4 | Discussion
4.1 | Main findings
In this systematic review and meta-analysis of data from large scale
participants-based studies, there is ample epidemiologic evidence to
show that BCG vaccine might be effective in preventing allergic disease,
especially asthma among European and American countries. However,
compared with asthma, the risk of developing allergic disease was not
reduced for both eczema and rhinitis. In both Asia and Africa, there was
no association between BCG vaccine and allergic disease. To the best of
our knowledge, this systematic review and meta-analysis is the most
comprehensive and latest study between BCG vaccination and allergic
disease.
In this study, we found that receiving a BCG vaccine in early childhood
reduced the risk of allergic disease, especially asthma. According to
other studies on BCG vaccination and asthma, the anti-inflammatory
properties of BCG has been tested in murine models of atopic asthma
where the mycobacteria were shown to inhibit allergen-induced airway
inflammation37. BCG altered the immune balance towards
Th1-like activity by decreasing the IL-4 and IL-10 production. The
mechanism of IFN-γ-induced inhibition of Th2 responses is not fully
understood, but could involve activation of macrophages, direct
suppression of developing Th2 lymphocytes, or altered antigen
presentation38. The mechanism responsible for the
effect of BCG on asthma is more complex than simple changes in the
Th1/Th2 balance39 and we hypothesized that early
childhood mycobacterial infection promotes the switch from a Th2 to a
Th1 profile, therefore inhibiting the expression of atopy.
In European and American countries, the performance of BCG vaccination
in preventing asthma is highly significant. This could be attributable
to the fact that children born into these regions of the world in which
helminth infections and tuberculosis are endemic might derive particular
benefits from BCG vaccine40. The protection level of
BCG vaccination appear to follow a gradient from poor protection in
countries close to the equator towards higher protection with increasing
distance from the equator, a gradient that overlaps with exposure to
environmental mycobacteria41. Early-life events or
diseases, such as perinatal circumstances or early allergen exposure are
also reported to increase the prevalence of allergic
diseases42. However, heterogeneity might not be
present in most stratified analyses among subjects at high risk or of
non-Western origin as a result of the small number of studies included.
Based on this meta- analysis, the positive protective role of BCG
vaccine in allergic disease requires further investigation, especially
more cohort studies on children from high risk areas.
As for rhinitis and eczema, there is significant association, even
though they may share the same genetic architecture with
asthma43. That is likely because some methodologic
limitations may have impacted limit our interpretation of the findings.
We expected that exploring heterogeneity according to methodologic
characteristics of the original studies may have been informative in
terms of pinpointing which and in what aspects specific studies have
contributed to heterogeneity. As these participants lacked information
on the severity of allergic disease especially eczema in the included
studies, the applicability of findings to children with varying degrees
of severity is therefore uncertain. This may have influenced the
resulting protective effective of BCG vaccination in eczema and
rhinitis.