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Biomedical subjects

Mark H Moss

Publications and source records attributed to Mark H Moss.

4 recordsLinked to original sources

Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma.

BACKGROUND: Outcome data are needed to base recommendations for controller asthma medication use in school-aged children. OBJECTIVE: We sought to determine intraindividual and interindividual response profiles and predictors of response to an inhaled corticosteroid (ICS) and a leukotriene receptor antagonist (LTRA). METHODS: An ICS, fluticasone propionate (100 mug twice daily), and an LTRA, montelukast (5-10 mg nightly, age dependent), were administered to children ages 6 to 17 years with mild-to-moderate persistent asthma using only as-needed bronchodilators in a multicenter, double-masked, 2-sequence, 16-week crossover trial. Clinical, pulmonary, and inflammatory responses to these controllers were evaluated. RESULTS: Improvements in most clinical asthma control measures occurred with both controllers. However, clinical outcomes (asthma control days [ACDs], the validated Asthma Control Questionnaire, and albuterol use), pulmonary responses (FEV(1)/forced vital capacity, peak expiratory flow variability, morning peak expiratory flow, and measures of impedance), and inflammatory biomarkers (exhaled nitric oxide [eNO]) improved significantly more with fluticasone than with montelukast treatment. eNO was both a predictor of ACDs (P = .011) and a response indicator (P = .003) in discriminating the difference in ACD response between fluticasone and montelukast. CONCLUSIONS: The more favorable clinical, pulmonary, and inflammatory responses to an ICS than to an LTRA provide pediatric-based group evidence to support ICSs as the preferred first-line therapy for mild-to-moderate persistent asthma in children. eNO, as a predictor of response, might help to identify individual children not receiving controller medication who achieve a greater improvement in ACDs with an ICS compared with an LTRA.

Acetates↗

Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis.

BACKGROUND: Rush immunotherapy (RIT) presents an attractive alternative to standard immunotherapy. However, RIT carries a much greater risk of acute allergic reactions, including anaphylaxis. OBJECTIVES: We hypothesized that omalizumab, a humanized monoclonal anti-IgE antibody, would be effective in enhancing both safety and efficacy of RIT. METHODS: Adult patients with ragweed allergic rhinitis were enrolled in a 3-center, 4-arm, double-blind, parallel-group, placebo-controlled trial. Patients received either 9 weeks of omalizumab (0.016 mg/kg/IgE [IU/mL]/mo) or placebo, followed by 1-day rush (maximal dose 1.2-4.0 mug Amb a 1) or placebo immunotherapy, then 12 weeks of omalizumab or placebo plus immunotherapy. RESULTS: Of the 159 patients enrolled, 123 completed all treatments. Ragweed-specific IgG levels increased >11-fold in immunotherapy patients, and free IgE levels declined >10-fold in omalizumab patients. Patients receiving omalizumab plus immunotherapy had fewer adverse events than those receiving immunotherapy alone. Post hoc analysis of groups receiving immunotherapy demonstrated that addition of omalizumab resulted in a 5-fold decrease in risk of anaphylaxis caused by RIT (odds ratio, 0.17; P = .026). On an intent-to-treat basis, patients receiving both omalizumab and immunotherapy showed a significant improvement in severity scores during the ragweed season compared with those receiving immunotherapy alone (0.69 vs 0.86; P = .044). CONCLUSION: Omalizumab pretreatment enhances the safety of RIT for ragweed allergic rhinitis. Furthermore, combined therapy with omalizumab and allergen immunotherapy may be an effective strategy to permit more rapid and higher doses of allergen immunotherapy to be given more safely and with greater efficacy to patients with allergic diseases.

Adolescent↗

Immunotherapy: first do no harm.

Immunotherapy continues to be a treatment modality that is used most exclusively by allergists. The acceptance of immunotherapy for treating children with allergic rhinitis or asthma has been limited by the lack of adequate numbers of pediatric double-blind, placebo-controlled trials of specific allergen immunotherapy; use of venom immunotherapy is more clearly supported by current data. Children represent a unique group of patients where allergic disease may not only be treated using immunotherapy resulting in reduction of symptoms, signs, and complications of disease, but may also hold the best potential for the evasive goal of prevention of the development of future allergic disease.

Allergens↗

Characterization of within-subject responses to fluticasone and montelukast in childhood asthma.

BACKGROUND: Responses to inhaled corticosteroids (ICSs) and leukotriene receptor antagonists (LTRAs) vary among asthmatic patients. OBJECTIVE: We sought to determine whether responses to ICSs and LTRAs are concordant for individuals or whether asthmatic patients who do not respond to one medication respond to the other. METHODS: Children 6 to 17 years of age with mild-to-moderate persistent asthma were randomized to one of 2 crossover sequences, including 8 weeks of an ICS, fluticasone propionate (100 microg twice daily), and 8 weeks of an LTRA, montelukast (5-10 mg nightly depending on age), in a multicenter, double-masked, 18-week trial. Response was assessed on the basis of improvement in FEV 1 and assessed for relationships to baseline asthma phenotype-associated biomarkers. RESULTS: Defining response as improvement in FEV 1 of 7.5% or greater, 17% of 126 participants responded to both medications, 23% responded to fluticasone alone, 5% responded to montelukast alone, and 55% responded to neither medication. Compared with those who responded to neither medication, favorable response to fluticasone alone was associated with higher levels of exhaled nitric oxide, total eosinophil counts, levels of serum IgE, and levels of serum eosinophil cationic protein and lower levels of methacholine PC(20) and pulmonary function; favorable response to montelukast alone was associated with younger age and shorter disease duration. Greater differential response to fluticasone over montelukast was associated with higher bronchodilator use, bronchodilator response, exhaled nitric oxide levels, and eosinophil cationic protein levels and lower methacholine PC(20) and pulmonary function values. CONCLUSIONS: Response to fluticasone and montelukast vary considerably. Children with low pulmonary function or high levels of markers associated with allergic inflammation should receive ICS therapy. Other children could receive either ICSs or LTRAs.

Acetates↗