The effect of inhaled nitric oxide in pediatric asthma.

Abstract

Nitric oxide (NO) appears to play an important role in regulating several biologic functions in the lung, including modulation of pulmonary arterial and bronchial smooth muscle tone. Recent studies have shown that relatively high concentrations of inhaled NO reduce the bronchoconstrictor effect of methacholine in animal models. This raises the possibility that NO inhalation might have therapeutic potential as an alternative bronchodilator. Although investigation of this potential in adults with airway reactivity or bronchial asthma has been reported, data are lacking on the role of NO in the pediatric asthma population. We therefore performed spirometry on 12 children with asthma (mean age 11.1 yrs) at baseline (B), immediately after inhaling 40 ppm NO (NO-1), 10 min after inhaling NO (NO-10), and after inhalation of a standard beta 2-agonist, albuterol (A). Baseline pulmonary functions (% predicted +/- SEM) were FVC of 103.2 +/- 5.6, FEV1 of 82.2 +/- 3.3, FEF-max of 97.0 +/- 3.6, and FEF25-75% of 53.5 +/- 3.3. There were no statistically significant differences between baseline and NO-1 or NO-10 between any of the four pulmonary function parameters measured. Inhaled albuterol, however, resulted in significant improvement (% predicted +/- SEM) in FVC to 109.8 +/- 3.5, FEV1 to 99.7 +/- 2.9, FEFmax to 106.5 +/- 5.1, and FEF25-75% to 84.4 +/- 6.4 compared with the baseline and NO inhalation groups. We conclude that NO inhaled at 40 ppm has no apparent bronchodilatory effect in pediatric subjects with asthma and mild airways disease. The clinical application of this gas as a therapeutic modality under these conditions is questionable.

Acute Effects of Inhaled Nitric Oxide on Pulmonary and Cardiac Function in Preterm Infants with Evolving Bronchopulmonary Dysplasia

“…This may also be in part due to insufficient dosage as animal experiments showed dosedependent effects of iNO on bronchodilation. 10,11 Moreover, data from healthy humans with induced bronchoconstriction 25 and asthma 26 suggests that iNO bronchodilation in humans may be weaker than in animal species.…”

Contribution of Nitric Oxide Synthases 1, 2, and 3 to Airway Hyperresponsiveness and Inflammation in a Murine Model of Asthma

“…NO has been reported to exhibit both beneficial and deleterious effects in asthma. It has been reported to be a weak bronchodilator (19)(20)(21); however, others have reported no effect on airway tone (22)(23)(24). Still others have reported that the formation of NO may have deleterious effects due to its reported cytotoxic effects (18), and finally it has been reported that NO may serve as a marker of inflammation (16,17,51).…”

“…It has been suggested that NO is a marker of inflammation (16,17) and a cytotoxic molecule contributing to epithelial damage (18). NO has also been reported to be a weak bronchodilator (19)(20)(21) or to have no effect on airway caliber (22)(23)(24). Nitric oxide is produced by a group of enzymes commonly referred to as nitric oxide synthases (NOSs).…”

Treatment of severe status asthmaticus with nitric oxide

“…Pfeffer and coworkers studied the effect of inhaled NO on pulmonary function in 12 asthmatic children, 5 to 16 years of age and compared it to the effect of beta-2 agonists. 8 The inhalation of 40 ppm of NO did not result in demonstrable bronchodilation. In the children who did demonstrate an increase in FEV 1 and/or FEF 25-75% following NO inhalation, this increase was small in comparison with the effect of inhaled beta-2 agonists.…”