Exhaled Levels of Nitric Oxide

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.

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.

Eligibility Criteria:
Inclusion Criteria:

1. Written informed consent.
2. Age between 18 and 65 years.
3. Able-bodied individuals, persons with mild asthma or individuals with tetraplegia for at least one year of duration.
4. Able to perform acceptable pulmonary function tests and follow procedures.

Exclusion Criteria:

1. coronary artery disease;
2. active cigarette smokers or previous smokers who stopped \<5 years ago;
3. MI or stroke within 3 months;
4. moderate to severe reduction in lung function defined as FEV1 \< 70 % predicted (except in individuals with tetraplegia);
5. hypertension;
6. medications known to affect the cardiovascular system;
7. pregnancy
8. current use of cholinesterase medication; and
9. lack of mental capacity to give informed consent Group specific exclusion criteria for

Asthmatic subjects:

1. Moderate to severe disease as per spirometric indices;
2. testing within 48 hours of last administration of long acting inhaled bronchodilator;
3. testing within 7 days of last administration of glucocorticoids;
4. testing within \> 24 hours since last administration of leukotriene modifiers; and
5. testing within 8 hours of last administration of a short acting bronchodilator medication