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T2-high asthma phenotypes across lifespan.


ABSTRACT:

Rationale

In adults, personalised asthma treatment targets patients with type 2 (T2)-high and eosinophilic asthma phenotypes. It is unclear whether such classification is achievable in children.

Objectives

To define T2-high asthma with easily accessible biomarkers and compare resulting phenotypes across all ages.

Methods

In the multicentre clinical All Age Asthma Cohort (ALLIANCE), 1125 participants (n=776 asthmatics, n=349 controls) were recruited and followed for 2 years (1 year in adults). Extensive clinical characterisation (questionnaires, blood differential count, allergy testing, lung function and sputum induction (in adults)) was performed at baseline and follow-ups. Interleukin (IL)-4, IL-5 and IL-13 were measured after stimulation of whole blood with lipopolysaccharide (LPS) or anti-CD3/CD28.

Measurements and main results

Based on blood eosinophil counts and allergen-specific serum IgE antibodies, patients were categorised into four mutually exclusive phenotypes: "atopy-only", "eosinophils-only", "T2-high" (eosinophilia + atopy) and "T2-low" (neither eosinophilia nor atopy). The T2-high phenotype was found across all ages, even in very young children in whom it persisted to a large degree even after 2 years of follow-up. T2-high asthma in adults was associated with childhood onset, suggesting early origins of this asthma phenotype. In both children and adults, the T2-high phenotype was characterised by excessive production of specific IgE to allergens (p<0.0001) and, from school age onwards, by increased production of IL-5 after anti-CD3/CD28 stimulation of whole blood.

Conclusions

Using easily accessible biomarkers, patients with T2-high asthma can be identified across all ages delineating a distinct phenotype. These patients may benefit from therapy with biologicals even at a younger age.

SUBMITTER: Maison N 

PROVIDER: S-EPMC9520028 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

T2-high asthma phenotypes across lifespan.

Maison Nicole N   Omony Jimmy J   Illi Sabina S   Thiele Dominik D   Skevaki Chrysanthi C   Dittrich Anna-Maria AM   Bahmer Thomas T   Rabe Klaus Friedrich KF   Weckmann Markus M   Happle Christine C   Schaub Bianca B   Meyer Meike M   Foth Svenja S   Rietschel Ernst E   Renz Harald H   Hansen Gesine G   Kopp Matthias Volkmar MV   von Mutius Erika E   Grychtol Ruth R   Fuchs Oliver O   Roesler Barbara B   Welchering Nils N   Kohistani-Greif Naschla N   Kurz Johanna J   Landgraf-Rauf Katja K   Laubhahn Kristina K   Liebl Claudia C   Ege Markus M   Hose Alexander A   Zeitlmann Esther E   Berbig Mira M   Marzi Carola C   Schauberger Christina C   Zissler Ulrich U   Schmidt-Weber Carsten C   Ricklefs Isabell I   Diekmann Gesa G   Liboschik Lena L   Voigt Gesche G   Sultansei Laila L   Nissen Gyde G   König Inke R IR   Kirsten Anne-Marie AM   Pedersen Frauke F   Watz Henrik H   Waschki Benjamin B   Herzmann Christian C   Abdo Mustafa M   Biller Heike H   Gaede Karoline I KI   Bovermann Xenia X   Steinmetz Alena A   Husstedt Berrit Liselotte BL   Nitsche Catharina C   Veith Vera V   Szewczyk Marlen M   Brinkmann Folke F   Malik Aydin A   Schwerk Nicolaus N   Dopfer Christian C   Price Mareike M   Jirmo Adan Chari AC   Habener Anika A   DeLuca David S DS   Gaedcke Svenja S   Liu Bin B   Calveron Mifflin-Rae MR   Weber Stefanie S   Schildberg Tom T   van Koningsbruggen-Rietschel Silke S   Alcazar Miguel M  

The European respiratory journal 20220929 3


<h4>Rationale</h4>In adults, personalised asthma treatment targets patients with type 2 (T2)-high and eosinophilic asthma phenotypes. It is unclear whether such classification is achievable in children.<h4>Objectives</h4>To define T2-high asthma with easily accessible biomarkers and compare resulting phenotypes across all ages.<h4>Methods</h4>In the multicentre clinical All Age Asthma Cohort (ALLIANCE), 1125 participants (n=776 asthmatics, n=349 controls) were recruited and followed for 2 years  ...[more]

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