Cover Gallery

The current diagnostic and therapeutic approaches are shifting to a more personalized patient care. We are beginning to understand how particularly the environmental exposure in addition to genetic traits impacts the course of disease and response to treatment. Bioinformatics and machine learning methods optimized for large data set integration and improved sampling methods facilitate the optimized intervention and treatment. Cover artwork by Prof. Susan L. Prescott

Over 1.5 billion people are affected by allergic diseases worldwide and its prevalence is on the rise due to increased exposure to harmful substances from pollution, industrialization and modernized life-style and poor diet. As such, there is an urgent need to elucidate the complex mechanisms underlying the pathogenesis of allergic diseases and identify specific endotypes towards a precision and personalized approach to patient care.

An improved understanding of the molecular mechanisms underlying allergic disorders together with advances in tools for allergen characterization have facilitated an earlier diagnosis and monitoring of allergic diseases, further improving the 100 years old historical way towards patient-tailored disease management. The cover image depicts a colored scanning electron microscopy image of a Plantago pollen. Photo credit: © M Oeggerli / Micronaut 2020, supported by Pathology, Univ. Hosp. Basel, and Bio EM Lab, Biozentrum, Univ. Basel.

In the last decades, research on the immune mechanisms underlying allergic inflammation has significantly advanced our understanding of allergic disorders. It is becoming increasingly clear that the pathology of allergic diseases is reflected by the long-term impact of allergic inflammation. The mechanisms underlying allergic inflammation involve a complex interplay between epithelial barriers, inflammatory cells and mediators, as well as numerous genetic and environmental factors.

The COVID-19 pandemic has presented new challenges to our healthcare system. It’s had a devastating impact on society, but thanks to the international scientific collaboration to develop vaccines and governmental policies to constrain the spread of the virus, we can now see the light at the end of the tunnel.

The rise in the prevalence of allergic and inflammatory diseases caused by environmental changes due to urbanization, industrialization and modernization calls for novel treatments for such complex diseases. As such, there is an urgent need to further improve our understanding of the key pathophysiological mechanisms involved and identify novel molecular targets. In recent years, biologicals as inhibitors of unwanted inflammatory pathways and novel drug delivery systems are receiving attention. The discovery of novel biomarkers is paving the way for precision medicine as a personalized treatment approach.

Allergen immunotherapy (AIT) is the monitored administration of allergen at incremental doses for the treatment of IgE-mediated allergic diseases. To date, AIT is still the only disease-modifying treatment that can potentially achieve allergen tolerance and suppress Th2-driven allergic inflammation. AIT acts by modulating the innate and adaptive immune responses. The shift towards tolerogenic responses requires maintaining regulatory T cell and regulatory B cells, normalizing allergen-specific T cells and B cells, regulating production of IgE and IgG, ameliorating activation thresholds for mast cells and basophils, and modulating non-allergen-specific immune cells.The cover image depicts a colored scanning electron micrograph of a house dust mite (Dermatophagoides farinae).
Photo credit: © M Oeggerli / Micronaut 2018, supported by Pathology, Univ. Hosp. Basel, and K N Goldie, Bio EM Lab, Biozentrum, Univ. Basel.

Environmental factors arising from industrialization, modernization and modern lifestyle damage the integrity of the epithelial barrier, predisposing an individual to allergic, autoimmune and chronic diseases. It is becoming increasingly evident that the epithelium, previously considered to simply function as a physical barrier is a crucial regulator of immune homeostasis. The epithelial cells interact with cytokines, microbes and their products and mediate the cross-talk with other immune cells in the mucosa. Cover artwork by Prof. Susan L. Prescott

The rapidly evolving concept of precision medicine involves accurate diagnosis and tailored treatment prompting our full understanding of the phenotypes and endotypes involved for the identification of disease biomarkers and the selection of appropriate therapeutic strategies. Asthma is a heterogenous disease with distinct phenotypes classified according to clinical categories (i.e., severity, age at onset), disease triggers (i.e., exercise, allergens, or irritants). These have important clinical implications, however, they do not necessary reflect the molecular and cellular mechanisms underlying the disease. As multiple physiopathological processes might be disguised as the same disease through common symptoms, delineating distinct mechanisms at the cellular and molecular levels, allow precise identification of asthma endotypes and are essential for improved asthma management.

Precision medicine is a healthcare concept based on combined interpretation of the patient’s molecular (genomic, transcriptomic, metabolomic, proteomic, etc.), phenotypic and health information that empowers clinicians with data to prevent diseases and recommend an optimized therapy. In contrast to the traditional “one size fits all” approach, precision medicine considers numerous factors, including genetic and environmental factors that shape a person's response to a particular treatment. It is an innovative approach that is able to develop personalized or tailor-made interventions and improve health outcomes.

The prevalence of allergic diseases worldwide continues to increase over time and poses significant challenges in terms of prevention, diagnosis, and treatment. The present issue of Allergy emphasizes the increasing scientific contributions by Chinese scholars in the field of allergic diseases. The cover image depicting a water dragon symbolizes the growth and impact of Chinese science.

It has been over two years since the whole world started the fight against the novel coronavirus. The unprecedented global collaboration leading to the development of several highly effective vaccines gives us hope that the pandemic will be soon behind us. However, the emergence of the new virus variants keeps reminding us the remaining challenges around every corner and we are still oscillating between less and more optimistic scenarios. Although it is too early to switch back to the ‘life before-COVID’, we look at the bright side and believe in the power of science.

Biomarkers are measurable indicators of normal or pathological processes. They are used as powerful tools to determine phenotype or endotype of a disease, predict clinical outcomes and monitor the response to treatment. In parallel with the development of novel therapeutic inventions, extensive research during the last decades has focused on the identification of biomarkers applicable in clinical practice.

Response to various environmental challenges engages the interplay between immune cells, microbiome and epithelium. This extensive crosstalk encompasses multifold interactions in both homeostasis and disease state. Epithelial cells constitute a physical barrier against exogeneous allergens and are key regulators in maintaining immune homeostasis. Their interactions with microbes and microbial-derived products mediate the crosstalk between the epithelium and other cell types in the mucosa. The microbiome plays a fundamental role in immune training, development and function, shaping both innate and adaptive responses. In return, the immune system allows the colonization of commensal microorganisms, forming a strictly regulated mutualistic network. A better understanding of these highly sophisticated cellular and molecular networks is warranted for the development of novel therapeutics for allergic diseases. The cover image depicts the human microbiome. Micrograph taken and edited by © M Oeggerli / Micronaut 2017, supported by Pathology, Univ. Hosp. Basel, and School of Life Sciences, FHNW, Muttenz.

The skin provides a protective barrier between the body and the environment, restricting water loss and preventing the entry of potentially harmful substances. In order to ensure an effective first line of defense against infections, the immune responses in the skin are undergoing strict regulation that involves extensive crosstalk between epithelial, stromal and immune cells, as well as microbial components. Dysregulation of these complex interactions underlie inflammatory skin disorders, such as atopic dermatitis and psoriasis.

Environmental changes are constantly challenging the immune system with a variety of potential stressing factors, including allergens, pathogens and toxins. To maintain homeostasis, the immune system identifies harmful agents and employs potent effector mechanisms to eliminate them, whilst avoiding an excessive self-damaging response. When these mechanisms are dysregulated, harmless substances are identified as threatening, resulting in a breakdown of immune tolerance that underlies allergic diseases such as allergic rhinitis, asthma, atopic dermatitis and food allergy. Currently, allergen-specific immunotherapy is the only approach to restoring immune tolerance in patients suffering from allergic diseases.

Allergens are defined as foreign proteins that induce an abnormal immunological Th2-type response that triggers an allergic reaction in predisposed individuals. This issue focuses on the characteristics of an allergen, including its structural features and function. The cover image depicts a colored scanning electron micrograph of an oak pollen, a common seasonal allergen. Micrograph taken and edited by Martin Oeggerli a.k.a. Micronaut. © M Oeggerli/ Micronaut 2016, supported by KN Goldie, Bio EM Lab, Biozentrum, Univ. Basel.

Allergic inflammation is orchestrated by a complex interplay between various inflammatory cells. It plays a crucial role in diseases such as asthma, atopic dermatitis, allergic rhinitis and allergic conjunctivitis. This issue cover image depicts the allergic inflammation “domino effect”, the chain of consecutive reactions that eventually lead to a serious socio- economic burden affecting the lives of millions of people worldwide. In recent decades, significant progress has been made to prevent the “domino effect” at various stages. Available therapies attenuate the inflammation, but the cure is yet to be discovered.

An unprecedented global colaboration between the life sciences industry, the research communities and healthcare systems has led to the development of several highly effective vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in less than a year from the identification of the virus. Allergy dedicates this issue to this extraordinary accomplishment and expresses great appreciation to everyone involved in this historical success.

This issue cover image represents the Greek myth of Pandora, who was given a box with a special gift inside and was warned never to open it. Unfortunately, Pandora’s curiosity won and she opened the box, releasing all the diseases. Scared by her action, she closed the box immediately, slamming the hope inside. Here, we present Pandora opening the box again and releasing the hope for the successful prevention and treatment of food allergy.

This fascinating cover image depicts a colored scanning electron micrograph of Sarcoptes scabiei, a parasitic mite causing scabies, a common contagious skin disease. Skin diseases with an allergic background impose a significant burden on patients and on the healthcare system. The heterogeneity of these diseases and their co-morbidities poses challenges in their management. Micrograph taken and edited by Martin Oeggerli a.k.a. Micronaut. © M Oeggerli / Micronaut 2016, supported by KN Goldie, Bio EM Lab, Biozentrum, Univ. Basel.

Since the beginning of the pandemic, the whole world spared no effort to defeat COVID-19. We have learned the rules of the game, got used to social distancing, wearing masks and obeying restrictions, in hope to contain the spread of the virus. Although the virus has played many good cards – virulence, high-affinity binding to the receptors, mutations and resistance to drugs, scientists and doctors continue with theirs – vaccines, protective or therapeutic antibodies and antiviral drugs. The game is not over yet, but we believe that we have an ace in our sleeve. Allergy dedicates this issue to leading research focused on the clinical features, outcomes, diagnosis, immunology, and pathogenesis of COVID-19.

The cover image depicts the Great Wall of China connected to a DNA helix directed towards the sky, inspired by the famous quote by Confucius - ‘Study the past if you would define the future’ (告往知来). The star constellations forming the letters 未来 (future) and 科学 (science) symbolize the growth in scientific achievements in allergy research during the past few years.

Biologicals have transformed the management and Systematic Reviews of severe disease phenotypes in asthma, atopic dermatis and chronic spontaneous urticaria. As a result, research towards novel biologicals for the treatment of chronic diseases is continuously increasing.

The term ‘biomarkers’ refers to a broad range of biological makers that are indicators of normal biological processes, pathogenic processes, or pharmacological responses to therapeutic intervention. Large number of studies have been investigating the biomarkers of allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, food allergy, urticaria and anaphylaxis. Various biomarkers have been developed by omics technologies, some of which lead to a better classification of distinct disease endotypes.

Adolescence is a challenging time for both patients and healthcare providers. Adolescent patients need additional support, while they experience the challenges associated with their age. They need specific training to learn the knowledge and skills required to confidently self-manage their allergies and/or asthma. Transitional care is a complex process, which should address the psychological, medical, educational and vocational needs of adolescent and young adult patients in the developmentally appropriate way.

The discovery of immunoglobulin E (IgE) in 1967 together with the identification of its central role in the pathogenesis of allergic inflammation was a breakthrough in the field of allergy and immunology. Understanding the mechanisms of allergic reactions and involvement of IgE has set the stage for the development of therapies directed at decreasing total IgE levels with anti-IgE monoclonal antibodies.

Since the beginning of the industrial revolution, the explosive process of urbanization dramatically affected environmental exposures. Air pollution has a significant impact on human health and contributes to the development of respiratory disease. Global climate change affects the distribution of allergens and increases the frequency and intensity of extreme climate events. This issue is dedicated to increase awareness of an impact of climate change on allergic diseases. Cover art by Prof. Susan L. Prescott conveys the message and illustrates the scientific content of this issue.

Recent changes in lifestyles, social interactions and diet in industrialized countries affect human microbiome and, as a consequence, increase the prevalence of allergies and asthma. Nutritional factors and their interaction with the gut microbiota influence immunological processes since an early age. The fermentation of fiber by commensal gut microbiota result in generation of short-chain fatty acids (SCFAs), including acetate, propionate and butyrate.

An outbreak of a new type of novel coronavirus disease (COVID-19) was first reported in Wuhan, China, in December 2019 and has subsequently spread rapidly to other areas across the globe. The disease is caused by human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, over 150 countries have reported COVID-19 cases, and the situation has progressed to a pandemic associated with substantial morbidity and mortality. The cover image is dedicated to all healthcare professionals who have lost and are continuously risking their lives caring for the patients during the current pandemic. We owe a profound debt of gratitude to all healthcare workers on the front line against COVID-19.

Over the past several decades, the prevalence of food allergy has continued to increase, affecting nowadays 6%-13% of the global population. Avoidance of allergenic foods and management of acute allergic reactions with antihistamines and epinephrine autoinjectors are the current standard of care. Allergen immunotherapy has been shown to increase the threshold of reactivity in the majority of food-allergic individuals.

New biological therapies have been developed for severe asthma and may be applied depending on asthma phenotype and endotype. Omalizumab, a humanized monoclonal anti-IgE antibody; mepolizumab and reslizumab, anti-IL-5 monoclonal antibodies; benralizumab, a monoclonal antibody that binds to the α subunit of IL-5 receptor, dupilumab, a monoclonal antibody directed against the α subunit of the IL-4 receptor are currently available for patients. The European Academy of Allergy and Clinical Immunology (EAACI) has developed clinical practice guidelines for the use of biologicals in patients with severe asthma.

Innate immune system, the first line of defense against invading pathogens, quickly recognizes microbes and foreign substances. Invading pathogens or other harmful substances trigger proinflammatory responses by activating innate immune cells, several of which are depicted on the cover image.

The development of biologicals, substances of a therapeutic potential, produced through a biological process often engaging biotechnological methods, remarkably advanced the management of many diseases, including cancer, autoimmunity, immune deficiencies, asthma and atopic dermatitis. Biologicals act through a specific blocking of certain molecular pathways involved in the disease pathogenesis. Although highly efficient, due to the costs, therapy with biologicals is often justified only in severe and chronic diseases. Another therapeutic option for patients with allergic asthma is allergen-specific immunotherapy.

Severe asthma, defined as inability to achieve or maintain optimal disease control despite use of high-dose medication and treatment of additional contributing factors, is a considerable challenge for patients and health care professionals, and a huge health burden. The evocative cover image in a surrealistic way depicts airway obstruction and emphasizes the severity of the disease.

Atopic dermatitis is a chronic inflammatory disease affecting 5-10% of adults and up to 20% of children. It has a complex etiology arising from a combination of genetic, immune and external factors. The cover image depicts the compromised barrier function, which is considered an initial step in the development of atopic dermatitis. Although a genetically determined barrier disruption predisposes to atopic dermatitis, there are many other pathological mechanisms that lead to development of this disease.

Allergic rhinitis, a Th3-driven inflammatory disorder, whose prevalence is constantly increasing, has become a disease of civilization. Scientists and physicians around the world are joining forces in the search for the new treatment options to target allergic rhinitis. Hence, the cover image refers to the legend of the Swiss national hero, Wilhelm Tell, who accurately shot an apple off his son’s head. In like manner, the current therapeutic approaches are aimed to precisely target the mechanisms that contribute to disease development without causing any harm to patients.

Allergic rhinitis is the most prevalent allergic disease characterized by sneezing, rhinorrhea, conjunctivitis, and nasal congestion. Due to these symptoms, patients suffering from allergic rhinitis experience sleep disruption, diminished activity and reduced productivity. The recent advances in the field of allergy pave the way towards precision medicine and opens novel approaches in order to improve the quality of life of patients with allergies. Hence, the cover image featuring a theatre mask shows two faces, allergic rhinitis on one side and a healthy and happy face on the other.

The discovery of IgE, the critical player of type-l hypersensitivity, has opened the door for extensive understanding of the mechanisms of allergic responses. Despite the tremendous progress that has been made over the last 50 years, numerous unanswered questions about the function of IgE and IgE-mediated anaphylaxis remain. Therefore, the cover image features a detective on the trail of IgE, immersed in his search for the mechanisms, causes and novel approaches to treat or avoid anaphylaxis.

Latin proverb – “Si vis pacem, para bellum” that one can translate to “If you want peace, prepare for war” perfectly pictures the intense battle that the innate immune system takes on every day. Athena, Greek goddess of wisdom and war, represents the wisdom of the innate immune system that strategically defends against the incoming threat. Poseidon, god of the seas, is the first line of defense and furiously attacks foreign invaders. The innate immune system, like the shedding skin of the snakes on Medusa’s head, is constantly being replenished and rejuvenated.

Allergen immunotherapy (AIT) is the only causal treatment that can modify the course of allergic disease, preventing the development of asthma and new allergen sensitization. On the cover, AIT is illustrated as a conductor of the immune system orchestra, amplifying the pleasant sound of the regulatory components and suppressing the dissonance coming from allergen-induced inflammation, ensuring the harmony.

The famous quote from Titus Lucretius Carus, a Roman philosopher-poet of the first century BC – “What is food to one, is to others bitter poison” – has become a food allergy motto. The number of people afflicted with food allergies appears to be steadily increasing. Oral tolerance is a normal physiologic response to ingested antigens. Breakdown of this tolerance results in sensitization to food allergens. The cover image presents a confused peanut under the spotlight, bringing attention to the growing problem of food allergy and raising the discussion of why food that has not caused harmful reactions for many centuries has become a current real threat.

Anaphylaxis is a life-threatening systemic hypersensitivity reaction with a sudden onset characterized by bronchospasm and hypotension. Anaphylaxis can occur after exposure to insect venoms, drugs, certain foods, immunotherapy injections, and during the perioperative period.

The European Academy of Allergy and Clinical Immunology (EAACI) has developed evidence-based recommendations for indications and contraindications to house dust mite (HDM) allergen immunotherapy (AIT) as add-on treatment for HDM-driven allergic asthma based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The authors have evaluated the body of evidence of the delivery route of HDM AIT for both adults and children. These guidelines are addressed to clinical allergists, respiratory physicians, pediatricians and other healthcare professionals.

The term ‘microbiome’ refers to the multi-species microbial communities that exist in the human host. It is a highly dynamic environment, the composition and diversity of which varies across different locations in the body and is subject to change substantially over time. These variations are responsible for the existence of the unique habitats within and between individuals. The interplay between immune system and microbiota shapes the human health status. Immune maturation and activity depend on the colonization with a host-specific microbiota. Alterations in the establishment of the microbial communities have been associated with increased risk of allergy and asthma development, which may be linked to lifestyle changes in industrialized countries. Microbial metabolism and short-chain fatty acids (SCFAs) production strongly influence the growth of beneficial bacteria.

The exposome can be defined as exogenous and endogenous complex exposures that humans experience throughout their lifespan, providing a holistic view on human health and many diseases. The exposomic approach is particularly applicable to study chronic diseases, since it provides a risk profile instead of single predictors.

Asthma is a chronic respiratory disease with complex clinical and pathophysiological features. To elucidate the pathophysiology behind each phenotype and their underlying endotypes, Tan et al. developed in vivo models of allergen-induced airway inflammation representing eosinophilic, mixed and neutrophilic inflammatory phenotypes of asthma. Eosinophilic asthma was characterised by strong dysregulation of networks involved in cytoskeleton reorganisation, cell adhesion and junctions. Significantly changed genes in neutrophilic asthma model belonged to innate immunity signalling, inflammasome as well as Th17-related networks and pathways. Mixed asthma model shared many of the changed genes with neutrophilic phenotype. These data link cellular phenotypes with molecular endotypes and open a new window for more precision approaches to asthma patients. The cover graphics designed by Zuzanna Łukasik paraphrases the STRING (https://string-db.org) analysis of transcriptome data from the mouse models representing different endotypes and phenotypes of asthmatic airway inflammation.

Thunderstorm asthma was first described by medical doctors in the UK in 1983. This phenomenon is a sudden increase of acute bronchospasm due to a local thunderstorm during pollen season. Weather conditions such as wind and torrential rain combined with a high pollen count were suggested to trigger severe asthma among susceptible people. The largest and most catastrophic thunderstrom-triggered asthma epidemic occured on November 21st 2016 in Melbourne. In this issue, Hew et al. present an interview of 1435 patients affected by this event. The authors explored individual susceptibility and summarized compunding risk factors for hospital admission. An editorial written by D’Amato describes recent thunderstorm asthma events and their etiopathogenetic aspects.