Obesity impairs apoptotic cell clearance in asthma

Fernandez-Boyanapalli, Ruby; Goleva, Elena; Kolakowski, Christena A.; Min, Elysia; Day, Brian J.; Leung, Donald Y.M.; Riches, David W. H.; Bratton, Donna L.; Sutherland, E. Rand

doi:10.1016/j.jaci.2012.09.028

Cited by 59 publications

(48 citation statements)

References 71 publications

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“…A large number of cross-sectional and longitudinal studies have reported worse asthma control and increased asthma severity in obese individuals. The significantly higher percentage of macrophages that we observed in the induced sputum of obese children, along with their altered phenotype [36] and activity [37], highlight the potential implication of airway macrophages on clinical aspects of obese asthma. Furthermore, the enhanced reactivity of alveolar macrophages from overweight/obese adult asthmatics to lipopolysaccharide, particularly when they were primed ex vivo with high dose of leptin, was demonstrated in an elegant study by LUGOGO et al [36].…”

Section: Discussionmentioning

confidence: 53%

Macrophage activation, age and sex effects of immunometabolism in obese asthma

et al. 2014

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Obese asthma is characterised by infiltration of adipose tissue by activated macrophages and mast cells. The aim of this study was to examine the age and sex effects of immunometabolism in obese asthma.Obese and non-obese asthmatic children and adults underwent spirometry, body composition assessment by dual energy X-ray absorptiometry and measurement of serum soluble CD163 (sCD163), tryptase, C-reactive protein (CRP) and other adipocytokines.Plasma CRP ( p<0.01) and leptin ( p<0.01) were elevated in obese asthmatic adults, and sCD163 ( p=0.003) was elevated in obese asthmatic children. We observed significantly higher sCD163 in obese female children compared to obese female adults and male children, and higher CRP in obese female adults compared to obese male children and adults. Serum tryptase concentrations were not significantly different across age groups. sCD163 positively correlated with the proportion of android fat in obese female children (r=0.70, p=0.003) and obese female adults (r=0.65, p=0.003). In obese female children, sCD163 was inversely associated with forced expiratory volume in 1 s % predicted (r=−0.55, p=0.02) and was positively associated with the Asthma Control Questionnaire (r=0.57, p=0.02).Obese children with asthma have sex-specific macrophage activation, which may contribute to worse asthma control and lung function. The heterogeneous systemic inflammatory profile across age and sex suggests the existence of sub-phenotypes in obese asthma at the molecular level. @ERSpublications Macrophage activation is a determinant of pro-inflammatory effects of immunometabolism in childhood obese asthma

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Section: Discussionmentioning

confidence: 53%

Macrophage activation, age and sex effects of immunometabolism in obese asthma

et al. 2014

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“…Patrolling monocytes, increased among obese subjects with asthma and associated with disease severity in our study, are rapidly recruited into lungs in response to inflammatory stimuli (22) and are potent producers of TNF (23), a cytokine that was higher among obese subjects with asthma than normal-weight subjects with asthma in our study. Furthermore, airway macrophages are derived from circulating patrolling monocytes (22), and are known to be proinflammatory in response to leptin (24) and have reduced efferocytosis in obese subjects with asthma compared with normal-weight subjects with asthma (25).…”

Section: Discussionmentioning

confidence: 99%

Inflammation, Metabolic Dysregulation, and Pulmonary Function among Obese Urban Adolescents with Asthma

Rastogi¹,

Fraser²,

Oh³

et al. 2015

Am J Respir Crit Care Med

167

176

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Rationale: Insulin resistance and low high-density lipoprotein (HDL) are associated with pulmonary morbidity, including asthma, but the underlying mechanisms are not well elucidated.Objectives: To investigate whether systemic inflammation underlies the association of metabolic abnormalities with pulmonary function among urban adolescents.Methods: Th-cell responses and monocyte subsets, and their association with serum homeostatic model assessment of insulin resistance (HOMA-IR) and HDL, and pulmonary function were quantified in 168 adolescents, including 42 obese subjects with asthma, 42 normal-weight subjects with asthma, 40 obese subjects without asthma, and 44 healthy control subjects. Th-cell responses (Th1 [CD4 ) monocytes, and their C-C chemokine receptor type-2 (CCR2) expression were quantified by flow cytometry.Measurements and Main Results: Th1/Th2 ratio to all three stimuli was higher in obese subjects with asthma than normal-weight subjects with asthma and directly correlated with HOMA-IR. Classical monocytes inversely associated with Th1/Th2 ratio to phytohemagglutinin (r = 20.43; P = 0.01) and directly with Asthma Control Test score (b = 1.09; P = 0.04), while patrolling monocytes correlated with Composite Asthma Severity Index score (b = 1.11; P = 0.04) only among obese subjects with asthma. HDL was inversely associated with patrolling monocytes and directly associated with CCR2 expression on resident monocytes. CCR2 expression on patrolling monocytes predicted residual volume (RV), RV/TLC ratio, and FRC, after adjusting for HDL, but not after adjusting for body mass index. Association of Th1/Th2 ratio with RV, FRC, and inspiratory capacity was attenuated after adjusting for HOMA-IR.Conclusions: Th1 polarization and monocyte activation among obese subjects with asthma correlates with metabolic abnormalities. Association of monocyte activation with pulmonary function is mediated by body mass index, whereas that of Th1 polarization is mediated by insulin resistance.

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“…Log-transformed data are presented as geometric mean (95% confidence interval). Sputum cytokine concentrations and eosinophilic inflammation in different compartments were presented in the subjects with asthma stratified by BMI (, 25 …”

Section: Discussionmentioning

confidence: 99%

“…The association of obesity and asthma has been evident from epidemiologic studies, including case control studies and crosssectional studies that have shown an increased risk of asthma in obese individuals based on the body mass index (BMI) (20)(21)(22)(23). Emerging evidence suggests that obesity might represent a distinct severe asthma phenotype (6) with changes in exhaled nitric oxide metabolism (24) and macrophage function (25,26). Its association with eosinophilic inflammation is contentious with some reports suggesting no association with sputum (27) or blood cell counts (6) and others suggesting there is a noneosinophilic obese phenotype (7).…”

mentioning

confidence: 99%

Elevated Sputum Interleukin-5 and Submucosal Eosinophilia in Obese Individuals with Severe Asthma

Desai

Newby

Symon

et al. 2013

Am J Respir Crit Care Med

201

138

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Rationale:The relationship between airway inflammation and obesity in severe asthma is poorly understood. Objectives: We sought to determine the relationship between sputum mediator profiles and the distribution of eosinophilic inflammation and obesity in people with severe asthma. Methods: Clinical parameters and eight mediators in sputum were assessed in 131 subjects with severe asthma from a single center categorized into lean, overweight, and obese groups defined by their body mass index. In an independent group of people with severe asthma (n ¼ 45) and healthy control subjects (n ¼ 19) eosinophilic inflammation was enumerated in bronchial submucosa, blood, and sputum and related to their body mass index. Measurements and Main Results: Sputum IL-5 geometric mean (95% confidence interval) (pg/ml) was elevated in the obese (1.8 [1.2-2.6]) compared with overweight (1.1 [0.8-1.3]; P ¼ 0.025) and lean (0.9 [0.6-1.2]; P ¼ 0.018) subjects with asthma and was correlated with body mass index (r ¼ 0.29; P , 0.001). There was no relationship among body mass index, the sputum cell count, or other sputum mediators. In the bronchoscopy group the submucosal eosinophil number in the subjects with asthma was correlated with body mass index (Spearman rank correlation, r s ¼ 0.38; P ¼ 0.013) and the median (interquartile range) number of submucosal eosinophils was increased in obese (19.4 [11.8-31.2]) (cells per square millimeter) versus lean subjects (8.2 [5.4-14.6]) (P ¼ 0.006). There was no significant association between sputum or peripheral blood eosinophil counts and body mass index. Conclusions: Sputum IL-5 and submucosal eosinophils, but not sputum eosinophils, are elevated in obese people with severe asthma. Whether specific antieosinophilic therapy is beneficial, or improved diet and lifestyle in obese asthma has antiinflammatory effects beyond weight reduction, requires further study.Keywords: asthma; obesity; cytokines; phenotypes; eosinophil Asthma is a common, complex inflammatory disorder affecting about 5% of adults in the general population, of which approximately 5-10% suffer from severe disease (1, 2). Severe disease is often associated with comorbidities, such as obesity, and is particularly important because these patients suffer from substantial morbidity and consume a disproportionately high amount of the overall healthcare resources spent on asthma management (3-6). Asthma, and in particular severe asthma, is a heterogeneous disease as highlighted by the different phenotypes identified using cluster analysis of clinical data (7-10) and cytokine profiles of airway samples (11-13). The key benefit of dividing a multidimensional disease, such as asthma, into distinct phenotypes is expected to be more effective treatment targeting. This has been effectively shown with the success of eosinophilic airway inflammationdirected corticosteroid (14-16) and anti-IL-5 treatment (17-19) to prevent asthma exacerbations in eosinophilic subjects with asthma. The association of obesity and asthma has been evident Support...

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Obesity impairs apoptotic cell clearance in asthma

Cited by 59 publications

References 71 publications

Macrophage activation, age and sex effects of immunometabolism in obese asthma

Macrophage activation, age and sex effects of immunometabolism in obese asthma

Inflammation, Metabolic Dysregulation, and Pulmonary Function among Obese Urban Adolescents with Asthma

Elevated Sputum Interleukin-5 and Submucosal Eosinophilia in Obese Individuals with Severe Asthma

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