Characterization of the Role of Histamine in Children With Asthma

Asthma, a chronic disease which produces significant morbidity and mortality in children, is
a significant health problem to a large segment of society. Despite considerable advances in
the diagnosis and treatment of asthma over the past several years, a sizeable portion of
patients do not respond to the "core" treatments. The investigators are now learning that
the underlying pathophysiology of disease is different among patients with asthma therefore;
treatments which are beneficial in some patient groups may be not achieve affect in other
groups.

Antihistamines have been studied in the past for the treatment of asthma. These studies have
shown that there may be a beneficial effect of antihistamines in patients with allergic
asthma where histamine likely plays a large role in disease and treatment response. However,
there is not enough evidence to include these drugs in the standard treatment of asthma.

The investigators hypothesize that histamine plays a definable, significant role in disease
pathogenesis and treatment response in children with allergic asthma. The investigators plan
to test this overall hypothesis through two specific aims. The first aim will characterize
the relative contribution of histamine in allergic vs. non-allergic asthma. This aim will be
accomplished by comparison of the microvasculature response to histamine in children with
allergic asthma and children with non-allergic asthma, measured by histamine iontophoresis
with laser Doppler (HILD) monitoring, to determine potential phenotype-associated
differences in the pharmacodynamic response to histamine. The investigators will also
investigate the role of genetic variation in the observed differences in HILD between the
two groups. The second aim will characterize the pharmacodynamic response to antihistamines
via HILD in children with an exaggerated histamine response compared to children with a low
histamine response. This aim will be accomplished through conduct of a randomized,
double-blind, placebo-controlled cross-over trial of levocetirizine (LCT) in the two groups
(high histamine and low histamine) and observing the difference in antihistamine
pharmacodynamics in the two groups. The investigators will also investigate the effect of
pharmacokinetic variation and genetic variation in the histamine pathway on the observed
pharmacodynamic drug response.