Biomarkers to Predict Response to Inhaled Corticosteroids and Long-Acting Muscarinic Antagonists in Adolescents and Adults with Mild Persistent Asthma

Jerry A. Krishnan, Stephen C. Lazarus, Kathryn V. Blake, Christine A. Sorkness, Ronina Covar, Anne Marie Dyer, Jason E. Lang, Njira L. Lugogo, David T. Mauger, Michael E. Wechsler, Sally E. Wenzel, Juan Carlos Cardet, Mario Castro, Elliot Israel, Wanda Phipatanakul, Tonya S. King

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Rationale: Whether biomarkers can be used to predict response to inhaled corticosteroids (ICS) or long-acting muscarinic antagonists (LAMA) in mild persistent asthma is unclear. Objectives: In a prespecified exploratory analysis of a randomized clinical trial of 295 participants 12 years of age or older with uncontrolled mild persistent asthma, we sought to identify biomarkers of treatment response after 12 weeks of ICS (mometasone, 200 μg or 220 μg twice/d), LAMA (tiotropium, 5 μg/d), or placebo in adults (>18 yr) and adolescents (12-17 yr) separately. Methods: The primary outcome was a composite outcome of asthma control (treatment failure, asthma control days, and forced expiratory volume in 1 second [FEV1]). Analyses examined type 2 inflammatory biomarkers and physiologic biomarkers. We assessed the area under the receiver operating characteristic curve (AUC) for response to ICS and LAMA (each versus placebo). An AUC of 0.5 suggests no discrimination, 0.7-0.8 is considered acceptable, more than 0.8-0.9 is considered excellent, and more than 0.9 is considered outstanding. Results: In 237 adults, sputum and blood eosinophil levels and fractional exhaled nitric oxide (FENO) each predicted ICS response (AUCs: 0.61 [95% confidence interval (CI), 0.53-0.69], 0.64 [95% CI, 0.56-0.72], and 0.62 [95% CI, 0.54-0.70], respectively; all P,0.01); the AUC for blood eosinophil levels and FENO together was 0.66 (95% CI, 0.58-0.74; P,0.001). In 58 adolescents, the number of positive aeroallergens and total serum immunoglobulin E each predicted ICS response (AUCs: 0.69 [95% CI, 0.52-0.85] and 0.73 [95% CI, 0.58-0.87], respectively; both P,0.03); the AUC for both together was 0.73 (95% CI, 0.58-0.87; P = 0.003). After ipratropium bromide, FEV1 reversibility predicted LAMA response in adults (AUC: 0.61 [95% CI, 0.53-0.69], P = 0.007) but not in adolescents. Conclusions: The AUCs of the type 2 inflammatory biomarkers and physiological biomarkers we examined may not be high enough to confidently identify individuals with asthma who respond to ICS and LAMA. However, our findings indicate that the biomarkers that predict response to ICS or LAMA may differ in adults versus adolescents with uncontrolled mild persistent asthma. Prospective, biomarker-stratified clinical trials are needed to confirm these findings and to identify first-line controllers tailored for each population.

Original languageEnglish (US)
Pages (from-to)372-380
Number of pages9
JournalAnnals of the American Thoracic Society
Volume19
Issue number3
DOIs
StatePublished - Mar 2022

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine

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