Inhalation of Nitric Oxide Modulates Adult Human Bronchial Tone

Abstract

We studied whether nitric oxide (NO), added at 80 ppm to inspired gas, can exert a bronchodilatory effect in humans. Four groups were studied: (1) healthy adult volunteers (n = 6), (2) adult subjects with hyperreactive airways (n = 6) during provocation with inhaled methacholine (MCh), (3) patients with bronchial asthma (n = 13), and (4) patients with chronic obstructive pulmonary disease (COPD, n = 6). All subjects were studied in a body plethysmograph, measuring volume-corrected specific airway conductance (SGaw). No patient or volunteer reacted with bronchoconstriction during NO inhalation. Nitric oxide did not affect SGaw in healthy volunteers or in patients with COPD. Inhaled NO modulated the MCh-induced bronchoconstriction toward dilatation. In patients with bronchial asthma, SGaw increased (p < 0.05) from 0.4 +/- 0.1 to 0.6 +/- 0.2 (kPa.s)-1. In a succeeding test with inhalation of a beta 2-agonist immediately after NO inhalation, a more marked increase in SGaw was seen, to 1.2 +/- 0.3 (kPa.s)-1 (p < 0.001). We conclude that NO inhaled at 80 ppm has no effect on airway tone in healthy volunteers, but modulates the response to MCh provocation toward bronchodilation. It exerts a weak bronchodilatory effect in bronchial asthma, but not in COPD.

Nitric oxide metabolites in induced sputum: a marker of airway inflammation in asthmatic subjects

“…Glucocorticoids such as dexamethasone, hydrocortisone, and cortisol inhibit the induction of the Ca 2þ -independent NOS with no effect on the activity of either the constitutive or inducible enzymes [29]. Inhalation of NO by patients with mild asthma with methacholine-induced bronchospasm results in a minor, but significant relaxation of airway tone [30,31]. Exhaled NO may be a useful way of monitoring the anti-inflammatory effects of glucocorticoids and other anti-inflammatory treatments in asthma [32].…”

The role of interferon-gamma on immune and allergic responses

“…Through the induction of NO production, IFN-γ inhibits IgE-mediated degranulation of mast cells (Eastmond et al 1997). Moreover, NO itself is a bronchodilator, and inhalation of high concentrations of NO has resulted in a small bronchodilatory response in asthmatic patients (Högman et al 1993). NO has also shown a role in inhibiting proliferation and DNA synthesis in airway smooth muscle cells (Patel et al 1999).…”

Inhaled nitric oxide: clinical applications, indications, and toxicology

“…6~ The same dose had no effect on airway tone of healthy volunteers and COPD patients, and only weak bronchodilatory effect in asthmatic patients. 61 There is a relative dose/effect relationship with increased doses showing successively stronger effects on oxygenation, pulmonary hypertension, and broncbomotor tone.…”

“…61 The safety levels of the above mentionned administrative authorities are based on earlier studies on NO and NO 2 toxicity. Interpretation of those studies in the context of long-term administration of inhNO is complicated by several factors.…”