The search for reliable biomarkers of type 2 (T2) inflammation across asthma, chronic obstructive pulmonary disease (COPD) and asthma–COPD overlap (ACO) has been a defining theme of respiratory research over the past decade. Blood eosinophils and fractional exhaled nitric oxide (FeNO) have emerged as clinically accessible markers with clear biological basics and demonstrated prognostic and therapeutic relevance, particularly in asthma and selected COPD populations.1 2 Yet, as biomarker research expands into large, heterogeneous cohorts, interpretation has become increasingly challenging.

In their Thorax paper, Muiser et al3 explore the associations of blood eosinophils and FeNO with exacerbation outcomes across asthma, COPD and asthma+COPD in the NOVELTY (NOVEL observational longiTudinal studY on patients with asthma and/or COPD) cohort. While the scale and international scope of NOVELTY are undeniable strengths, several of the reported findings—most notably the inverse association between FeNO and exacerbation risk in COPD—raise important conceptual and…