Type-2 Inflammation in Health and Disease: Prevalence, Risk Factors and Multimorbidity

Background: In patients with airflow obstruction, the levels of biomarkers of Type-2 (T2) inflammation serve to predict the effectiveness of inhaled corticosteroid and biological therapies. Elevated biomarkers of T2 inflammation, including fractional exhaled nitric oxide (FeNO, ≥20 ppb) and blood eosinophil counts (BEC, ≥300 cells/µL), were investigated in a population-based cohort of the Austrian LEAD study. Methods: A total of 4976 individuals (aged 18-82 years) were categorised into four groups based on their FeNO and BEC levels: normal with FeNO < 20 ppb and BEC < 300 cells/µL (n = 2634); FeNO ≥ 20 ppb only (n = 1623); BEC ≥ 300 cells/µL only (n = 340); and FeNO ≥ 20 ppb and BEC ≥ 300 cells/µL (n = 379). Results: In age- and sex-adjusted regression models, individuals with elevated BEC only were most associated with chronic cough and sputum production (odds ratios [95% CI]: 1.22 [0.78, 1.84] and 1.37 [1.13, 2.62], respectively), whilst individuals with both elevated T2 biomarkers were most associated with wheezing, dyspnoea and asthma (odds ratios [95% CI]: 2.27 [1.56, 3.26], 1.32 [0.64, 2.50] and 3.63 [2.69, 4.88] respectively). Elevated levels of both FeNO and BEC presented an additive effect in extrapulmonary conditions, particularly in allergy, eczema and rhino conjunctivitis (odds ratios [95% CI]: 2.30 [1.84, 2.88], 1.37 [1.03, 1.81] and 2.95 [2.34, 3.70], respectively). Conclusions: T2 inflammation marked by elevated levels of FeNO and/or BEC is not only associated with respiratory conditions but also extends to extrapulmonary characteristics, with an additive effect.