Exhaled Breath Condensate Biomarkers of Inflammation in Individuals With Chronic Cervical Spinal Cord Injury
Condition: Tetraplegia; Asthma
MeSH terms: Spinal Cord Injuries; Quadriplegia; Inflammation
Study type: Observational

Summary: 
      The purpose of this study is to obtain markers of airway inflammation from the exhaled breath
      condensate (the moisture in exhaled air) for comparison to blood based markers. These markers
      will be compared in tetraplegic, asthmatic and able-bodied control groups. Additionally, lung
      function testing will be performed, and the associations between breath condensate and blood
      markers and pulmonary function explored between groups.
    

Detailed description: 
      The predominant mechanism for pulmonary dysfunction in individuals with chronic tetraplegia
      is respiratory muscle paralysis. This leads to inadequate ventilation and inability to clear
      secretions placing these patients at a greater risk for the development of respiratory
      complications. Furthermore, individuals with chronic tetraplegia exhibit baseline increases
      in airway tone (bronchoconstriction), restoration of normal airway caliber following
      bronchodilator administration, and non-specific airway hyperresponsiveness (AHR) following
      inhalation of methacholine, histamine, an aerosolized distilled water. These findings in
      persons with spinal cord injury (SCI) represent pulmonary features commonly seen in
      individuals with asthma. Alternatively, airway inflammation may play a role in the
      obstructive physiology observed in individuals with tetraplegia. In this population,
      identification of cellular inflammation would confirm the presence of underlying inflammation
      with a sputum induction. However, this method is hard to perform due to an impaired cough.

      The emerging field of exhaled breath condensate (EBC) biomarkers of inflammation offers a
      non-invasive technique to define the presence of, and potentially address the contributing
      factors of airway inflammation in the respiratory tract of individuals with tetraplegia. It
      is thought that EBC composition reflects biochemical changes of airway lining fluid. EBC
      contains a large number of mediators, including adenosine, ammonia, hydrogen peroxide (H2O2),
      isoprostanes, leukotrienes, prostanoids, peptides and cytokines. Looking at exhaled breath
      profiles of various biomarkers may be used to differentiate their different
      pathophysiological mechanism of inflammation. In addition, measurements of some chemokines
      (TNF-ά, interleukin (IL)-6) and inflammatory biomarkers (LTB4) in EBC and blood
      simultaneously may help differentiate the degree of local vs. systemic inflammation.
      Understanding the underlying mechanisms involved in pulmonary dysfunction observed in persons
      with chronic cervical SCI may identify treatment options, such as use of inhaled steroids.
      This approach would be expected to ultimately improve quality of life in affected
      individuals, decreasing the rate of re-hospitalizations due to respiratory complications and
      the socioeconomic burden placed on these with SCI and the health care system.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        1. Chronic stable tetraplegia (duration of injury > 1 year) matched for age, gender, and
             BMI with healthy control subjects, and clinically stable mild asthmatic subjects. The
             subjects approached will have already consented to, or be actively participating in
             "Effects of Nitric Oxide Synthase Inhibitor on Levels of Exhaled NO and Airway Tone in
             Subjects with Chronic Cervical Spinal Cord Injury" study.

          2. Clinically stable mild asthmatic subjects (as defined by NIH asthma guidelines) [51].

          3. Healthy able-bodied individuals.
      
Biospecimen description: 
      Exhaled Breath Condensate Blood Serum
    
Keywords: Airway inflammation; Tetraplegia; Asthma; Exhaled breath condensate; Spirometry; Pulmonary Function Testing