Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma

Breiteneder, Heimo; Peng, Yaqi; Agache, Ioana; Diamant, Zuzana; Eiwegger, Thomas; Fokkens, Wytske J.; Traidl‐Hoffmann, Claudia; Nadeau, Kari; O’Hehir, Robyn E; O’Mahony, Liam; Pfaar, Oliver; Torres, Marı́a José; Wang, De Yun; Zhang, Luo; Akdiş, Cezmi A.

doi:10.1111/all.14582

Cited by 161 publications

(172 citation statements)

References 362 publications

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“…T2-high asthmatic patients had higher sputum eosinophil counts, which is the canonical marker of T2-high asthma [5,9,12,16], as well as blood eosinophil, which is in line with our findings. This indicates that eosinophilic and T2-mediated airway inflammation represents one of the most important traits in asthma, and in addition to Th2 cells, innate ILC-2 cells have been found in the airways of asthmatic patients [13,[16][17][18].…”

Section: Discussionsupporting

confidence: 92%

“…Several cells and mediators have been linked to T2-low asthma, including the activation of Th1 and Th17, neutrophil infiltration, and cytokines IL-8, IL-17, IL-21, and IL-22. However, no clinically applicable biomarkers and/or targeted treatment are currently available in T2-low asthma [9,13,17]. This high heterogeneity was also noted in our T2-low asthmatics.…”

Section: Discussionmentioning

confidence: 73%

“…Although we have shown that molecular profiling in induced sputum can be translated to clinical practice, the technique is complex and could only be performed in specialized and expert centers for specific cases in which other broadly used methods failed to classify patients as having T2-high or T2-low asthma. Currently, clinically applicable biomarkers, such as serum specific IgE, FeNO, and blood and sputum eosinophil counts, can to some extent help with the decision-making in selecting the most appropriate treatment options, including biologics [9,13,17]. However, these biomarkers are not specific enough to identify different asthma endotypes of individual patients, which is crucial to select the most suitable targeting treatment of the underlying inflammatory mechanism [9,13,17].…”

Section: Discussionmentioning

confidence: 99%

“…Currently, clinically applicable biomarkers, such as serum specific IgE, FeNO, and blood and sputum eosinophil counts, can to some extent help with the decision-making in selecting the most appropriate treatment options, including biologics [9,13,17]. However, these biomarkers are not specific enough to identify different asthma endotypes of individual patients, which is crucial to select the most suitable targeting treatment of the underlying inflammatory mechanism [9,13,17]. Therefore, the identification of novel and more specific biomarkers for asthma endotyping is the subject of intense research [13].…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, several biomarkers of clinical response for asthma endotypes have been proposed. Gene expression profiling in induced sputum cells has been shown as a robust method for classification of asthma into different endotypes, especially T2-high/T2-low, each having specific inflammatory, remodeling, and treatment response characteristics [4][5][6][7][8][9][10]. T2 asthma is characterized by airway inflammation driven by T2 cytokines including interleukins IL-4, IL-5, and IL-13 [5].…”

Section: Introductionmentioning

confidence: 99%

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T2-high Asthma, Classified by Sputum mRNA Expression of IL4, IL5, and IL13, is Characterized by Eosinophilia and Severe Phenotype

Rijavec

Krumpestar

Škrgat

et al. 2021

Life

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Asthma is a common chronic disease, with different underlying inflammatory mechanisms. Identification of asthma endotypes, which reflect a variable response to different treatments, is important for more precise asthma management. T2 asthma is characterized by airway inflammation driven by T2 cytokines including interleukins IL-4, IL-5, and IL-13. This study aimed to determine whether induced sputum samples can be used for gene expression profiling of T2-high asthma classified by IL4, IL5, and IL13 expression. Induced sputum samples were obtained from 44 subjects, among them 36 asthmatic patients and eight controls, and mRNA expression levels of IL4, IL5, and IL13 were quantified by RT-qPCR. Overall, gene expression levels of IL4, IL5, and IL13 were significantly increased in asthmatic patients’ samples compared to controls and there was a high positive correlation between expressions of all three genes. T2 gene mean was calculated by combining the expression levels of all three genes (IL4, IL5, and IL13) and according to T2 gene mean expression in controls, we set a T2-high/T2-low cutoff value. Twenty-four (67%) asthmatic patients had T2-high endotype and those patients had significantly higher eosinophil blood and sputum counts. Furthermore, T2-high endotype was characterized as a more severe, difficult-to-treat asthma, and often uncontrolled despite the use of inhaled and/or oral corticosteroids. Therefore, the majority of those patients (15 [63%] of 24) needed adjunct biological therapy to control their asthma symptoms/exacerbations. In conclusion, we found that interleukins IL4, IL5, and IL13 transcripts could be effectively detected in sputum from asthmatic patients. Implementation of T2 gene mean can be used as sputum molecular biomarker to categorize patients into T2-high endotype, characterized by eosinophilia and severe, difficult-to-treat asthma, and often with a need for biological treatment.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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T2-high Asthma, Classified by Sputum mRNA Expression of IL4, IL5, and IL13, is Characterized by Eosinophilia and Severe Phenotype

Rijavec

Krumpestar

Škrgat

et al. 2021

Life

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Barrier‐forming, drug‐free nasal spray reduces allergic symptoms induced by house dust mite allergen

Couroux

Grosse²,

Salapatek

et al. 2023

Clinical & Translational All

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Background House Dust Mite (HDM) is the most common indoor allergen triggering allergic symptoms. First‐line pharmacotherapy treatment is recommended in international guidelines, while the avoidance of allergens represents a still unmet guideline principle. AM‐301 is a new non‐pharmacological nasal spray that creates a protective gel‐like barrier on the nasal mucosa, preventing the contact with the allergens. Methods This randomized, open‐label, 3‐period crossover study assessed the efficacy and safety of AM‐301. The objective was to determine whether AM‐301 reduces allergic rhinitis (AR) symptoms in patients exposed to HDM allergens. Adults with confirmed Perennial Allergic Rhinitis (PAR; n = 37) were exposed to HDM allergen in a controlled Allergen Exposure Chamber before and during a treatment course of AM‐301 (in six different sequences) within 3 weeks (A: One spray AM‐301 per nostril/B: Two sprays AM‐301 per nostril/C: no treatment). For the primary efficacy analysis, data from the total nasal symptom score (TNSS) were pooled from treatment A + B (D) and analyzed with Analysis of Covariance Model. As secondary endpoints, single time points, visits and symptoms were analyzed. Results The primary endpoint (overall change in TNSS from baseline over all three visits) showed significant results (p = 0.0085). A comparable alleviation of all four symptoms (itchy nose, nasal congestion, runny nose, sneezing) by the protective layer started to emerge after 40 min and lasted up to 180 min (end of challenge). AM‐301 resulted to be safe and well‐tolerated. Conclusion AM‐301 significantly reduced HDM‐related allergic symptoms in a standardized allergen challenge. Protection was observed to last up to 180 min.

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Different Phenotypes in Asthma: Clinical Findings and Experimental Animal Models

Lourenço

Ribeiro

Lopes

et al. 2021

Clinic Rev Allerg Immunol

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Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 161 publications

References 362 publications

T2-high Asthma, Classified by Sputum mRNA Expression of IL4, IL5, and IL13, is Characterized by Eosinophilia and Severe Phenotype

T2-high Asthma, Classified by Sputum mRNA Expression of IL4, IL5, and IL13, is Characterized by Eosinophilia and Severe Phenotype

Barrier‐forming, drug‐free nasal spray reduces allergic symptoms induced by house dust mite allergen

Different Phenotypes in Asthma: Clinical Findings and Experimental Animal Models

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