Exposure to indoor microbial agents, allergens and pets, and their relation to asthma and allergy prevalence in farmers' children and their peers from rural areas : Diploma thesis

Background In ‘westernised’ countries, the prevalence of childhood asthma and allergy have risen throughout the last three decades. Changes in lifestyle and environmental factors like an increase in exposure to air pollutants, environmental tobacco smoke, or indoor allergen and pet exposure have been considered as plausible explanations. However, little evidence in support of these causal risk factors for these common chronic childhood diseases has been found. Lower risk of hay fever and atopic sensitisation were reported in children with more siblings, and later also in children who attended day care centres early in infancy. These findings were summarised in the so-called ‘hygiene hypothesis’: limited exposure to bacterial and viral pathogens during early childhood results in a higher risk of developing allergic diseases. Recent allergy research has focused on the interaction between the innate and adaptive immunity: innate immunity receptors of pathogens seem to modulate the activation of adaptive immunity mechanisms. Three independent studies showed reduced prevalence of asthma and allergy among farmers’ children compared to their peers from the same rural areas from Switzerland, Austria, and Germany. A series of epidemiological studies in Europe, Canada, and Australia consistently confirmed and extended these findings. These results have been seen as an extension of the ‘hygiene hypothesis’, since a farm environment provides an enormous habitat for micro-organisms. A potential candidate that may explain these differences in the prevalence of childhood asthma and allergy is environmental exposure to endotoxin, a component of the outer membrane of gram-negative bacteria. Aim To assess the exposure to indoor microbial agents, allergens and pets in farmers’ children and their peers of non-farming families, and to estimate whether these exposures are associated with the prevalence of childhood asthma and allergies. Methods The ALEX (Allergy and Endotoxin) study was a cross-sectional survey in rural areas of Germany, Austria, and Switzerland. 2618 parents of 6-13 year-old children completed a standardised questionnaire including questions about asthma and allergy from the ISAAC study
and questions about the child’s activities on farms, and characteristics of the home environment.
Blood samples were obtained from selected children and tested for atopic sensitisation,
specially for specific IgE and IgG4 antibodies to grass pollen and cat allergen. Endotoxin and
cat allergen levels were measured in indoor dust samples and in settled dust from stables.
Complete data were available for 812 children. In a subgroup of 553 children mattress dust
muramic acid levels, another marker for exposure to bacteria, were determined.
Results
Higher levels of indoor endotoxin exposure were associated with reduced allergen sensitisation,
decreased prevalence of hay fever, atopic asthma and wheeze in a dose-dependent
manner. The associations were equally strong among the sub sample children from nonfarming
families, indicating that even lower levels of endotoxin may favourably influence the
risk of atopic diseases.
Endotoxin levels in stables were not correlated with the amount of endotoxin measured
indoors, but a dose-dependent association between the child’s activity on the farm and indoor
home endotoxin levels was observed, both in farmers’ and in non-farmers’ children. Pet keeping,
full time farming (compared to part time farming), and younger age of the children contributed
additionally to increased indoor endotoxin levels. Endotoxin levels in stables increased
with the number of cattle (but only up to the highest quartile), with hay feeding (compared
to feeding of mainly silage), and additionally with provision of accommodation of
horses, pigs, sheep or goats in the cattle stable. All these predictors might be surrogate measures
for traditional dairy farming in hilly German speaking areas.
Children’s mattress’ muramic acid levels were significantly higher in farmers’ children
than in non-farmers’ children. Mattress muramic acid and endotoxin levels were partially correlated,
indicating that both substances are markers for the exposure to micro-organisms. Independent
of being a farmers’ child, mattress dust from homes heated with wood or coal and
less frequently cleaned mattresses showed increasing muramic acid levels.
Independent of the endotoxin exposure, increasing muramic acid levels in mattress dust
was associated with a lower frequency of current wheeze, but not with atopic sensitisation or
hay fever. The protective effect on wheeze and diagnosed asthma was more pronounced in
non-sensitised children. The different effect spectrum for muramic acid and endotoxin exposure
suggest that different micro-organisms might contribute to the lower prevalence of
asthma and allergy among farmers’ children, compared to non-farmers’ children.
Current contact to dogs was inversely associated with diagnosed hay fever, asthma, and
specific sensitisation to grass pollen and to cat allergen, but not with increased IgG4 levels.
Early and current exposure to cats – but not to dogs – was associated with lower frequency of
wheeze and grass pollen sensitisation. None of these inverse associations were greatly affected
by additionally taking into account the indoor endotoxin or cat allergen levels, but additionally
adjustment for early or current exposure to farm animals attenuated the protective
effects. Although pet exposure was frequent in this rural population, the protective effects of
pet keeping observed in other peer-reviewed studies may be masked by frequent contact to
farming environments.
Conclusions and outlook
Endotoxin and muramic acid may be surrogate markers of a much broader spectrum of
microbial compounds. Thus, further studies have not only to confirm the lower risk of children
with contact to livestock or with higher exposure to micro-organisms early in life, but
also to find the relevant mixture of protective components in the farm dust. In addition, as
ingestion is another plausible route of exposure to micro-organisms, epidemiology may focus
on differences in nutrition and their association with childhood asthma and allergy. The PARSIFAL
(Prevention of allergy – Risk factors for sensitisation in children related to farming
and anthroposophic lifestyle) study offers the opportunity to do so, as this study include children’s
populations growing up with different lifestyles. Experimental studies may focus on
the relevant exposure route (inhalation, ingestion) of different patterns of micro-organisms.
The genetic dimension has to be kept in mind in the discussion of environmental exposure to
micro-organisms by identifying particularly sensitive groups through genetic investigations,
as the available data in the ALEX study was limited.
Current scientific evidence has not developed strongly enough to provide a reliable
course of action for primary prevention or therapy. Infectious diseases resulting from exposure
to pathogens continue to be a serious public health problem. Thus, the protective effect
of a microbial environment on the development of asthma and atopy should be balanced
against the benefits of established hygiene standards.