New approaches to allergen immunotherapy.

OBJECTIVE: New insights into mechanisms should enable strategic improvement of allergen immunotherapy, aiming to make it safer, faster, more effective, and able to induce long-term tolerance. We review novel approaches with potential to translate into clinical use. DATA SOURCES: Database searches were conducted in PubMed, Scopus, and Google Scholar. STUDY SELECTIONS: Search terms were based on current and novel approaches in immunotherapy. Literature was selected primarily from recent randomized double-blinded placebo-controlled trials and meta-analyses. RESULTS: Alum, microcrystalline tyrosine, and calcium phosphate are adjuvants in current use. Toll-like receptor-4 agonists combined with allergen have potential to shorten duration of treatment. Other novel adjuvants, nanoparticles, and virus-like particles in combination with allergen have shown early promise. Omalizumab lessens systemic side effects but does not improve efficacy. Intralymphatic immunotherapy for aeroallergens, epicutaneous immunotherapy for food allergens, and use of modified allergens (allergoids), recombinant allergens (and hypoallergenic variants), and T- and B-cell peptide approaches have shown evidence of efficacy and permitted shortened courses but have only rarely been compared with conventional extracts. CONCLUSION: Novel routes of immunotherapy, use of modified allergens, and combination of allergens with immunostimulatory adjuvants or immune modifiers have been developed to augment downregulation of T-helper cell type 2 immunity and/or induce "protective" blocking antibodies. Although these strategies have permitted shortened courses, confirmatory phase 3 trials are required to confirm efficacy and safety and head-to-head trials are required for comparative efficacy. Currently, subcutaneous and sublingual immunotherapies using in-house standardized crude extracts remain the only approaches proved to induce long-term tolerance.

Risk of anaphylaxis in complementary and alternative medicine.

PURPOSE OF REVIEW: Complementary and alternative medicine (CAM) use is widespread across the world. Patients with asthma and allergy regularly use CAM therapies. Allergic and anaphylactic reactions to CAM have been reported. RECENT FINDINGS: Recent attempts to regulate and monitor adverse reaction to these therapies have given us further insight into potential causes of severe allergic reactions. Several culprits identified including Andrographis paniculata, Echinacea species, bee products, Ginkgo biloba and Ginseng are discussed here. SUMMARY: Knowing the factors that increase the risk of anaphylaxis allows reactions to be recognized, reported and further investigated. Research to identify key causative allergens is necessary in the future. Collaboration between the allergy community and CAM practitioners can allow better understanding of allergy to these therapies.

Experimental rhinovirus infection in COPD: implications for antiviral therapies.

Chronic obstructive pulmonary disease (COPD) is a major public health problem and will be one of the leading global causes of mortality over the coming decades. Much of the morbidity, mortality and health care costs of COPD are attributable to acute exacerbations, the commonest causes of which are respiratory infections. Respiratory viruses are frequently detected in COPD exacerbations but direct proof of a causative relationship has been lacking. We have developed a model of COPD exacerbation using experimental rhinovirus infection in COPD patients and this has established a causative relationship between virus infection and exacerbations. In addition it has determined some of the molecular mechanisms linking virus infections to COPD exacerbations and identified potential new therapeutic targets. This new data should stimulate research into the role of antiviral agents as potential treatments for COPD exacerbations. Testing of antiviral agents has been hampered by the lack of a small animal model for rhinovirus infection and experimental rhinovirus infection in healthy volunteers has been used to test treatments for the common cold. Experimental rhinovirus infection in COPD subjects offers the prospect of a model that can be used to evaluate the effects of new treatments for virus-induced COPD exacerbations, and provide essential data that can be used in making decisions regarding large scale clinical trials.