Skin, gut, and lung barrier: physiological interface and target of intervention for preventing and treating allergic diseases

The epithelial barriers of the skin, gut, and respiratory tract are critical interfaces between the environment and the host, and they orchestrate both homeostatic and pathogenic immune responses. The mechanisms underlying epithelial barrier dys-function in allergic and inflammatory conditions, such as atopic dermatitis, food al-lergy, eosinophilic oesophagitis, allergic rhinitis, chronic rhinosinusitis, and asthma, are complex and influenced by the exposome, microbiome, individual genetics, and epigenetics. Here, we review the role of the epithelial barriers of the skin, digestive tract, and airways in maintaining homeostasis, how they influence the occurrence and progression of allergic and inflammatory conditions, how current treatments target the epithelium to improve symptoms of these disorders, and what the unmet needs are in the identification and treatment of epithelial disorders.Funding for open access charge: Universidad de Málaga/CBUA

Direct intranasal application of the solid phase of ImmunoCAP ® increases nasal specific immunoglobulin E detection in local allergic rhinitis patients

The measurement of nasal specific IgE (NsIgE) in local allergic rhinitis (LAR) patients is challenging and shows variability. The objective of this work was to evaluate a minimally-invasive method of direct detection of NsIgE in patients with LAR to Dermatophagoides pteronyssinus (DP) using an automated immunoassay. Methods: Fifty patients participated (LAR, n = 14; allergic rhinitis (AR), n = 20; healthy controls [HC], n = 16). Detection of NsIgE was performed by direct application of the solid phase of a commercialDPImmunoCAP ® test 24 hours a er DP nasal provocation. Results: There was no difference in the median volume of secretion absorbed by the solid phase of the Immuno- CAP test in the 3 studied groups (p = 0.17). According to receiver operating characteristic (ROC) curve analysis. NsIgE 0.1450 was the optimal cutoff point, obtaining in LAR patients 42.86% sensitivity with the highest specificity (100%), and 75% sensitivity and 100% specificity for AR. Conclusion: This study demonstrates the detection of NsIgE to DP in LAR by using a simple, commercial device with high specificity

Organ-specific allergen challenges in airway allergy: Current utilities and future directions

Atopy has been long used as the screening method for airway allergy. Nevertheless, aeroallergens can trigger respiratory symptoms not only in atopic patients (atopic res piratory allergy, ARA), but also in non-atopic subjects (local respiratory allergy, LRA). Moreover, ARA and LRA can coexist in the same patient, and this clinical scenario has been called dual respiratory allergy (DRA). When the clinical history cannot determine the relevance of sensitizations in ARA patients, nasal, conjunctival or bronchial aller gen challenges (NAC, CAC, and BAC, respectively) should be conducted. Moreover, these tests are required to identify patients with LRA and DRA. The clarification of the allergic triggers of airway diseases has a profound impact on the management strategies the patients can be offered. Importantly, allergen immunotherapy (AIT) remains as the only disease-modifying intervention for ARA. Recent data indicate that AIT might have a similar effect on LRA patients. Nevertheless, AIT success relies largely on the correct phenotyping of allergic individuals, and NAC, CAC, and BAC are very helpful tools in this regard. In this review, we will summarize the main indications and methodology of CAC, NAC, and BAC. Importantly, the clinical implementation of these tests might translate into precision medicine approaches and better health outcomes for patients with airway allergy.Consejería de Salud, Junta de Andalucía, Grant/Award Number: P20_00405; Instituto de Salud Carlos III, Grant/Award Number: PI20/01715, RD21/0002/0008, CM21/00262, CM20/00160, JR22/00048 and JR19/00029. Funding for open access charge: Universidad de Málaga / CBUA

Real-life impact of COVID-19 pandemic lockdown on the management of pediatric and adult asthma:A survey by the EAACI Asthma Section

Background The restrictions imposed by the COVID-19 pandemic impact heavily the management of chronic diseases like asthma. This study aimed to evaluate the management of adults and children with asthma during COVID-19-related lockdown. Methods A survey was launched by the European Academy of Allergy and Clinical Immunology (EAACI) via e-mail, website, and social media to EAACI members and members of peer societies. Results The survey was completed by 339 healthcare professionals from 52 countries. 79% of follow-up consultations were replaced by phone calls, whereas 49% of newly referred patients attended the clinic. 62%, 76%, 66%, 76%, and 87% of responders did not conduct spirometry, impulse oscillometry, bronchodilator test, FeNO, or methacholine provocation, respectively, for asthma diagnosis in adults. The numbers were similar for children. 73% of responders based the initial asthma diagnosis and the prescription of inhaled therapy on clinical parameters only. Lung function tests were used in 29% of cases to monitor asthma worsening, and only 56% of participants were recommended to their patients ambulatory peak expiratory flow (PEF) measurements. Using a 1 (not at all) to 5 (very much) scale, the responders considered that the quality of healthcare provided and the patients' asthma status had deteriorated during the lockdown with 3.2 points and 2.8 points, respectively. Conclusion Collectively, these results suggest that all necessary resources should be allocated to ensure the performance of lung function tests for initial diagnosis, whereas digital remote monitoring should be reinforced for the follow-up of children and adults with asthma

Biomarkers predicting the controller dose of omalizumab in patients with chronic spontaneous urticaria

Background Clinical trials showed the efficacy of 300 mg/4 weeks of omalizumab (OMA) during 6 months in patients with severe chronic spontaneous urticaria (CSU). Nevertheless, in real life, many patients require higher doses and/or longer treatment. This study assesses the real-life performance of OMA in severe CSU and identifies factors associated with the response. Methods CSU patients eligible for OMA were recruited prospectively. Clinical data and a blood test were collected before OMA initiation. Urticaria Activity Score 7 (UAS7) was calculated at baseline and every 3 months during OMA treatment. CSU control was defined as UAS7 <7 points. This work was partially sponsored by OMA manufacturer. Results Eighty-nine adults (19.1% males) with severe CSU were recruited. Median duration of CSU prior to OMA initiation was 2 years, and median severity by UAS7 at baseline was 24 points (range 10–42 points). OMA controlled 94.4% of patients, but 17.9% of responders required doses >300 mg/4 weeks. A blood basophil count >20 cells/μL (OR 13.33; 95% CI 3.32–52.63; p 29 months at the end of the study (active responders, AR). AR had received OMA for a median of 45 months (30–100 months). There were no significant differences in clinical or analytical factors between RR and AR patients. Conclusions Low blood basophil count and the presence of hypothyroidism might serve as biomarkers for the controller dose of OMA in severe CSU patients.Funding for open Access charge: Universidad de Málaga / CBUA. Instituto de Salud Carlos III; Novartis Pharmaceuticals Corporation; Consejería de Salud y Bienestar Social, Junta de Andalucí

Real-life impact of COVID-19 pandemic lockdown on the management of pediatric and adult asthma: A survey by the EAACI Asthma Section

Background: The restrictions imposed by the COVID-19 pandemic impact heavily the management of chronic diseases like asthma. This study aimed to evaluate the management of adults and children with asthma during COVID-19-related lockdown. Methods: A survey was launched by the European Academy of Allergy and Clinical Immunology (EAACI) via e-mail, website, and social media to EAACI members and members of peer societies. Results: The survey was completed by 339 healthcare professionals from 52 countries. 79% of follow-up consultations were replaced by phone calls, whereas 49% of newly referred patients attended the clinic. 62%, 76%, 66%, 76%, and 87% of responders did not conduct spirometry, impulse oscillometry, bronchodilator test, FeNO, or methacholine provocation, respectively, for asthma diagnosis in adults. The numbers were similar for children. 73% of responders based the initial asthma diagnosis and the prescription of inhaled therapy on clinical parameters only. Lung function tests were used in 29% of cases to monitor asthma worsening, and only 56% of participants were recommended to their patients ambulatory peak expiratory flow (PEF) measurements. Using a 1 (not at all) to 5 (very much) scale, the responders considered that the quality of healthcare provided and the patients’ asthma status had deteriorated during the lockdown with 3.2 points and 2.8 points, respectively. Conclusion: Collectively, these results suggest that all necessary resources should be allocated to ensure the performance of lung function tests for initial diagnosis, whereas digital remote monitoring should be reinforced for the follow-up of children and adults with asthma

Allergen exposure boosts peripheral Th9 responses in patients with local allergic rhinitis

Key points ∙ Intranasal allergen exposure increases peripheral total Th2 and Th9 cells in patients with local allergic rhinitis (LAR). ∙ Peripheral T-cell response seems dominated by Th9 cells in patients with LAR, whereas Th2 responses prevail in patients with allergic rhinitis. ∙ Our results identify Th9 cells as potential therapeutic targets for patients with LAR.Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Science and Competitiveness, Grant/Award Number: PI20/01715; Regional Ministry of Health of Andalucia through research projects, Grant/Award Numbers: PI-0346-2016, PI-0176-2018; Regional Ministry of Education of Andalucia through a research project, Grant/Award Number: P20-00405; Francisca Palomares holds a Senior Postdoctoral Program contract, Grant/Award Number: RH-0028-2021; Almudena Testera-Montes a “Rio Hortega” contract, Grant/Award Number: CM20/00160; Carlos Jose Aranda a “Sara Borrell” contract, Grant/Award Number: CD21/00034; Carmen Alba-Linero a “Río Hortega” contract, Grant/Award Number: CM21/00262; Ibon Eguiluz-Gracia a “Juan Rodes” contract, Grant/Award Number: JR19/00029; Cristobalina Mayorga holds a “Nicolas Monardes” contract, Grant/Award Number: RC-0004-2021; Asma, ReaccionesAdversas y Alérgicas-ARADyAL, Grant/ Award Number: RD16/0006/0001; Redes de InvestigacionCooperativaOrientadas al Resultado en Salud: Enfermedades Inflamatorias, Grant/Award Number: RD21/0002/0008 Funding for open access charge: Universidad de Málaga/CBU

Diagnosis and Treatment in Asthma and Allergic Rhinitis: Past, Present, and Future

Respiratory diseases are pathological conditions that affect airways, hampering breathing and causing high mortality. In particular, asthma and allergic rhinitis (AR) are two of the most common airway diseases that affect millions of people and have a high prevalence in childhood and adulthood. Asthma is a heterogeneous chronic inflammatory disease characterized by wheezing, chest tightness, shortness of breath, and cough. AR occurs with rhinorrhea, nasal congestion, and sneezing. Indeed, these pathologies share common physiopathological mechanisms such as airway hyperresponsiveness and similar immunopathology such as tissue eosinophilia and T-helper type 2 inflammation. Moreover, AR can be an important risk factor for suffering asthma. Thus, early diagnosis and effective treatment are crucial to improving the health and quality of life of these patients. Classical drugs such as corticosteroids have been used; however, in the last decades, efforts to improve treatments have increased, focusing on biological agents and specific allergen immunotherapy development. Moreover, more precise diagnostic tools have been elaborated, besides classical methods (medical history, physical examination, and pulmonary function tests), such as basophil activation test, and specific cellular and molecular biomarkers (microRNAs, sputum/blood eosinophils, IgE serum, and periostin levels). Therefore, in this review, we compile all these important issues for managing asthma and AR.Espada-Sánchez M, Sáenz de Santa María R, Martín-Astorga MdC, Lebrón-Martín C, Delgado MJ, Eguiluz-Gracia I, Rondón C, Mayorga C, Torres MJ, Aranda CJ, Cañas JA. Diagnosis and Treatment in Asthma and Allergic Rhinitis: Past, Present, and Future. Applied Sciences. 2023; 13(3):1273. https://doi.org/10.3390/app1303127

PTGDR2 expression in peripheral blood as a potential biomarker in adult patients with asthma

[EN]Background: Precision medicine is a promising strategy to identify biomarkers, stratify asthmatic patients according to different endotypes, and match them with the appropriate therapy. This proof-of-concept study aimed to investigate whether gene expression in peripheral blood could provide a valuable noninvasive approach for the molecular phenotyping of asthma. Methods: We performed whole-transcriptome RNA sequencing on peripheral blood of 30 non-atopic non-asthmatic controls and 30 asthmatic patients. A quantitative PCR (qPCR) validation study of PTGDR2 that encodes for CRTH2 receptor, expressed in cells involved in T2 inflammation, was developed in a cohort of 361 independent subjects: 94 non-asthmatic non-atopic controls, 187 asthmatic patients [including 82 with chronic rhinosinusitis with nasal polyposis (CRSwNP) and 24 with aspirin-exacerbated respiratory disease (AERD)], 52 with allergic rhinitis, and 28 with CRSwNP without asthma. Results: PTGDR2 was one of the most differentially overexpressed genes in asthmatic patients' peripheral blood (p-value 2.64 × 106). These results were confirmed by qPCR in the validation study, where PTGDR2 transcripts were significantly upregulated in asthmatic patients (p < 0.001). This upregulation was mainly detected in some subgroups such as allergic asthma, asthma with CRSwNP, AERD, eosinophilic asthma, and severe persistent asthma. PTGDR2 expression was detected in different blood cell types, and its correlation with eosinophil counts showed differences in some groups of asthmatic patients. Conclusions: We found that PTGDR2 expression levels could identify asthma patients, introduce a minimally invasive biomarker for adult asthma molecular phenotyping, and add additional information to blood eosinophils. Although further studies are required, analyzing PTGDR2 expression levels in peripheral blood of asthmatics might assist in selecting patients for treatment with specific antagonists. Keywords: PTGDR2; aspirin exacerbated respiratory disease (AERD); asthma; biomarker; chronic rhinosinusitis with nasal polyps (CRSwNP); gene expression.Instituto de Salud Carlos III; Juan Rodés contract; Junta de Castilla y Leó

Omics technologies in allergy and asthma research: An EAACI position paper

Allergic diseases and asthma are heterogenous chronic inflammatory conditions with several distinct complex endotypes. Both environmental and genetic factors can influence the development and progression of allergy. Complex pathogenetic pathways observed in allergic disorders present a challenge in patient management and successful targeted treatment strategies. The increasing availability of high-throughput omics technologies, such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics allows studying biochemical systems and pathophysiological processes underlying allergic responses. Additionally, omics techniques present clinical applicability by functional identification and validation of biomarkers. Therefore, finding molecules or patterns characteristic for distinct immune-inflammatory endotypes, can subsequently influence its development, progression, and treatment. There is a great potential to further increase the effectiveness of single omics approaches by integrating them with other omics, and nonomics data. Systems biology aims to simultaneously and longitudinally understand multiple layers of a complex and multifactorial disease, such as allergy, or asthma by integrating several, separated data sets and generating a complete molecular profile of the condition. With the use of sophisticated biostatistics and machine learning techniques, these approaches provide in-depth insight into individual biological systems and will allow efficient and customized healthcare approaches, called precision medicine. In this EAACI Position Paper, the Task Force “Omics technologies in allergic research” broadly reviewed current advances and applicability of omics techniques in allergic diseases and asthma research, with a focus on methodology and data analysis, aiming to provide researchers (basic and clinical) with a desk reference in the field. The potential of omics strategies in understanding disease pathophysiology and key tools to reach unmet needs in allergy precision medicine, such as successful patients’ stratification, accurate disease prognosis, and prediction of treatment efficacy and successful prevention measures are highlighted