T2-high asthma phenotypes across lifespan
Authors: Maison Nicole , Omony Jimmy , Illi Sabina , Thiele Dominik , Skevaki Chrysanthi , Dittrich Anna-Maria , Bahmer Thomas , Rabe Klaus Friedrich , Weckmann Markus , Happle Christine , Schaub Bianca , Meyer Meike , Foth Svenja , Rietschel Ernst , Renz Harald , Hansen Gesine , Kopp Matthias Volkmar , von Mutius Erika , Grychtol Ruth ,   the ALLIANCE Study Group,   the ALLIANCE Study Group, Fuchs Oliver , Roesler Barbara , Welchering Nils , Kohistani-Greif Naschla , Kurz Johanna , Landgraf-Rauf Katja , Laubhahn Kristina , Liebl Claudia , Ege Markus , Hose Alexander , Zeitlmann Esther , Berbig Mira , Marzi Carola , Schauberger Christina , Zissler Ulrich , Schmidt-Weber Carsten , Ricklefs Isabell , Diekmann Gesa , Liboschik Lena , Voigt Gesche , Sultansei Laila , Nissen Gyde , König Inke R. , Kirsten Anne-Marie , Pedersen Frauke , Watz Henrik , Waschki Benjamin , Herzmann Christian , Abdo Mustafa , Biller Heike , Gaede Karoline I. , Bovermann Xenia , Steinmetz Alena , Husstedt Berrit Liselotte , Nitsche Catharina , Veith Vera , Szewczyk Marlen , Brinkmann Folke , Malik Aydin , Schwerk Nicolaus , Dopfer Christian , Price Mareike , Jirmo Adan Chari , Habener Anika , DeLuca David S. , Gaedcke Svenja , Liu Bin , Calveron Mifflin-Rae , Weber Stefanie , Schildberg Tom , van Koningsbruggen-Rietschel Silke , Alcazar Miguel 
Published: February 2022

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.