Decreased Asthma Exacerbations Research Articles

Prevalence of viral respiratory tract infections in children with asthma

BackgroundPrevious studies support a strong association between viral respiratory tract infections and asthma exacerbations. The effect of newly discovered viruses on asthma control is less well defined.ObjectiveWe sought to determine the contribution of respiratory viruses to asthma exacerbations in children with a panel of PCR assays for common and newly discovered respiratory viruses.MethodsRespiratory specimens from children aged 2 to 17 years with asthma exacerbations (case patients, n = 65) and with well-controlled asthma (control subjects, n = 77), frequency matched by age and season of enrollment, were tested for rhinoviruses, enteroviruses, respiratory syncytial virus, human metapneumovirus, coronaviruses 229E and OC43, parainfluenza viruses 1 to 3, influenza viruses, adenoviruses, and human bocavirus.ResultsInfection with respiratory viruses was associated with asthma exacerbations (63.1% in case patients vs 23.4% in control subjects; odds ratio, 5.6; 95% CI, 2.7- 11.6). Rhinovirus was by far the most prevalent virus (60% among case patients vs 18.2% among control subjects) and the only virus significantly associated with exacerbations (odds ratio, 6.8; 95% CI, 3.2-14.5). However, in children without clinically manifested viral respiratory tract illness, the prevalence of rhinovirus infection was similar in case patients (29.2%) versus control subjects (23.4%, P > .05). Other viruses detected included human metapneumovirus (4.6% in patients with acute asthma vs 2.6% in control subjects), enteroviruses (4.6% vs 0%), coronavirus 229E (0% vs 1.3%), and respiratory syncytial virus (1.5% vs 0%).ConclusionSymptomatic rhinovirus infections are an important contributor to asthma exacerbations in children.Clinical implicationsThese results support the need for therapies effective against rhinovirus as a means to decrease asthma exacerbations.

Advances in upper airway diseases and allergen immunotherapy

The purpose of this review is to highlight important articles on upper airway disease and immunotherapy that appeared in the Journal of Allergy and Clinical Immunology and elsewhere during 2005. In recent studies of tissue from patients with chronic hypertrophic eosinophilic sinusitis, increased leukotriene C4 synthase and 5-lipoxygenase activity and increased levels of cysteinyl leukotriene production were demonstrated that correlated with disease severity but not with whether the patient was aspirin sensitive. However, the cysteinyl leukotriene 1 receptor was increased in leukocytes in the sinus tissue only in those patients with aspirin sensitivity. Major basic protein, released by eosinophils into the mucus in the paranasal sinus lumen, was found to reach concentrations capable of damaging the sinus epithelium, predisposing to bacterial infections. Testing the hypothesis that chronic hypertrophic eosinophilic sinusitis represents a reaction to common fungi, a double-blind trial of intranasal instillation of amphotericin B was conducted. There were marginal but significant differences in favor of amphotericin B treatment for sinus mucosal thickening on the basis of computed tomography and the evidence of eosinophilic inflammation in the sinus mucus. The effectiveness of topical nasal corticosteroids for treatment of nasal polyps was confirmed in 2 large studies. Improvement in sleep quality and daytime drowsiness in patients with allergic rhinitis treated with nasal corticosteroids was reported to correlate with reduction in nasal obstruction. The statistical analysis behind studies that reported a decrease in asthma exacerbations with nasal corticosteroids or oral antihistamines has been questioned. It appears that the results of at least one of these studies are indeed too good to be true. Although caution is still indicated in administering immunotherapy to patients receiving beta-adrenergic blocking agents, the prohibition might not be absolute. A study in patients with Hymenoptera sensitivity given venom immunotherapy revealed no increase in serious adverse reactions to venom injections and no greater incidence of reactions to insect stings in those taking beta-blocking agents. Sublingual immunotherapy for 8 to 12 weeks in patients with hazelnut sensitivity significantly increased their tolerance to hazelnut in double-blind, placebo-controlled challenges while inducing increased IgG4 and IL-10 levels, indicating induction of regulatory T cells. There were a number of articles in the Journal of Allergy and Clinical Immunology in 2005 that addressed the entity of chronic hypertrophic eosinophilic sinusitis. In addition, an update of the "Practice parameters on sinusitis" was published. The major focus in allergen immunotherapy continues to be sublingual administration.

Anti-IgE as novel therapy for the treatment of asthma.

Immunoglobulin-E (IgE) is believed to be the central effector antibody reacting to allergen in patients with allergic asthma. Clinical manifestations of allergic asthma result from the release of chemical mediators from mast cells and basophils on exposure to allergen. A humanized murine monoclonal antibody to IgE, rhuMAb-E25, recognizes the specific Fc epsilon3 portion of circulating IgE that binds to the high-affinity IgE receptor, Fc epsilonRI. In clinical studies, single and multiple doses of subcutaneous and intravenous rhuMAb-E25 have been shown to reproducibly reduce the serum free IgE concentrations in a dose-dependent manner. Clinical trials conducted in aeroallergen bronchoprovocation laboratories demonstrated that decreasing circulating IgE resulted in significant attenuation of the early and late asthmatic responses. Studies completed in moderate to severe allergic asthmatics have extended the safety and efficacy of rhuMAb-E25. Significant improvements in asthma symptoms, meaningful reductions in corticosteroid agents while decreasing reliance on bronchodilator rescue drugs, decreased asthma exacerbations, and improved quality of life have been documented. Because of the remarkable protein engineering and the humanization technology now available, rhuMAb-E25 therapy has elicited no antibody responses and has been safely administered to atopic subjects. rhuMAb-E25 as a novel monoclonal antibody, the first to be applied to lung diseases, holds promise for the control of many IgE-mediated diseases.