1 | Introduction
Allergy is defined by an inappropriate immune response to one or more
foreign antigens. This response can give rise to conditions such as
allergic asthma, atopic dermatitis (eczema), allergic rhinitis (hay
fever) and anaphylaxis.1Allergic diseases are characterized
by a latency period between primary exposure (sensitization) and
symptoms (elicitation) that develop upon subsequent exposures, and may
involve Ig-E and/or non-Ig-E-mediated responses. An Ig-E-mediated
allergic reaction (sometimes called immediate-type hypersensitivity
(Type I)) involves the production of Th2 cytokines, which initiate Ig-E
production by B cells2. Allergic and autoimmune
diseases seem to have increased in prevalence in many countries. In
recent decades the prevalence of allergic disorders, including hay fever
and bronchial asthma, has increased worldwide. This has mostly occurred
in western countries where up to 20% of the
population3 and
one
in three children in economically developed countries4are affected by allergic diseases. Furthermore, allergic diseases, are
also leading common chronic diseases; they may have great social and
economic impact on both individuals and their families. They are
leading
causes of chronic illness in young people, having a negative impact on
the quality of life and school performance5, for which
the reasons are not fully clear. A recent register-based study showed
that the lifetime prevalence of asthma and allergic rhinitis at age 10
was 15.6% and 20.4% respectively.6
Vaccination is used worldwide for preventing infectious
diseases7. Childhood vaccination plays an important
role in the early development of the immune system8.
Furthermore, most children with allergic diseases start to have symptoms
early in life; these early childhood influences are crucial in the
development of allergic diseases.9 The link between
vaccination and the risk of allergy was first published in 1994 by Odent
et al.10 Since then, numerous publications have
investigated this hypothesis11-15. However, most
commonly researched is the relationship between
Bacille
Calmette Guerin (BCG) vaccine and allergic disease, but the consequences
remain controversial. The BCG vaccine has been used for almost 100 years
to prevent tuberculosis16 and is standard in childhood
immunization programs of many countries. Since BCG has been demonstrated
to inhibit TH2 immunologic response and antagonize atopy in both human
and animal models, it is also a therapeutic model to investigate the
effect of early-life stimulation of TH1 cells.17 A
recent study showed that BCG may have non-specific beneficial effects on
the infant immune system, reducing early atopic
diseases.18 The association between BCG and childhood
atopic disease has been studied with conflicting
results.19 Given the relationship between sample size
and statistical power, we conducted a meta-analysis of studies with
sample size >100 and assessed as high-quality. We examined
the association between BCG vaccine and allergic disease and explored
the implications of evidence from existing trials for clinical practice
and future research.