Early Detection of Asthma: Exploring Inflammatory Biomarkers in Symptomatic Adults with Normal Spirometry

We previously showed that individuals without a prior history of asthma, presenting with unexplained respiratory symptoms and normal spirometry, may exhibit airway hyperresponsiveness and underlying eosinophilic (T2) inflammation, features suggestive of undiagnosed early-stage asthma. Improving our understanding of the inflammatory processes that contribute to asthma onset is essential, as it may ultimately lead to earlier detection, timely intervention and improved long-term outcomes.

This study aimed to evaluate several key inflammatory biomarkers in this well-characterized population and examine their associations with clinical presentation to identify early signs of asthma.

This retrospective, observational cohort sub-study included Canadian adults with respiratory symptoms and normal pre- and post-bronchodilator spirometry. Demographics and clinical data were extracted from study files. Plasma and serum levels of biomarkers associated with T2 airway inflammation and epithelial shedding, including IL-4, IL-5, IL-13, IL-25, IL-33, eotaxin, eotaxin-3, TARC, periostin and TNF-α, were measured using ELISA and multiplex electrochemiluminescent assays. Airway hyperresponsiveness was defined as a PC₂₀ <16 mg/mL, and T2 airway inflammation as sputum eosinophils >2% and/or FeNO >25 ppb.

Among 128 adults (mean age ±SD: 58.0 ±13.9 years, 52% women), 45 (35%) had T2 airway inflammation. Most biomarker levels were low or undetectable, with substantial inter-individual variability. No significant differences in biomarker levels were observed between individuals with and without airway hyperresponsiveness or T2 airway inflammation. Eotaxin levels negatively correlated with post-bronchodilator FEV₁/FVC ratio (r=-0.18, P=0.0433), and eotaxin-3 positively correlated with FeNO (r=0.18, P=0.0482).

This panel of clinically accessible T2 biomarkers may not reliably reflect early pathophysiological signs of asthma in symptomatic adults with normal spirometry. Longitudinal follow-up of this cohort, along with the integration of airway sampling, may provide further insight into the role of these biomarkers in asthma development and progression.