Obese asthma phenotypes display distinct plasma biomarker profiles

Abstract

Background Obese asthma is a complex phenotype and further characterization of the pathophysiology is needed. This study aimed to explore inflammation‐related plasma biomarkers in lean and overweight/obese asthmatics. Methods We elucidated levels of inflammation‐related plasma proteins in obese asthma phenotypes in the population‐based cohort BAMSE (Swedish: Children, Allergy, Milieu, Stockholm, Epidemiology) using data from 2069 24‐26‐year‐olds. Subjects were divided into lean asthma (n = 166), lean controls (n = 1440), overweight/obese asthma (n = 73) and overweight/obese controls (n = 390). Protein levels (n = 92) were analysed using the Olink Proseek Multiplex Inflammation panel. Results Of the 92 included proteins, 41 were associated with lean and/or overweight/obese asthma. The majority of proteins associated with overweight/obese asthma also associated with overweight/obesity among non‐asthmatics. Beta‐nerve growth factor (BetaNGF), interleukin 10 (IL‐10), and matrix metalloproteinase 10 (MMP10) were associated only with lean asthma while C‐C motif chemokine 20 (CCL20), fibroblast growth factor 19 (FGF19), interleukin 5 (IL‐5), leukemia inhibitory factor (LIF), tumor necrosis factor ligand superfamily member 9 (TNFRSF9), and urokinase‐type plasminogen activator (uPA) were associated only with overweight/obese asthma. Overweight/obesity modified the association between asthma and 3 of the proteins: fibroblast growth factor 21 (FGF21), interleukin 4 (IL‐4), and urokinase‐type plasminogen activator (uPA). In the overweight/obese group, interleukin‐6 (IL‐6) was associated with non‐allergic asthma but not allergic asthma. Conclusion These data indicate distinct plasma protein phenotypes in lean and overweight/obese asthmatics which, in turn, can impact upon therapeutic approaches.

Impact of obesity on airway remodeling in asthma: pathophysiological insights and clinical implications

“…Distinct plasma biomarkers were identified in asthma subjects with lean body mass compared to individuals with overweight/obesity, including β-nerve growth factor (β-NGF), interleukin 10 (IL-10), and matrix metalloproteinase 10 (MMP10), which were exclusively associated with asthma subjects with lean body mass. On the other hand, C-C motif chemokine ligand 20 (CCL20), fibroblast growth factor 19 (FGF19), IL-5, leukemia inhibitory factor (LIF), tumor necrosis factor ligand superfamily member 9 (TNFRSF9), and urokinase-type plasminogen activator (uPA) were associated only with individuals with overweight/obesity ( 43 ), but these were not found to be associated with airway remodeling. Several studies have proposed such as galectin-3 ( 44 , 45 ), chitinase-like protein YKL-40 ( 46 , 47 ), periostin ( 48 ), and sestrin-2 ( 49 , 50 ) as potential predictors of airway remodeling.…”

Genomics of Treatable Traits in Asthma

“…Further innate inflammatory pathways involving ILC-3s expressing IL-17 and IL-22 have been also described in obesity-associated asthma [ 59 ]. The proinflammatory cytokine IL-6, produced in adipocytes and adipose tissue macrophages, has been associated with obese T2-low asthma but not with obese atopic asthma [ 59 , 60 ]. Moreover, a reduction in arginine and nitric oxide (NO) bioavailability has been related to the increased oxidative stress occurring both in obesity and obese adults with the late-onset asthma phenotype [ 61 ].…”

“…In addition, the levels of specific cytokines have been positively related to body-mass index (BMI) [58]. Further innate inflammatory pathways involving ILC-3s expressing IL-17 and IL-22 have been also described in obesity-associated asthma [59]. The proinflammatory cytokine IL-6, produced in adipocytes and adipose tissue macrophages, has been associated with obese T2-low asthma but not with obese atopic asthma [59,60].…”

The Role of Leukemia Inhibitory Factor in Counteracting the Immunopathology of Acute and Chronic Lung Inflammatory Diseases

“…Serum LIF levels are higher in subjects with mild asthma than in normal subjects [90]. Higher levels of LIF are observed in obese asthmatics compared to lean asthmatic subjects [91]. A genetic study in Germany identified that the LIFR gene along with three other genes was associated with asthma symptoms [92].…”