Exhaled Levels of Nitric Oxide
Condition: Tetraplegia; Asthma
MeSH terms: Quadriplegia
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Previously it was observed that individuals with tetraplegia have reduced baseline airway
      caliber and exhibit non-specific airway hyperresponsiveness (AHR). In persons with
      tetraplegia we have suggested that this is due to overriding cholinergic airway tone. In
      asthma, the mechanisms underlying bronchoconstriction and AHR are more closely tied to airway
      inflammation. Whether AHR in tetraplegia is also related to chronic airway inflammation is
      unknown.

      Recently, a non-invasive technique for assessing airway inflammation has been established in
      asthma that involves measurement of nitric oxide (NO) concentrations (FeNO) in expired air.
      FeNO is elevated in asthma likely due to excess NO production by inflammatory cells within
      the airway Measurement of FeNO in persons with tetraplegia would help in assessing the role
      of airway inflammation in this population. This may have therapeutic significance in such
      individuals. NO in the lung is felt to be the principal inhibitory neurotransmitter of the
      non-adrenergic, non-cholinergic (NANC) system. It is thought that inhalation of NO has no
      effect on airway tone in healthy individuals but reduces methacholine responsiveness while
      having weak direct bronchodilatory effect in asthmatics.

      The primary purpose of this study is to determine the levels of exhaled NO (FeNO) in
      individuals with chronic cervical spinal cord injury (SCI), and to compare them with those
      obtained in age and sex matched able-bodied individuals and subjects with stable mild to
      moderate asthma. If the FeNO levels are high and comparable to those found in asthmatic
      subjects, this will imply the role of chronic inflammation in reduced baseline airway caliber
      and non-specific airway hyper-responsiveness (AHR) exhibited by individuals with chronic
      cervical SCI. If the FeNO levels are comparable with those found in able-bodied controls,
      this will support our previous statement that unopposed cholinergic innervation is
      responsible for low baseline airway caliber and AHR in individuals with chronic tetraplegia.
      Further scientific conclusions about NO and its role in control of airway tone, pulmonary
      resistances and blood pressure will be drawn upon intravenous and inhaled administration of
      L-NAME. This compound has been shown promising results for the treatment and prevention of
      orthostatic hypotension in individuals with tetraplegia. Knowing its effects on airways and
      potential of easier mode of delivery (inhalation vs. intravenous) is of utmost importance.
    

Detailed description: 
      The study requires a maximum of five study visits in the following order: 1. nebulized normal
      saline, 2. nebulized 1mg/kg of L-NAME (see below), 3. intravenous normal saline, 4.
      intravenous 1 mg/kg L-NAME, 5. intravenous 2 mg/kg L-Name.
    

Intervention name(s): N-Nitro L-arginine-methylester (L-NAME)
Intervention type(s): Drug
Intervention description(s): A non-specific inhibitor of the nitric oxide synthase enzyme.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Tetraplegia; Mild asthma; Exhaled Nitric Oxide; NOS inhibitor; Spinal cord injury; Pulmonary Function