Abstract
The specialties of allergy and clinical immunology have entered the era of precision medicine with the stratification of diseases into distinct disease subsets, specific diagnoses, and targeted treatment options, including biologicals and small molecules. This article reviews recent developments in research and patient care and future trends in the discipline. The section on basic mechanisms of allergic diseases summarizes the current status and defines research needs in structural biology, type 2 inflammation, immune tolerance, neuroimmune mechanisms, role of the microbiome and diet, environmental factors, and respiratory viral infections. In the section on diagnostic challenges, clinical trials, precision medicine and immune monitoring of allergic diseases, asthma, allergic and nonallergic rhinitis, and new approaches to the diagnosis and treatment of drug hypersensitivity reactions are discussed in further detail. In the third section, unmet needs and future research areas for the treatment of allergic diseases are highlighted with topics on food allergy, biologics, small molecules, and novel therapeutic concepts in allergen‐specific immunotherapy for airway disease. Unknowns and future research needs are discussed at the end of each subsection.
Highlights
The past decades have witnessed extensive progress in unraveling cellular and molecular mechanisms of immune regulation in asthma, allergic diseases, organ transplantation, autoimmune diseases, tumor biology, and chronic infections.[1,2] a better understand‐ ing of the functions, the reciprocal regulation, and the counterbal‐ ance of subsets of immune and inflammatory cells and structural cells—for example, epithelial and vascular cells, airway smooth mus‐ cle cells, neuroendocrine system—that interact via various intercel‐ lular messengers will indicate avenues for immune interventions and novel treatment modalities of allergic diseases and immunological disorders
Can we provide the diagnostic standard of nasal eosinophil count for nonallergic rhinitis with eosinophilia syndrome?
Leukotriene modifiers (LM), and cysteinyl leukotriene (CysLT) receptor 1 antagonists (LTRA), are the first small molecule agents widely applied for targeted treat‐ ment of asthma and comorbid allergic rhinitis (AR) both in adults and in children.[198]
Summary
The past decades have witnessed extensive progress in unraveling cellular and molecular mechanisms of immune regulation in asthma, allergic diseases, organ transplantation, autoimmune diseases, tumor biology, and chronic infections.[1,2] a better understand‐ ing of the functions, the reciprocal regulation, and the counterbal‐ ance of subsets of immune and inflammatory cells and structural cells—for example, epithelial and vascular cells, airway smooth mus‐ cle cells, neuroendocrine system—that interact via various intercel‐ lular messengers will indicate avenues for immune interventions and novel treatment modalities of allergic diseases and immunological disorders. Apart from parenteral monoclonal antibodies directed against key inflamma‐ tory targets, small molecules comprise another class of systemic medication interfering with inflammatory pathways underlying these disorders.[197] Leukotriene modifiers (LM), and cysteinyl leukotriene (CysLT) receptor 1 antagonists (LTRA), are the first small molecule agents widely applied for targeted treat‐ ment of asthma and comorbid AR both in adults and in children.[198] Being launched in an evolving era and lacking adequate biomark‐ ers, initial positioning of anti‐leukotrienes in asthma treatment has been mainly based on their efficacy in clinical models and not on adequate patient stratification which may have delayed proper po‐ sitioning of this targeted therapy.[199] Another class of lipid mediator antagonists entered clinical development: antagonists of the prostaglandin D2 (PGD2) receptor DP2 known as chemoattractant recep‐ tor‐homologous molecule expressed on Th2 cells (CRTH2).[200] DP2/CRTH2 receptors are present on several inflammatory cells including mast cells, T‐helper 2 cells, type 2 ILCs, and eosinophils, and PGD2 plays an important role in linking both the in‐ nate and adaptive immune system through type 2 responses.[201] two compounds showed (modest) efficacy in allergen challenge,[202,203] many CRTH2 antagonists failed in later clinical phases, possibly due to inadequate (non‐type 2) patient popula‐ tions. Munological mechanisms Optimal AIT clinical trials that reduce bias and heterogeneity Collaboration between physicians, patient organizations, companies, and regulators
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