Adults with obesity and asthma have a mixed pattern of inflammation in the lungs that differs from the inflammation pattern in non-obese adults with asthma, according to systematic review and meta-analysis findings published in Thorax.
Obesity, a frequent comorbidity of asthma and severe asthma, is correlated with increased asthma exacerbation risk, reduced quality of life, and poorer asthma control.
Investigators sought to explore whether obesity is associated with increased airway inflammation, systemic inflammation, and adipokines among adults with asthma. Primary endpoints were airway inflammation (sputum neutrophils, sputum eosinophils, fractional exhaled nitric oxide [FeNO]), systemic inflammation (C-reactive protein, interleukin 6 [IL-6]), and adipokines (leptin, adiponectin).
Investigators conducted a random effects meta-analysis on 40 studies conducted through August 2021 reporting measures of systemic inflammation, airway inflammation, and/or adipokines in adults with asthma and obesity vs adults with asthma but no obesity. Obesity was defined as body mass index at least 30kg/m2.
Neutrophil, eosinophil, and macrophage counts were skewed in all studies, inhibiting meta-analysis.
Our findings suggest obesity is driving a mixed pattern of inflammation in the lungs that is dependent on the compartment being examined, with an increased proportion of neutrophils in the lumen (sputum) and an increased number of eosinophils in the lung tissue.
With respect to inflammation, the researchers found sputum neutrophils were 5% higher in those with asthma and obesity vs asthma without obesity in 4 studies (n=2297; mean difference [MD], 5.0%; 95% CI, 1.2-8.9; P =.01; I2=42%), and 3 of the 4 studies reported no difference between groups. Blood neutrophil count was higher in those with asthma and obesity vs asthma without obesity (n=1761; standardized mean difference [SMD], 0.29; 95% CI, 0.10-0.48; P =.003; I2=59%); there was no statistically significant difference in blood neutrophil percentage.
The researchers noted bronchial submucosal eosinophil count and sputum interleukin 5 were higher in those with asthma and obesity (n=181; SMD, 0.58; 95% CI, 0.25-0.91; P <.001; I2=0.0%) vs asthma without obesity (n=198; SMD, 0.46; 95% CI, 0.17-0.75; P <.002; I2=0.0%). There was no significant difference in sputum eosinophil percentage. In 5 studies, no difference in sputum eosinophil count was observed between obese vs non-obese groups. Among those with asthma and obesity, lower sputum macrophage count was reported in 1 study and no difference between groups was reported in another study.
Blood C-reactive protein, IL-6, and leptin were higher in those with asthma and obesity. Three studies measuring concentrations of sputum IL-6 showed no observed difference in those with asthma and obesity vs asthma without obesity. FeNO was 4.5 ppb lower in individuals with asthma and obesity (n=2601; MD, -4.5ppb; 95% CI, -7.1ppb to -1.8ppb; P <.001; I2=40%). The researchers noted no difference in sputum tumor necrosis factor concentration in asthma with obesity vs asthma without obesity.
Overall, there were 2 studies investigating airway adipokines, and 1 study found no difference in sputum leptin concentration in asthma with obesity vs without (BMI, 18.5kg/m2-25.0kg/m2), and 1 study found a significantly higher bronchoalveolar lavage (BAL) leptin concentration and no difference in BAL adiponectin concentration in those with asthma and obesity.
Leptin in circulating adipokine concentrations was significantly higher in asthma with obesity vs without obesity (n=457; SMD, 1.73; 95% CI, 1.30-2.16; P <.001; I2=71%) and adiponectin was lower (n=484; SMD, -0.72; 95% CI, -1.31 to -0.13; P <.001; I2=88%); both results had significant heterogeneity, the researchers noted.
Review and meta-analysis limitations include considerable heterogeneity in systemic inflammation and adipokine outcomes; inability to determine the impact of oral or inhaled corticosteroids on airway inflammation; inability to determine whether associations between obesity and inflammation in adults with asthma is influenced by sex; and inability to determine clinical consequences or mechanisms responsible for inflammatory effects.
“Our findings suggest obesity is driving a mixed pattern of inflammation in the lungs that is dependent on the compartment being examined, with an increased proportion of neutrophils in the lumen (sputum) and an increased number of eosinophils in the lung tissue,” investigators concluded. These findings may help identify therapies for adults with asthma and obesity, said study authors, adding that further studies are needed to determine whether inflammation related to obesity contributes to worse asthma control and severity.
Disclosure: This review was supported by Astra-Zeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.