Characterization of the Role of Histamine in Children With Asthma
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.
Inclusion Criteria:

 -  children age 7-17 years old

 -  with the diagnosis of allergic asthma or non-allergic asthma (n=102

 Exclusion Criteria:

 -  history of immunodeficiency, mastocytosis

 -  chronic abnormal conditions of the skin, liver or kidney

 -  neoplastic disease

 -  movement or neurologic disorders

 -  active eczema on the forearms at the time of study

 -  history of a previous anaphylactic episode

 -  evidence of pregnancy (by urinary hCG) or lactation at the time of the study