Vol 44 # 4 December 2012 - Kma.org.kw

December 2012
KUWAIT MEDICAL JOURNAL 278
but asthma is a serious problem that can cause severe
difficulties in breathing. The real significance of
asthma is demonstrated by the number of visits to
the doctor and to the emergency room and days spent
in the hospital [11] ; in fact, the number of visits to the
doctor for hypertension or for pregnancy or general
examination is each fewer than the number of visits
for asthma. Indeed, the single most common reason for
a visit to the emergency room in the Western world is
an asthma attack.
Asthma is a worldwide disease and a common one.
With about 5% of the population in Western countries
affected, there is no reason to assume that the incidence
of asthma is lower in Kuwait and the Arabian Gulf.
In fact, despite low allergen exposure, the pattern of
childhood asthma in Kuwait follows that described
in Western communities [12,13] . In Kuwait, the average
annual admission rate for asthma per 100,000 people
was 217 in the 1992-1994 period and the mean annual
death rate per 100,000 people was about 1.6. The
number of Kuwaiti patients being admitted for asthma
has increased [13] . A survey made by the Asthma Insights
and Reality in the Gulf and Near East (AIRGNE) of
Jordan, Kuwait, Lebanon, Oman and the UAE in 2009
showed that the comparative population prevalence of
diagnosed current asthma was high, ranging from 23%
in Kuwait to 32% in Lebanon [14] .
IMMUNOPATHOGENESIS OF ASTHMA
Asthma, also known as reversible obstructive airway
disease, is characterized by hyperresponsiveness
of the tracheobronchial tree to respiratory irritants
and bronchoconstrictor chemicals producing attacks
of wheezing, dyspnea, chest tightness and cough.
This chronic respiratory disease is characterized by
episodes of inflammation and narrowing of small
airways in response to triggers of asthma. Asthma can
be triggered by a variety of factors including allergens,
infections, exercise, abrupt changes in the weather and
exposure to airway irritants such as tobacco smoke.
Asthma attacks can vary from mild to life-threatening.
Asthma can be due to either an allergic response
or a non-allergic response. Asthma due to an allergic
response is also known as allergic asthma, extrinsic
asthma, atopic asthma or immunologic asthma. 50% of
asthma cases are “allergic-asthma” [4] . Allergic asthma
is triggered by air-borne or blood-borne allergens
such as pollen, dust, fumes, insect products or viral
products. Non-allergic asthma, also known as intrinsic
or idiopathic asthma, is induced by cold or exercise,
apparently independently of allergens. However,
regardless of the presence or absence of allergy, all
asthmatic patients have the cardinal features of airway
hyperreactivity, airway obstruction and eosinophilia.
Allergic asthma in genetically susceptible
individuals is a result of dysregulated immune
responses to common environmental antigens. The
pathogenesis of asthma involves cytokine production
from T helper 2 (Th2) lymphocytes that in turn
orchestrate the allergic inflammatory response. Upon
recognition of an allergen, Th2 cells produce cytokines
that induce IgE synthesis, activate eosinophils and mast
cells, and up-regulate expression of adhesion molecules
on endothelial and epithelial cells. Eosinophils are
a key component of chronic allergic disease and
contribute to many of the pathological processes of
asthma producing molecules that stimulate vasomotor
activity, bronchoconstriction and mucus secretion. They
also produce a variety of pro-inflammatory cytokines
such as tumor necrosis factor (TNF) α, interleukin
(IL)-1 and IL-6. Anti-allergen IgE antibodies first bind
to mast cells; subsequent exposure to the allergen
triggers an IgE-mediated release of mediators that
may cause an asthmatic attack. IgE-sensitized mast
cells and basophils secrete several mediators such as
histamine, leukotrienes and prostaglandins which
lead to bronchoconstriction, vasodilation and buildup
of mucus. Subsequently, other mediators including
eosinophil-chemotactic factor, platelet-activating factor
and the cytokines IL-4, IL-5 and TNFα are released;
these mediators increase endothelial cell adhesion
and recruit inflammatory cells such as eosinophils and
neutrophils into the bronchial tissue.
As Th2 reactivity is critical to the development
of asthma, it is pertinent to elaborate on Th1/Th2
dichotomy at this point.
Th1 AND Th2 REACTIVITY
One of the most significant advances in our
understanding of immune responses has been the
delineation of the Th1/Th2 paradigm, which provides
a framework for understanding how the immune
system directs responses to different types of pathogens
and antigens. The two major subsets of CD4 + T helper
cells, Th1 and Th2, have different patterns of cytokine
production and different roles in immune responses.
Each subset induces functions that are effective at
handling certain types of pathogens, but can be
ineffective, or may even have pathological effects if
made in response to other types of pathogens [15, 16] .
Th1 cells secrete IFNγ, TNFβ, IL-2 and TNFα, the so
called Th1-type cytokines. Th1-type cytokines activate
cell-mediated reactions important in resistance to
infection by intracellular pathogens, and in cytotoxic
and delayed-type hypersensitivity (DTH) reactions.
Th2 cells, on the other hand, secrete IL-4, IL-5, IL-6, IL-
10 and IL-13; these Th2-type cytokines promote robust
antibody production and are therefore commonly
found in association with strong antibody responses
that are important in combating infections with
extracellular organisms. Which type of reactivity, Th1
or Th2 is activated first may influence the subsequent