An Update on Allergen Immunotherapy and Asthma
Purpose of review The aim is to review recent literature up to July 2013 concerning the effect of allergen-specific immunotherapy (AIT) on asthma. AIT, effective in combined allergic rhinitis and asthma, was previously described as a convenient approach able to improve clinical outcomes and reduce bronchial hyperresponsiveness. In addition, long-term and preventive effects on the onset of new sensitizations and progression from allergic rhinitis to asthma have been shown.
Recent findings Recent investigations, mainly based on observational or small open trials, confirmed previous findings, showing improvement in asthma control, symptoms and medication usage and steroid-sparing effects, sometimes inconsistent with changes in lung function. Some meta-analyses support the clinical benefit on adult and paediatric asthma. Only few trials, however, were specifically designed to explore asthma endpoints.
Summary Clinical studies primarily have focused on AIT, and research on asthma endpoints is scarce; however, the evidence of beneficial effect of AIT for the treatment of adults and children affected by allergic rhinitis with or without asthma suggests that this treatment can favourably affect asthma. In children, sublingual AIT has been more extensively investigated than injective. Confirmatory, adequately powered trials are needed to reinforce the evidence of efficacy for individual AIT products. The main drawback in using injective AIT for asthma is the risk of serious adverse reactions and uncontrolled asthma. The sublingual route is better tolerated and does not appear inferior. As standard controller pharmacotherapy seems unable to affect the natural course of asthma, the potentially disease-modifying effect of AIT represents an appealing perspective that requires further investigation.
Allergen-specific immunotherapy (AIT) is the practice of administering allergen extracts to patients with allergic disorders, in order to modify or abolish the clinical manifestations caused by natural exposure to the allergens. A precise diagnosis and identification of the provocative allergen is a prerequisite for AIT. Although the fine mechanisms involved remain partially uncertain, a significant body of clinical evidence is available to support the use of AIT. AIT results in profound immunological changes in the response to allergens, characterized by a down-modulation of the T-helper 2 (Th2) responses and an induction of regulatory T cells, producing interleukin-10 (IL-10) and transforming growth factor-β (TGF-β).
AIT was introduced at the beginning of the previous century by Noon and Freeman, on an empirical basis. It was initially characterized by unjustified and often incorrect prescriptions, clinical empiricism and absence of specific guidelines, leading to concerns about its clinical efficacy and safety. During the last 25 years, there has been an impressive development of basic and clinical research in the field of AIT, and recently clinical trials following the principles of the modern methodology of research have confirmed its effectiveness when properly indicated and conducted. Since the official statements of the WHO in 1998, AIT has been validated as a causal treatment for respiratory allergy (rhinitis and asthma) and venom allergy. Allergen desensitization is very effective in those diseases with predominant immunoglobulin E (IgE)-mediated reaction, such as venom allergy, whereas in respiratory allergy, in particular asthma, many different underlying pathophysiological mechanisms are involved, which may justify the heterogeneous responses to AIT in this population.
Subcutaneous immunotherapy (SCIT) remained for several decades the only available administration route. Although SCIT is effective and generally well tolerated, a remote risk of severe side-effects exists, mainly when improperly prescribed or administered. The concerns about safety have resulted in limited use of SCIT for asthma treatment in some countries and have stimulated the search for safer administration routes. Among them, sublingual immunotherapy (SLIT) has gained progressive credibility and was introduced in official documents as a viable alternative to the classic allergy injections. SLIT is currently commercially available and largely employed in European countries as tablets or drops, marketed in standardized extracts either biologically or immunologically based on an in-house reference. No US Food and Drug Administration-approved formulation for SLIT is still available in the United States, but some registration clinical trials were recently published or are currently ongoing.
Abstract and Introduction
Abstract
Purpose of review The aim is to review recent literature up to July 2013 concerning the effect of allergen-specific immunotherapy (AIT) on asthma. AIT, effective in combined allergic rhinitis and asthma, was previously described as a convenient approach able to improve clinical outcomes and reduce bronchial hyperresponsiveness. In addition, long-term and preventive effects on the onset of new sensitizations and progression from allergic rhinitis to asthma have been shown.
Recent findings Recent investigations, mainly based on observational or small open trials, confirmed previous findings, showing improvement in asthma control, symptoms and medication usage and steroid-sparing effects, sometimes inconsistent with changes in lung function. Some meta-analyses support the clinical benefit on adult and paediatric asthma. Only few trials, however, were specifically designed to explore asthma endpoints.
Summary Clinical studies primarily have focused on AIT, and research on asthma endpoints is scarce; however, the evidence of beneficial effect of AIT for the treatment of adults and children affected by allergic rhinitis with or without asthma suggests that this treatment can favourably affect asthma. In children, sublingual AIT has been more extensively investigated than injective. Confirmatory, adequately powered trials are needed to reinforce the evidence of efficacy for individual AIT products. The main drawback in using injective AIT for asthma is the risk of serious adverse reactions and uncontrolled asthma. The sublingual route is better tolerated and does not appear inferior. As standard controller pharmacotherapy seems unable to affect the natural course of asthma, the potentially disease-modifying effect of AIT represents an appealing perspective that requires further investigation.
Introduction
Allergen-specific immunotherapy (AIT) is the practice of administering allergen extracts to patients with allergic disorders, in order to modify or abolish the clinical manifestations caused by natural exposure to the allergens. A precise diagnosis and identification of the provocative allergen is a prerequisite for AIT. Although the fine mechanisms involved remain partially uncertain, a significant body of clinical evidence is available to support the use of AIT. AIT results in profound immunological changes in the response to allergens, characterized by a down-modulation of the T-helper 2 (Th2) responses and an induction of regulatory T cells, producing interleukin-10 (IL-10) and transforming growth factor-β (TGF-β).
AIT was introduced at the beginning of the previous century by Noon and Freeman, on an empirical basis. It was initially characterized by unjustified and often incorrect prescriptions, clinical empiricism and absence of specific guidelines, leading to concerns about its clinical efficacy and safety. During the last 25 years, there has been an impressive development of basic and clinical research in the field of AIT, and recently clinical trials following the principles of the modern methodology of research have confirmed its effectiveness when properly indicated and conducted. Since the official statements of the WHO in 1998, AIT has been validated as a causal treatment for respiratory allergy (rhinitis and asthma) and venom allergy. Allergen desensitization is very effective in those diseases with predominant immunoglobulin E (IgE)-mediated reaction, such as venom allergy, whereas in respiratory allergy, in particular asthma, many different underlying pathophysiological mechanisms are involved, which may justify the heterogeneous responses to AIT in this population.
Subcutaneous immunotherapy (SCIT) remained for several decades the only available administration route. Although SCIT is effective and generally well tolerated, a remote risk of severe side-effects exists, mainly when improperly prescribed or administered. The concerns about safety have resulted in limited use of SCIT for asthma treatment in some countries and have stimulated the search for safer administration routes. Among them, sublingual immunotherapy (SLIT) has gained progressive credibility and was introduced in official documents as a viable alternative to the classic allergy injections. SLIT is currently commercially available and largely employed in European countries as tablets or drops, marketed in standardized extracts either biologically or immunologically based on an in-house reference. No US Food and Drug Administration-approved formulation for SLIT is still available in the United States, but some registration clinical trials were recently published or are currently ongoing.
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