Heterogeneity in response, genetics and inflammation and the risk for allergic and non-allergic respiratory health problems: The veterinarians' Health Study. Part-II

According to the hygiene hypothesis the decreased infectious burden during
childhood has caused a misbalance between the Th1/Th2 immune balance resulting
in a th2 allergy prone status. Studies assessing the relationship between
infectious diseases and allergy have both confirmed and rejected this theory.
The same holds for the suggested protective effect of exposure to microbial
bio-aerosols and allergy. Several studies have suggested a protective effect of
endotoxin. However, in environmental and occupational studies, endotoxin
exposure has been associated with acute asthma-like symptoms and bronchial
hyperresponsiveness as well. More recently, interest moved beyond the Th1/Th2
paradigm of the hygiene hypothesis and focussed on a possible role of T
regulatory (Treg) cells. It is hypothesised that a decrease in Treg cells could
lead to reduced immune suppression of allergic reactions. The relationship
between microbial stimulation, Treg cells and the effect on allergy is still
unclear although the regulating influence of infectious and non-infectious
microbial exposure on the development of allergy implies that the pathogen
recognition receptors (PPRs) on cells of the immune system recognizing pathogen
associated molecular patterns (PAMPs), and genes encoding these PPRs might play
an important role. Inconsistent results have been reported on innate immunity
associated gene polymorphisms and the presence of asthma and allergy.
Veterinarians are potentially exposed to allergens, endotoxin and zoonotic
agents. Previously, prevalence rates ranging from 17 to 66% for self-reported
atopic and allergic diseases have been described in veterinarians. A Dutch
survey among veterinarians showed that the mean dust and endotoxin exposure was
high in swine, poultry and cattle practitioners and relatively low in companion
animal practitioners. A study in animal-health technology apprentices starting
exposure to laboratory animals showed an incidence of 8.9% of work-related
sensitisation and an incidence of occupational asthma of 2.7%. Sensitisation,
symptoms and disease occurred in the first 2 to 3 years after exposure to
laboratory animals began and predictors of sensitisation were atopy, nasal and
respiratory symptoms in the pollen season and number of contact hours with
rodents.

The main aim of this follow-up study is to assess the incidence of respiratory
disorders, like allergy, asthma and asthma like-syndrome, in association with
the interaction of environmental and genetic risk factors in veterinary
students. In order to study this, both health outcomes and environmental,
genetic and intermediate factors such as inflammatory markers need to be
established.

A population-based prospective follow-up study is performed among first year
veterinary students. For the duration of three years, all first year veterinary
students (n=225/year) are contacted to participate in the follow-up study that
will follow the students during the course of their study, being at least 6
years. At baseline every student is asked to fill out a baseline health
questionnaire, to give blood and to take part in a baseline health
investigation. This health investigation consists of several tests to establish
lung function (spirometry, bronchial hyperresponsiveness test and NO
concentration measurement in exhaled air). Furthermore a nasal swab will be
taken at baseline and stored frozen to possibly test, in a later stage when
methods to do so are developed, for nasal carriage of infectious
micro-organisms.
In the following years, each student is contacted annually to fill out the
follow-up questionnaire and for a blood draw, the first to verify changes in
health symptoms and the latter to verify changes in serological outcomes, like
atopy. Additionally, nasal swabs will be collected and stored annually to study
changes in nasal carriage of infectious micro-organisms.
A nested case-control study is performed on the basis of the outcomes of the
questionnaire. Cases and incidence density sampled controls will be invited to
repeat the health investigation. Cases are defined by the answer yes to a
minimum number of respiratory and allergic health complaints suggestive for
allergy, asthma or asthma-like disorder. Controls, not reporting these symptoms
will be selected in a 1:2 ratio compared to the number of cases.

Filling out a questionnaire is hardly associated with any burden or risk. The
measurements performed during the health investigation and taking blood give
light burden but no real additional risks, bearing in mind that all performed
tests are standard diagnostic tools used in daily clinical practice.
The benefit for participating students is the gaining knowledge of exposure and
associated health problems that can occure during veterinary education. With
this information work methods can be changed, thereby decreasing exposure and
decreasing associated health problems.