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2. Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology

Author

Roth-Walter, F., Adcock, I. M., Benito-Villalvilla, C., Bianchini, R., Bjermer, L., Caramori, G., Cari, L., Chung, K. F., Diamant, Z., Eguiluz-Gracia, I., Knol, E. F., Jesenak, M., Levi-Schaffer, F., Nocentini, G., O'Mahony, L., Palomares, O., Redegeld, F., Sokolowska, M., Van Esch, B. C.A.M., Stellato, C., Roth-Walter, F., Adcock, I. M., Benito-Villalvilla, C., Bianchini, R., Bjermer, L., Caramori, G., Cari, L., Chung, K. F., Diamant, Z., Eguiluz-Gracia, I., Knol, E. F., Jesenak, M., Levi-Schaffer, F., Nocentini, G., O'Mahony, L., Palomares, O., Redegeld, F., Sokolowska, M., Van Esch, B. C.A.M., and Stellato, C.

Abstract

The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune-driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence-related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for

Published
2024

3. Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology

Author

CTI Research, MS Dermatologie/Allergologie, Infection & Immunity, Anatomie, Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E F, Jesenak, M, Levi-Schaffer, F, Nocentini, G, O'Mahony, L, Palomares, O, Redegeld, F, Sokolowska, M, Van Esch, B C A M, Stellato, C, CTI Research, MS Dermatologie/Allergologie, Infection & Immunity, Anatomie, Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E F, Jesenak, M, Levi-Schaffer, F, Nocentini, G, O'Mahony, L, Palomares, O, Redegeld, F, Sokolowska, M, Van Esch, B C A M, and Stellato, C

Published
2024

4. Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology

Author

Roth‐Walter, F; https://orcid.org/0000-0001-5005-9228, Adcock, I M; https://orcid.org/0000-0003-2101-8843, Benito‐Villalvilla, C; https://orcid.org/0000-0002-5544-0199, Bianchini, R; https://orcid.org/0000-0003-0351-6937, Bjermer, L; https://orcid.org/0000-0002-3441-8099, Caramori, G; https://orcid.org/0000-0002-9807-327X, Cari, L; https://orcid.org/0000-0003-0698-3872, Chung, K F; https://orcid.org/0000-0001-7101-1426, Diamant, Z; https://orcid.org/0000-0003-0133-0100, Eguiluz‐Gracia, I; https://orcid.org/0000-0002-3774-931X, Knol, E F; https://orcid.org/0000-0001-7368-9820, Jesenak, M; https://orcid.org/0000-0001-7976-2523, Levi‐Schaffer, F; https://orcid.org/0000-0003-0620-2810, Nocentini, G; https://orcid.org/0000-0002-5209-0488, O'Mahony, L; https://orcid.org/0000-0003-4705-3583, Palomares, O; https://orcid.org/0000-0003-4516-0369, Redegeld, F; https://orcid.org/0000-0001-8830-7960, Sokolowska, M; https://orcid.org/0000-0001-9710-6685, Van Esch, B C A M; https://orcid.org/0000-0001-9961-750X, Stellato, C; https://orcid.org/0000-0002-1294-8355, Roth‐Walter, F; https://orcid.org/0000-0001-5005-9228, Adcock, I M; https://orcid.org/0000-0003-2101-8843, Benito‐Villalvilla, C; https://orcid.org/0000-0002-5544-0199, Bianchini, R; https://orcid.org/0000-0003-0351-6937, Bjermer, L; https://orcid.org/0000-0002-3441-8099, Caramori, G; https://orcid.org/0000-0002-9807-327X, Cari, L; https://orcid.org/0000-0003-0698-3872, Chung, K F; https://orcid.org/0000-0001-7101-1426, Diamant, Z; https://orcid.org/0000-0003-0133-0100, Eguiluz‐Gracia, I; https://orcid.org/0000-0002-3774-931X, Knol, E F; https://orcid.org/0000-0001-7368-9820, Jesenak, M; https://orcid.org/0000-0001-7976-2523, Levi‐Schaffer, F; https://orcid.org/0000-0003-0620-2810, Nocentini, G; https://orcid.org/0000-0002-5209-0488, O'Mahony, L; https://orcid.org/0000-0003-4705-3583, Palomares, O; https://orcid.org/0000-0003-4516-0369, Redegeld, F; https://orcid.org/0000-0001-8830-7960, Sokolowska, M; https://orcid.org/0000-0001-9710-6685, Van Esch, B C A M; https://orcid.org/0000-0001-9961-750X, and Stellato, C; https://orcid.org/0000-0002-1294-8355

Abstract

The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune‐driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence‐related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for st

Published
2024

5. Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology

Author

Afd Pharmacology, Pharmacology, Roth-Walter, F., Adcock, I. M., Benito-Villalvilla, C., Bianchini, R., Bjermer, L., Caramori, G., Cari, L., Chung, K. F., Diamant, Z., Eguiluz-Gracia, I., Knol, E. F., Jesenak, M., Levi-Schaffer, F., Nocentini, G., O'Mahony, L., Palomares, O., Redegeld, F., Sokolowska, M., Van Esch, B. C.A.M., Stellato, C., Afd Pharmacology, Pharmacology, Roth-Walter, F., Adcock, I. M., Benito-Villalvilla, C., Bianchini, R., Bjermer, L., Caramori, G., Cari, L., Chung, K. F., Diamant, Z., Eguiluz-Gracia, I., Knol, E. F., Jesenak, M., Levi-Schaffer, F., Nocentini, G., O'Mahony, L., Palomares, O., Redegeld, F., Sokolowska, M., Van Esch, B. C.A.M., and Stellato, C.

Published
2024

6. A tumor-associated heparan sulfate-related glycosaminoglycan promotes the generation of functional regulatory T cells

Author

Ministerio de Economía y Competitividad (España), Ministerio de Ciencia e Innovación (España), Martín-Cruz, Leticia [0000-0002-2546-1183], Viñuela, Marcos [0009-0002-8338-1832], Kalograiaki, Ioanna [0000-0001-7950-2334], Angelina, Alba [0000-0001-5282-9767], Oquist Phillips, Mayra Paola [0000-0003-4418-3892], Real-Arévalo, Irene [0000-0002-4234-3509], Cañada, F. Javier [0000-0003-4462-1469], Moreno-Sierra, Jesús [0000-0001-6837-7718], Subiza, José L. [0000-0002-0134-5321], Palomares, O. [0000-0003-4516-0369], Martín-Cruz, Leticia, Viñuela, Marcos, Kalograiaki, Ioanna, Angelina, Alba, Oquist Phillips, Mayra Paola, Real-Arévalo, Irene, Cañada, F. Javier, Tudela, José Ignacio, Moltó, Luis, Moreno-Sierra, Jesús, Subiza, José L., Palomares, O., Ministerio de Economía y Competitividad (España), Ministerio de Ciencia e Innovación (España), Martín-Cruz, Leticia [0000-0002-2546-1183], Viñuela, Marcos [0009-0002-8338-1832], Kalograiaki, Ioanna [0000-0001-7950-2334], Angelina, Alba [0000-0001-5282-9767], Oquist Phillips, Mayra Paola [0000-0003-4418-3892], Real-Arévalo, Irene [0000-0002-4234-3509], Cañada, F. Javier [0000-0003-4462-1469], Moreno-Sierra, Jesús [0000-0001-6837-7718], Subiza, José L. [0000-0002-0134-5321], Palomares, O. [0000-0003-4516-0369], Martín-Cruz, Leticia, Viñuela, Marcos, Kalograiaki, Ioanna, Angelina, Alba, Oquist Phillips, Mayra Paola, Real-Arévalo, Irene, Cañada, F. Javier, Tudela, José Ignacio, Moltó, Luis, Moreno-Sierra, Jesús, Subiza, José L., and Palomares, O.

Abstract

Functional Tregs play a key role in tumor development and progression, representing a major barrier to anticancer immunity. The mechanisms by which Tregs are generated in cancer and the influence of the tumor microenvironment on these processes remain incompletely understood. Herein, by using NMR, chemoenzymatic structural assays and a plethora of in vitro and in vivo functional analyses, we demonstrate that the tumoral carbohydrate A10 (Ca10), a cell-surface carbohydrate derived from Ehrlich’s tumor (ET) cells, is a heparan sulfate-related proteoglycan that enhances glycolysis and promotes the development of tolerogenic features in human DCs. Ca10-stimulated human DCs generate highly suppressive Tregs by mechanisms partially dependent on metabolic reprogramming, PD-L1, IL-10, and IDO. Ca10 also reprograms the differentiation of human monocytes into DCs with tolerogenic features. In solid ET-bearing mice, we found positive correlations between Ca10 serum levels, tumor size and splenic Treg numbers. Administration of isolated Ca10 also increases the proportion of splenic Tregs in tumor-free mice. Remarkably, we provide evidence supporting the presence of a circulating human Ca10 counterpart (Ca10H) and show, for the first time, that serum levels of Ca10H are increased in patients suffering from different cancer types compared to healthy individuals. Of note, these levels are higher in prostate cancer patients with bone metastases than in prostate cancer patients without metastases. Collectively, we reveal novel molecular mechanisms by which heparan sulfate-related structures associated with tumor cells promote the generation of functional Tregs in cancer. The discovery of this novel structural-functional relationship may open new avenues of research with important clinical implications in cancer treatment.

Published
2023

7. Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology.

Author

Roth‐Walter, F., Adcock, I. M., Benito‐Villalvilla, C., Bianchini, R., Bjermer, L., Caramori, G., Cari, L., Chung, K. F., Diamant, Z., Eguiluz‐Gracia, I., Knol, E. F., Jesenak, M., Levi‐Schaffer, F., Nocentini, G., O'Mahony, L., Palomares, O., Redegeld, F., Sokolowska, M., Van Esch, B. C. A. M., and Stellato, C.

Subjects
LUNG diseases, CELLULAR aging, AGING, TASK forces, CHRONIC obstructive pulmonary disease
Abstract

The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune‐driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence‐related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for strategies aimed at disease prevention and supporting healthy aging. [ABSTRACT FROM AUTHOR]

Published
2024
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9. COVID-19 vaccination in patients receiving allergen immunotherapy (AIT) or biologicals—EAACI recommendations

Author

Jutel M., Torres M.J., Palomares O., Akdis C.A., Eiwegger T., Untersmayr E., Barber D., Zemelka-Wiacek M., Kosowska A., Palmer E., Vieths S., Mahler V., Canonica W.G., Nadeau K., Shamji M.H., Agache I., Akdis M., Khaitov M., Alvarez-Perea A., Alvaro-Lozano M., Atanaskovic-Markovic M., Backer V., Barbaud A., Bavbek S., de Blay F., Bonini M., Bonini S., van Boven J.F.M., Brockow K., Cazzola M., Chatzipetrou A., Chivato T., Cianferoni A., Corren J., Cristoph-Caubet J., Dunn-Galvin A., Ebisawa M., Firinu D., Gawlik R., Gelincik A., del Giacco S., Mortz C.G., Jurgen Hoffmann H., Hoffmann-Sommergruber K., Klimek L., Knol E., Lauerma A., de Llano L.P., Matucci A., Meyer R., Moreira A., Morita H., Patil S.U., Pfaar O., Popescu F.-D., del Pozo V., Price O.J., van Ree R., Fernandez-Rivas M., Rogala B., Romano A., Santos A., Sediva A., Skypala I., Smolinska S., Sokolowska M., Sturm G., Vultaggio A., Walusiak-Skorupa J., Worm M., University of Zurich, Shamji, Mohamed H, Agache, Ioana, Ear, Nose and Throat, Experimental Immunology, AII - Inflammatory diseases, APH - Global Health, APH - Personalized Medicine, Groningen Research Institute for Asthma and COPD (GRIAC), Value, Affordability and Sustainability (VALUE), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)

Subjects
DOWN-REGULATION, COVID-19 Vaccines, Immunology, 610 Medicine & health, IMMUNOGENICITY, 10183 Swiss Institute of Allergy and Asthma Research, VACCINES, INFECTION, Hypersensitivity, Humans, Immunology and Allergy, SARS, 2403 Immunology, Biological Products, T-CELL RESPONSES, SARS-CoV-2, IMMUNE-RESPONSES, Vaccination, AIT, Allergens, Immunoglobulin E, allergy, Asthma, mRNA vaccines, biologicals, Desensitization, Immunologic, SAFETY, 2723 Immunology and Allergy, immunotherapy, INFLUENZA VACCINATION, Covid-19, SEVERE ASTHMA, allergen
Abstract

Immune modulation is a key therapeutic approach for allergic diseases, asthma and autoimmunity. It can be achieved in an antigen-specific manner via allergen immunotherapy (AIT) or in an endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: immunoglobulin (Ig)E, interleukin (IL)-5 and IL-4/IL-13 or non-type 2 response: anti-cytokine antibodies and B-cell depletion via anti-CD20. Coronavirus disease 2019 (COVID-19) vaccination provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. The vaccine exerts its effects through immune modulation, induces and amplifies the response against the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Thus, as there may be a discernible interference between these treatment modalities, recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) assembled an expert panel under its Research and Outreach Committee (ROC). This expert panel evaluated the evidence and have formulated recommendations on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals.

Published
2022
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10. From trained immunity in allergy to trained immunity-based allergen vaccines.

Author

Martín-Cruz, L., Sevilla-Ortega, C., Angelina, A., Domínguez-Andrés, J., Netea, M.G., Subiza, J.L., Palomares, O., Martín-Cruz, L., Sevilla-Ortega, C., Angelina, A., Domínguez-Andrés, J., Netea, M.G., Subiza, J.L., and Palomares, O.

Abstract

01 februari 2023, Item does not contain fulltext, Innate immune cells experience long lasting metabolic and epigenetic changes after an encounter with specific stimuli. This facilitates enhanced immune responses upon secondary exposition to both the same and unrelated pathogens, a process termed trained immunity. Trained immunity-based vaccines (TIbV) are vaccines able to induce innate immune memory, thus conferring heterologous protection against a broad range of pathogens. While trained immunity has been well documented in the context of infections and multiple immune-mediated diseases, the role of innate immune memory and its contribution to the initiation and maintenance of chronic allergic diseases remains poorly understood. Over the last years, different studies attempting to uncover the role of trained immunity in allergy have emerged. Exposition to environmental factors impacting allergy development such as allergens or viruses induces the reprogramming of innate immune cells to acquire a more pro-inflammatory phenotype in the context of asthma or food allergy. Several studies have convincingly demonstrated that prevention of viral infections using TIbV contributes to reduce wheezing attacks in children, which represent a high-risk factor for asthma development later in life. Innate immune cells trained with specific stimuli might also acquire anti-inflammatory features and promote tolerance, which may have important implications for chronic inflammatory diseases such as allergies. Recent findings showed that allergoid-mannan conjugates, which are next generation vaccines for allergen-specific immunotherapy (AIT), are able to reprogram monocytes into tolerogenic dendritic cells by mechanisms depending on metabolic and epigenetic rewiring. A better understanding of the underlying mechanisms of trained immunity in allergy will pave the way for the design of novel trained immunity-based allergen vaccines as potential alternative strategies for the prevention and treatment of allergic diseases.

Published
2023

11. Tonsillar transcriptional profiles in atopic and non-atopic subjects

Author

Hanif, T. (Tanzeela), Ivaska, L. E. (Lotta E.), Ahmad, F. (Freed), Tan, G. (Ge), Mikola, E. (Emilia), Puhakka, T. (Tuomo), Palomares, O. (Oscar), Akdis, C. A. (Cezmi A.), Toppila-Salmi, S. (Sanna), Jartti, T. (Tuomas), Hanif, T. (Tanzeela), Ivaska, L. E. (Lotta E.), Ahmad, F. (Freed), Tan, G. (Ge), Mikola, E. (Emilia), Puhakka, T. (Tuomo), Palomares, O. (Oscar), Akdis, C. A. (Cezmi A.), Toppila-Salmi, S. (Sanna), and Jartti, T. (Tuomas)

Abstract

Background: Emerging research suggests that local lymphatic tissue such as tonsils have important role in regulating the immune responses. However, allergen sensitization-induced alterations in transcriptome of tonsils are not known. Objective: To examine the key differences in tonsillar gene expression between atopic and non-atopic subjects and further by type of sensitization. Methods: RNA-sequencing was performed on 52 tonsillar samples from atopic and non-atopic tonsillectomy patients. Sensitization to common food- and aero-allergen was defined by allergen specific IgE. Following groups were studied: (1) aero- and food-allergen sensitized (AS+FS) versus non-sensitized (NS), (2) aeroallergen-sensitized (AS) versus food-allergen sensitized (FS), (3) AS versus NS, (4) FS versus NS. Bioinformatics analysis was done using DESeq2(v3.10.2), WGCNA and GATK pipeline in R software (v3.3.1). Protein–protein interaction network was made from String database. Results: We studied 13 aeroallergen-sensitized, 6 food-allergen sensitized, 4 both food-and aero-allergen-sensitized and 29 non-sensitized tonsillectomy patients. Overall, 697 unique differentially expressed genes (DEGs) were detected in all sensitized subgroups including chemokines (CXCL2, CXCL8, CXCL10, CXCL11), IL-20RA, MUC1 and MUC20. When comparing different groups, the gene expression profiles overlapped except the AS versus FS group comparison, suggesting significantly different gene expression between the two sensitization subgroups. Furthermore, aeroallergen-sensitized subjects had more prominent immune responses compared with non-sensitized and food-allergen sensitized subjects including gene expression for IL-17 pathway and Toll-like receptor signalling pathway. Conclusion: Allergic sensitization is associated with extensive tonsillar transcriptomic alterations and changes in immune related genes and pathways. Distinct differences were found between aero-allergen and food-allergen sensitization.

Published
2023

12. Transcriptional analysis of nasal polyps fibroblasts reveals a new source of pro-inflammatory signaling in CRSwNP

Author

Porras-González, Cristina, Palacios-García, José María, Sánchez-Gómez, Serafín, Maza-Solano, J. M., Alba, Gonzalo, Sánchez-Margalet, Víctor, Palomares, O., Cuvillo Bernal, Alfonso del, Cordero Varela, Juan Antonio, Moreno Luna, Rafael, Muñoz-Bravo, José Luis, Porras-González, Cristina, Palacios-García, José María, Sánchez-Gómez, Serafín, Maza-Solano, J. M., Alba, Gonzalo, Sánchez-Margalet, Víctor, Palomares, O., Cuvillo Bernal, Alfonso del, Cordero Varela, Juan Antonio, Moreno Luna, Rafael, and Muñoz-Bravo, José Luis

Abstract

[Background] Fibroblasts and others mesenchymal cells have recently been identified as critical cells triggering tissue-specific inflammatory responses. Persistent activation of fibroblasts inflammatory program has been suggested as an underlying cause of chronic inflammation in a wide range of tissues and pathologies. Nevertheless, the role of fibroblasts in the emergence of chronic inflammation in the upper airway has not been previously addressed. We aimed to elucidate whether fibroblasts could have a role in the inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP)., [Methodology] We performed whole-transcriptome microarray in fibroblast cultured from CRSwNP samples and confirmed our results by qRT-PCR. We selected patients without other associated diseases in upper airway. To investigate shifts in transcriptional profile we used fibroblasts from nasal polyps and uncinate mucosae from patient with CRSwNP, and fibroblasts from uncinate mucosae from healthy subjects as controls., [Results] This study exposes activation of a pro-inflammatory and pro-fibrotic transcriptional program in nasal polyps and CRSwNP fibroblasts when compared to controls. Our Gene-set Enrichment Analysis (GSEA) pointed to common up-regulation of several pro-inflammatory pathways in patients-derived fibroblasts, along with higher mRNA expression levels of cytokines, growth factors and extracellular matrix components., [Conclusions] Our work reveals a potential new source of inflammatory signaling in CRSwNP. Furthermore, our results suggest that deregulated inflammatory signaling in tissue-resident fibroblasts could support a Type-2 inflammatory response. Further investigations will be necessary to demonstrate the functionality of these novel results.

Published
2023

13. Rhinitis associated with asthma is distinct from rhinitis alone:The ARIA-MeDALL hypothesis

Author

Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickman, M, Akdis, M, Aguilar, D, Bedbrook, A, Bindslev-Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia-Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makela, M, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Ansotegui, I J, Arshad, S H, Asayag, E, Barbara, C, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, M, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R S, Bush, A, Calderon, M, Calvo-Gil, M, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia de Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, A F, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Grutta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohammad, Y, Moniuszko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, M S, Robalo Cordeiro, C, Roche, N, Rodriguez-Gonzalez, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Serpa, F S, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, Van Ganse, E, van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, Anto, J M, Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickman, M, Akdis, M, Aguilar, D, Bedbrook, A, Bindslev-Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia-Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makela, M, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Ansotegui, I J, Arshad, S H, Asayag, E, Barbara, C, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, M, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R S, Bush, A, Calderon, M, Calvo-Gil, M, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia de Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, A F, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Grutta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohammad, Y, Moniuszko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, M S, Robalo Cordeiro, C, Roche, N, Rodriguez-Gonzalez, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Serpa, F S, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, Van Ganse, E, van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, and Anto, J M

Abstract

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one-airway-one-disease,” coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one-airway-one-disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases., Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

Published
2023

14. Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis

Author

Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickmann, M, Aguilar, D, Akdis, M, Ansotegui, I J, Barbara, C, Bedbrook, A, Bindslev Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves-Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Arshad, H S, Asayag, E, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, Michael, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R, Bush, A, Calderon, M, Calvo, G, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia da Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, O, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Gruta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Mäkelä, M J, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohamad, Y, Moniusko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R E, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, R, Roballo-Cordeiro, C, Roche, N, Rodriguez-Gonzales, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Sarquis-Serpa, F, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, van Ganse, E, Van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, Anto, J M, Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickmann, M, Aguilar, D, Akdis, M, Ansotegui, I J, Barbara, C, Bedbrook, A, Bindslev Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves-Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Arshad, H S, Asayag, E, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, Michael, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R, Bush, A, Calderon, M, Calvo, G, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia da Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, O, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Gruta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Mäkelä, M J, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohamad, Y, Moniusko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R E, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, R, Roballo-Cordeiro, C, Roche, N, Rodriguez-Gonzales, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Sarquis-Serpa, F, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, van Ganse, E, Van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, and Anto, J M

Abstract

Asthma, rhinitis and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease", coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitisation and multimorbidity, (iii) advances in mHealth for novel phenotype definition, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis". This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitisation patterns (mono- or pauci-sensitisation versus polysensitisation), (iii) severity of symptoms and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and auto-immune diseases. [Abstract copyright: This article is protected by copyright. All rights reserved.]

Published
2023

15. Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA‐MeDALL hypothesis

Author

Bousquet, J., primary, Melén, E., additional, Haahtela, T., additional, Koppelman, G. H., additional, Togias, A., additional, Valenta, R., additional, Akdis, C. A., additional, Czarlewski, W., additional, Rothenberg, M., additional, Valiulis, A., additional, Wickman, M., additional, Akdis, M., additional, Aguilar, D., additional, Bedbrook, A., additional, Bindslev‐Jensen, C., additional, Bosnic‐Anticevich, S., additional, Boulet, L. P., additional, Brightling, C. E., additional, Brussino, L., additional, Burte, E., additional, Bustamante, M., additional, Canonica, G. W., additional, Cecchi, L., additional, Celedon, J. C., additional, Chaves Loureiro, C., additional, Costa, E., additional, Cruz, A. A., additional, Erhola, M., additional, Gemicioglu, B., additional, Fokkens, W. J., additional, Garcia‐Aymerich, J., additional, Guerra, S., additional, Heinrich, J., additional, Ivancevich, J. C., additional, Keil, T., additional, Klimek, L., additional, Kuna, P., additional, Kupczyk, M., additional, Kvedariene, V., additional, Larenas‐Linnemann, D. E., additional, Lemonnier, N., additional, Lodrup Carlsen, K. C., additional, Louis, R., additional, Makela, M., additional, Makris, M., additional, Maurer, M., additional, Momas, I., additional, Morais‐Almeida, M., additional, Mullol, J., additional, Naclerio, R. N., additional, Nadeau, K., additional, Nadif, R., additional, Niedoszytko, M., additional, Okamoto, Y., additional, Ollert, M., additional, Papadopoulos, N. G., additional, Passalacqua, G., additional, Patella, V., additional, Pawankar, R., additional, Pham‐Thi, N., additional, Pfaar, O., additional, Regateiro, F. S., additional, Ring, J., additional, Rouadi, P. W., additional, Samolinski, B., additional, Sastre, J., additional, Savouré, M., additional, Scichilone, N., additional, Shamji, M. H., additional, Sheikh, A., additional, Siroux, V., additional, Sousa‐Pinto, B., additional, Standl, M., additional, Sunyer, J., additional, Taborda‐Barata, L., additional, Toppila‐Salmi, S., additional, Torres, M. J., additional, Tsiligianni, I., additional, Valovirta, E., additional, Vandenplas, O., additional, Ventura, M. T., additional, Weiss, S., additional, Yorgancioglu, A., additional, Zhang, L., additional, Abdul Latiff, A. H., additional, Aberer, W., additional, Agache, I., additional, Al‐Ahmad, M., additional, Alobid, I., additional, Ansotegui, I. J., additional, Arshad, S. H., additional, Asayag, E., additional, Barbara, C., additional, Baharudin, A., additional, Battur, L., additional, Bennoor, K. S., additional, Berghea, E. C., additional, Bergmann, K. C., additional, Bernstein, D., additional, Bewick, M., additional, Blain, H., additional, Bonini, M., additional, Braido, F., additional, Buhl, R., additional, Bumbacea, R. S., additional, Bush, A., additional, Calderon, M., additional, Calvo‐Gil, M., additional, Camargos, P., additional, Caraballo, L., additional, Cardona, V., additional, Carr, W., additional, Carreiro‐Martins, P., additional, Casale, T., additional, Cepeda Sarabia, A. M., additional, Chandrasekharan, R., additional, Charpin, D., additional, Chen, Y. Z., additional, Cherrez‐Ojeda, I., additional, Chivato, T., additional, Chkhartishvili, E., additional, Christoff, G., additional, Chu, D. K., additional, Cingi, C., additional, Correia de Sousa, J., additional, Corrigan, C., additional, Custovic, A., additional, D’Amato, G., additional, Del Giacco, S., additional, De Blay, F., additional, Devillier, P., additional, Didier, A., additional, do Ceu Teixeira, M., additional, Dokic, D., additional, Douagui, H., additional, Doulaptsi, M., additional, Durham, S., additional, Dykewicz, M., additional, Eiwegger, T., additional, El‐Sayed, Z. A., additional, Emuzyte, R., additional, Fiocchi, A., additional, Fyhrquist, N., additional, Gomez, R. M., additional, Gotua, M., additional, Guzman, M. A., additional, Hagemann, J., additional, Hamamah, S., additional, Halken, S., additional, Halpin, D. M. G., additional, Hofmann, M., additional, Hossny, E., additional, Hrubiško, M., additional, Irani, C., additional, Ispayeva, Z., additional, Jares, E., additional, Jartti, T., additional, Jassem, E., additional, Julge, K., additional, Just, J., additional, Jutel, M., additional, Kaidashev, I., additional, Kalayci, O., additional, Kalyoncu, A. F., additional, Kardas, P., additional, Kirenga, B., additional, Kraxner, H., additional, Kull, I., additional, Kulus, M., additional, La Grutta, S., additional, Lau, S., additional, Le Tuyet Thi, L., additional, Levin, M., additional, Lipworth, B., additional, Lourenço, O., additional, Mahboub, B., additional, Martinez‐Infante, E., additional, Matricardi, P., additional, Miculinic, N., additional, Migueres, N., additional, Mihaltan, F., additional, Mohammad, Y., additional, Moniuszko, M., additional, Montefort, S., additional, Neffen, H., additional, Nekam, K., additional, Nunes, E., additional, Nyembue Tshipukane, D., additional, O’Hehir, R., additional, Ogulur, I., additional, Ohta, K., additional, Okubo, K., additional, Ouedraogo, S., additional, Olze, H., additional, Pali‐Schöll, I., additional, Palomares, O., additional, Palosuo, K., additional, Panaitescu, C., additional, Panzner, P., additional, Park, H. S., additional, Pitsios, C., additional, Plavec, D., additional, Popov, T. A., additional, Puggioni, F., additional, Quirce, S., additional, Recto, M., additional, Repka‐Ramirez, M. S., additional, Robalo Cordeiro, C., additional, Roche, N., additional, Rodriguez‐Gonzalez, M., additional, Romantowski, J., additional, Rosario Filho, N., additional, Rottem, M., additional, Sagara, H., additional, Serpa, F. S., additional, Sayah, Z., additional, Scheire, S., additional, Schmid‐Grendelmeier, P., additional, Sisul, J. C., additional, Sole, D., additional, Soto‐Martinez, M., additional, Sova, M., additional, Sperl, A., additional, Spranger, O., additional, Stelmach, R., additional, Suppli Ulrik, C., additional, Thomas, M., additional, To, T., additional, Todo‐Bom, A., additional, Tomazic, P. V., additional, Urrutia‐Pereira, M., additional, Valentin‐Rostan, M., additional, Van Ganse, E., additional, van Hage, M., additional, Vasankari, T., additional, Vichyanond, P., additional, Viegi, G., additional, Wallace, D., additional, Wang, D. Y., additional, Williams, S., additional, Worm, M., additional, Yiallouros, P., additional, Yusuf, O., additional, Zaitoun, F., additional, Zernotti, M., additional, Zidarn, M., additional, Zuberbier, J., additional, Fonseca, J. A., additional, Zuberbier, T., additional, and Anto, J. M., additional

Published
2023
Full Text
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16. The ARIA-MeDALL hypothesis

Author

Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickmann, M, Bonini, M, Braido, F, Buhl, R, Bumbacea, R, Bush, A, Calderon, M, Calvo, G, Camargos, P, Caraballo, L, Cardona, V, Aguilar, D, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Akdis, M, Christoff, G, Chu, D K, Cingi, C, Correia da Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Ansotegui, I J, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Barbara, C, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Bedbrook, A, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Bindslev Jensen, C, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, O, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Gruta, S, Bosnic-Anticevich, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Mäkelä, M J, Martinez-Infante, E, Matricardi, P, Miculinic, N, Boulet, L P, Migueres, N, Mihaltan, F, Mohamad, Y, Moniusko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R E, Brightling, C E, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Brussino, L, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, R, Roballo-Cordeiro, C, Roche, N, Burte, E, Rodriguez-Gonzales, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Sarquis-Serpa, F, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Bustamante, M, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Canonica, G W, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, van Ganse, E, Van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Cecchi, L, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Celedon, J C, Zuberbier, T, Anto, J M, Chaves-Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Arshad, H S, Asayag, E, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, M, Blain, H, UCIBIO - Applied Molecular Biosciences Unit, Comprehensive Health Research Centre (CHRC) - pólo NMS, and NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)

Subjects
SDG 3 - Good Health and Well-being
Abstract

Asthma, rhinitis and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease", coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitisation and multimorbidity, (iii) advances in mHealth for novel phenotype definition, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis". This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitisation patterns (mono- or pauci-sensitisation versus polysensitisation), (iii) severity of symptoms and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and auto-immune diseases. authorsversion epub_ahead_of_print

Published
2023

17. Rhinitis associated with asthma is distinct from rhinitis alone: TARIA‐MeDALL hypothesis

Author

Bousquet, Jean, Melén, Erik, Haahtela, Tari, Koppelman, Gerard, Togias, Alkis, Valenta, Rudolf, Akdis, Cezmi, Czarlewski, Wienczyslawa, Rothenberg, Marc, Valiulis, Arunas, Wickman, Magnus, Vichyanond, Pakit, Moniuszko, Marcin, Ėmužytė, Regina, Bush, Andrew, Chu, Derek K, Viegi, Giovanni, Wallace, Dana, Durham, Stephen, Wang, De Yun, Vandenplas, O., Just, Jocelyne, Carlsen, Karin C. Lodrup, Passalacqua, Giovanni, Williams, Siân, Linnemann, Désirée Larenas, Loureiro, Cláudia Chaves, Sagara, Hironori, Worm, Margitta, Yiallouros, Panayiotis, Yusuf, Osman, Zaitoun, Fares, Bonini, Matteo, Hrubiško, Martin, Cingi, C., Dykewicz, Mark, Zernotti, Mario, Calderon, Moises, Halpin, David M.G., Zidarn, Mihaela, Patella, Vincenzo, Sheikh, Aziz, Zuberbier, Jaron, Papadopoulos, Nikolaos, Louis, Renaud, Suppli Ulrik, Charlotte, Fonseca, João P., Zuberbier, Torsten, Anto, M. J., Costa, Elisio, Eiwegger, Thomas, Bosnic-Anticevich, Sinthia, Cruz, Alvaro, Sousa, Jaime Correia de, Louis-Philippe, Boulet, Erhola, Marina, Cardona, Victoria, Carr, Warner, Gemicioglu, Bilun, Pawankar, Ruby, Fokkens, Wytske, Calvo, Mário, Garcia-Aymerich, J., Mäkelä, Mika J., Hofmann, Maja Ann, Klimek, Ludger, Makris, Michael, Mohamed Sayed, Zeinab, Maurer, Marcus, D'Amato, G., Momas, Isabelle, Siroux, Valérie, Almeida, Mário Morais, Corrigan, Chris, Mullol, Joaquim, Montefort, Stephen, Jutel, Marek, Pham Thi, Nhan, Hossny, Elham, Akdis, Mubeccel, Pfaar, Oliver, Ventura, Maria Teresa, Regateiro, Frederico S., Bindslev-Jensen, Carsten, Ring, Johannes, Bustamante, Mariona, Pinto, Bernardo Sousa, Kaidashev, Igor, Guerra, Stefano, Standl, Marie, Sunyer, J., Keil, Thomas, Barata, Luís Taborda, Camargos, Paulo, Weiss, Scott, Naclerio, Robert, Yorgancıoglu, Arzu, Zhang, Luo, Nadeau, Kari, Abdul Latiff, Amir, Aberer, Werner, Heinrich, Joachim, Sisul, Juan, Nunes, Elizabete, Plavec, Davor, Agache, Ioana, Al-Ahmad, Mona, Serpa, Faradiba, Alobid, Isam, Kalayci, Omer, Giacco, S. Del, Fiocchi, Alessandro, Ansotegui Zubeldia, Ignacio Javier, Custovic, Adnan, Martins, Pedro Carreiro, Rouadi, Philip, Arshad, Syed Hasan, Asayag, Estrella, Bárbara, Cristina, Abdullah, Baharudin, Tomazic, Peter Valentin, Popov, T. A., Sayah, Zineb, Lkhagvaa, Battur, Nyembue Tshipukane , Dieudonne, Thomas, Mike, Bennoor, Kazi Saifuddin, Fyhrquist, Nanna Theresia, Irani, Carla, Berghea, Elena Camelia, De Blay, Frédéric, Toppila-Salmi, Sanna Katriina, Bergmann, Karl-Christian, Bernstein, D., Bewick, M., Casale, Thomas, Scheire, Sophie, Bumbacea, Roxana Silvia, Cepeda Sarabia, Alfonso, Puggioni, Francesca, Chandrasekharan, Ramanathan, Ohta, Ken, Okubo, Kimihiro, Charpin, Denis, Gomez, R Maximiliano, Chen, Y. Z., O'Hehir, Robyn, Cherrez Ojeda, Ivan, Bedbrook, Anna, To, Teresa, Devillier, Philippe, Schmid-Grendelmeier, Peter, Didier, Alain, Repka-Ramirez, María Susana, Teixeira, Maria Do Céu, Ispayeva, Zhanat, Dokic, Dejan, Quirce, Santiago, Douagui , Habib, Ivancevich, Juan Carlos, Gotua, Maia, Todo-Bom, Ana, Blain, Hubert, Guzman, Maria Antonieta, Kalyoncu, Ali Fuat, Hagemann, Jan, Buhl, Roland, Hamamah, Samir, Caraballo, Luis, Jares, Edgardo, Chivato, Tomás, Jartti, Tuomas, Jassem, Ewa, Christoff, George, Julge, Kalev, Ogulur, Ismail, Kardas, Przemyslaw, Doulaptsi, Maria, Kirenga, Bruce, Helga, Kraxner, Kull, Inger, Kulus, Marek, Daniel, Aguilar, Shamji, Mohamed, Kuna, Piotr, Nadif, Rachel, La Grutta, Stefania, Brightling, Chris, Samoliński, Bolesław, Lau, Susanne, Cordeiro, Carlos Manuel Da Silva Robalo, Solé, Dirceu, Le Thi Tuyet, Lan, Recto, Marysia, Ouedraogo, Solange, Halken, Susanne, Levin, Michael, Lipworth, Brian, Lourenço, Olga, Mahboub, Bassam, Niedoszytko, Marek, Sastre, Joaquin, Martinez‐Infante, E., Kupczyk, Maciej, Torres, María Jose, Matricardi, Paolo Maria, Cecchi, Lorenzo, Celedón, Juan C, Miculinic, Neven, Roche, Nicolas, Migueres, Nicolas, Brussino, Luisa, Florin, Mihaltan, Olze, Heidi, Savouré, Marine, Nekam, Kristof, Pali, Isabella, Okamoto, Yoshitaka, Palomares, O., Lemonnier, Nathanaël, Palosuo, Kati, Soto-Martinez, Manuel, Panaitescu, Carmen, Kvedarienė, Violeta, Panzner, P., Braido, Fulvio, Tsiligianni, Ioanna, Rodriguez-Gonzalez, Monica, Scichilone, Nicola, Canonica, Giogio Walter, Romantowski, Jan, Urrutia-Pereira, Marilyn, Filho, Nelson Augusto Rosario, Ollert, Markus W., Rottem, Menachem, Chkhartishvili, Ekaterine, Sova, Milan, Valovirta, Erkka, Mohammad, Yousser, Sperl, Annette, Spranger, Otto, Neffen, Hugo, Stelmach, Rafael, Burte, Emilie, Valentin Rostan, Marylin, Park, Hae-Sim, Van Ganse, Eric, Van Hage, Marianne, Pitsios, Constantinos, Vasankari, Tuula, and uBibliorum

Subjects
IL-33, Multimorbidity, Asthma, Toll-like receptors, Rhinitis
Abstract

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one-airway-one-disease,” coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one-airway-one-disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis.

Published
2023

21. Challenges in the implementation of EAACI guidelines on allergen immunotherapy: A global perspective on the regulation of allergen products

Author

Bonertz, A., Roberts, G. C., Hoefnagel, M., Timon, M., Slater, J. E., Rabin, R. L., Bridgewater, J., Pini, C., Pfaar, O., Akdis, C., Goldstein, J., Poulsen, L. K., van Ree, R., Rhyner, C., Barber, D., Palomares, O., Sheikh, A., Pawankar, R., Hamerlijnk, D., Klimek, L., Agache, I., Angier, E., Casale, T., Fernandez‐Rivas, M., Halken, S., Jutel, M., Lau, S., Pajno, G., Sturm, G., Varga, E. M., Gerth van Wijk, R., Bonini, S., Muraro, A., and Vieths, S.

Published
2018
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22. MODERFOREST: más que una aplicación para la elección de especie y origen de la semilla en repoblaciones forestales

Author

Alonso Ponce, R., Gómez Sanz, V., López-Senepleda, E., Ruiz-Peinado, R., Montero, G., Sánchez-Palomares, O., Serrada Hierrro, R., Alonso Ponce, R., and Gómez Sanz, V.

Subjects
Modelización ecológica, Parámetros climáticos, Parámetros edáficos, Autoecología, Similitud ecológica, Restauración
Abstract

17 Pág. Centro de Investigación Forestal (CIFOR), ModERFoRest es el acrónimo de Modelling Environmental Requirements for Forest Restoration (Modelización de los requerimientos ambientales para la restauración forestal), ya que es una aplicación especialmente diseñada para la elección de especie y el origen del material forestal de reproducción idóneos en tareas de restauración de la vegetación. Sin embargo, la actual versión ya disponible de la aplicación facilita, además, otra serie de funcionalidades como son: i) la modelización de la distribución de especies, con dos algoritmos diferentes, a partir de datos exclusivamente de presencias; ii) el cálculo masivo de hasta 38 variables climáticas a partir de datos de precipitación y temperaturas mensuales; y iii) la síntesis de hasta 23 variables edáficas a escala perfil derivados de los datos brutos de laboratorio por horizontes, incluyendo la generación de fichas hídricas. La aplicación se distribuye de manera gratuita y recoge toda la información sobre autoecología de 22 taxones arbóreos de relevancia en España, así como de los rodales semilleros selectos cuya caracterización ecológica completa está disponible hasta la fecha. ModERFoRest constituye una herramienta de fácil manejo, versátil, de uso libre y en continuo desarrollo que puede ser de utilidad tanto a gestores como investigadores del ámbito de la restauración de la vegetación.

Published
2022

25. Anwendung von Biologika bei allergischen und Typ-2- entzündlichen Erkrankungen in der aktuellen COVID-19-Pandemie – ein Positionspapier von AeDA, DGAKI, GPA, ÖGAI, LGAI, ÖGP, ARIA und EAACI

Author

Klimek, L., Pfaar, O., Worm, M., Eiwegger, T., Hagemann, J., Ollert, M., Untersmayr, E., Hoffmann-Sommergruber, K., Vultaggio, A., Agache, I., Bavbek, S., Bossios, A., Casper, I., Chan, S., Chatzipetrou, A., Vogelberg, C., Firinu, D., Kauppi, P., Kolios, A., Kothari, A., Matucci, A., Palomares, O., Szépfalusi, Z., Pohl, W., Hötzenecker, W., Rosenkranz, A. R., Bergmann, K. C., Bieber, T., Buhl, R., Buters, J., Darsow, U., Keil, T., Kleine-Tebbe, J., Lau, S., Maurer, M., Merk, H., Mösges, R., Saloga, J., Staubach, P., Jappe, U., Rabe, K. F., Rabe, U., Vogelmeier, C., Biedermann, T., Jung, K., Schlenter, W., Ring, J., Chaker, A., Wehrmann, W., Becker, S., Freudelsperger, L., Mülleneisen, N., Nemat, K., Czech, W., Wrede, H., Brehler, R., Fuchs, T., Tomazic, P. V., Aberer, W., Fink-Wagner, A. H., Horak, F., Wöhrl, S., Niederberger-Leppin, V., Pali-Schöll, I., Roller-Wirnsberger, R., Spranger, O., Valenta, R., Akdis, M., Matricardi, P. M., Spertini, F., Khaltaev, N., Michel, J. P., Nicod, L., Schmid-Grendelmeier, P., Idzko, M., Hamelmann, E., Jakob, T., Werfel, T., Wagenmann, M., Taube, C., Jensen-Jarolim, E., Korn, S., Hentges, F., Schwarze, J., O'Mahony, L., Knol, E. F., del Giacco, S., Chivato Pérez, T., Bousquet, J., Zuberbier, T., Akdis, C., and Jutel, M.

Subjects
Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Omalizumab, Dupilumab, Immunoglobulin E, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Reslizumab, Immunology and Allergy, Medicine, 030223 otorhinolaryngology, Mepolizumab, biology, SARS-CoV-2, business.industry, Benralizumab, Telemedicine, 030228 respiratory system, chemistry, Immunology, biology.protein, Covid-19, business, medicine.drug
Published
2020
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26. Candida albicans V132 induces trained immunity and enhances the responses triggered by the polybacterial vaccine MV140 for genitourinary tract infections

Author

Martín-Cruz, L., Angelina, A., Baydemir, I., Bulut, Ö, Luis Subiza, Jose, Netea, M.G., Dominguez Andres, J., Palomares, O., Martín-Cruz, L., Angelina, A., Baydemir, I., Bulut, Ö, Luis Subiza, Jose, Netea, M.G., Dominguez Andres, J., and Palomares, O.

Abstract

Contains fulltext : 286907.pdf (Publisher’s version ) (Open Access)

Published
2022

27. MODERFOREST: más que una aplicación para la elección de especie y origen de la semilla en repoblaciones forestales

Author

Alonso Ponce, R.[0000-0002-7061-0547], Gómez, Valentín [0000-0002-4661-1654], Ruiz-Peinado, Ricardo [0000-0003-0126-1651], Serrada, Rafael [0000-0003-0868-6038], Alonso Ponce, R., Gómez, Valentín, López-Senespleda, Eduardo, Ruiz-Peinado, Ricardo, Montero, G., Sánchez-Palomares, O., Serrada, Rafael, Alonso Ponce, R.[0000-0002-7061-0547], Gómez, Valentín [0000-0002-4661-1654], Ruiz-Peinado, Ricardo [0000-0003-0126-1651], Serrada, Rafael [0000-0003-0868-6038], Alonso Ponce, R., Gómez, Valentín, López-Senespleda, Eduardo, Ruiz-Peinado, Ricardo, Montero, G., Sánchez-Palomares, O., and Serrada, Rafael

Abstract

ModERFoRest es el acrónimo de Modelling Environmental Requirements for Forest Restoration (Modelización de los requerimientos ambientales para la restauración forestal), ya que es una aplicación especialmente diseñada para la elección de especie y el origen del material forestal de reproducción idóneos en tareas de restauración de la vegetación. Sin embargo, la actual versión ya disponible de la aplicación facilita, además, otra serie de funcionalidades como son: i) la modelización de la distribución de especies, con dos algoritmos diferentes, a partir de datos exclusivamente de presencias; ii) el cálculo masivo de hasta 38 variables climáticas a partir de datos de precipitación y temperaturas mensuales; y iii) la síntesis de hasta 23 variables edáficas a escala perfil derivados de los datos brutos de laboratorio por horizontes, incluyendo la generación de fichas hídricas. La aplicación se distribuye de manera gratuita y recoge toda la información sobre autoecología de 22 taxones arbóreos de relevancia en España, así como de los rodales semilleros selectos cuya caracterización ecológica completa está disponible hasta la fecha. ModERFoRest constituye una herramienta de fácil manejo, versátil, de uso libre y en continuo desarrollo que puede ser de utilidad tanto a gestores como investigadores del ámbito de la restauración de la vegetación.

Published
2022

28. COVID-19 vaccination in patients receiving allergen immunotherapy (AIT) or biologicals—EAACI recommendations

Author

Jutel, M. Torres, M.J. Palomares, O. Akdis, C.A. Eiwegger, T. Untersmayr, E. Barber, D. Zemelka-Wiacek, M. Kosowska, A. Palmer, E. Vieths, S. Mahler, V. Canonica, W.G. Nadeau, K. Shamji, M.H. Agache, I. Akdis, M. Khaitov, M. Alvarez-Perea, A. Alvaro-Lozano, M. Atanaskovic-Markovic, M. Backer, V. Barbaud, A. Bavbek, S. de Blay, F. Bonini, M. Bonini, S. van Boven, J.F.M. Brockow, K. Cazzola, M. Chatzipetrou, A. Chivato, T. Cianferoni, A. Corren, J. Cristoph-Caubet, J. Dunn-Galvin, A. Ebisawa, M. Firinu, D. Gawlik, R. Gelincik, A. del Giacco, S. Mortz, C.G. Jürgen Hoffmann, H. Hoffmann-Sommergruber, K. Klimek, L. Knol, E. Lauerma, A. de Llano, L.P. Matucci, A. Meyer, R. Moreira, A. Morita, H. Patil, S.U. Pfaar, O. Popescu, F.-D. del Pozo, V. Price, O.J. van Ree, R. Fernández-Rivas, M. Rogala, B. Romano, A. Santos, A. Sediva, A. Skypala, I. Smolinska, S. Sokolowska, M. Sturm, G. Vultaggio, A. Walusiak-Skorupa, J. Worm, M.

Abstract

Immune modulation is a key therapeutic approach for allergic diseases, asthma and autoimmunity. It can be achieved in an antigen-specific manner via allergen immunotherapy (AIT) or in an endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: immunoglobulin (Ig)E, interleukin (IL)-5 and IL-4/IL-13 or non-type 2 response: anti-cytokine antibodies and B-cell depletion via anti-CD20. Coronavirus disease 2019 (COVID-19) vaccination provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. The vaccine exerts its effects through immune modulation, induces and amplifies the response against the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Thus, as there may be a discernible interference between these treatment modalities, recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) assembled an expert panel under its Research and Outreach Committee (ROC). This expert panel evaluated the evidence and have formulated recommendations on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals. © 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

Published
2022

30. Immunology of COVID‐19: mechanisms, clinical outcome, diagnostics and perspectives – a report of the European Academy of Allergy and Clinical Immunology (EAACI)

Author

European Academy of Allergy and Clinical Immunology, Swiss National Science Foundation, Ministerio de Economía y Competitividad (España), Research Foundation - Flanders, Istituto Italiano di Tecnologia, Fondazione Telethon, Ministero della Salute, Comunidad de Madrid, German Research Foundation, European Commission, Sokolowska, Milena [0000-0001-9710-6685], Agache, Ioana [0000-0001-7994-364X], Akdis, Cezmi A. [0000-0001-8020-019X], Akdis, Mubeccel [0000-0003-0554-9943], Barcik, Weronika [0000-0001-8580-9690], Brough, Helen [0000-0001-7203-0813], Eiwegger, Thomas [0000-0002-2914-7829], Eliaszewicz, Andrzej [0000-0002-8980-1474], Feleszko, Wojciech [0000-0001-6613-2012], Gómez-Casado, C. [0000-0002-7707-6367], Hoffmann-Sommergruber, Karin [0000-0002-8830-058X], Janda, Jozef [0000-0001-9958-5683], Jiménez Saiz, Rodrigo [0000-0002-0606-3251], Knol, Edward [0000-0001-7368-9820], Krohn, Kortekaas [0000-0003-3649-1131], Kothari, Akash [0000-0003-1980-161X], Moniuszko, Marcin [0000-0001-7183-3120], Morita, Hideaki [0000-0003-0928-8322], Nadeau, Kari C. [0000-0002-2146-2955], Ozdemir, Cevdet [0000-0002-9284-4520], Pali-Schöll, Isabella [0000-0003-2089-6011], Palomares, O. [0000-0003-4516-0369], Papaleo, Francesco [0000-0002-6326-0657], Prunicki, Mary [0000-0002-5511-8896], Schmidt-Weber, C. B. [0000-0002-3203-8084], Schwarze, Jürgen [0000-0002-6899-748X], Tramper-Stranders, Gerdien [0000-0002-0228-5375], Veen, Willem van de [0000-0001-9951-6688], Untersmayr, Eva [0000-0002-1963-499X], Sokolowska, Milena, Lukasik, Z., Agache, Ioana, Akdis, Cezmi A., Akdis, D., Akdis, Mubeccel, Barcik, Weronika, Brough, Helen, Eiwegger, Thomas, Eliaszewicz, Andrzej, Eyerich, Stephanie, Feleszko, Wojciech, Gómez-Casado, C., Hoffmann-Sommergruber, Karin, Janda, Jozef, Jiménez Saiz, Rodrigo, Jutel, Marek, Knol, Edward, Krohn, Kortekaas, Kothari, Akash, Makowska, J., Moniuszko, Marcin, Morita, Hideaki, O’Mahony, L., Nadeau, Kari C., Ozdemir, Cevdet, Pali-Schöll, Isabella, Palomares, O., Papaleo, Francesco, Prunicki, Mary, Schmidt-Weber, C. B., Sediva, A., Schwarze, Jürgen, Shamji, M. H., Tramper-Stranders, Gerdien, Veen, Willem van de, Untersmayr, Eva, European Academy of Allergy and Clinical Immunology, Swiss National Science Foundation, Ministerio de Economía y Competitividad (España), Research Foundation - Flanders, Istituto Italiano di Tecnologia, Fondazione Telethon, Ministero della Salute, Comunidad de Madrid, German Research Foundation, European Commission, Sokolowska, Milena [0000-0001-9710-6685], Agache, Ioana [0000-0001-7994-364X], Akdis, Cezmi A. [0000-0001-8020-019X], Akdis, Mubeccel [0000-0003-0554-9943], Barcik, Weronika [0000-0001-8580-9690], Brough, Helen [0000-0001-7203-0813], Eiwegger, Thomas [0000-0002-2914-7829], Eliaszewicz, Andrzej [0000-0002-8980-1474], Feleszko, Wojciech [0000-0001-6613-2012], Gómez-Casado, C. [0000-0002-7707-6367], Hoffmann-Sommergruber, Karin [0000-0002-8830-058X], Janda, Jozef [0000-0001-9958-5683], Jiménez Saiz, Rodrigo [0000-0002-0606-3251], Knol, Edward [0000-0001-7368-9820], Krohn, Kortekaas [0000-0003-3649-1131], Kothari, Akash [0000-0003-1980-161X], Moniuszko, Marcin [0000-0001-7183-3120], Morita, Hideaki [0000-0003-0928-8322], Nadeau, Kari C. [0000-0002-2146-2955], Ozdemir, Cevdet [0000-0002-9284-4520], Pali-Schöll, Isabella [0000-0003-2089-6011], Palomares, O. [0000-0003-4516-0369], Papaleo, Francesco [0000-0002-6326-0657], Prunicki, Mary [0000-0002-5511-8896], Schmidt-Weber, C. B. [0000-0002-3203-8084], Schwarze, Jürgen [0000-0002-6899-748X], Tramper-Stranders, Gerdien [0000-0002-0228-5375], Veen, Willem van de [0000-0001-9951-6688], Untersmayr, Eva [0000-0002-1963-499X], Sokolowska, Milena, Lukasik, Z., Agache, Ioana, Akdis, Cezmi A., Akdis, D., Akdis, Mubeccel, Barcik, Weronika, Brough, Helen, Eiwegger, Thomas, Eliaszewicz, Andrzej, Eyerich, Stephanie, Feleszko, Wojciech, Gómez-Casado, C., Hoffmann-Sommergruber, Karin, Janda, Jozef, Jiménez Saiz, Rodrigo, Jutel, Marek, Knol, Edward, Krohn, Kortekaas, Kothari, Akash, Makowska, J., Moniuszko, Marcin, Morita, Hideaki, O’Mahony, L., Nadeau, Kari C., Ozdemir, Cevdet, Pali-Schöll, Isabella, Palomares, O., Papaleo, Francesco, Prunicki, Mary, Schmidt-Weber, C. B., Sediva, A., Schwarze, Jürgen, Shamji, M. H., Tramper-Stranders, Gerdien, Veen, Willem van de, and Untersmayr, Eva

Abstract

With the worldwide spread of the novel Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS‐CoV‐2‐induced Coronavirus disease‐19 (COVID‐19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS‐CoV‐2 infection and COVID‐19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multi‐organ disease. The similarities of the human immune response to SARS‐CoV‐2 and the SARS‐CoV and MERS‐CoV are underlined. We also summarize known and potential SARS‐CoV‐2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender and age in development of COVID‐19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID‐19 studies.

Published
2020

36. COVID-19 pandemic: Practical considerations on the organization of an allergy clinic—An EAACI/ARIA Position Paper

Author

Pfaar, O. Klimek, L. Jutel, M. Akdis, C.A. Bousquet, J. Breiteneder, H. Chinthrajah, S. Diamant, Z. Eiwegger, T. Fokkens, W.J. Fritsch, H.-W. Nadeau, K.C. O’Hehir, R.E. O’Mahony, L. Rief, W. Sampath, V. Schedlowski, M. Torres, M.J. Traidl-Hoffmann, C. Wang, D.Y. Zhang, L. Bonini, M. Brehler, R. Brough, H.A. Chivato, T. Del Giacco, S.R. Dramburg, S. Gawlik, R. Gelincik, A. Hoffmann-Sommergruber, K. Hox, V. Knol, E.F. Lauerma, A. Matricardi, P.M. Mortz, C.G. Ollert, M. Palomares, O. Riggioni, C. Schwarze, J. Skypala, I. Untersmayr, E. Walusiak-Skorupa, J. Ansotegui, I.J. Bachert, C. Bedbrook, A. Bosnic-Anticevich, S. Brussino, L. Canonica, G.W. Cardona, V. Carreiro-Martins, P. Cruz, A.A. Czarlewski, W. Fonseca, J.A. Gotua, M. Haahtela, T. Ivancevich, J.C. Kuna, P. Kvedariene, V. Larenas-Linnemann, D.E. Abdul Latiff, A.H. Mäkelä, M. Morais-Almeida, M. Mullol, J. Naclerio, R. Ohta, K. Okamoto, Y. Onorato, G.L. Papadopoulos, N.G. Patella, V. Regateiro, F.S. Samoliński, B. Suppli Ulrik, C. Toppila-Salmi, S. Valiulis, A. Ventura, M.-T. Yorgancioglu, A. Zuberbier, T. Agache, I.

Subjects
education
Abstract

Background: The coronavirus disease 2019 (COVID-19) has evolved into a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Allergists and other healthcare providers (HCPs) in the field of allergies and associated airway diseases are on the front line, taking care of patients potentially infected with SARS-CoV-2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics. Method: The scientific information on COVID-19 was analysed by a literature search in MEDLINE, PubMed, the National and International Guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library, and the internet. Results: Based on the diagnostic and treatment standards developed by EAACI, on international information regarding COVID-19, on guidelines of the World Health Organization (WHO) and other international organizations, and on previous experience, a panel of experts including clinicians, psychologists, IT experts, and basic scientists along with EAACI and the “Allergic Rhinitis and its Impact on Asthma (ARIA)” initiative have developed recommendations for the optimal management of allergy clinics during the current COVID-19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies. Conclusions: This international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients while ensuring the necessary safety measures in the current COVID-19 pandemic. © 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Published
2021

37. EAACI statement on the diagnosis, management and prevention of severe allergic reactions to COVID-19 vaccines

Author

Sokolowska M, Eiwegger T, Ollert M, Torres MJ, Barber D, Del Giacco S, Jutel M, Nadeau KC, Palomares O, Rabin RL, Riggioni C, Vieths S, Agache I, and Shamji MH

Subjects
SARS-CoV, COVID, virus
Abstract

The first approved COVID-19 vaccines include Pfizer/BioNTech BNT162B2, Moderna mRNA-1273 and AstraZeneca recombinant adenoviral ChAdOx1-S. Soon after approval, severe allergic reactions to the mRNA-based vaccines that resolved after treatment were reported. Regulatory agencies from the European Union, Unites States and the United Kingdom agree that vaccinations are contraindicated only when there is an allergy to one of the vaccine components or if there was a severe allergic reaction to the first dose. This position paper of the European Academy of Allergy and Clinical Immunology (EAACI) agrees with these recommendations and clarifies that there is no contraindication to administer these vaccines to allergic patients who do not have a history of an allergic reaction to any of the vaccine components. Importantly, as is the case for any medication, anaphylaxis may occur after vaccination in the absence of a history of allergic disease. Therefore, we provide a simplified algorithm of prevention, diagnosis and treatment of severe allergic reactions and a list of recommended medications and equipment for vaccine centres. We also describe potentially allergenic/immunogenic components of the approved vaccines and propose a workup to identify the responsible allergen. Close collaboration between academia, regulatory agencies and vaccine producers will facilitate approaches for patients at risks, such as incremental dosing of the second injection or desensitization. Finally, we identify unmet research needs and propose a concerted international roadmap towards precision diagnosis and management to minimize the risk of allergic reactions to COVID-19 vaccines and to facilitate their broader and safer use.

Published
2021

38. EAACI Biologicals Guidelines—Recommendations for severe asthma

Author

Agache, I. Akdis, C.A. Akdis, M. Canonica, G.W. Casale, T. Chivato, T. Corren, J. Chu, D.K. Del Giacco, S. Eiwegger, T. Flood, B. Firinu, D. Gern, J.E. Hamelmann, E. Hanania, N. Hernández-Martín, I. Knibb, R. Mäkelä, M. Nair, P. O’Mahony, L. Papadopoulos, N.G. Papi, A. Park, H.-S. Pérez de Llano, L. Pfaar, O. Quirce, S. Sastre, J. Shamji, M. Schwarze, J. Palomares, O. Jutel, M.

Abstract

Severe asthma imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of severe asthma, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include selection of a certain biological (as they all target overlapping disease phenotypes), the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based) and its cost-effectiveness. The EAACI Guidelines on the use of biologicals in severe asthma follow the GRADE approach in formulating recommendations for each biological and each outcome. In addition, a management algorithm for the use of biologicals in the clinic is proposed, together with future approaches and research priorities. © 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Published
2021

39. Efficacy and safety of treatment with biologicals for severe chronic rhinosinusitis with nasal polyps: A systematic review for the EAACI guidelines

Author

Agache, I, Song, Y, Alonso-Coello, P, Vogel, Y, Rocha, C, Sola, I, Santero, M, Akdis, C, Akdis, M, Canonica, GW, Chivato, T, del Giacco, S, Eiwegger, T, Fokkens, W, Georgalas, C, Gevaert, P, Hopkins, C, Klimek, L, Lund, V, Naclerio, R, O'Mahony, L, Palkonen, S, Pfaar, O, Schwarze, J, Soyka, MB, Wang, DY, Zhang, L, Canelo-Aybar, C, Palomares, O, and Jutel, M

Subjects
chronic rhinosinusitis, dupilumab, mepolizumab, omalizumab, reslizumab
Abstract

This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared with the standard of care. PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CRSwNP-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. RCTs evaluated (dupilumab-2, omalizumab-4, mepolizumab-2, and reslizumab-1) included 1236 adults, with follow-up of 20-64 weeks. Dupilumab reduces the need for surgery (NFS) or oral corticosteroid (OCS) use (RR 0.28; 95% CI 0.20-0.39, moderate certainty) and improves with high certainty smell evaluated with UPSIT score (mean difference (MD) +10.54; 95% CI +9.24 to +11.84) and quality of life (QoL) evaluated with SNOT-22 (MD -19.14; 95% CI -22.80 to -15.47), with fewer treatment-related adverse events (TAEs) (RR 0.95; 95% CI 0.89-1.02, moderate certainty). Omalizumab reduces NFS (RR 0.85; 95% CI 0.78-0.92, high certainty), decreases OCS use (RR 0.38; 95% CI 0.10-1.38, moderate certainty), and improves high certainty smell (MD +3.84; 95% CI +3.64 to +4.04) and QoL (MD -15.65; 95% CI -16.16 to -15.13), with increased TAE (RR 1.73; 95% CI 0.60-5.03, moderate certainty). There is low certainty for mepolizumab reducing NFS (RR 0.78; 95% CI 0.64-0.94) and improving QoL (MD -13.3; 95% CI -23.93 to -2.67) and smell (MD +0.7; 95% CI -0.48 to +1.88), with increased TAEs (RR 1.64; 95% CI 0.41-6.50). The evidence for reslizumab is very uncertain.

Published
2021

40. Management of anaphylaxis due to COVID-19 vaccines in the elderly

Author

Bousquet, J. Agache, I. Blain, H. Jutel, M. Ventura, M.T. Worm, M. Del Giacco, S. Benetos, A. Bilo, B.M. Czarlewski, W. Abdul Latiff, A.H. Al-Ahmad, M. Angier, E. Annesi-Maesano, I. Atanaskovic-Markovic, M. Bachert, C. Barbaud, A. Bedbrook, A. Bennoor, K.S. Berghea, E.C. Bindslev-Jensen, C. Bonini, S. Bosnic-Anticevich, S. Brockow, K. Brussino, L. Camargos, P. Canonica, G.W. Cardona, V. Carreiro-Martins, P. Carriazo, A. Casale, T. Caubet, J.-C. Cecchi, L. Cherubini, A. Christoff, G. Chu, D.K. Cruz, A.A. Dokic, D. El-Gamal, Y. Ebisawa, M. Eberlein, B. Farrell, J. Fernandez-Rivas, M. Fokkens, W.J. Fonseca, J.A. Gao, Y. Gavazzi, G. Gawlik, R. Gelincik, A. Gemicioğlu, B. Gotua, M. Guérin, O. Haahtela, T. Hoffmann-Sommergruber, K. Hoffmann, H.J. Hofmann, M. Hrubisko, M. Illario, M. Irani, C. Ispayeva, Z. Ivancevich, J.C. Julge, K. Kaidashev, I. Khaitov, M. Knol, E. Kraxner, H. Kuna, P. Kvedariene, V. Lauerma, A. Le, L.T.T. Le Moing, V. Levin, M. Louis, R. Lourenco, O. Mahler, V. Martin, F.C. Matucci, A. Milenkovic, B. Miot, S. Montella, E. Morais-Almeida, M. Mortz, C.G. Mullol, J. Namazova-Baranova, L. Neffen, H. Nekam, K. Niedoszytko, M. Odemyr, M. O’Hehir, R.E. Okamoto, Y. Ollert, M. Palomares, O. Papadopoulos, N.G. Panzner, P. Passalacqua, G. Patella, V. Petrovic, M. Pfaar, O. Pham-Thi, N. Plavec, D. Popov, T.A. Recto, M.T. Regateiro, F.S. Reynes, J. Roller-Winsberger, R.E. Rolland, Y. Romano, A. Rondon, C. Rottem, M. Rouadi, P.W. Salles, N. Samolinski, B. Santos, A.F. S Sarquis, F. Sastre, J. M. G. A. Schols, J. Scichilone, N. Sediva, A. Shamji, M.H. Sheikh, A. Skypala, I. Smolinska, S. Sokolowska, M. Sousa-Pinto, B. Sova, M. Stelmach, R. Sturm, G. Suppli Ulrik, C. Todo-Bom, A.M. Toppila-Salmi, S. Tsiligianni, I. Torres, M. Untersmayr, E. Urrutia Pereira, M. Valiulis, A. Vitte, J. Vultaggio, A. Wallace, D. Walusiak-Skorupa, J. Wang, D.-Y. Waserman, S. Yorgancioglu, A. Yusuf, O.M. Zernotti, M. Zidarn, M. Chivato, T. Akdis, C.A. Zuberbier, T. Klimek, L.

Abstract

Older adults, especially men and/or those with diabetes, hypertension, and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritized to receive COVID-19 vaccines due to high risk of death. In very rare instances, the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society) Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients. © 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Published
2021

41. Biologicals in atopic disease in pregnancy: An EAACI position paper

Author

Pfaller, B. José Yepes-Nuñez, J. Agache, I. Akdis, C.A. Alsalamah, M. Bavbek, S. Bossios, A. Boyman, O. Chaker, A. Chan, S. Chatzipetrou, A. du Toit, G. Jutel, M. Kauppi, P. Kolios, A. Li, C. Matucci, A. Marson, A. Bendien, S. Palomares, O. Rogala, B. Szepfalusi, Z. Untersmayr, E. Vultaggio, A. Eiwegger, T.

Abstract

Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scarce and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, preconception counseling and healthcare provider education are crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy. © 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Published
2021

42. Efficacy and safety of treatment with dupilumab for severe asthma : A systematic review of the EAACI guidelines-Recommendations on the use of biologicals in severe asthma

Author

Agache, I, Song, Y, Rocha, C, Beltran, J, Posso, M, Steiner, C, Alonso-Coello, P, Akdis, C, Akdis, M, Canonica, GW, Casale, T, Chivato, T, Corren, J, del Giacco, S, Eiwegger, T, Firinu, D, Gern, JE, Hamelmann, E, Hanania, N, Makela, M, Martin, IH, Nair, P, O'Mahony, L, Papadopoulos, NG, Papi, A, Park, HS, de Llano, LP, Quirce, S, Sastre, J, Shamji, M, Schwarze, J, Canelo-Aybar, C, Palomares, O, Jutel, M, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Hospital Area

Subjects
severe asthma, INFORMATION, oral corticosteroids, WILLINGNESS-TO-PAY, EURONHEED, GRADE, exacerbations, ECONOMIC EVALUATIONS, dupilumab, 3121 General medicine, internal medicine and other clinical medicine, QUALITY, FENO, BURDEN, CONSENSUS, cost-effectiveness, SURROGATES
Abstract

Dupilumab, a fully human monoclonal antibody against interleukin-4 receptor alpha, is approved as add-on maintenance treatment for inadequately controlled type 2 severe asthma. This systematic review evaluated the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled severe asthma. PubMed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. Three RCTs including 2735 subjects >12 years old and 24-52 weeks of follow-up were included. Dupilumab reduced with high certainty severe asthma exacerbations (Incidence rate ratio 0.51; 95% CI 0.45-0.59) and the percentage use of oral corticosteroid use (mean difference (MD) -28.2 mg/d; 95% CI -40.7 to -15.7). Asthma control (ACQ-5), quality of life (AQLQ) and rescue medication use [puffs/d] improved, without reaching the minimal important clinical difference: ACQ-5 MD -0.28 (95% CI -0.39 to -0.17); AQLQ MD +0.28 (95% CI 0.20-0.37); and rescue medication MD -0.35 (95% CI -0.73 to +0.02). FEV1 increased (MD +0.15; 95% CI +0.11 to +0.18) (moderate certainty). There was an increased rate of dupilumab-related adverse events (AEs) (moderate certainty) and of drug-related serious AEs (low certainty). The incremental cost-effectiveness ratio of dupilumab versus standard therapy was 464 000$/QALY (moderate certainty). More data on long-term safety are needed both for children and for adults, together with more efficacy data in the paediatric population.

Published
2020

44. Immune modulation via T regulatory cell enhancement: disease-modifying therapies for autoimmunity and their potential for chronic allergic and inflammatory diseases - An EAACI position paper of the Task Force on Immunopharmacology (TIPCO)

Author

Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Boyman, O, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E F, Kolios, Aga, Levi-Schaffer, F, Nocentini, G, Palomares, O, Redegeld, F, Van Esch, B, Stellato, C, Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Boyman, O, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E F, Kolios, Aga, Levi-Schaffer, F, Nocentini, G, Palomares, O, Redegeld, F, Van Esch, B, and Stellato, C

Abstract

Therapeutic advances using targeted biologicals and small molecule drugs have achieved significant success in the treatment of chronic allergic, autoimmune and inflammatory diseases particularly for some patients with severe, treatment-resistant forms. This has been aided by improved identification of disease phenotypes. Despite these achievements, not all severe forms of chronic inflammatory and autoimmune diseases are successfully targeted, and current treatment options, besides allergen immunotherapy for selected allergic diseases, fail to change the disease course. T cell-based therapies aim to cure diseases through the selective induction of appropriate immune responses following the delivery of engineered, specific cytotoxic or regulatory T cells (Tregs). Adoptive cell therapies (ACT) with genetically engineered T cells have revolutionized the oncology field, bringing curative treatment for leukemia and lymphoma, while therapies exploiting the suppressive functions of Tregs have been developed in non-oncological settings, such as in transplantation and autoimmune diseases. ACT with Tregs are also being considered in non-oncological settings such as cardiovascular disease, obesity and chronic inflammatory disorders. After describing the general features of T cell-based approaches and current applications in autoimmune diseases, this position paper reviews the experimental models testing or supporting T cell-based approaches, especially Treg-based approaches, in severe IgE-mediated responses and chronic respiratory airway diseases, such as severe asthma and COPD. Along with an assessment of challenges and unmet needs facing the application of ACT in these settings, this article underscores the potential of ACT to offer curative options for patients with severe or treatment-resistant forms of these immune-driven disorders.

Published
2021

45. Persistent human bocavirus 1 infection and tonsillar immune responses

Author

Ivaska, L. E. (Lotta E.), Silvoniemi, A. (Antti), Palomares, O. (Oscar), Turunen, R. (Riitta), Waris, M. (Matti), Mikola, E. (Emilia), Puhakka, T. (Tuomo), Söderlund-Venermo, M. (Maria), Akdis, M. (Mübeccel), Akdis, C. A. (Cezmi A.), Jartti, T. (Tuomas), Ivaska, L. E. (Lotta E.), Silvoniemi, A. (Antti), Palomares, O. (Oscar), Turunen, R. (Riitta), Waris, M. (Matti), Mikola, E. (Emilia), Puhakka, T. (Tuomo), Söderlund-Venermo, M. (Maria), Akdis, M. (Mübeccel), Akdis, C. A. (Cezmi A.), and Jartti, T. (Tuomas)

Abstract

Background: Persistent human bocavirus 1 (HBoV1) infection is a common finding in patients suffering from chronic tonsillar disease. However, the associations between HBoV1 infection and specific immune reactions are not completely known. We aimed to compare in vivo expression of T-cell cytokines, transcription factors, and type I/III interferons in human tonsils between HBoV1-positive and -negative tonsillectomy patients. Methods: Tonsil tissue samples, nasopharyngeal aspirate (NPA), and serum samples were obtained from 143 immunocompetent adult and child tonsillectomy patients. HBoV1 and 14 other respiratory viruses were detected in NPAs and tonsil tissues by polymerase chain reaction (PCR). Serology and semi-quantitative PCR were used for diagnosing HBoV1 infections. Expression of 14 cytokines and transcription factors (IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2, Tbet) was analyzed by quantitative reverse-transcription (RT)-PCR in tonsil tissues. Results: HBoV1 was detected by PCR in NPA and tonsils from 25 (17%) study patients. Serology results indicated prior nonacute infections in 81% of cases. Tonsillar cytokine responses were affected by HBoV1 infection. The suppression of two transcription factors, RORC2 and FOXP3, was associated with HBoV1 infection (p < 0.05). Furthermore, intratonsillar HBoV1-DNA loads correlated negatively with IFN-λ family cytokines and IL-13. Conclusions: Our study shows distinctively decreased T-helper₁₇ and T-regulatory type immune responses in local lymphoid tissue in HBoV1-positive tonsillectomy patients. HBoV1 may act as a suppressive immune modulator.

Published
2021

46. Immune modulation via T regulatory cell enhancement: disease-modifying therapies for autoimmunity and their potential for chronic allergic and inflammatory diseases - An EAACI position paper of the Task Force on Immunopharmacology (TIPCO)

Author

Afd Pharmacology, Pharmacology, Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Boyman, O, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E F, Kolios, Aga, Levi-Schaffer, F, Nocentini, G, Palomares, O, Redegeld, F, Van Esch, B, Stellato, C, Afd Pharmacology, Pharmacology, Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Boyman, O, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E F, Kolios, Aga, Levi-Schaffer, F, Nocentini, G, Palomares, O, Redegeld, F, Van Esch, B, and Stellato, C

Published
2021

47. Immune modulation via T regulatory cell enhancement: disease-modifying therapies for autoimmunity and their potential for chronic allergic and inflammatory diseases - An EAACI position paper of the Task Force on Immunopharmacology (TIPCO)

Author

CTI Research, CTI, MS Dermatologie/Allergologie, Infection & Immunity, Anatomie, Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Boyman, O, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E F, Kolios, Aga, Levi-Schaffer, F, Nocentini, G, Palomares, O, Redegeld, F, Van Esch, B, Stellato, C, CTI Research, CTI, MS Dermatologie/Allergologie, Infection & Immunity, Anatomie, Roth-Walter, F, Adcock, I M, Benito-Villalvilla, C, Bianchini, R, Bjermer, L, Boyman, O, Caramori, G, Cari, L, Chung, K F, Diamant, Z, Eguiluz-Gracia, I, Knol, E F, Kolios, Aga, Levi-Schaffer, F, Nocentini, G, Palomares, O, Redegeld, F, Van Esch, B, and Stellato, C

Published
2021

48. COVID-19 pandemic: Practical considerations on the organization of an allergy clinic - an EAACI/ARIA Position Paper

Author

CTI Research, CTI, MS Dermatologie/Allergologie, Infection & Immunity, Pfaar, O, Klimek, L, Jutel, M, Akdis, C A, Bousquet, J, Breiteneder, H, Chinthrajah, S, Diamant, Z, Eiwegger, T, Fokkens, W J, Fritsch, H W, Nadeau, K C, O'Hehir, R E, O'Mahony, L, Rief, W, Sampath, V, Schedlowski, M, Torres, M, Traidl-Hoffmann, C, Wang, D Y, Zhang, L, Bonini, M, Brehler, R, Brough, H A, Chivato, T, Del Giacco, S, Dramburg, S, Gawlik, R, Gelincik, A, Hoffmann-Sommergruber, K, Hox, V, Knol, E, Lauerma, A, Matricardi, P M, Mortz, C G, Ollert, M, Palomares, O, Riggioni, C, Schwarze, J, Skypala, I, Untersmayr, S, Walusiak-Skorupa, J, Ansotegui, I, Bachert, C, Bedbrook, A, Bosnic-Anticevich, S, Brussino, L, Canonica, G W, Cardona, V, Carreiro-Martins, P, Cruz, A A, Czarlewski, W, Fonseca, J A, Gotua, M, Haatela, T, Ivancevich, J C, Kuna, P, Kvedariene, V, Larenas-Linnemann, D, Latiff, A, Morais-Almeida, M, Mullol, J, Naclerio, R, Ohta, K, Okamoto, Y, Onorato, G L, Papadopoulos, N G, Patella, V, Regateiro, F S, Samolinski, B, Suppli Ulrik, C, Toppila-Salmi, S, Valiulis, A, Ventura, M T, Yorgancioglu, A, Zuberbier, T, Agache, I, CTI Research, CTI, MS Dermatologie/Allergologie, Infection & Immunity, Pfaar, O, Klimek, L, Jutel, M, Akdis, C A, Bousquet, J, Breiteneder, H, Chinthrajah, S, Diamant, Z, Eiwegger, T, Fokkens, W J, Fritsch, H W, Nadeau, K C, O'Hehir, R E, O'Mahony, L, Rief, W, Sampath, V, Schedlowski, M, Torres, M, Traidl-Hoffmann, C, Wang, D Y, Zhang, L, Bonini, M, Brehler, R, Brough, H A, Chivato, T, Del Giacco, S, Dramburg, S, Gawlik, R, Gelincik, A, Hoffmann-Sommergruber, K, Hox, V, Knol, E, Lauerma, A, Matricardi, P M, Mortz, C G, Ollert, M, Palomares, O, Riggioni, C, Schwarze, J, Skypala, I, Untersmayr, S, Walusiak-Skorupa, J, Ansotegui, I, Bachert, C, Bedbrook, A, Bosnic-Anticevich, S, Brussino, L, Canonica, G W, Cardona, V, Carreiro-Martins, P, Cruz, A A, Czarlewski, W, Fonseca, J A, Gotua, M, Haatela, T, Ivancevich, J C, Kuna, P, Kvedariene, V, Larenas-Linnemann, D, Latiff, A, Morais-Almeida, M, Mullol, J, Naclerio, R, Ohta, K, Okamoto, Y, Onorato, G L, Papadopoulos, N G, Patella, V, Regateiro, F S, Samolinski, B, Suppli Ulrik, C, Toppila-Salmi, S, Valiulis, A, Ventura, M T, Yorgancioglu, A, Zuberbier, T, and Agache, I

Published
2021

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