Allergen immunotherapy for asthma.

BACKGROUND: Allergen specific immunotherapy has long been a controversial treatment for asthma. Although beneficial effects upon clinically relevant outcomes have been demonstrated in randomised controlled trials, there remains a risk of severe and sometimes fatal anaphylaxis. The recommendations of professional bodies have ranged from cautious acceptance to outright dismissal. With increasing interest in new allergen preparations and new methods of delivery, it was time to conduct another systematic review of allergen specific immunotherapy for asthma. OBJECTIVES: The objective of this review was to assess the effects of allergen specific immunotherapy for asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register up to June 2001, MEDLINE, Dissertation Abstracts, Current Contents and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials using various forms of allergen specific immunotherapy to treat asthma and reporting at least one clinical outcome. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed eligibility of studies for inclusion. Two reviewers independently performed quality assessment of studies. MAIN RESULTS: Seventy-five trials were included (52 of 54 previously included trials and 23 new trials). A total of 3,506 participants (3,188 with asthma) were involved. There were 36 trials of immunotherapy for house mite allergy; 20 pollen allergy trials; ten animal dander allergy trials; two Cladosporium mould allergy, one latex and six trials looking at multiple allergens. Concealment of allocation was assessed as clearly adequate in only 15 of these trials. Significant heterogeneity was present in a number of comparisons. Overall, there was a significant reduction in asthma symptoms and medication and improvement in bronchial hyper-reactivity following immunotherapy. There was a significant improvement in asthma symptom scores (standardised mean difference -0.72, 95% confidence interval -0.99 to -0.33) and it would have been necessary to treat 4 (95%CI 3 to 5) patients with immunotherapy to avoid one deterioration in asthma symptoms. Overall it would have been necessary to treat 5 (95%CI 4 to 6) patients with immunotherapy to avoid one requiring increased medication. Allergen immunotherapy significantly reduced allergen specific bronchial hyper-reactivity, with some reduction in non-specific bronchial hyper-reactivity as well. There was no consistent effect on lung function. REVIEWER'S CONCLUSIONS: Immunotherapy reduces asthma symptoms and use of asthma medications and improves bronchial hyper-reactivity. One trial found that the size of the benefit is possibly comparable to inhaled steroids. The possibility of adverse effects (such as anaphylaxis) must be considered.

Allergen immunotherapy for asthma.

BACKGROUND: Allergen specific immunotherapy has long been a controversial treatment for asthma. Although beneficial effects upon clinically relevant outcomes have been demonstrated in randomised controlled trials, there remains a risk of severe and sometimes fatal anaphylaxis. The recommendations of professional bodies have ranged from cautious acceptance to outright dismissal. With increasing interest in new allergen preparations and new methods of delivery, it was time to conduct a systematic review of allergen specific immunotherapy for asthma. OBJECTIVES: Allergen specific immunotherapy involves injecting an extract of the allergen under the skin. It is also known as hyposensitisation or desensitisation, and carries a risk of potentially fatal anaphylaxis. The objective of this review was to assess the effects of allergen specific immunotherapy for asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register up to 1997, Dissertation Abstracts, WorldCat and ArticleFirst. SELECTION CRITERIA: Randomised trials using various forms of allergen specific immunotherapy to treat asthma. DATA COLLECTION AND ANALYSIS: Eligibility of studies for inclusion was decided by three reviewers independently. Quality assessment of studies was performed by two reviewers independently. MAIN RESULTS: Fifty-four trials were included. There were 25 trials of immunotherapy for house mite allergy; 13 pollen allergy trials; eight animal dander allergy trials; two Cladosporium mould allergy and six trials looking at multiple allergens. Concealment of allocation was assessed as clearly adequate in only 11 of these trials. Significant heterogeneity was present in a number of comparisons. Overall, there was a significant reduction in asthma symptoms and medication following immunotherapy. There was also a significant improvement in asthma symptom scores (standardised mean difference -0.52, 95% confidence interval -0.70 to -0.35). People receiving immunotherapy were less likely to report a worsening of asthma symptoms than those randomised to placebo (odds ratio 0.27, 95% confidence interval 0.21 to 0.35). People randomised to immunotherapy were less likely to require medication than those randomised to placebo (odds ratio 0.28, 95% confidence interval 0.19 to 0.42). Allergen immunotherapy reduced allergen specific bronchial hyper-reactivity, with some reduction in non-specific bronchial hyper-reactivity as well. There was no consistent effect on lung function. REVIEWER'S CONCLUSIONS: Immunotherapy may reduce asthma symptoms and use of asthma medications, but the size of the benefit compared to other therapies is not known. The possibility of adverse effects (such as anaphylaxis) must be considered.

Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials.

OBJECTIVE: To determine whether intranasal corticosteroids are superior to oral H1 receptor antagonists (antihistamines) in the treatment of allergic rhinitis. DESIGN: Meta-analysis of randomised controlled trials comparing intranasal corticosteroids with oral antihistamines. SETTING: Randomised controlled trials conducted worldwide and published between 1966 and 1997. SUBJECTS: 2267 subjects with allergic rhinitis in 16 randomised controlled trials. MAIN OUTCOME MEASURES: Nasal blockage, nasal discharge, sneezing, nasal itch, postnasal drip, nasal discomfort, total nasal symptoms, nasal resistance, and eye symptoms and global ratings. Outcomes measured on different scales were combined to determine pooled odds ratios (categorical outcomes) or standardised mean differences (continuous outcomes). Assessment of heterogeneity between studies, and subgroup analyses of eye symptoms, were undertaken. RESULTS: Intranasal corticosteroids produced significantly greater relief than oral antihistamines of nasal blockage (standardised mean difference 0.63, 95% confidence interval - 0.73 to - 0.53), nasal discharge (-0.5, - 0.6 to - 0.4), sneezing (- 0.49, - 0.59 to - 0.39), nasal itch (- 0.38,- 0.49 to - 0.21), postnasal drip (- 0.24,- 0.42 to - 0.06), and total nasal symptoms (- 0.42,- 0.53 to - 0.32), and global ratings gave an odds ratio for deterioration of symptoms of 0.26 (0.08 to 0.8). There were no significant differences between treatments for nasal discomfort, nasal resistance, or eye symptoms. The effects on sneezing, total nasal symptoms, and eye symptoms were significantly heterogeneous between studies. Other combined outcomes were homogeneous between studies. Subgroup analysis of the outcome of eye symptoms suggested that the duration of assessment (averaged mean score over the study period versus mean score at end of study period) might have accounted for the heterogeneity. CONCLUSION: The results of this systematic review, together with data on safety and cost effectiveness, support the use of intranasal corticosteroids over oral antihistamines as first line treatment for allergic rhinitis.

Is allergen immunotherapy effective in asthma? A meta-analysis of randomized controlled trials.

A meta-analysis of clinical trials of allergen immunotherapy was undertaken to assess the efficacy of this controversial form of therapy in asthma. A computerized bibliographic search revealed 20 randomized placebo controlled double-blind trials of allergen immunotherapy for asthma. The results extracted included asthmatic symptoms, medication requirements, lung function, and bronchial hyperreactivity (BHR). Categorical outcomes were expressed as odds ratios and continuous outcomes as effect sizes. The combined odds of symptomatic improvement from immunotherapy with any allergen were 3.2 (95% CI 2.2 to 4.9). The odds for reduction in medication after mite immunotherapy were 4.2 (95% CI 2.2 to 7.9). The combined odds for reduction in BHR were 6.8 (95% CI 3.8 to 12.0). The mean effect size for any allergen immunotherapy on all continuous outcomes was 0.71 (95% CI 0.43 to 1.00), which would correspond to a mean 7.1% predicted improvement in FEV1 from immunotherapy. Although the benefits of allergen immunotherapy could be overestimated because of unpublished negative studies, an additional 33 such studies would be necessary to overturn these results. Allergen immunotherapy is a treatment option in highly selected patients with extrinsic ("allergic") asthma.

Studies on the mechanism of multiple drug allergies. Structural basis of drug recognition.

The multiple drug allergy syndrome, that is, allergic recognition of a variety of drugs that may be both pharmacologically and structurally different, has been little studied and, consequently, the underlying mechanism(s) is unknown. The molecular basis of drug recognition by IgE antibodies found in the sera of subjects exhibiting multiple allergic drug sensitivities was studied by direct binding and quantitative hapten inhibition assays in experiments employing a wide range of carefully selected drugs and other chemicals. Drug recognition was shown to be related to the presence of tertiary and quaternary mono-, di- and trialkyl amino groups, but only if the alkyl groups were 'small' viz., methyl or, perhaps, ethyl. Primary, secondary, and tertiary (with R = 'large' alkyl) groups showed no direct antibody binding or antibody inhibitory activities. Near-neighbour effects of amide and hydroxyl groups appeared to promote weaker antigenic recognition. Results indicate that the antibody recognition and clinical drug allergy spectra of at least some subjects with multiple drug allergies are due to wide ranging immunological cross-reactivities with drugs containing tertiary amino and quaternary ammonium groups which are present in many different pharmacologically active agents. Separate populations of antibodies to other non-cross reacting drugs, for example, beta-lactam antibiotics, may also be present in the sera of such subjects.