Research needs in allergy: an EAACI position paper, in collaboration with EFA

Abstract

In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.

Figure 1

Mechanisms of allergic inflammation in asthma. Epithelial cell activation by allergens, viruses, bacteria and pollutants takes place and their proinflammatory cytokines and chemokines induce inflammation and contribute to Th2 response with TNF-α, IL-13, TSLP, IL-31, IL-33. Th2 response involves multiple cytokines such as IL-4, IL-5, IL-9, IL-13, IL-25, IL-33, eosinophilia, and local and systemic IgE production. A series of chemokines are produced and migration of inflammatory cells to the allergic tissues takes place. In addition, other effector T cell subsets, such as Th9, Th17 and Th22 cells play inflammatory roles. Cross-linking of IgE receptor FcεRI on the surface of mast cells and basophils and their degranulation, induces a type 1 allergic response. The activation of smooth muscle cells, myofibroblasts, angiogenesis and subepithelial fibrosis, lead to remodeling. Bronchial hyperreactivity takes place, with enhanced susceptibility to bronchoconstriction. Innate lymphoid cells may contribute to many aspects of allergic inflammation by the help of multiple cytokines. Epithelial apoptosis and shedding are essential in the mechanisms of eczema and asthma [23,24]. Survival and reactivation of migrating inflammatory cells and their interaction with resident tissue cells and other inflammatory cells augment allergic inflammation.

Figure 2

Pathophysiology of asthma at steady state and during an exacerbation. The airways of asthmatic individuals are characterized by pathological changes, including thickened basement membrane, collagen deposition and hypertrophic smooth muscle, collectively called ‘airway remodeling’. Inflammation is triggered by a variety of factors, including allergens and respiratory viruses. These factors also induce hyperreactive responses in the asthmatic airways, associated with mucus and cell debris released into the lumen, oedema and bronchoconstriction, leading to airway obstruction and related acute exacerbations. Although pathophysiological changes related to asthma are generally reversible, recovery may be partial.