Immunotherapy For Allergic Asthma Research Articles

Sublingual immunotherapy in allergic asthma: Current evidence and needs to meet

Allergen-specific immunotherapy is aimed at modifying the natural history of allergy by inducing tolerance to the causative allergen. In its traditional, subcutaneous form, immunotherapy has complete evidence of efficacy in allergic asthma. However, subcutaneous immunotherapy (SCIT) has a major flaw in side effects, and especially in possible anaphylactic reactions, and this prompted the search for safer ways of administration of allergen extracts. Sublingual immunotherapy (SLIT) has met such need while maintaining a clinical efficacy comparable to SCIT. In fact, the safety profile, as outlined by a systematic revision of the available literature, was substantially free from serious systemic reactions. A number of meta-analyses clearly showed that SLIT is effective in allergic rhinitis by significantly reducing the clinical symptoms and the use of anti-allergic drugs, while the efficacy in allergic asthma is still debated, with some meta-analyses showing clear effectiveness but other giving contrasting results. Besides the efficacy on symptoms, the preventive activity and the cost-effectiveness are important outcomes of SLIT in asthma. The needs to meet include more data on efficacy in house dust mite asthma, optimal techniques of administration and, as previously done with SCIT, introduction of adjuvants able to enhance the immunologic response and use of recombinant allergens.

Allergen-specific subcutaneous immunotherapy in allergic asthma: immunologic mechanisms and improvement

Allergic asthma is a disease characterized by persistent allergen-driven airway inflammation, remodeling, and airway hyperresponsiveness. CD4+ T-cells, especially T-helper type 2 cells, play a critical role in orchestrating the disease process through the release of the cytokines IL-4, IL-5, and IL-13. Allergen-specific immunotherapy (SIT) is currently the only treatment with a long-term effect via modifying the natural course of allergy by interfering with the underlying immunological mechanisms. However, although SIT is effective in allergic rhinitis and insect venom allergy, in allergic asthma it seldom results in complete alleviation of the symptoms. Improvement of SIT is needed to enhance its efficacy in asthmatic patients. Herein, the immunoregulatory mechanisms underlying the beneficial effects of SIT are discussed with the ultimate aim to improve its treatment efficacy.

Peptide immunotherapy in allergic asthma generates IL-10–dependent immunological tolerance associated with linked epitope suppression

Treatment of patients with allergic asthma using low doses of peptides containing T cell epitopes from Fel d 1, the major cat allergen, reduces allergic sensitization and improves surrogate markers of disease. Here, we demonstrate a key immunological mechanism, linked epitope suppression, associated with this therapeutic effect. Treatment with selected epitopes from a single allergen resulted in suppression of responses to other (“linked”) epitopes within the same molecule. This phenomenon was induced after peptide immunotherapy in human asthmatic subjects and in a novel HLA-DR1 transgenic mouse model of asthma. Tracking of allergen-specific T cells using DR1 tetramers determined that suppression was associated with the induction of interleukin (IL)-10+ T cells that were more abundant than T cells specific for the single-treatment peptide and was reversed by anti–IL-10 receptor administration. Resolution of airway pathophysiology in this model was associated with reduced recruitment, proliferation, and effector function of allergen-specific Th2 cells. Our results provide, for the first time, in vivo evidence of linked epitope suppression and IL-10 induction in both human allergic disease and a mouse model designed to closely mimic peptide therapy in humans.

Sublingual immunotherapy for allergic respiratory diseases: An evaluation of meta-analyses

Five published meta-analyses (MAs) seem to prove the efficacy of sublingual immunotherapy in allergic asthma and rhinoconjunctivitis. We aimed to assess the consistency, magnitude, and robustness of the results of these MAs. The data reported in the MAs were checked with the data reported in the original studies. Funnel plots were performed to test for potential publication bias, and the trim-and-fill method was used to assess and correct the estimate of the effects if asymmetry was present. The 5 MAs included 43 studies; 17 were used in more than one MA. There were discrepancies among the MAs in the data reported from the same original studies: the MAs reported different estimates for the same outcome or the same estimates for different outcomes in 16 of those 17 studies. The MAs evaluated 15 main outcomes, 10 of which showed benefits that reached statistical significance. Funnel plots showed asymmetry in 7 outcomes, and correction by using the trim-and-fill method led to a decrease in their effect estimates and even to a loss of statistical significance in 4 of the previously significant outcomes. There was inconsistency among the MAs in the benefits when considering age, disease, allergen, or symptoms and medication use. Because of discrepancies, inconsistencies, and lack of robustness, the MAs on sublingual immunotherapy do not provide enough evidence to support its current routine management in patients with allergic asthma or rhinoconjunctivitis. Sensitivity to potential publication bias should be tested and reported in all MAs.

Allergen immunotherapy and asthma: Efficacy, safety, and other considerations

The efficacy of allergen immunotherapy (AIT) for allergic asthma is often debated despite multiple controlled trails and three meta-analyses that have established a significant effect on subjective and objective outcomes. Indications for AIT in allergic asthma include suboptimal control with medications, adverse effect of medications, and/or environmental control measures; patient's desire to avoid long-term pharmacotherapy; and presence of comorbid allergic conditions. Symptomatic asthma is a risk factor for AIT systemic reactions (SRs) and asthma should be controlled at the time of the AIT administration. The vast majority of studies in AIT for asthma have used single allergens although the majority of allergic patients in the United States are not monosensitized. There have been conflicting results in the limited number of studies that have investigated the effect of multiallergen AIT or as add-on therapy to asthmatic patients who are optimally controlled with medications and environmental controls. Several studies have suggested that AIT may prevent the development of asthma in subjects with allergic rhinitis and new allergen sensitizations. The recently updated Allergen Immunotherapy Practice Parameters lists possible prevention of asthma in patients with allergic rhinitis as one of the indications for AIT. Currently, subcutaneous immunotherapy is the only route with Federal Drug Administration approved formulations in the United States but sublingual immunotherapy is currently under investigation. This review examines the efficacy, safety, and preventive effects of these two routes of immunotherapy.

Assessment of sublingual immunotherapy efficacy in children with house dust mite‐induced allergic asthma optimally controlled by pharmacologic treatment and mite‐avoidance measures

Although several studies have demonstrated the efficacy of subcutaneous immunotherapy in allergic asthma, few have shown the same benefit using sublingual immunotherapy (SLIT) in asthmatic patients. This study was conducted to assess the efficacy of house dust mite (HDM) SLIT in addition to allergen avoidance and standard pharmacologic treatment. A double-blind, placebo-controlled trial was performed in 111 children (aged 5-15 yr) with HDM-induced mild-to-moderate asthma. After a 4-week baseline phase, patients were randomly assigned to receive SLIT with tablets of HDM extract (n = 55) or placebo (n = 56) for 18 months. Pharmacologic treatment was adjusted every 3 months following a step-down approach. Asthma symptom scores, reduction in use of inhaled corticosteroids and inhaled beta(2)-agonists, rhinitis symptoms, lung function tests, skin sensitivity to HDM, dust mite-specific immunoglobulin (Ig) E and IgG(4), and quality of life (QoL) were assessed during the study. After 18 months of treatment, diurnal and nocturnal asthma symptoms scores did not show significant differences between SLIT and placebo groups. Inhaled corticosteroids and inhaled beta(2)-agonists use was reduced in both groups without significant differences between groups. There were no significant differences in lung function (forced expiratory volume in 1 s and peak flow rate variations) between groups. Rhinitis symptom score decreased in both groups, with no difference between the two groups. The severity dimension of QoL was significantly improved in the SLIT group (age 6-12 yr). SLIT induced a significant reduction of skin sensitivity to HDM (p < 0.01) and a significant increase in HDM-specific IgE and IgG(4) antibodies (p < 0.001) in the SLIT group compared with the placebo group. SLIT was well tolerated with mild/moderate local adverse events. No severe systemic reactions were reported. This study indicates that, when mild-moderate asthmatic children are optimally controlled by pharmacologic treatment and HDM avoidance, SLIT does not provide additional benefit, despite a significant reduction in allergic response to HDM. Under such conditions, only a complete, but ethically unfeasible, discontinuation of inhaled corticosteroid would have demonstrated a possible benefit of SLIT.

2 Role of allergen-immunotherapy in asthma(Symposium 7 Immunotherapy, Update and Future)

2 Role of allergen-immunotherapy in asthma(Symposium 7 Immunotherapy, Update and Future)

Effect of specific immunotherapy added to pharmacologic treatment and allergen avoidance in asthmatic patients allergic to house dust mite

BackgroundAlthough several studies support the efficacy of specific immunotherapy in allergic asthma, its benefit compared with that of standardized pharmacologic intervention remains unknown. ObjectiveA double-blind, placebo-controlled trial in 72 patients with mild-to-moderate asthma and allergy to house dust mite (HDM; Dermatophagoides species) was conducted to assess the effects of specific immunotherapy added to guideline-adjusted pharmacologic treatment and allergen avoidance. MethodsAfter 1 observational year of pharmacologic treatment and standard measures of HDM avoidance, 2 groups of asthmatic subjects were randomly assigned to receive specific immunotherapy consisting of subcutaneous injections of either a mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae vaccine (n=41) or placebo (n=31) for 3 years. Medications were adjusted every 3 months according to the Global Initiative for Asthma guidelines. ResultsThe adjustment of treatment was associated with a reduction in asthma symptom scores in all subjects. The addition of specific immunotherapy was associated with a decrease in the number of subjects requiring rescue bronchodilators, an increase in morning and evening peak expiratory flow, and a reduced skin sensitivity to HDM extracts. The addition of specific immunotherapy had no significant effects on the cumulative dose of inhaled corticosteroids, asthma symptoms, lung volumes, or bronchial responsiveness to methacholine. ConclusionThese results suggest that specific immunotherapy added to pharmacologic treatment and HDM avoidance provides marginal but statistically significant clinical benefits, possibly by reducing the allergic response of asthmatic patients sensitized to HDM.

Allergen immunotherapy for asthma.

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. The objective of this review was to assess the effects of allergen specific immunotherapy for asthma. We searched the Cochrane Airways Group trials register up to June 2001, MEDLINE, Dissertation Abstracts, Current Contents and reference lists of articles. Randomised controlled trials using various forms of allergen specific immunotherapy to treat asthma and reporting at least one clinical outcome. Three reviewers independently assessed eligibility of studies for inclusion. Two reviewers independently performed quality assessment of studies. 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. 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.

Specific immunotherapy in allergic asthma

Specific immunotherapy in allergic asthma

Pathophysiology of bronchial inflammation: chemoreceptors as therapeutic targets.

Asthma is an inflammatory disease characterized by reversible airway obstruction from a combination of bronchoconstriction and inflammatory changes including airway edema, infiltration of inflammatory cells such as eosinophils, mast cells, CD4+ T helper cells and monocyte/macrophages. Pharmacotherapy approaches include relievers of acute symptoms and controllers of inflammation. Inhaled corticosteroids are the sentinel therapy for asthma inflammation but are not always totally effective for a variety of reasons. With the increased understanding about the molecular basis for asthma inflammation, new therapies are emerging to target specific molecular networks, including antibodies against IgE and the TH2 cytokine IL-5; soluble IL-4 receptors and recombinant TH1 cytokines such as IL-12. Further, allergen immunotherapy for asthma is based upon its ability to change a TH2 to a TH1 response by inhibiting IL-4 and/or stimulating IFN gamma production. Although each of these modalities have their potential strengths and weaknesses, the approach offers a fresh attempt to better define the syndrome called asthma, show diversity of etiologies within even the same patient, and develop more effective, long lasting therapies for patients with this condition.

Assessing allergen immunotherapy for asthma

Assessing allergen immunotherapy for asthma

Trends in asthma therapy in the United States: 1965-1992.

Many recent studies indicate an increasing morbidity and mortality of asthma in the past two decades. This study uses data from the National Disease and Therapeutic Index (NDTI) to document and analyze trends in drug therapy for asthma in the United States from 1965 through 1992. The NDTI maintains a continuous rotating national sampling of approximately 1% of US physicians in office-based practice proportionately representative of practicing generalists and specialists who report issuance of drugs in treatment by diagnosis for all patient encounters for a period of two days every 3 months. Annual summaries of five demographic categories and 14 drug categories, characterizing the asthma patient-physician encounters as percent of visits for the 28-year period of 1965 through 1992 are analyzed and characterized. Physician visits for asthma treatment have shifted somewhat from generalists to specialists in internal medicine and pediatrics. Allergists treat a significant proportion of the asthmatic population. Most patients are seen in the office. There has been no significant change in rates of inpatient visits. Age distribution of the population of patient visits for asthma has been stable, but there is a steady drop in ratio of males to females. Since the mid-1970s, inhaled adrenergic bronchodilator prescriptions have been issued at a markedly increasing rate. Concurrently, issuance of xanthines and oral adrenergic drugs also rose dramatically but then decreased beginning in the mid-1980s. Corticosteroids are used in 15% to 20% of visits, but only recently has the inhaled route of administration shown prominence. Allergen immunotherapy for asthma has decreased more than 10-fold. Cromolyn is prescribed infrequently. Major changes have occurred in drug treatment by physicians for asthma in the US since 1965. Bronchodilating drugs predominate, and they are being prescribed in more effective forms at a generally increasing rate. Corticosteroid use has increased at a slower rate and in smaller proportion of patient-visits, while allergen immunotherapy has dramatically declined. The male-to-female ratio of asthmatic patients who visit doctors for treatment appears to be decreasing.

Indications and efficacy of allergen immunotherapy in asthma

Clinical & Experimental AllergyVolume 23, Issue s3 p. 7-10 Indications and efficacy of allergen immunotherapy in asthma First published: August 1993 https://doi.org/10.1111/j.1365-2222.1993.tb00379.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume23, Issues3August 1993Pages 7-10 RelatedInformation

Specific IgE, IgG and IgG4 antibodies against house dust mite in patients with bronchial asthma.

Serum levels of total IgE, specific IgE, IgG and IgG4 against house dust mite were measured in mite-sensitive asthma patients receiving immunotherapy with house dust. Serum levels of total IgE, mite specific IgE and IgG did not significantly change during the course of hyposensitization. Increased levels of mite specific IgG4 were observed in patients during immunotherapy. The increase in specific IgG4 was dependent on the total dose of house dust administered in both children (r = 0.636, p less than 0.001) and adults (r = 0.629, p less than 0.01). However, the increase of specific IgG4 in adults was not as apparent as in children. These results might suggest that mite specific IgG4 is a useful immunological marker in the immunotherapy for allergic asthma, and that IgG4 antibody acts as a blocking antibody in atopic bronchial asthma.

Allergen immunotherapy in asthma: Evidence for efficacy

A recent article in this JOURNAL reviewed the efficacy of immunotherapy in allergic rhinitis.’ There are fewer studies of immunotherapy in allergic asthma. The use of immunotherapy in asthma remains controversial, and the reasons for this are probably related to difficulties in defining allergic asthma. In this article, an attempt will be made to define allergic asthma and then to discuss the design of an adequate trial of immunotherapy. Finally, the available evidence for efficacy and how this relates to specific indications will be summarized.

Immunotherapy in cat-induced asthma. Double-blind trial with evaluation of in vivo and in vitro responses

The efficacy of immunotherapy in cat-induced asthma was studied by use of a purified fraction of cat-pelt extract and a double-blind protocol. Nine active-treatment subjects who received a mean cumulative dose of cat allergen, 1 of 10.9 units, and eight placebo-treatment subjects completed the study. Active treatment resulted in significant reductions in bronchial sensitivity ( p < 0.05) and prick test titer ( p < 0.01). In addition, active treatment resulted in a significant delay in the onset of ocular ( p < 0.05) and pulmonary ( p < 0.02) symptoms on exposure to living cats. Significant increases in IgG antibody to cat allergen 1 ( p < 0.001) and cat albumin ( p < 0.01) also occurred with active treatment. There was no significant change in bronchial reactivity to methacholine or in the sensitivity of circulating basophils. These results confirm the validity of immunotherapy in allergic asthma where there is careful patient selection and well defined treatment preparations.