Obese Asthma is Characterized by Multi-faceted Inflammation Accompanied by Epithelial Remodeling

Background: Adipokines have been claimed for the link between obesity and asthma. The aim of the present study was to evaluate the roles of leptin and adiponectin in children with asthma and/or obesity and their effect on pulmonary functions. Methods: Obese (n=71) and lean asthmatics (n=72), obese non-asthmatics (n=46), and lean healthy children (n=49) were included in the study. Serum leptin and adiponectin levels were compared according to groups and sex. Results: Mean leptin levels of obese asthmatics were higher than those of lean asthmatics (13.1±9.1 vs. 3.7±4.4; p<0.001). Serum adiponectin levels of lean asthmatics (16±7.1) were significantly higher than those of obese asthmatics (12.1±6.9; p<0.001) and of their lean healthy (13.2±5.9; p<0.05) counterparts. In obese asthmatics, adiponectin levels were positively correlated with the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio, and serum leptin levels were inversely correlated with forced expiratory flow (FEF25–75). Leptin/adiponectin ratio was inversely correlated with FEV1/FVC ratio in lean and obese asthmatic patients. Conclusions: The present findings suggest that adiponectin may have protective disease modifying effect(s) in asthmatic children. Anti-inflammatory mechanisms regarding adiponectin may work better in girls than in boys.

Background: In the last years, there has been interest in the role of small airways abnormalities in asthma. However, the role of small airways functioning in obese asthma patients is not well described. Aim: To explore differences in small-airways functioning between obese and non-obese asthma patients; To explore differences in small-airways functioning between obese asthma patients with and without increased factional exhaled nitric oxide (FeNO). Methods: The Netherlands Epidemiology of Obesity (NEO) study is a population based cohort study in 6671 participants of whom 513 had asthma. 57 patients were excluded due to missing values. Differences in small airways functioning (forced expiratory flow at 25-75% of FVC (FEF25-75)) between obese (BMI≥30 kg/m2) and non-obese asthma patients were explored using linear regression analysis. In the non-obese and obese subgroups FEF25-75 was compared between patients with high (≥25 ppb) and low ( Results: Among 465 asthma patients, 51% was obese and 25% had high FeNO levels. The predicted FEF25-75 did not differ between non-obese and obese asthma patients (adjusted mean difference (MD) -0.66 % predicted, 95% CI: -4.6 to 5.9). In non-obese asthma patients, the FEF25-75 did not differ significantly between patients with low and high FeNO (adjusted MD -8.7 %, 95% CI: -17.5 to 0.1). In obese asthma patients, the FEF25-75 was lower in patients with high FeNO compared to patients with low FeNO (adjusted MD -10.7 %, 95% CI -18.9 to -2.5). Conclusions: Obese and non-obese asthma patients do not differ regarding small airways functioning. Small airways functioning was decreased in patients with high FeNO levels, suggesting that FEF25-75 might contribute to the diagnosis of asthma.

The incidence of asthma and obesity is increasing worldwide, and reports suggest that obese patients have more severe asthma. We investigated whether obese asthma patients have more severe airway obstruction and airway hyper-responsiveness and a different type of airway inflammation than lean asthmatics. Furthermore, we assessed the effect of obesity on corticosteroid treatment response. Patient data from four well-documented asthma cohorts were pooled (n = 423). We evaluated FEV(1) , bronchial hyper-responsiveness (PC(20) ) to either methacholine/histamine or adenosine 5'-monophosphate (AMP) (differential) cell counts in induced sputum and blood and corticosteroid treatment response in 118 patients. At baseline, FEV(1) , PC(20) methacholine or histamine, and PC(20) AMP values were comparable in 63 obese (BMI ≥ 30 kg/m(2) ) and 213 lean patients (BMI <25 kg/m(2) ). Obese patients had significantly higher blood neutrophils. These higher blood neutrophils were only seen in obese women and not in obese men. After a two-week treatment with corticosteroids, we observed less corticosteroid-induced improvement in FEV(1) %predicted in obese patients than in lean patients (median 1.7% vs 6.3% respectively, P = 0.04). The percentage of sputum eosinophils improved significantly less with higher BMI (P = 0.03), and the number of blood neutrophils increased less in obese than in lean patients (0.32 x10(3) /μl vs 0.57 x10(3) /μl, P = 0.046). We found no differences in asthma severity between obese and nonobese asthmatics. Interestingly, obese patients demonstrated more neutrophils in sputum and blood than nonobese patients. The smaller improvement in FEV(1) and sputum eosinophils suggests a worse corticosteroid treatment response in obese asthmatics.

Clarifying inflammatory processes and categorising asthma into phenotypes and endotypes improves asthma management. Obesity worsens severe asthma and reduces quality of life, although its specific molecular impact remains unclear. We previously demonstrated that hsa-miR-26a-1-3p and hsa-miR-376a-3p, biomarkers related to an inflammatory profile, discriminate eosinophilic from non-eosinophilic asthmatics. We aimed to study hsa-miR-26a-1-3p, hsa-miR-376a-3p, and their target genes in asthmatic subjects with or without obesity to find biomarkers and comprehend obese asthma mechanisms. Lung tissue samples were obtained from asthmatic patients (n = 16) and healthy subjects (n = 20). We measured miRNA expression using RT-qPCR and protein levels (IGF axis) by ELISA in confirmation samples from eosinophilic (n = 38) and non-eosinophilic (n = 39) obese (n = 26) and non-obese (n = 51) asthma patients. Asthmatic lungs showed higher hsa-miR-26a-1-3p and hsa-miR-376a-3p expression than healthy lungs. A study of seven genes regulated by these miRNAs revealed differential expression of IGFBP3 between asthma patients and healthy individuals. In obese asthma patients, we found higher hsa-miR-26a-1-3p and IGF-1R values and lower values for hsa-miR-376a-3p and IGFBP-3. Hsa-miR-26a-1-3p and IGFBP-3 were directly and inversely correlated with body mass index, respectively. Hsa-miR-26a-1-3p and hsa-miR-376a-3p could be used as biomarkers to phenotype patients with eosinophilic and non-eosinophilic asthma in relation to comorbid obesity.

Background: Obesity increases the risk of asthma. Obesity-related asthma is recognized as a distinct phenotype. More evidence on differences between obese and non-obese asthma patients can help to improve diagnostic accuracy and to optimize treatment. Aim: To explore differences in lung function, inflammation and symptoms between obese and non-obese asthma patients. Method: The Netherlands Epidemiology of Obesity (NEO) study is a population based cohort study in 6671 participants(592 with asthma). Differences in lung function, fractional exhaled nitric oxide(FeNO) and symptoms between obese and non-obese asthma patients were explored using regression analysis, corrected for age, sex, smoking, ethnicity, education, physical activity, inhaled corticosteroids use. Results: Among 592 asthma patients, 318 were obese(BMI≥30 kg/m2). Non-obese asthma patients had better predicted forced expiratory volume in 1s (FEV1%)(100.2±18.6 vs. 96.5±18.1,p=0.026) and forced vital capacity (FVC%)(112.1±18.0 vs. 107.0±15.8,p Conclusions: Non-obese asthma patients have a better lung function than obese asthma patients. Obese patients more often experience wheezing and their symptoms worsen more during activity. Our results suggest that despite similar levels of inflammation as assessed by FeNO, obese asthma patients are more symptomatic and have a lower lung function than non-obese patients.

BackgroundAsthma is a complex condition largely attributed to the interactions among genes and environments as a heterogeneous phenotype. Obesity is significantly associated with asthma development, and genetic studies on obese vs. non-obese asthma are warranted.MethodsTo investigate asthma in the minority African American (AA) population with or without obesity, we performed a whole genome sequencing (WGS) study on blood-derived DNA of 4289 AA individuals, included 2226 asthma patients (1364 with obesity and 862 without obesity) and 2006 controls without asthma. The burden analysis of functional rare coding variants was performed by comparing asthma vs. controls and by stratified analysis of obese vs. non-obese asthma, respectively.ResultsAmong the top 66 genes with P < 0.01 in the asthma vs. control analysis, stratified analysis by obesity showed inverse correlation of natural logarithm (LN) of P value between obese and non-obese asthma (r = − 0.757, P = 1.90E−13). Five genes previously reported in a genome-wide association study (GWAS) on asthma, including TSLP, SLC9A4, PSMB8, IGSF5, and IKZF4 were demonstrated association in the asthma vs. control analysis. The associations of IKZF4 and IGSF5 are only associated with obese asthma; and the association of SLC9A4 is only observed in non-obese asthma. In addition, the association of RSPH3 (the gene is related to primary ciliary dyskinesia) is observed in non-obese asthma.ConclusionsThese findings highlight genetic heterogeneity between obese and non-obese asthma in patients of AA ancestry.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12931-022-02039-0.

The impact of weight loss beyond lung function: benefit with respect to asthma outcomes

Coexistence of obesity and asthma determines a distinct respiratory metabolic phenotype

Asthma heterogeneity and severity—why is comprehensive phenotyping important?

Background: The effects of pulmonary rehabilitation in patients with asthma and obesity are largely unknown. Objective: To compare the effects of an outpatient pulmonary rehabilitation (PR) program on exercise tolerance and asthma control in obese and non-obese asthmatics. Methods: Non-obese (BMI Results: A total of 138 asthma patients were included in this study. Fifty-two patients were obese (BMI 25.4, FEV1 90%) and 85 patients were non–obese (BMI 35.0, FEV1 90%). At baseline, obese asthma patients had a lower level of exercise tolerance reflected by a lower 6MWD (525m vs 621m, p Conclusion: our results suggest that a standardized PR program is feasible in obese asthmatics and that they benefit as much as non-obese asthma patients. It is unclear whether an adapted lifestyle program with emphasis on weight loss and self-management strategies could improve the effects on exercise capacity, asthma control and quality of life these obese asthmatics.

ABSTRACTBackground: Mechanisms underlying the association between asthma and obesity remain poorly understood. Obesity appears to be a risk factor for asthma, and obese asthmatics fare poorly compared to lean asthmatics. Objectives: To explore the possibility that reduced regulatory T cell (Treg) number and function contribute to the obesity-asthma association. We concentrated on obese females with childhood-onset asthma, since Treg may be involved in this phenotype. Methods: We recruited 64 women (ages 18–50) into four groups: lean (BMI 18–25 kg/m2) controls (n = 17) and asthmatics (n = 13), and obese (BMI ≥ 35 kg/m2) controls (n = 17) and asthmatics (n = 17). Asthmatics had atopy and childhood-diagnosed asthma. We assessed lung function, asthma control and quality of life. Peripheral blood CD4+/CD25+/FoxP3+ Treg cells were identified and counted by flow cytometry and expressed as % total CD4+ T cells. We assessed Treg cell function by the ability of CD4+/CD25+ Treg cells to suppress autologous CD4+/CD25- responder T cell (Tresp) proliferation and measured as % suppression of Tresp cell proliferation. Results: Obese asthmatics had worse lung function, asthma control, and quality of life compared to lean asthmatics. Compared to lean or obese control groups, the number of Treg cells in the obese asthmatics was approximately 1.58- or 1.73-fold higher. The ability of Treg cells from obese-asthmatics to suppress Tresp cell proliferation was reduced. Conclusions: Obese, atopic women with childhood diagnosed asthma demonstrate increased Treg cell number and mildly decreased Treg cell function. Our data do not support the view that reduced Treg cell number contributes to this obese-asthma phenotype.

Introduction: The differences in phenotypes of the asthma are increasingly recognized with potential implications in treatments of these phenotypes. We investigated the difference in exhaled nitric oxide (eNO) level in patients with obese and non-obese asthmatics. Materials and Methods: 135 patients with asthma without prior history of treatment with inhaled or systemic steroids were selected from a respiratory subspecialty clinic in Tabriz, Iran. After full history and physical examination all patients had eNO measurement (using NObreath provided by Bedfont, UK) and spirometry (using Jaeger spirometer, Germany) performed with standard techniques. The level of eNO compared in asthma patients from different BMI groups and also the correlation of the eNO with different parameters of pulmonary function was analyzed. Results: The eNo levels in overweight and obese asthmatics with BMI of 25 kg/m2 or higher were significantly lower than asthma patients with BMI less than 25 kg/m2( 44.1 ppb versus 63.9 ppb respectively; p Conclusion and Clinical Implications: These findings indicates that eNO is lower in overweight and obese asthmatic patients with associated metabolic and mitochondrial changes compared with normal weight asthmatics and this is in line with possible differences in disease mechanisms with potential clinical implications of varied efficacy of drugs in these phenotypes of asthma.

The majority of patients with severe or difficult-to-control asthma in the United States are obese. Epidemiological studies have clearly established that obese patients tend to have worse asthma control and increased hospitalizations and do not respond to standard controller therapy as well as lean patients with asthma. Less clear are the mechanistic underpinnings for the striking clinical differences between lean and obese patients with asthma. Because obesity is principally a disorder of metabolism and energy regulation, processes fundamental to the function of every cell and system within the body, it is not surprising that it affects the respiratory system; it is perhaps surprising that it has taken so long to appreciate how dysfunctional metabolism and energy regulation lead to severe airway disease. Although early investigations focused on identifying a common factor in obesity that could promote airway disease, an appreciation has emerged that the asthma of obesity is a manifestation of multiple anomalies related to obesity affecting all the different pathways that cause asthma, and likely also to de novo airway dysfunction. Consequently, all the phenotypes of asthma currently recognized in lean patients (which are profoundly modified by obesity), as well as those unique to one's obesity endotype, likely contribute to obese asthma in a particular individual. This perspective reviews what we have learned from clinical studies and animal models about the phenotypes of asthma in obesity, which show how specific aspects of obesity and altered metabolism might lead to de novo airway disease and profoundly modify existing airway disease.

465 - Protein S-Acylation in Pulmonary Disease

Background : Asthma is a worldwide problem, with an estimated 300 million affected individuals. Although central (visceral) adipocytes are the most important source ofadiponectin (APN), there is a tendency for reduced serumadiponectin concentration among obese subjects suggesting that decreased APN levels may contribute to the increased inflammatory state as in asthma. Aim of the work: The aim of this work was to determine whether serum concentration of adiponectin changed in asthmatic patients during acute attack and in remission or not. Subjects and Methods: Fifty five subjects were included in this study from Chest department, Benha university hospital .40 patients with bronchial asthma(20 obese and 20 nonobese) and 15 age related healthy subject(7 obese and 8 nonobese) as a control. All asthmatic patients and control group were divided into non-obese and obese according to their body mass index(BMI) Those with BMI 18.5 were considered non-obese, Those with BMI> 30 were considered obese .Those with BMI . 25 and. 30 were considered overweight and were not included in this study (NIH/NHLBI, 1998). All subjects were submitted to the following, Full history taking ,Complete physical examination(General & Local),Plain x-ray chest P-A & left lateral views ,Complete blood count , Erythrocyte sedimentation rate, Liver and kidney function tests, Fasting and post prandial blood sugar, Ventilatory function tests , Venous blood samples were taken for Adiponectin level measurement. Results : Serum adiponectin(μg/ml) in obese control subjects (3.25 ± 0.65 μg/ml) was highly significant lower than that in nonobese control subjects(10.51 ± 1.55μg/ml), (P-value < 0.001). Also serum adiponectin revealed highly significant decrease in obese asthmatics during attack (1.58 ± 0.724 μg /ml) than in obese asthmatics during remission (2.08 ± 0.74 μg /ml) and that in obese control subjects (3.25 ± 0.65 μg /ml), (P-value < 0.001).Serum adiponectin(μg/ml) was significantly higher in nonobese asthmatics during remission (9.49 ± 2.49 μg /ml) than in nonobese asthmatics during attack (7.89 ± 2.7 μg /ml) and both was lower than that in nonobese control subjects , (p-value < 0.05 ).Serum adiponectin (μg /ml) was highly significant lower in obese asthmatics during attack (1.58 ±0.72 μg/ml) than in obese asthmatics during remission(2.08 ± 0.74 μg /ml), (P-value < 0.001) and highly significant higher in nonobese asthmatics during attack (7.89 ± 2.7 ig/ml) than in nonobese asthmatics during remission (9.49 ± 2.49 μg /ml), (P-value < 0.001). Conclusion: Serum adiponectin was significantly decreased in asthmatic patients (obese and nonobese) than control subjects also serum adiponectin level was significantly lower during attack than in remission.