Study to Evaluate the Effects of Weight Loss on Airway Inflammation and Mechanics in Subjects With Asthma (Asthma-Bariatric Surgery Study)
Condition: Asthma
MeSH terms: Asthma; Inflammation; Weight Loss
Study type: Observational

Summary: 
      Current research shows that obesity greatly increases the risk of developing asthma. Although
      the two conditions are clearly related, experts do not fully understand why they are linked.
      Some researchers believe that hormones released in the fat cells (adipokines) play a role.
      Others believe that excess weight pressing on the lungs triggers the hyperreactive response
      in the airways that is typical of asthma.

      The goal of the Asthma-Bariatric Surgery Study is to determine how weight loss affects lung
      function and various biological parameters. Bariatric (weight loss) surgery refers to the
      various surgical procedures performed to treat obesity. Specifically, this study is designed
      to answer the following questions:

        -  Does bariatric surgery help patients control their asthma?

        -  How much asthma control can be achieved through weight loss?

        -  How does weight loss influence lung function?

      Participants in this observational research study will be asked to complete study visits at
      enrollment, 1 month, 6 months, and 12 months. Questionnaires, pulmonary function tests, and
      blood samples will be required at each time point.

      This research study is observational only; it does not cover the cost of (or provide)
      bariatric surgery. Optional genetic and bronchoscopy substudies are included as well.
    

Detailed description: 
      This study is designed to explain the unexpected effects of obesity on NO bioavailability in
      the airways of asthmatics: Specifically, that obesity induces systemic oxidative stress in
      part through increased production of reactive oxygen species (ROS) in adipose tissue and, in
      parallel (or as a consequence), increased systemic levels of tumor necrosis factor (TNF-α)and
      8-isoprostanes. Furthermore, it creates an imbalance in the regulation of protective
      anti-oxidant thiol/disulfide pairs such as glutathione/glutathione disulfide. We hypothesize
      that in asthmatics, the lung is a target-organ of this obesity-related systemic oxidative
      stress. This is manifested as increased oxidation of airway NO into nitrate and reactive
      nitrogen species (RNS) including peroxynitrate and nitrotyrosine, thereby reducing NO
      bioavailability and exhaled NO levels. NO has many key physiological properties including
      bronchodilation, anti-tumoral/bactericidal activity, and anti-inflammatory and anti-oxidative
      activity. Thus, reduced NO bioavailability in obese asthmatics could favor increased
      bronchoconstriction and impair the lung's ability to respond to further oxidative or
      inflammatory challenges. Therefore, we hypothesize that: 1) obesity causes redox stress in
      the airway, which in turn decreases the bioavailability of NO by shunting it into RNS, 2)
      that weight loss will decrease systemic oxidative stress and thereby increase NO
      bioavailability due to decreased oxidation into RNS, and 3) that by decreasing systemic
      oxidative stress, weight loss will reduce bronchial hyper-reactivity.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Obese asthmatics
      
Biospecimen description: 
      Blood and exhaled breath condensate samples will obtained at all time points (baseline, 1
      month, 6 months, and 1 year.
    
Keywords: Asthma, obesity, bariatric