MEDLINE Abstracts: New and Alternative Asthma Therapies
MEDLINE Abstracts: New and Alternative Asthma Therapies
What's new concerning the latest in asthma therapy? Find out in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape Pulmonary Medicine.
Ward GW Jr, Woodfolk JA, Hayden ML, Jackson S, Platts-Mills TA
J Allergy Clin Immunol 1999 Sep;104(3 Pt 1):541-546
Although the etiology of intrinsic or late-onset asthma is generally not known, some cases are associated with overt dermatophyte infection and immediate hypersensitivity to proteins derived from fungi of the genus Trichophyton.
Objective: We sought to test the efficacy of oral antifungal treatment for Trichophyton-induced asthma by using fluconazole in a placebo-controlled trial.
Methods: Eleven patients with severe or moderately severe asthma were randomized to treatment with fluconazole 100 mg daily or placebo for 5 months (phase 1); during the following 5 months, all patients received active drug (phase 2). Subjects were evaluated by skin tests, bronchial provocation tests, and measurement of serum antibodies to Trichophyton species antigens. Clinical response was monitored by changes in peak flow values measured during a 2-week period at the end of each phase and by changes in bronchial sensitivity, symptoms, and steroid requirements.
Results: At the end of the first 5 months of active treatment, there was a highly significant decrease in bronchial sensitivity to Trichophyton (P = .012) and in oral steroid requirement (P = .01). At the end of phase 2, mean peak expiratory flow rates increased in 9 of 11 patients. An improvement in symptoms, peak flow, and steroid use was maintained up to 36 months after starting fluconazole in patients who continued to receive treatment.
Conclusion: The results show that fluconazole can be useful in the treatment of patients with severe or moderately severe asthma who have dermatophytosis. These findings are consistent with the argument that proteins derived from fungi on the skin and nails can contribute to allergic disease.
Valenta R, Vrtala S, Focke-Tejkl M, Bugajska-Schretter, Ball T, Twardosz A, Spitzauer S, Gronlund H, Kraft D
Biol Chem 1999 Jul-Aug;380(7-8):815-824
Type I allergy, a hypersensitivity disease affecting almost 20% of the population worldwide, is based on the IgE recognition of otherwise harmless antigens (ie, allergens). Allergen-induced crosslink of effector cell-bound IgE antibodies leads to the release of biological mediators and thus to immediate disease symptoms (allergic rhinitis, conjunctivitis and asthma). Specific immunotherapy, the only causative treatment of type I allergy, is based on the administration of increasing doses of allergens to allergic patients in order to yield allergen-specific non-responsiveness. Major disadvantages are: 1. that current forms of allergen immunotherapy are performed with allergens difficult to standardize which cannot be matched to the patient's reactivity profile, and 2. that the administration of active allergen preparations can cause anaphylactic side effects. Through the application of molecular biological techniques, many relevant environmental allergens have been produced as active recombinant proteins which allow component-resolved allergy diagnosis and thus represent the basis for patient-tailored forms of immunotherapy. Here we review molecular strategies which have been recently applied to generate genetically engineered and synthetic hypoallergenic allergen derivatives for patient-tailored and safe vaccination against type I allergy.
Rosenthal RR, Busse WW, Kemp JP, Baker JW, Kalberg C, Emmett A, Rickard KA
Chest 1999 Sep;116(3):595-602
Study Objectives: To determine the effect of long-term salmeterol aerosol therapy on airway hyperresponsiveness measured by methacholine challenge.
Design: Randomized, double-blind, placebo-controlled, multicenter study.
Setting: Thirty-one clinical centers in the United States.
Patients: Four hundred eight asthmatic patients > or = 12 years of age with baseline FEV1 of > or = 70% of predicted values. Patients were not using inhaled corticosteroids.
Interventions: Twice-daily salmeterol aerosol, 42 micrograms, or placebo via metered-dose inhaler for 24 weeks. Backup albuterol was available.
Measurements and Results: Pulmonary function tests were performed before, during, and after treatment. Subjects recorded asthma-related symptoms, morning and evening peak expiratory flow (PEF) levels, and use of supplemental albuterol daily on diary cards. Methacholine challenges were performed 10 to 14 hours post dose at weeks 4, 12, and 24, and 3 and 7 days post-treatment. Over 24 weeks of treatment, salmeterol provided significant (P < 0.001) protection against methacholine-induced bronchoconstriction of approximately one doubling dose of methacholine when compared to placebo with no evidence for a progressive decrease in protection. A rebound increase in airway hyperresponsiveness was not observed 3 and 7 days after cessation of salmeterol therapy. Salmeterol treatment resulted in sustained improvements of 0.21 to 0.26 L in morning premedication FEV1 and an improvement of 26.2 L/min in morning PEF when compared to placebo (P < 0.001). The use of salmeterol significantly reduced combined daytime asthma symptoms by 20% when compared to placebo (P = 0.005). A total of 34 and 48 exacerbations, respectively, were reported in the salmeterol and placebo groups, and no evidence was present for a difference in the severity of asthma exacerbations between groups. Adverse event profiles were similar for the salmeterol and placebo groups.
Conclusions: Regular long-term use of salmeterol aerosol resulted in sustained improvements in pulmonary function and asthma symptom control over the 24-week treatment period. There was no increase in bronchial hyperresponsiveness or loss of bronchoprotection at 24 weeks from that seen following 4 weeks of therapy. There was no evidence of rebound airway hyperresponsiveness after cessation of salmeterol treatment. Regular treatment with the long-acting beta-agonist salmeterol does not lead to clinical instability or vulnerability to unpredictable asthma attacks.
What's new concerning the latest in asthma therapy? Find out in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape Pulmonary Medicine.
Ward GW Jr, Woodfolk JA, Hayden ML, Jackson S, Platts-Mills TA
J Allergy Clin Immunol 1999 Sep;104(3 Pt 1):541-546
Although the etiology of intrinsic or late-onset asthma is generally not known, some cases are associated with overt dermatophyte infection and immediate hypersensitivity to proteins derived from fungi of the genus Trichophyton.
Objective: We sought to test the efficacy of oral antifungal treatment for Trichophyton-induced asthma by using fluconazole in a placebo-controlled trial.
Methods: Eleven patients with severe or moderately severe asthma were randomized to treatment with fluconazole 100 mg daily or placebo for 5 months (phase 1); during the following 5 months, all patients received active drug (phase 2). Subjects were evaluated by skin tests, bronchial provocation tests, and measurement of serum antibodies to Trichophyton species antigens. Clinical response was monitored by changes in peak flow values measured during a 2-week period at the end of each phase and by changes in bronchial sensitivity, symptoms, and steroid requirements.
Results: At the end of the first 5 months of active treatment, there was a highly significant decrease in bronchial sensitivity to Trichophyton (P = .012) and in oral steroid requirement (P = .01). At the end of phase 2, mean peak expiratory flow rates increased in 9 of 11 patients. An improvement in symptoms, peak flow, and steroid use was maintained up to 36 months after starting fluconazole in patients who continued to receive treatment.
Conclusion: The results show that fluconazole can be useful in the treatment of patients with severe or moderately severe asthma who have dermatophytosis. These findings are consistent with the argument that proteins derived from fungi on the skin and nails can contribute to allergic disease.
Valenta R, Vrtala S, Focke-Tejkl M, Bugajska-Schretter, Ball T, Twardosz A, Spitzauer S, Gronlund H, Kraft D
Biol Chem 1999 Jul-Aug;380(7-8):815-824
Type I allergy, a hypersensitivity disease affecting almost 20% of the population worldwide, is based on the IgE recognition of otherwise harmless antigens (ie, allergens). Allergen-induced crosslink of effector cell-bound IgE antibodies leads to the release of biological mediators and thus to immediate disease symptoms (allergic rhinitis, conjunctivitis and asthma). Specific immunotherapy, the only causative treatment of type I allergy, is based on the administration of increasing doses of allergens to allergic patients in order to yield allergen-specific non-responsiveness. Major disadvantages are: 1. that current forms of allergen immunotherapy are performed with allergens difficult to standardize which cannot be matched to the patient's reactivity profile, and 2. that the administration of active allergen preparations can cause anaphylactic side effects. Through the application of molecular biological techniques, many relevant environmental allergens have been produced as active recombinant proteins which allow component-resolved allergy diagnosis and thus represent the basis for patient-tailored forms of immunotherapy. Here we review molecular strategies which have been recently applied to generate genetically engineered and synthetic hypoallergenic allergen derivatives for patient-tailored and safe vaccination against type I allergy.
Rosenthal RR, Busse WW, Kemp JP, Baker JW, Kalberg C, Emmett A, Rickard KA
Chest 1999 Sep;116(3):595-602
Study Objectives: To determine the effect of long-term salmeterol aerosol therapy on airway hyperresponsiveness measured by methacholine challenge.
Design: Randomized, double-blind, placebo-controlled, multicenter study.
Setting: Thirty-one clinical centers in the United States.
Patients: Four hundred eight asthmatic patients > or = 12 years of age with baseline FEV1 of > or = 70% of predicted values. Patients were not using inhaled corticosteroids.
Interventions: Twice-daily salmeterol aerosol, 42 micrograms, or placebo via metered-dose inhaler for 24 weeks. Backup albuterol was available.
Measurements and Results: Pulmonary function tests were performed before, during, and after treatment. Subjects recorded asthma-related symptoms, morning and evening peak expiratory flow (PEF) levels, and use of supplemental albuterol daily on diary cards. Methacholine challenges were performed 10 to 14 hours post dose at weeks 4, 12, and 24, and 3 and 7 days post-treatment. Over 24 weeks of treatment, salmeterol provided significant (P < 0.001) protection against methacholine-induced bronchoconstriction of approximately one doubling dose of methacholine when compared to placebo with no evidence for a progressive decrease in protection. A rebound increase in airway hyperresponsiveness was not observed 3 and 7 days after cessation of salmeterol therapy. Salmeterol treatment resulted in sustained improvements of 0.21 to 0.26 L in morning premedication FEV1 and an improvement of 26.2 L/min in morning PEF when compared to placebo (P < 0.001). The use of salmeterol significantly reduced combined daytime asthma symptoms by 20% when compared to placebo (P = 0.005). A total of 34 and 48 exacerbations, respectively, were reported in the salmeterol and placebo groups, and no evidence was present for a difference in the severity of asthma exacerbations between groups. Adverse event profiles were similar for the salmeterol and placebo groups.
Conclusions: Regular long-term use of salmeterol aerosol resulted in sustained improvements in pulmonary function and asthma symptom control over the 24-week treatment period. There was no increase in bronchial hyperresponsiveness or loss of bronchoprotection at 24 weeks from that seen following 4 weeks of therapy. There was no evidence of rebound airway hyperresponsiveness after cessation of salmeterol treatment. Regular treatment with the long-acting beta-agonist salmeterol does not lead to clinical instability or vulnerability to unpredictable asthma attacks.