Obesity and Asthma: Determinants of Inflammation and Effect of Intervention
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 110
- 试验地点
- 2
- 主要终点
- exhaled nitric oxide, [eNO] change
研究概览
简要总结
Obesity is recognized as a pro-inflammatory condition associated with multiple chronic diseases, including asthma. The specific mechanisms linking asthma and obesity remain hypothetical. Our primary hypothesis is that inflammatory SNPs may regulate the degree of the inflammatory response, with obesity modifying the severity of the disease. In this instance, asthma that develops in the context of obesity demonstrates the potential deleterious relationship between a specific proinflammatory state (obesity) and the genetic regulators of inflammation (SNPs). Our secondary hypothesis proposes that short-term (12-weeks) weight loss by diet alone, but not exercise alone, will reduce lung specific inflammation and diminish the pro-inflammatory responses in female African American obese adolescents with asthma compared to a waiting list control group who after their initial 12 weeks then receive a combined 12-week diet plus exercise program (waiting list control/combined). A third exploratory hypothesis proposes that the frequency of identified SNPs will be significantly related to the amount of fat loss through diet, exercise or combined program and will further be mediated by specific airway and, pro-and-anti-inflammatory markers.These hypotheses will be tested using the following Specific Aims:
- To determine the frequency of single nucleotide polymorphisms and SNP haplotypes in pro- and anti-inflammatory genes in female African American obese and non-obese asthmatic and non-asthmatic adolescents, 13-19 years or age.
- To examine the effects of diet or exercise on lung specific inflammation (exhaled nitric oxide, [eNO]) and pro-and-anti-inflammatory responses in female African-American obese asthmatic and non-asthmatic adolescents compared to a waiting list control/ combined group.
In addition we will examine the following Exploratory Aim:
To determine the effects of the inflammatory SNPs in the modulation of several inflammatory markers and lung specific inflammation (eNO) in female African-American obese asthmatic and non-asthmatic adolescents before and after weight loss through diet, exercise or both.
详细描述
Our primary hypothesis is that inflammatory SNPs may regulate the degree of the inflammatory response, with obesity modifying the severity of the disease. In this instance, asthma that develops in the context of obesity demonstrates the potential deleterious relationship between a specific proinflammatory state (obesity) and the genetic regulators of inflammation (SNPs).
Our secondary hypothesis proposes that short-term (12-weeks) weight loss by diet alone, but not exercise alone, will reduce lung specific inflammation and diminish the pro-inflammatory responses in female African American obese adolescents with asthma compared to a waiting list control group who after their initial 12 weeks then receive a combined 12-week diet plus exercise program (waiting list control/combined). A third exploratory hypothesis proposes that the frequency of identified SNPs will be significantly related to the amount of fat loss through diet, exercise or combined program and will further be mediated by specific airway and, pro-and-anti-inflammatory markers. Specific aims include:
- To determine the frequency of single nucleotide polymorphisms and SNP haplotypes in pro- and anti-inflammatory genes in female African American obese and non-obese asthmatic and non-asthmatic adolescents, 13-19 years or age.
- To examine the effects of diet or exercise on lung specific inflammation (exhaled nitric oxide, [eNO]) and pro-and-anti-inflammatory responses in female African-American obese asthmatic and non-asthmatic adolescents compared to a waiting list control/ combined group.
- To determine the effects of the inflammatory SNPs in the modulation of several inflammatory markers and lung specific inflammation (eNO) in female African-American obese asthmatic and non-asthmatic adolescents before and after weight loss through diet, exercise or both.
We will conduct a cross-sectional analysis of 4 groups of African American adolescent (13-19 years) females as follows: Group 1A: Obese with asthma Group 1B: Non-obese with asthma Group 1C: Obese non-asthmatics Group 1D: Non-obese, non-asthmatics
Patients included in this part of the study will be female African American obese and non-obese asthmatic adolescents, 13-19 years, as defined by United States Centers for Disease control (USCDC 2000 sex specific Body Mass Index (BMI)-for-age growth charts. As controls we will include female African American obese, non asthmatic adolescents and healthy age matched controls (non-obese, non-asthmatics).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 13 Years 至 19 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •African American Females with an age of 13-19 years will be recruited. Our aim is to target high school age youth who are most likely to exhibit autonomy and authority to control both their nutrition and exercise regimens. In addition this age range is representative of the age group most likely to access school based health centers for recruitment purposes. Lastly, the study includes the collection of blood samples for the purpose of examining varied physiologic parameters that are affected by maturation. Participants above the age of 13 are most likely pubertal and thus, less likely to be affected by maturation issues.
排除标准
- •Presence of other chronic pulmonary or systemic disease.
- •Presence of moderate or severe atopic dermatitis or allergic rhinitis.
- •Severe asthmatic based upon American Thoracic Society (ATS) standards and/or NIH guidelines.
- •Acute lower respiratory infection in the last 2 weeks before baseline eNO evaluation.
- •Pregnant are nursing mothers Study participants and parents (s) will be advised of the known risks and consequences associated with the testing and also of the reasonably known risks and consequences of not undergoing testing.
- •Severe or uncontrolled asthmatics will not be allowed to participate.
- •Participants with a recent (in the last 2 weeks) lower respiratory infection will not be allowed to participate.
结局指标
主要结局
exhaled nitric oxide, [eNO] change
时间窗: Baseline visit and and post intervention at 13 to 15 weeks
Exhaled nitric-oxide (eNO; to be performed at baseline visit and post intervention at 13 to 15 weeks): The eNO level will be measured by chemiluminescence gas analyzer (Niox®), standardized according to the American Thoracic Society guidelines, 1999 \[29\]. NO is produced in healthy airway for normal physiologic functions (maintaining airway patency). It is formed during airway inflammation and may contribute to oxidative stress. It is overproduced in the lungs of asthmatic patient. Evidence suggests that eNO may be used as marker for lung inflammation \[30-33; 112\].
次要结局
- Body Mass Index Change(Baseline visit and and post intervention at 13 to 15 weeks)
- HbA1C (Hemoglobin A1C or Glycosylated hemoglobin change(Baseline visit and and post intervention at 13 to 15 weeks)
- HOMA-IR (homeostasis model assessment-estimated insulin resistance change(Baseline visit and and post intervention at 13 to 15 weeks)
- Weight in kilograms(Baseline visit and and post intervention at 13 to 15 weeks)
- Single nucleotide polymorphisms (SNPs)(Baseline clinical visit)
- Serum inflammatory markers change(Baseline visit and and post intervention at 13 to 15 weeks)
- Lipid profile change(Baseline visit and and post intervention at 13 to 15 weeks)
- Arginase activity(Baseline clinical visit)
- myeloid-derived suppressor cells (MDSC)(Baseline clinical visit)
- Height in centimeters(Baseline visit and and post intervention at 13 to 15 weeks)
研究者
Melinda Sothern
Professor
Louisiana State University Health Sciences Center in New Orleans