Risks for asthma exacerbations in patients with type 2-low endotype

Background: Previously we showed that air-flow limitation, GG genotype of IL4RA rs8832, and A allele of ADAM33 T_2 rs2280090 were independent risks of adult asthma patients with both exacerbations and type 2-high endotype (Sunadome, et al. ATS2016). Meanwhile, little is known about risks of asthma exacerbations in type 2-low patients. Aims: To determine clinical and genetic risks that may contribute to exacerbations in asthma patients with type 2-low endotype. Methods: This is a follow-up study of asthmatics on inhaled corticosteroids treatment who were enrolled in the Kinki Hokuriku Airway disease Conference multicenter study. Associations between asthma exacerbations requiring systemic corticosteroids during the 2 years of follow-up and clinical and genetic factors were examined in patients with type 2-low endotype. Type 2-low endotype was defined as serum periostin of ORMDL3 rs7216389, IL4RA rs8832 and CDHR3 rs6967330 were assessed. Results: Among 134 type 2-low patients (106 females, average age 61.6 years), 33 had one or more exacerbations during subsequent 2 years. Multivariate analysis showed that female [Odds ratio (95% confidence interval); 7.9 (1.6-66.7), p = 0.02], body mass index [1.2 (1.1-1.5), p = 0.008], recent exacerbations [10.5 (2.5-56.0), p = 0.003], ORMDL3 rs7216389 TT genotype [3.5 (1.2-11.5), p = 0.03] and IL4RA rs8832 GG genotype [0.03 (0.001-0.024), p = 0.007] were associated with exacerbations in patients with type 2-low endotype. CDHR3 rs6967330 was unrelated to exacerbations in type 2-low patients. Conclusions: Clinical and genetic risks of asthma exacerbations may be different between type 2-high and type 2-low patients.