Body Mass and Glucocorticoid Response in Asthma

Sutherland, E. Rand; Goleva, Elena; Strand, Matthew; Beuther, David A.; Leung, Donald Y.M.

doi:10.1164/rccm.200801-076oc

Cited by 305 publications

(228 citation statements)

References 34 publications

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“…Obese (BMI, .30) and overweight (BMI, 25-30) subjects were pooled into one group denoted as "OA" for overweight/obese asthma and "ON" for normal control subjects (20). Subjects with asthma met National Asthma Education and Prevention Program criteria for mild asthma; had physiciandiagnosed asthma, the presence of reversible airflow obstruction, and a methacholine PC 20 (provocative concentration of methacholine causing a 20% fall in FEV 1 ) not greater than 8 mg/ml; and used only rescue bronchodilators. Healthy subjects had a methacholine PC 20 greater than 16 mg/ml, no evidence of airflow obstruction, and no history of pulmonary disease.…”

Section: Study Subjectsmentioning

confidence: 99%

Alveolar Macrophages from Overweight/Obese Subjects with Asthma Demonstrate a Proinflammatory Phenotype

Lugogo¹,

Hollingsworth

Howell³

et al. 2012

Am J Respir Crit Care Med

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Rationale: Obesity is associated with increased prevalence and severity of asthma. Adipose tissue macrophages can contribute to the systemic proinflammatory state associated with obesity. However, it remains unknown whether alveolar macrophages have a unique phenotype in overweight/obese patients with asthma. Objectives: We hypothesized that leptin levels would be increased in the bronchoalveolar lavage fluid from overweight/obese subjects and, furthermore, that leptin would alter the response of alveolar macrophages to bacterial LPS. Methods: Forty-two subjects with asthma and 46 healthy control subjects underwent research bronchoscopy. Bronchoalveolar lavage fluid from 66 was analyzed for the level of cellular inflammation, cytokines, and soluble leptin. Cultured primary macrophages from 22 subjects were exposed to LPS, leptin, or leptin plus LPS. Cytokines were measured in the supernatants. Measurements and Main Results: Leptin levels were increased in overweight/obese subjects, regardless of asthma status (P ¼ 0.013), but were significantly higher in overweight/obese subjects with asthma. Observed levels of tumor necrosis factor-a were highest in overweight/obese subjects with asthma. Ex vivo studies of primary alveolar macrophages indicated that the response to LPS was most robust in alveolar macrophages from overweight/obese subjects with asthma and that preexposure to high-dose leptin enhanced the proinflammatory response. Leptin alone was sufficient to induce production of proinflammatory cytokines from macrophages derived from overweight/obese subjects with asthma. Conclusions: Ex vivo studies indicate that alveolar macrophages derived from overweight/obese subjects with asthma are uniquely sensitive to leptin. This macrophage phenotype, in the context of higher levels of soluble leptin, may contribute to the pathogenesis of airway disease associated with obesity.Keywords: tumor necrosis factor-a; leptin; innate immunity; lipopolysaccharide; environmental lung disease There is an increased risk of developing asthma in individuals who are overweight and obese (subsequently referred to as overweight/obese) (1-5). The risk of asthma increases steadily with increasing body mass index (BMI) and is higher in women (1, 6). Furthermore, BMI negatively impacts asthma quality of life scores, asthma control scores, severity of exacerbations, and asthma-related hospitalizations (6-9). Together, these studies suggest a role of obesity in the pathogenesis of asthma. However, the mechanisms by which obesity may contribute to airway disease remain poorly understood.Evidence suggests that adipose tissue is metabolically active, participating not only in energy homeostasis but also in inflammation (12). Adipose tissue secretes biologically active cytokines, including tumor necrosis factor (TNF)-a and IL-6, as well as adipokines, including leptin, adiponectin, plasminogen activator inhibitor (PAI)-1, and resistin (10, 11). Obesity is associated with systemic inflammation, which is characterized by elevated serum levels of...

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Section: Study Subjectsmentioning

confidence: 99%

Alveolar Macrophages from Overweight/Obese Subjects with Asthma Demonstrate a Proinflammatory Phenotype

Lugogo¹,

Hollingsworth

Howell³

et al. 2012

Am J Respir Crit Care Med

View full text Add to dashboard Cite

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“…[4][5][6][7][8][9][10] Although the mechanisms driving the association between obesity and in-hospital outcomes are not fully known, for asthma it is believed that adipocytes expressing inflammatory markers create a low level of systemic inflammation, thereby increasing the severity of allergic-type illnesses and decreasing the response to anti-inflammatory medications, such as steroids. [11][12][13][14][15][16][17][18] The relationship of obesity and in-hospital asthma outcomes is of particular interest because status asthmaticus is the most common reason for admission in children aged 3 to 12 years, accounting for approximately 150,000 admissions (7.4% of all hospitalizations for children and adolescents) and $835 million in hospital costs annually. 19 Few prior studies have examined the association of obesity and asthma outcomes in the in-hospital setting.…”

Section: Resultsmentioning

confidence: 99%

“…The median number of albuterol treatments in the inpatient setting was 14 (IQR, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. When albuterol treatments given in the ED were included, the median number of treatments increased to 38 (IQR, .…”

Section: Los and Resource Utilizationmentioning

confidence: 99%

Childhood obesity and in-hospital asthma resource utilization

et al. 2014

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OBJECTIVE: To examine the relationship between pediatric obesity and inpatient length of stay (LOS), resource utilization, readmission rates, and total billed charges for inhospital status asthmaticus. DESIGN/METHODS:We conducted a cross-sectional study of patients 5 to 17 years old hospitalized with status asthmaticus to 1 free-standing children's hospital system over 12 months. Only hospitalized patients initially treated in the hospital's emergency department were included to ensure all therapies/charges were examined. Patients with complex chronic conditions, pneumonia, or lacking recorded body mass index (BMI) were excluded. The primary exposure was BMI percentile for age. The primary outcome was LOS (in hours). Secondary outcomes were 90-day readmission rate, billed charges, and resource utilization: number of albuterol treatments, chest radiographs, intravenous fluids, intravenous or intramuscular steroids, and intensive care unit admission. Bivariate, adjusted Poisson and logistic regression model analyses were performed. RESULTS:Five hundred eighteen patients met inclusion criteria. Most had a normal BMI (59.7%); 36.7% were overweight or obese. LOS, readmissions, and resource utilization outcomes were not associated with BMI category on bivariate analyses. After adjustment for demographic/ clinical characteristics, LOS decreased by 2% for each decile increase in BMI percentile for age. BMI percentile for age was not associated with billed charges, readmissions, or other measures of resource utilization.CONCLUSIONS: Although BMI decile for age is inversely associated with LOS for in-hospital pediatric status asthmaticus, the effect likely is not clinically meaningful. Pediatric hospitalizations for obesity-related conditions have doubled in the last decade, mirroring the trend of higher levels of childhood obesity in the United States. [1][2][3] Recent studies have demonstrated worsened pediatric in-hospital outcomes, including mortality and increased resource utilization, for children with obesity across a range of diagnoses. [4][5][6][7][8][9][10] Although the mechanisms driving the association between obesity and in-hospital outcomes are not fully known, for asthma it is believed that adipocytes expressing inflammatory markers create a low level of systemic inflammation, thereby increasing the severity of allergic-type illnesses and decreasing the response to anti-inflammatory medications, such as steroids. [11][12][13][14][15][16][17][18] The relationship of obesity and in-hospital asthma outcomes is of particular interest because status asthmaticus is the most common reason for admission in children aged 3 to 12 years, accounting for approximately 150,000 admissions (7.4% of all hospitalizations for children and adolescents) and $835 million in hospital costs annually. 19 Few prior studies have examined the association of obesity and asthma outcomes in the in-hospital setting. The studies examining this association have found patients with obesity to have a longer hospital length of stay (LOS) and i...

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“…Factors associated with a diminished dose response to ICSs include genetic polymorphisms, COPD, smoking, severe asthma, obesity, and vitamin D insufficiency (8,(19)(20)(21)(22). Patients with asthma who are homozygous for the variant allele rs37973, which maps to the glucocorticoid-induced transcript 1 gene (GLCCI1), show about one third the lung function response of that of those homozygous for the wild-type allele (19).…”

Section: Pharmacokineticsmentioning

confidence: 99%