Levels of Serum Resistin in Asthmatics as a Potential Marker of Systemic Inflammation and Disease State.
Condition: Asthma
MeSH terms: Inflammation
Study type: Observational

Summary: 
      The purpose of this study is to determine whether serum resistin levels in asthmatics are
      elevated. We will recruit subjects from the allergy/immunology clinic with a prior diagnosis
      of moderate to severe persistent asthma in addition to subjects being seen for evaluation of
      drug allergies. Based on the inclusion and exclusion criteria below, subjects will be placed
      into a control and asthma group. Each subject will undergo one blood draw in the main lab at
      WHMC, and return a lavender top tube to the allergy/immunology clinic for the EIA resistin
      assay. The patient will then have a brief encounter with a physician to determine an up to
      date history of asthma symptoms prior to participating in the exhaled NO test. The entire
      subject encounter will take place with one clinic visit, and requires no follow up visits as
      part of the study. The greatest risk to each subject will be the blood draw, as the exhaled
      NO is a completely non-invasive test.

      Plasma from each subject will be stored in a -70° freezer for no more than one month. Samples
      will be analyzed for resistin levels using an EIA assay run monthly. Mean values from serum
      CRP, serum glucose, serum resistin, and exhaled NO will be compared using a students T-test.
    

Detailed description: 
      Resistin is part of the FIZZ (found in inflammatory zones) family of genes, and was first
      characterized in murine models where it has been extensively studied as a potential link
      between type II diabetes and obesity. The murine FIZZ gene family consists of three related
      gene products: a)FIZZ-1 or Relm-a is found in adipocytes and lung tissue, b)FIZZ-2 or Relm-b
      found in the gastrointestinal tract, and c)FIZZ-3 or Resistin also found in adipocytes.1
      Mouse models have shown resistin to be linked to obesity and insulin resistance, and
      thiazolidinedione has been shown to decrease resistin expression in mouse adipocytes.2
      Distribution of the FIZZ gene products in humans is similar to mouse models: a)Relm-a is
      found in adipose, heart, and lung, b)Relm-b is found in the gastrointestinal tract, and
      c)Resistin is found in adipocytes and interestingly, is also found in circulating
      macrophages.3 Given the findings correlating obesity with diabetes in the mouse model,
      several studies were done in humans attempting to illustrate this same link. A study
      comparing middle age type II diabetics with matched controls found serum resistin levels to
      be increased in the diabetic group (16.6 vs 13.5, p<0.004), but this elevation was
      independent of adiposity, BMI, or insulin resistance. Elevation in C-reactive protein (CRP)
      in the diabetic group was the only factor that consistently correlated with elevation in
      resistin levels in this study.4 A second study comparing older (60-75 years of age) type II
      diabetics also found a significant elevation in serum resistin in the diabetic group that was
      independent of gender, insulin resistance, BMI, blood pressure, or total cholesterol.
      Interestingly, this study did find an association with plasma glucose concentration and serum
      resistin levels.5 Although there seems to be no direct link between resistin and insulin
      resistance in humans, the above data suggest a role for insulin in systemic inflammation
      commonly associated with diabetes. Adipocytes are known to be a source of inflammatory
      cytokines such as TNF-a and IL-6. TNF-a has been shown to be elevated in obesity, and many
      acute phase reactants and cytokines are associated with diabetes and the metabolic syndrome.6
      In addition, resistin has been shown to induce VCAM-1, ICAM-1, and long pentraxin 3 (markers
      of vascular inflammation) in mouse models. The resistin related induction of VCAM-1 was
      partially blocked with a statin, indicating a role for resistin in vascular inflammation that
      may contribute to atherosclerosis and coronary artery disease seen in diabetics and the
      metabolic syndrome.7 Given the effects on vascular inflammation, resistin may be an important
      cytokine involved in a common inflammatory pathway seen in both diabetics and asthmatics.

      Like diabetes, asthma is a disease marked by chronic inflammation. The inflammation
      associated with asthma has been predominantly illustrated in the airways, however, studies
      have shown that induced bronchoconstriction and asthma do illicit a systemic response with
      elevations in CRP thought to be mediated by IL-1, IL-6, and TNF-a via activated
      macrophages.8,9 In addition, CCL2 contributes to airway hyper-reactivity and cell migration,
      and thiazolidinedione has been shown to inhibit the IL-1b and TNF-a induced expression of
      CCL2 in the lung.10 Finally, a recent study illustrated an IL-4 and IL-13 induction of Relm-b
      via STAT-6 in response to allergic asthma.11 The level of serum resistin in human asthmatics
      is currently unknown, and may represent an important systemic marker of inflammation in this
      disease. Relating levels of serum resistin with disease state in conjunction with
      measurements of serum CRP and glucose would be an important aspect of further understanding
      the potential systemic inflammatory implications of asthma. In addition, unpublished data on
      exhaled NO have shown a positive correlation with asthma that could be used to further
      strengthen evidence of systemic inflammation with airway inflammation.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients enrolled to Wilford Hall Medical Center meeting the above eligibility criteria.
      
Keywords: Resistin; Asthma; CRP; Diabetes; FIZZ