasant reactions. This gives rise to a spurious “beneficial” effect of
light drinking and absurd recommendations of safe amounts of alcohol for
everyone.
Alcohol drinking also encourages an overgrowth of bacteria or fungi
in the bowel and excessive fermentation. Food is converted into small
amounts of alcohol in the blood (the Auto-brewery Syndrome).5 Treatment
with anti-fungal medication, a low yeast, low sugar diet and avoidance of
alcoholic drinks, often has dramatically effect in treating atopy,
especially dermatitis.
1 Murr C, Schroecksnadel K, Winkler C, Ledochowski M, Fuchs D.
Antioxidants may increase the probability of developing allergic diseases
and asthma. Med Hypotheses 2005;64:973-7.
2 Fogarty A, Lewis S, Weiss S, Britton J. Dietary vitamin E, IgE
concentrations, and atopy. Lancet 2000 ; 356: 1573-4.
3 Bando N, Yamanishi R, Terao J. Inhibition of immunoglobulin E
production in allergic model mice by supplementation with vitamin E and
beta-carotene. Biosci Biotechnol Biochem. 2003; 67: 2176-82.
4 Tsoureli-Nikita E, Hercogova J, Lotti T, Menchini G. Evaluation of
dietary intake of vitamin E in the treatment of atopic dermatitis: a study
of the clinical course and evaluation of the immunoglobulin E serum
levels. Int J Dermatol. 2002; 41: 146-50.
5 Eaton KK, McLaren Howard J, Hunnisett A, Harris M. Abnormal gut
fermentation laboratory studies reveal deficiency of B vitamins, zinc, and
magnesium. J Nutr Environ Med 2004; 14: 115-120.
Competing interests:
None declared
Competing interests: No competing interests
Increase of atopy was reported in middle aged men during the past 25
years [1]. Usually such an increase is referred to increased hygienic
behaviour, but no relationship between allergy and infection could be
found by Law and coworkers [1]. Recently we have observed that antioxidant
vitamins [2, 3] and beverages rich in antioxidants [4] potently inhibit
production of Th1-type cytokine interferon-g in peripheral blood
mononuclear cells stimulated with mitogens. Such an inhibition is very
often associated with an upregulation of Th2-type immunity which will
increase the development of atopy and allergy [5].
This relationship
suggests that the improved quality of food and even more its fortification
with antioxidant vitamins may increase the strength of Th2-type immune
response and thus the probability of developing allergic reactions when an
allergen is met. This conclusion does not disregard the advantage which
antioxidant vitamins may have, e.g., in the prevention of cardiovascular
and cerebrovascular disorders. However, it seems that the increase of
allergic diseases could represent the price we have to pay if the intake
of antioxidants becomes too high and a kind of “antioxidant stress” is
developing. It appears that the changes in food behaviour more than
improved hygiene has contributed to the increased prevalence of atopy in
the past 25 years.
Katharina Schroecksnadel
Christiana Winkler
Dietmar Fuchs
Division of Biological Chemistry, Biocentre
Innsbruck Medical University, 6020 Innsbruck, Austria
1. Law M, Morris JK, Wald N, Luczynska C, Burney P. Changes in atopy
over a quarter of a century, based on cross sectional data at three time
periods. BMJ 2005; April 15: bmj.38435.582975.AEv1
2. Wirleitner B, Schroecksnadel K, Winkler C, Schennach H, Fuchs D.
Resveratrol suppresses interferon-gamma-induced biochemical pathways in
human peripheral blood mononuclear cells in vitro. Immunol Lett (in
press).
3. Winkler C, Schroecksnadel K, Schennach H, Fuchs D. In vitro
effects of antioxidant vitamins C (ascorbic acid) and E (a-tocopherol on
stimulated peripheral blood mononuclear cells. Pteridines (in press).
4. Zvetkova E, Wirleitner B, Tram NT, Schennach H, Fuchs D. Aqueous
extracts of Crinum latifolium (L.) and Camellia sinensis show
immunomodulatory properties in human peripheral blood mononuclear cells.
Int Immunopharmacol 2001;1:2143-50.
5. Murr C, Schroecksnadel K, Winkler C, Ledochowski M, Fuchs D.
Antioxidants may increase the probability of developing allergic diseases
and asthma. Med Hypotheses 2005;64:973-7.
Competing interests:
None declared
Competing interests: No competing interests
The allergic march should be revisited
Allan Linneberg responding to Law et al (1) asks whether the allergic
epidemic has spread to old age. We have recently tried to answer a similar
question by reviewing our patients’ records. The results of this
retrospective study have been presented, as an abstract, at the last
Annual Meeting of the American Academy of Allergy, Asthma, Immunology (2)
and can be summarized as follows.
In the last 5 years 956 (M/F: 306/650)
patients aged 60 years and over (median 76, range 60-93) were referred to
our Allergy Clinic for suspected atopic conditions. All of them underwent
skin prick testing with the most common inhalant allergens and 318 (33%)
were found positive with a wheal of at least 3 mm, men being more
frequently positive than women (40% vs 30%, p<_0.005. the="the" median="median" age="age" of="of" these="these" subjects="subjects" was="was" _65="_65" years="years" range="range" _60-86.="_60-86." allergen="allergen" profile="profile" skin="skin" positivity="positivity" similar="similar" in="in" two="two" genders="genders" and="and" characterized="characterized" by="by" a="a" clear="clear" _-cut="_-cut" prevalence="prevalence" pollens="pollens" _78="_78" vs="vs" _75="_75" over="over" dust="dust" mites="mites" _41="_41" _36="_36" animal="animal" danders="danders" _16="_16" moulds="moulds" _6="_6" _8.="_8." rhinitis="rhinitis" hay="hay" fever="fever" most="most" common="common" complaint="complaint" _74="_74" whereas="whereas" asthma="asthma" present="present" _33.="_33." _70="_70" _318="_318" cases="cases" _22="_22" clinical="clinical" onset="onset" atopy="atopy" at="at" or="or" after="after" their="their" _60th="_60th" birthday.="birthday." p="p"/>In conclusion, the answer is: yes, atopy is spreading
to old age. We need to be aware of this phenomenon in order not to
underestimate the role of atopy in the respiratory conditions affecting
the elderly. We will also need to draw specific guidelines for the
management (allergen avoidance, pharmacologic treatment, immunotherapy) of
atopy in patients, who often have important comorbidities.
1. Law M, Morris JK, Wald N, Luczynska C, Burney P. Changes in atopy over
a quarter of a century, based on cross sectional data at three time
periods. BMJ 15 April 2005.
2. Zauli D, Bortolotti R, Grassi A, Ballardini G, D’Ecclesia A, Bianchi
FB. Does atopy last forever? J Allergy Clin Immunol 2005;115:S252.
Competing interests:
None declared
Competing interests: No competing interests