Resolving the etiology and treatments of allergic diseases

It has now been over 3 years since the coronavirus disease 2019 (COVID-19) was declared a global pandemic, and its end now appears to be in sight. Governmental restrictions imposed during the pandemic are gradually softening. In early 2023, China also changed its epidemic prevention policy and global academic exchanges are returning to normal. This reminds us of the first step in understanding the role of allergy in the susceptibility and prognosis of COVID-19, provided by Chinese scholars in Wuhan. Zhang and colleagues1 characterized 140 hospitalized subjects with COVID-19 in China (admission date from January 16 to February 3, 2020), and first demonstrated that allergic diseases and asthma were not risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study has subsequently become one of the most cited articles in Allergy. It has directed the focus of numerous studies to improve our understanding of the relationship between SARS-CoV-2 infection and allergic diseases. It was published on February 19, 2020 online as the first paper reporting human to human contact, clinical and laboratory aspects and risk groups for COVID-19.1 In this regard, Chinese scholars have committed vast resources and time to understand the pathophysiology of the coronavirus. Prime examples are the studies by Cao and colleagues,2-4 which have characterized the emergence and evolution of variants of SARS-CoV-2 and have been recently published in top-tier journals such as Cell and Nature.2-4 Despite the COVID-19 pandemic, many Chinese scholars have persistently conducted research in allergic diseases. The latest progress and contributions of these scholars in understanding the “epithelial barrier theory” as the gateway to allergic diseases, allergen recognition, and promising treatments are highlighted in this special “China Issue” of Allergy (Figure 1). Indeed, intact skin and mucosal barriers play a crucial role in protecting host tissues against infections, pollutants, and allergens.5 Environmental exposure to toxic substances, epithelial barrier damage, activation of the epithelial cells, and release of alarmins, activation of the local and systemic immune response, bacterial dysbiosis, and loss of biodiversity of commensals are involved in the development of allergic diseases by causing epithelial barrier damage.5, 6 In this context，a recent low-latitude multi-city study from China has demonstrated that increases in air pollutant concentrations and changes in meteorological conditions (temperature, humidity, and wind speed) might be associated with the number of outpatient visits for allergic rhinitis (AR).7 Accordingly, addressing both air pollution and climate change by imposing strict governmental policies might lower the incidence of allergic decrease and long-lasting health effects.8 The role of lipids from sebaceous glands in barrier dysfunction of atopic dermatitis (AD) has been under-recognized. Yin and colleagues9 noticed that aberrant lipid metabolism in sebaceous glands was correlated with skin inflammation and barrier dysfunction, and contributed to the pathogenesis of AD. Another group indicated that human CST1 protein suppressed asthma symptoms by protecting the asthmatic bronchial epithelial barrier through inhibiting allergenic protease activity, indicating CST1 as a potential biomarker for asthma control.10 The “allergic march” from early AD to asthma and/or AR later in life as well as the extensive comorbidity of allergic disorders has frequently been observed in real life. Data from a real-life study investigating the effectiveness of dupilumab for AD patients of different ages suggest that pediatric patients may respond to dupilumab to a significantly greater level than adults.11 Whether understanding the barrier function status of infants versus adults or intervention at the “leaky epithelial barrier” at an early stage has beneficial or adverse consequences, remains an open question that warrants further research. Yang and colleagues expounded two possible pathways contributing to pollen’s effect on COVID-19 infection using a multiple-adjusted generalized additive (GAM) model.12 Besides further recognizing the features of allergy,13 knowing the allergen-encoding genes and their isoforms at the chromosomal level may also help us to detect novel allergens.14 Zhao and colleagues have identified three well-recognized mango fruit allergen molecules by using combined omics tools and immunological methods. The authors showed that these allergen molecules can be used in component-resolved diagnosis or spiked into the extract to improve diagnostic efficacy.15 In terms of allergic disease treatments, especially asthma, more recently Liang and colleagues have indicated that circS100A11 and S100A11 promoted M2a macrophage activation and lung inflammation in a murine asthma model and children with asthma, suggesting M2a to be a potential therapeutic and diagnostic target in children with asthma.16 Employing a murine asthma model, Sun and colleagues have demonstrated that Fedratinib-incorporated nanoparticles can overcome the shortcomings of free Fedratinib to alleviate asthma by reducing the number of eosinophils and CD4+ T cells in the lung tissue of asthmatic animals.17 More recently, a multicenter prospective study by Gao and colleagues has suggested that in asthmatic pre-schoolers, standard childhood vaccinations to common respiratory pathogens, including Haemophilus influenzae, Streptococcus pneumoniae, and influenza, have beneficial effects on asthma control and may modulate immune responses relevant to asthma pathogenesis.18 Reportedly, microglia might enhance the activation of GRPR+neurons through the NLRP3/caspase-1/IL-1β/IL1R1 axis, providing novel therapeutic strategies for patients with chronic itch.19 Huang reported that arsenic exposure was associated with pruritus and β-endorphin served as a biomarker of pruritus. Besides, naloxone could relieve pruritus due to arseniasis.20 Wang and colleague summmarized the mesenchymal stem cells (MSCs) in allergic airway disease, bringing a promising new view for AR treatment.21 In addition, Liao's data supported a potential application of thermally modified MC-derived exosomes in the treatment of chronic airway diseases.22 Hopefully, the achievements of the Chinese scholars highlighted in this issue of Allergy will provide new directions in the overall framework of allergic disease and lead to a greater international cooperation and communication to overcome global health problems. C. A. Akdis has received research grants from the Swiss National Science Foundation, European Union (EU CURE, EU Syn-Air-G), Novartis Research Institutes, (Basel, Switzerland), Stanford University (Redwood City, Calif), Seed Health (Boston, USA), and SciBase (Stockholm, Sweden); and is the Co-Chair for EAACI Guidelines on Environmental Science in Allergic diseases and Asthma; Chair of the EAACI Epithelial Cell Biology Working Group is on the Advisory Boards of Sanofi/Regeneron (Bern, Switzerland, New York, USA), Stanford University Sean Parker Asthma Allergy Center (CA, USA), Novartis (Basel, Switzerland), Glaxo Smith Kline (Zurich, Switzerland), Bristol-Myers Squibb (New York, USA), Seed Health (Boston, USA), and SciBase (Stockholm, Sweden); and is the Editor-in-Chief of Allergy.