Background: Obesity exacerbates a number of chronic inflammatory diseases including asthma, with increasing adiposity observed to worsen asthma severity and disease control. This exacerbation may arise as gut-derived bacterial fragments (endotoxin) and associated markers of endotoxin (lipopolysaccharide binding protein (LPB)), enter the circulation through a damaged gut barrier, provoking systemic inflammation. This study investigated the role of body weight on gut permeability and systemic inflammation, to influence asthma control and asthma status.
Methods: Fasted blood was collected from Caucasian men (age:52.72±16.08yrs; BMI: 29.16±5.69 Kg/m2; n=29) and women (age: 46.42±14.60yrs; BMI: 32.34±7.48 Kg/m2; n=69) with severe asthma, with and without obesity. Gut permeability marker Calprotectin, LBP and inflammatory markers (granzyme-A, IL-5, IL-6, CCL-4) were assessed in serum and plasma by ELISA. Anthropometric data and Asthma Control Questionnaire-6 (ACQ-6) data were collected.
Results: Our findings highlighted that BMI significantly correlated with self-reported impaired asthma control (ACQ-6score≥1.5;P<0.05). Significant positive correlations were identified between BMI and pro-inflammatory biomarkers (granzyme A,P<0.001;IL-6, CCL-4, IL-5, all P<0.0001). In addition, analysis of circulating LBP showed that patients with poorly controlled asthma (ACQ-6 score≥1.5) had increased LBP levels compared with well controlled patients with asthma (LBP:15.10±7.88µg/mL Vs 10.95±4.5 µg/mL; P=0.0279). Furthermore, irrespective of asthma control, LBP was increased in patients with obesity (LBP:17.06±8.35µg/mL) compared with patients who were overweight (LPB:11.83±6.6µg/mL; P=0.0003) or lean (LBP:11.36±4.27µg/mL; P=0.0004). LBP levels were also significantly positively correlated with BMI (P<0.0001), permeability marker (P<0.0001) and inflammatory biomarkers (P<0.05).
Conclusion: In summary, patients with asthma and obesity were observed to experience impaired asthma control, with increased gut permeability and raised inflammatory mediators and markers. These data therefore suggest that reducing body weight, or therapeutically targeting the gut to reduce gut permeability, may offer people with obesity and severe asthma some improvement in their chronic inflammation conditions and disease management
14 Nov 2022 - 16 Nov 2022