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

Charmaine J M Lim; Christoph Gross; Marie-Kathrin Breyer; Robab Breyer-Kohansal; Emiel F M Wouters; Sylvia Hartl

doi:10.3390/jcm13226662

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

J Clin Med. 2024 Nov 6;13(22):6662. doi: 10.3390/jcm13226662.

Authors

Charmaine J M Lim^{1

2}, Christoph Gross^{1

2}, Marie-Kathrin Breyer^{1

3}, Robab Breyer-Kohansal^{1

4}, Emiel F M Wouters^{1

2

5}, Sylvia Hartl^{1

2}

Affiliations

¹ Ludwig Boltzmann Institute for Lung Health, 1140 Vienna, Austria.
² Faculty of Medicine, Sigmund Freud Private University, 1020 Vienna, Austria.
³ Department of Respiratory and Pulmonary Diseases, Clinic Penzing, Vienna Healthcare Group, 1140 Vienna, Austria.
⁴ Department of Respiratory and Pulmonary Diseases, Clinic Hietzing, Vienna Healthcare Group, 1130 Vienna, Austria.
⁵ Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands.

Abstract

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.

Keywords: COPD introduction; blood eosinophil counts; extrapulmonary; fractional exhaled nitric oxide; pulmonary function.

Grants and funding

The Austrian LEAD study is supported by the Ludwig Boltzmann Gesellschaft, the Municipal Departments of Health and Environment of Vienna, the Federal State Governmental Department of Health of Lower Austria and unrestricted scientific grants from Astra Zeneca, Chiesi Farmaceutici, GlaxoSmithKline, and Menarini Pharma. None of the supporting parties participated in the data collection or interpretation, nor did they contribute to the design or content of the manuscript.