Burden of Uncontrolled Severe Asthma With and Without Elevated Type-2 Inflammatory Biomarkers

BACKGROUND:Many patients with asthma have Type-2 airway inflammation, identified by the presence of biomarkers, including history of allergy, high blood eosinophil (EOS) count, and high fractional exhaled nitric oxide (FeNO) levels. OBJECTIVE:To assess disease burden in relation to Type-2 inflammatory biomarker status (history of allergy, blood EOS count, and FeNO level) in patients with uncontrolled and controlled severe asthma in the NOVEL observational longiTudinal studY (NOVELTY) (NCT02760329). METHODS:Asthma diagnosis and severity were physician-reported. Control was defined using Asthma Control Test (ACT) score (uncontrolled <20, controlled ≥20) and/or ≥1 severe physician-reported exacerbation in the previous year. Biomarker distribution (history of allergy, blood EOS count, and FeNO level), symptom burden (ACT score, modified Medical Research Council [mMRC] dyspnea scale), health status (St George's Respiratory Questionnaire [SGRQ]), exacerbations, and healthcare resource utilization were assessed. RESULTS:Of 647 patients with severe asthma, 446 had uncontrolled and 123 had controlled asthma. Among uncontrolled asthma: 196 (44%) had ≥2 positive biomarkers; 187 (42%) had one positive biomarker; 325 (73%) had low blood EOS; and 63 (14%) were triple-negative. Disease burden was similarly high across uncontrolled subgroups, irrespective of biomarker status, with poor symptom control (ACT score 14.9-16.6), impaired health status (SGRQ total score 46.7-49.4), clinically important breathlessness (mMRC grade ≥2 in 47.3-57.1%), and ≥1 severe exacerbation (70.6-76.2%). CONCLUSION:Type-2 inflammatory biomarkers did not differentiate disease burden in patients with severe asthma. Patients with low Type-2 inflammatory biomarker levels have few biologic therapy options; their needs should be addressed.