T2-high asthma phenotypes across lifespan

Abstract

RationaleIn adults, personalised asthma treatment targets patients with T2-high and eosinophilic asthma phenotypes. It is unclear whether such classification is achievable in children.ObjectivesTo define T2-high asthma with easily accessible biomarkers and compare resulting phenotypes across all ages.MethodsIn the multicenter 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 LPS or anti-CD3/CD28.Measurements and Main ResultsBased on blood eosinophil counts and allergen-specific serum IgE antibodies (sIgE), 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.ConclusionsUsing 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 younger age.

Long noncoding RNA antisense noncoding RNA in the INK4 locus inhibition alleviates airway remodeling in asthma through the regulation of the microRNA‐7‐5p/early growth response factor 3 axis

“…Using readily available biomarkers, people with T2 high asthma can be identified at all ages, and different phenotypes can be depicted. 42 The level of C4Ma3 is elevated in the phenotype of severe and aggravating allergic asthma, and C4Ma3 can be used as a new biomarker to predict the response to anti IgE treatment. 43 IgA positive memory B cells are significantly increased in patients with asthma and small airway dysfunction, which indicates the direction for future selection of asthma prevention and treatment strategies guided by B cells.…”

“…It is unclear whether this classification is feasible for children. Using readily available biomarkers, people with T2 high asthma can be identified at all ages, and different phenotypes can be depicted 42 . The level of C4Ma3 is elevated in the phenotype of severe and aggravating allergic asthma, and C4Ma3 can be used as a new biomarker to predict the response to anti IgE treatment 43 .…”

Decoding the genetic and epigenetic basis of asthma

“…2,4 More recently, the field has adopted a distinction based on the presence ("T2-high") or absence ("T2-low") of substantial type-2 inflammation in the airways. 3,16 T2high asthma mainly involves allergic disease types and affects most children with asthma as well as approximately 50% of adult patients.…”

“…However, this classification turned out to be an oversimplification, 15 as extensive inflammatory and clinical heterogeneity exists among asthma patients that is not captured by the allergic/non‐allergic dichotomy 2,4 . More recently, the field has adopted a distinction based on the presence (“T2‐high”) or absence (“T2‐low”) of substantial type‐2 inflammation in the airways 3,16 . T2‐high asthma mainly involves allergic disease types and affects most children with asthma as well as approximately 50% of adult patients.…”

Exposure to violence and asthma in Puerto Rican youth with high Th2 immunity

“…5,6 In industrialized countries, children are more likely to have high Th2 immunity -and thus T2-high asthma-than adults. 6,7 During childhood, high Th2 immunity is often defined by sensitization to allergens (atopy), a high total IgE, and peripheral blood eosinophilia.…”