Obese Asthmatic Patients Research Articles

The content of matrix metalloproteinase-1, -9 and tissue inhibitor of matrix metalloproteinase-1 in patients with bronchial asthma and obesity

Airway remodeling is a significant factor in the progression of respiratory failure in bronchial asthma (BA). Obesity can contribute to inflammation, and consequently – airway remodeling, by increased production of matrix proteinase (MMP). However, the mechanisms of remodeling in different phenotypes of BA, especially in comorbid patients, remain poorly understood. The aim of the research was to examine the levels of remodeling markers MMP-1, MMP-9 and tissue inhibitor of matrix proteinases (TIMP-1) in obese asthmatic patients, taking into account their age at the onset of BA, the severity of symptoms and the level of control. Material and methods. 195 patients with BA associated with obesity were examined. The control group consisted of 95 practically healthy people. Patients were divided into two groups: Group I included 100 patients with early onset, and Group II included 95 patients with late onset of BA. The study was approved by the Bioethics Commission of the Medical Institute of Sumy State University. Statistical analysis of the obtained results was carried out using the SPSS-17 program. Results. The content of MMP-1, -9 and TIMP-1 was higher in patients with early (129.40 ± 7.86; 177.30 ± 9.19; 142.40 ± 12.22 ng/ml, respectively) and late (196.60 ± 9.62; 289.80 ± 16.23; 187.50 ± 11.34 ng/ml, respectively) BA with obesity compared to practically healthy individuals (р < 0.005). Patients with late-onset BA associated with obesity likely had higher indicators than those with early BA. In patients with early BA, the levels of MMP-1, -9, and TIMP-1 were not significantly different depending on the severity of the disease (р > 0.05). However, in patients with severe late BA, the levels of these markers were higher compared to those with mild BA (р < 0.05). Levels of MMP-1 and MMP-9 in patients with early-onset and late-onset BA with obesity were higher in the absence of disease control compared to those in complete and partial control, but in late-onset exceeded those in early-onset. Conclusions. Considering the obtained results, it can be assumed that the level of MMP-1, MMP-9 and TIMP-1 in obese patients with BA can serve as biomarkers of airway remodeling, namely, the severity and the level of BA control.

Body mass index affects spirometry indices in patients with chronic obstructive pulmonary disease and asthma.

Background: Body mass index (BMI) is known to affect the outcomes of spirometry indices. However, its association with spirometry indices in COPD and asthma is less studied. We aimed to explore the impact of BMI on these patients. Methods: Patients with COPD or asthma who completed bronchodilator tests (BDTs) between 2017 and 2021 were reviewed. Spirometry indices were compared among patients with COPD or asthma that were subclassified as underweight (BMI< 18.5kg/m2), normal weight (≥18.5 to < 25), overweight (≥ 25 to < 30), and obesity (≥ 30). Results. Results: Analysis was conducted on 3891 COPD patients (age:66.5 ± 7.8years) and 1208 asthma patients (age:59.7 ± 7.5years). COPD patients classified as underweight demonstrated significantly lower values of pre-and post FEV1 (L, %), pre-and post FVC (L, %), and pre- and post-FEV1/FVC (all p < 0.05). In contrast, COPD patients who were overweight or obese exhibited higher values for pre-and post FEV1 (L, %), and pre and post FEV1/FVC (all p < 0.05). Within the cohort of asthma patients, those underweight had lower pre-and post FEV1 (L, %), pre and post FVC (L, %), pre and post FEV1/FVC %. Obese asthma patients displayed higher pre and post FEV1/FVC (all p < 0.05). Conclusion: Significant BMI category differences in spirometry indices can be seen in patients with COPD or asthma. Both underweight and obesity could affect the diagnosis and severity of these diseases. Recognizing these effects is essential to better management and diagnosis of these patients.

Physical Health-Related Quality of Life in Relation to Mediterranean Diet Adherence in a Sample of Greek Asthma Patients: A Pilot Study.

The role of nutrition in the management of asthma in obese patients is of increasing interest due to their limited response to inhaled corticosteroids. Some studies note that through diet and lifestyle, there can be an improvement in asthma control. The aim of the present study was to investigate the adherence to the Mediterranean Diet and its association with asthma severity and quality of life in patients with bronchial asthma. This is a cross-sectional study of 85 patients (70.6% female), with a mean age of 57 years, from the General University Hospital of Larissa and, more specifically, patients of the outpatient asthma clinic. Data were collected with the use of specific questionnaires. In relation to BMI, 12.9% of participants were of a normal weight, 45.9% were overweight, 25.9% were obese level I, 5.9% were obese level II, and 9.4% were in the morbidly obese range. Based on the Med Diet Score (ranging from 21 to 35), most participants (85.9%) reported moderate adherence to the Mediterranean Diet. Further analysis examined the correlations of the PCS-12 score with the frequency of consumption of each of the 11 food categories, as well as all demographic and health behavior variables. The ranked correlations indicated a significant relationship between PCS-12 score and Med Diet adherence and the consumption of alcoholic beverages (r = 0.437, p < 0.05), in accordance with the Mediterranean Diet suggestions, as well as a negative relationship with BMI score (r = -0.454, p < 0.010). Moreover, significant correlations were also present between the physical quality of life and AQLQ score and work type, as well as gender, age, and marital status. The results of our study showed a high rate of obesity in patients with asthma at the General University Hospital of Larissa and moderate adherence to the Mediterranean Diet. Increased BMI and alcoholic beverage consumption in asthma patients were significant predictors of lower physical health-related quality of life. In conclusion, personal and society-level interventions are required to effectively address obesity and poor diet in patients with asthma.

The relationships between Physical activity and asthma control and Body Mass Index (BMI) in patients with asthma

Objective Asthma is one of the most common chronic conditions in developed countries. We examined whether physical activity (PA) is related to asthma control and body mass index (BMI) in asthma patients. Methods Cross-sectional data collected on PA (ActiGraph GT3X-BT), asthma control (the Asthma Control Questionnaire; ACQ), and BMI were examined in 206 adults (mean[sd] age 47.2[13.8] years; 49.5% had an obese BMI) with clinically diagnosed asthma. Relationships between PA and continuous BMI and asthma control were assessed using linear regression. Differences in PA across obesity (non-obese: <30 Kg/m2/obese: ≥30 Kg/m2) and asthma control categories (controlled: ≤0.75/uncontrolled: >0.75 ACQ score) were also examined. Results Median (p25, p75) steps counts and peak cadence were 6035 (4248, 8461) steps/day and 123 (115, 133) steps in a minute, respectively. There were nearly 2000 fewer steps/day among those with uncontrolled asthma versus controlled and among those with obese BMI versus nonobese, respectively (both p < 0.05). In regression models adjusted for relevant covariates each 1-unit increase in ACQ score was associated with −686 [95%CI −997, −13] (p ≤ 0.05) average steps/day. The statistical significance of these findings was attenuated (p ≥ 0.05) when BMI was added to the model. However, the point estimate was not reduced (-766 [95%CI −1060, 34]. Conclusions Overall step counts were low in this population despite peak cadence values suggesting that most participants could perform moderate intensity activity. Increasing step counts should be considered an important lifestyle intervention goal in obese and non-obese asthma patients with low PA levels.

Clinical characteristics and cytokine profiles of adult obese asthma with type2 inflammation

Obesity-related non-eosinophilic asthma has been identified as a phenotype of asthma. However, mepolizumab and omalizumab improve asthma control in severe asthma with obesity, implying that type-2 cytokines may be involved in the deterioration of control in obese asthma. Despite this, the clinical details of obese asthma with positive type-2 inflammation markers have not yet been reported. The objective of this study was to investigate the clinical characteristics of patients with obese asthma with positive type-2 inflammation markers. Adult obese asthmatic patients were enrolled and were classified into two groups: obese asthma with positive type-2 inflammation markers (T2) and obese asthma with negative type-2 inflammation markers (NT2), then data were compared. In total, 434 patients were enrolled (85% of patients were at GINA therapy step 4–5). The T2 group had a higher proportion of patients with persistent asthma since childhood and with allergic rhinitis. A higher percentage of patients used high-dose inhaled corticosteroids (ICS) and experienced acute exacerbations (annual exacerbation ratio ≥ 1) in the T2 group. Multivariate logistic regression analysis showed that the T2 group was independently associated with younger age, comorbidity of allergic rhinitis, persistent asthma since childhood, use of high-dose ICS, and acute exacerbation rate ≥ 1. Adipocytokine levels were similar between the groups. Collectively, obese asthma with positive type-2 inflammation markers is characterised by a higher percentage of persistent asthma since childhood and more severe asthma.

The Impact of Body Mass Index on Asthma Attacks Severity in Children with Asthma

Background: Obesity is a major concern that increases children's asthma risk. Obese asthmatic patients have more severe symptoms and attacks and less responsiveness to medication. Objectives: We aimed to investigate whether obese children have more asthma attacks, severe exacerbations, and respiratory distress. Methods: This cross-sectional study was performed on 149 children diagnosed with asthma attacks at Taleghani Children's Hospital in Gorgan, Iran, in 2018 - 2019. The relationship between body mass index (BMI) and the severity of asthma attacks in pediatric patients was investigated in 2020. The obtained data were analyzed using SPSS-18 software. Fisher's exact test and Spearman's rank correlation coefficient were used to analyze the data. Results: The mean age of the patients was 8.8 ± 2.76 years; 60.4% were boys, and 39.6% were girls. According to the BMI-age chart, 1.3% of the patients were underweight, 70.5% were in the normal range, 21.5% were overweight, and 6.7% were obese. Patients with higher BMI had more severe asthma attacks (P-value = 0.029) and respiratory distress (P-value = 0.015). In the pulmonary function testing, Forced Vital Capacity (FVC) and Forced Expiratory Volume in the first second (FEV1) were significantly lower in obese children. In addition, pCO2 and HCO3 were higher in overweight patients (P-value = 0.01 and 0.041, respectively). Conclusions: Patients with higher BMI had more severe attacks, exacerbations, and respiratory distress. Also, FVC and FEV1 were significantly lower in obese children. Obesity and asthma have many common pathophysiological mechanisms, and obesity increases the severity of asthma attacks and makes treatment challenging. Different mechanisms are involved in obese patients with asthma, including airway hyperreactivity, inflammation, and airway remodeling. Although the exact relationship between asthma attacks and obesity is still unclear, its understanding could lead to more therapeutic options.

Obese Asthma Phenotype Is Associated with hsa-miR-26a-1-3p and hsa-miR-376a-3p Modulating the IGF Axis.

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.

Effect of Obesity on the Expression of Genes Associated with Severe Asthma-A Pilot Study.

Asthma is a complex condition resulting from the interaction of genes and environment. Obesity is a risk factor to develop asthma and contributes to poor response to asthma therapy and severity. The aim of the study was to evaluate the effect of obesity on the expression levels of genes previously associated with severe asthma. Three groups of subjects were studied: non-obese asthmatics (NOA), obese asthma patients (OA), and non-asthmatic obese subjects (O). Previously reported overexpressed (IL-10, MSR1, PHLDA1, SERPINB2, and CD86) and underexpressed genes (CHI3L1, CPA3, IL-8, and PI3) in severe asthma were analyzed by RT-qPCR in peripheral blood mononuclear cells (PBMCs). In the overexpressed genes, obesity significantly decreased the expression of MSR1 and PHLDA1 and had no effects on CD86, IL-10, and SERPINB2. In underexpressed genes, obesity did not affect PI3, CHI3L1, and IL-8 and significantly reduced CPA3 expression. The results of this study show that obesity should be included among the known factors that can contribute toward modifying the expression of genes associated with asthma and, in particular, severe asthma.

1-O-alkyl-glycerols from Squid Berryteuthis magister Reduce Inflammation and Modify Fatty Acid and Plasmalogen Metabolism in Asthma Associated with Obesity.

Asthma associated with obesity is considered the most severe phenotype and can be challenging to manage with standard medications. Marine-derived 1-O-alkyl-glycerols (AGs), as precursors for plasmalogen synthesis, have high biological activity, making them a promising substance for pharmacology. This study aimed to investigate the effect of AGs from squid Berryteuthis magister on lung function, fatty acid and plasmalogen levels, and cytokine and adipokine production in obese patients with asthma. The investigational trial included 19 patients with mild asthma associated with obesity who received 0.4 g of AGs daily for three months in addition to their standard treatment. The effects of AGs were evaluated at one and three months of treatment. The results of the study demonstrated that intake of AGs increased the FEV1 and FEV1/VC ratios, and significantly decreased the ACQ score in 17 of the 19 patients after three months of treatment. The intake of AGs increased concentration of plasmalogen and n-3 PUFA in plasma, and modified leptin/adiponectin production by adipose tissue. The supplementation of AGs decreased the plasma levels of inflammatory cytokines (TNF-α, IL-4, and IL-17a), and oxylipins (TXB2 and LTB4), suggesting an anti-inflammatory property of AGs. In conclusion, 1-O-alkyl-glycerols could be a promising dietary supplement for improving pulmonary function and reducing inflammation in obese asthma patients, and a natural source for plasmalogen synthesis. The study highlighted that the beneficial effects of AG consumption can be observed after one month of treatment, with gradual improvement after three months of supplementation.

Role of Leptin as a Link between Asthma and Obesity: A Systematic Review and Meta-Analysis.

Asthma and obesity are considered as highly prevalent diseases with a great impact on public health. Obesity has been demonstrated to be an aggravating factor in the pathogenesis of asthma. Adipose tissue secretes proinflammatory cytokines and mediators, including leptin, which may promote the development and severity of asthma in obese patients. This study is a systematic review and a meta-analysis based on the relationship between leptin and asthma during obesity. MEDLINE, Cochrane, EMBASE and CINAHL databases were used. Data heterogeneity was analyzed using Cochran's Q and treatment effect with the DerSimonian and Laird method. Random effect analyses were carried out to test data sensitivity. Asymmetry was estimated using Begg's and Egger's tests. All studies showed significant differences in leptin levels. The effect of the measures (p &lt; 0.001), data sensitivity (p &lt; 0.05) and data asymmetry were statistically significant, as well as tBegg's test (p = 0.010) and Egge's test (p &lt; 0.001). Despite the existing limiting factors, the results of this study support the relevant role of leptin in the pathophysiology of asthma in obese subjects. Nevertheless, further studies are needed to obtain better insight in the relationship between leptin and asthma in obesity.

Correlation of hs-CRP, Exhaled Nitric Oxide and Atopic Status in Non-Obese and Obese Bronchial Asthma Patients

Correlation of hs-CRP, Exhaled Nitric Oxide and Atopic Status in Non-Obese and Obese Bronchial Asthma Patients

Burden of rare coding variants reveals genetic heterogeneity between obese and non-obese asthma patients in the African American population.

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.

Association between the clinical-functional parameters and lipid markers of systemic inflammation in mild asthma complicated with obesity

Aim. To identify the features of the association between the clinical-functional conditions and lipid markers of systemic inflammation (fatty acids, eicosanoids, plasmalogens) of patients with mild asthma and obesity. Materials and methods. Obese (n=80) and nonobese (n = 55) adults with mild, partially controlled asthma aged 28 to 65 years, and nonobese (n = 30) healthy controls had venous blood samples analysed. The ACQ-5 test, spirometry were evaluated. Serum thromboxane B2 (ТХВ2) and leukotriene B4 (LTB4) were analyzed by the enzyme immunoassay method. Fatty acidsas methyl esters (FAMEs) and plasmalogens in the form of dimethyl acetals (DMA) were estimated in blood plasma by gas chromatography-mass spectrometry. Results. In obese patients with asthma, the ACQ-5 test was lower in comparison to nonobese patients. FEV1 decreased by 8 %, FVC by 12% (p &lt; 0.05). A decrease in the level of DMA16: 0 by 17.5 % and DMA18: 0 by 25 % was established in obese asthma patients. The ratio of DMA16:0/FAME 16: 0 declined by 21 %, DMA18:0/FAME18: 0 − by 28 %. A fall in eicosapentaenoic acid (20: 5n3) and a change in the 20:4n6/20:5n3 ratio were found. The level of ТХВ2 and LTB4 was increased regardless of body weight. There was a positive correlation between body mass index and levels of LTB4 (r = 0.46), ТХВ2 (r = 0.49); and a negative correlation between ACQ and ТХВ2 (r = - 0.58). Indicators of lung function (FEV1, FVC, VC) had correlative links with DMA18:0, DMA20:0, eicosapentaenoic acid. Conclusion. We showed the change in the inflammatory fatty acids and eicosanoids synthesis and plasmalogen deficiency in obese-asthma. Established relationships between clinical and functional parameters and lipid markers of systemic inflammation, plasmalogen deficiency in patients with asthma and obesity reveal new pathogenetic mechanisms of the systemic inflammatory process in chronic respiratory diseases.

Reference Gene Validation for RT-qPCR in PBMCs from Asthmatic Patients with or without Obesity.

Obesity is known to impair the efficacy of glucocorticoid medications for asthma control. Glucocorticoid-induced gene expression studies may be useful to discriminate those obese asthmatic patients who present a poor response to glucocorticoids. The expression of genes of interest is normalized with respect to reference genes (RGs). Ideally, RGs have a stable expression in different samples and are not affected by experimental conditions. The objective of this work was to analyze suitable RGs to study the role of glucocorticoid-induced genes in obese asthmatic patients in further research. The gene expression of eight potential RGs (GUSB, B2M, POLR2A, PPIA, ACTB, GAPDH, HPRT1, and TBP) was assessed with reverse transcription–quantitative polymerase chain reaction in peripheral blood mononuclear cells (PBMCs) from asthmatic, obese asthmatic, and healthy individuals. Their stability was analyzed using four different algorithms—BestKeeper, ΔCt, geNorm, and NormFinder. geNorm analysis recommended the use of a minimum of three genes for normalization. Moreover, intergroup variation due to the treatment was calculated by NormFinder, which found that B2M was the gene that was least affected by different treatments. Comprehensive rankings indicated GUSB and HPRT1 as the best RGs for qPCR in PBMCs from healthy and asthmatic subjects, while B2M and PPIA were the best for obese asthmatic subjects. Finally, our results demonstrated that B2M and HPRT1 were the most stable RGs among all groups, whereas ACTB, TBP, and GAPDH were the worst shared ones.

Involvement of autophagy in exacerbation of eosinophilic airway inflammation in a murine model of obese asthma

ABSTRACT Obesity is a common comorbidity in patients with asthma, and obese asthma patients present the most refractory phenotype among patients with severe asthma. Similar to the observations in non-obese asthma patients, clinical studies have revealed heterogeneity in obese asthma patients, including the occurrences of T helper (Th)2-high and Th2-low phenotypes. However, the mechanisms underlying obesity-related asthma are not completely understood. Though macroautophagy/autophagy is involved in asthma and obesity, its role in obesity-associated asthma is unknown. We hypothesized that autophagy is involved in the pathogenesis of obese asthma. For our investigations, we used high-fat diet-induced Atg5 (autophagy related 5)-deficient mice and epithelial cell-specific atg5−/− (Scgb1a1/CCSP-atg5−/− ) obesity-induced mice. House dust mite (HDM)-sensitized atg5−/− obese mice exhibited marked eosinophilic inflammation and airway hyper-reactivity (AHR), compared to wild-type (WT) obese mice. Analyses of atg5−/− obese mice showed increased levels of Th2 cells but not ILC2s together with elevated expression of Th2 cytokines in the lung. In response to the HDM challenge, activated epithelial autophagy was observed in lean but not obese WT mice. Epithelium-specific deletion of Atg5 induced eosinophilic inflammation in Scgb1a1/CCSP-atg5−/− obese mice, and genetic analyses of epithelial cells from HDM-immunized atg5−/− obesity-induced mice showed an elevated expression of thymic stromal lymphopoietin (TSLP) and IL33. Notably, HDM-sensitized atg5−/− mice developed TSLP- and IL33-dependent eosinophilic inflammation and AHR. Our results suggest that autophagy contributes to the exacerbation of eosinophilic inflammation in obese asthma. Modulations of autophagy may be a therapeutic target in obesity-associated asthma.

Impulse Oscillometry Parameters in Childhood Asthma, Childhood Obesity and Childhood Obesity with Asthma

Background: Monitoring of lung function is necessary to detect irreversible airway obstruction in both asthma and obesity. Impulse oscillometry (IOS), a novo non-invasive equipment, is increasing popularity to measure airway resistance in young children worldwide. Aims: To compare IOS parameters among Thai asthmatic children and Thai obese children with and without asthma. Methods: A cross-sectional study was conducted in 120 participants, aged 4-15 years old. Forty children were in each group (asthma, obesity, and obesity with asthma). All volunteers were consented to measure airway resistance by IOS technique (Jaeger, Germany). Results: Seventy-three percent of patients were male with the mean age at 8.8 + 2.61 years old. Mean X5 was found normal in childhood obesity (-0.13) when compared to children with asthma (-0.23) and obesity with asthma (-0.19) (p &lt; 0.001 and 0.013 respectively). The cut-off value of X5, according to ROC curve, for predicting asthma in obese patients was -0.16 kPa/L/s with 70% sensitivity, 70% specificity and 70% accuracy (AUC= 0.69). However, with the bronchodilator effect (adjusted by duration of asthma control), we found significant higher percentage change of IOS parameters, including resonant frequency, area of reactance and R5-R20, in asthma (Fres -24.57 + 15.82, AX -58.28 + 13.37, R5-R20 -51.32 + 20.13) than in asthma with obesity (Fres -13.77 + 16.42, AX -43.35 + 21.4, R5-R20 -34.72 + 18.21), (p = 0.014, 0.004, 0.002 respectively). Conclusions: X5 and percentage changes after bronchodilator of Fres, AX, and R5-R20 are useful parameters to differentiate airway dysfunction in asthmatic children from obese children.

Subgroup Analysis of a Randomized Trial of the Effects of Positive Messaging on Patient-Reported Outcomes with Asthma - Effect of Obesity.

Asthma in obese patients represents a specific phenotype that is associated with increased symptoms, more frequent and severe exacerbations, reduced responsiveness to treatment, and decreased quality of life. Marketing and placebos have been shown to alter subjective responses to interventions in both asthma and obesity. We evaluated obesity as a potential treatment effect modifier of the effects enhanced drug messaging or placebos on subjective asthma outcomes. We conducted a secondary analysis of a multicenter, randomized clinical trial that studied the effect of messaging and placebos on asthma outcomes. A total of 601 participants were randomized (1:1:1:1:1) to one of 5 groups: enhanced messaging with montelukast or placebo, neutral messaging with montelukast or placebo, or usual care and followed for 4 weeks after randomization. We compared baseline characteristics by obesity status for 600 participants with data on body weight. Obesity was evaluated as an effect modifier for enhanced messaging (versus neutral messaging) and on placebo effects (versus usual care) in 362 participants assigned to a placebo group or usual care for three asthma questionnaires: Asthma Control Questionnaire, Asthma Quality of Life Questionnaire and Asthma Symptoms Utility Index. Overall, 227 (37%) of participants were obese. Obese participants were older (mean age 41 vs 34), more likely female (82% vs 67%) and self-identified as Black (44% vs 25%) than non-obese participants. As previously published, enhanced messaging was associated with improvements in patient-reported asthma scores, but there was no evidence for a placebo effect. Obesity status did not influence the message effects nor did it modify responses to placebo. Obesity has been shown to be an important factor associated with asthma outcomes and an effect modifier of drug treatment effects. We conducted a post hoc, subgroup analysis of data from a multicenter randomized trial of enhanced messaging and placebo associated with drug treatment on asthma outcomes. Our findings suggest that observed differences in treatment effects between obese and non-obese patients sometimes seen in trials of asthma treatments are unlikely to be due to different "placebo" effects of treatment and may reflect differential physiologic effects of active agents.

IN-HOSPITAL OUTCOMES IN PATIENTS WITH OBESITY AND ACUTE ASTHMA EXACERBATION

TOPIC: Obstructive Lung Diseases TYPE: Original Investigations PURPOSE: According to United States national surveys, prevalence of obesity is 42.4% and asthma is 7.7%. Obesity is a known risk factor and disease modifier of asthma. The purpose of this study is to evaluate the effect of obesity on in-hospital mortality, intubation rates, and length of stay in hospitalized patients with acute asthma exacerbation. METHODS: We performed a retrospective study by utilizing the 2016 National inpatient sample database, which comprises data on 20% of hospital discharges for that year. We included patients aged 18 or older who were admitted to the hospital with a principal diagnosis of acute asthma exacerbation or acute hypoxic respiratory failure with a secondary diagnosis of asthma in the study. Obesity was defined as Body Mass Index of 30 or greater. Diagnosis data was obtained by utilizing ICD 10 CM codes. The sample size was adjusted to the weights provided. A multivariate logistic regression model was used to analyze the effect of obesity on mortality and intubation rate. Linear regression was used to analyze the effect of obesity on length of stay. All outcomes were adjusted to age, sex, race, insurance status, Charlson Comorbidity Index, hospital location and characteristics. RESULTS: A total of 135,710 patients were included in the study, of which 34,845 patients met criteria for having acute asthma exacerbation with obesity (AOE). Mean age was 50.1 years (SD 14.9) and 81.01% of patients were female. A total of 10.04% (350) died and 5.4 % intubated in the AOE group. Adjusted Odds Ratio for mortality 0.74 (CI 0.54-0.99, p = 0.045), and intubation 0.8 (CI 0.71-0.91, p = 0.01). Mean length of stay was 4.07 for the AOE group and 3.4 for acute asthma exacerbation without obesity. Adjusted length of stay was a 0.56-day longer in the obese group. CONCLUSIONS: Obese patients with an acute asthma exacerbation were found to have 26% lower odds of in-hospital death and 20% lower intubation rate compared with non-obese patients in a large nationally representative sample. A longer length of stay, however, was found in the obese group compared to the non-obese group. Female gender, 81% of obese asthma patients in cohort, may be one contributing factor to the lower adjusted mortality and intubation rates. CLINICAL IMPLICATIONS: To our knowledge, there are no studies that looked at in-hospital outcomes in patients with acute asthma exacerbation and obesity. This paradox of obesity being beneficial was reported in patients with stroke, myocardial infarction, heart failure, sepsis, renal disease, and requirement of intensive care admission. Future studies looking for pathophysiological mechanisms of obesity reducing acute asthma exacerbation inpatient mortality might help to improve outcomes in acute asthma. DISCLOSURES: No relevant relationships by aniesh bobba, source=Web Response No relevant relationships by karthik Gangu, source=Web Response No relevant relationships by Zachary Holliday, source=Web Response No relevant relationships by Tarang Patel, source=Web Response No relevant relationships by Esha Sharma, source=Web Response

Particularities of asthma in obese patients

AimTo evaluate the impact of obesity on the control and the severity of asthma in a Tunisian population. MethodsIt was a retrospective, descriptive and analytic study, including asthmatic patients regularly followed up in the pulmonology department of Charles Nicolle's hospital of Tunis, during 18 months (January 2016 to June 2017). Data were collected from medical records, including characteristics of asthma and nutritional status based on body mass index. ResultsOut of the 170 included patients, 126 (74%) were women. They had an average BMI of 28.6 kg/m2±5.8 (17 to 54.5 kg/m2). Obesity was present in 32.9% of patients. Asthma was well controlled in 56% of cases and no controlled in 37%. It was classified as moderate in 48.8% and severe in 15.9%. Compared to normal weight asthmatics, obese asthmatics were more advanced (P=0.002), mostly women (P=0.002) and had more co-morbidities (P=0.049). They were more symptomatic (P=0.037) and had lower Forced Vital Capacity (P<0.001) and lower Forced Expiatory Volume 1st second (P=0.017).Multivariate analysis, after adjustment for age, smoking and GERD, revealed that obesity tripled the risk of uncontrolled asthma (OR=3; 95% CI [1.2-7.6]; P=0.019). However, asthma severity was not impacted by obesity. ConclusionsDespite the discrepancy of our results with those reported in the literature regarding the relationship between obesity and asthma severity, our study was able to confirm the deleterious effect of obesity on asthma control. We, therefore, emphasize the importance of taking account of obesity and its management, especially in patients with poorly controlled asthma.

Dysregulated Metabolism in the Pathophysiology of Non-Allergic Obese Asthma.

Asthma is an obstructive airway disease that is characterized by reversible airway obstruction and is classically associated with atopic, TH2 driven inflammation. Landmark studies in the second half of the twentieth century identified eosinophils as a key mediator of inflammation and steroids, both inhaled and systemic, as a cornerstone of therapy. However, more recently other phenotypes of asthma have emerged that do not respond as well to traditional therapies. In particular, obese patients who develop asthma as adults are less likely to have eosinophilic airway inflammation and do not respond to traditional therapies. Obese patients often have metabolic comorbidities such as impaired glucose tolerance and dyslipidemias, also known as metabolic syndrome (MetS). The unified pathophysiology of metabolic syndrome is not known, however, several signaling pathways, such as the neuropeptide glucagon-like peptide-1 (GLP-1) and nitric oxide (NO) signaling have been shown to be dysregulated in MetS. These pathways are targeted by commercially available medications. This review discusses the potential roles that dysregulation of the GLP-1 and NO signaling pathways, along with arginine metabolism, play in the development of asthma in obese patients. GLP-1 receptors are found in high density in the lung and are also detectable in bronchoalveolar lavage fluid. NO has long been associated with asthma. We hypothesize that these derangements in metabolic signaling pathways underpin the asthmatic phenotype seen in obese patients with non-eosinophilic airway inflammation and poor response to established therapies. While still an active area of research, novel interventions are needed for this subset of patient who respond poorly to available asthma therapies.