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Endogenous nitric oxide in allergic airway disease

https://doi.org/10.1067/mai.2000.104938Get rights and content

Abstract

There has been intense research into the role nitric oxide (NO) plays in physiologic and pathologic mechanisms. The presence of NO in exhaled breath and the high concentrations in nasal airways stimulated many studies examining exhaled and nasal NO as potential markers of airway inflammation, enabling repeated monitoring of airway inflammation not possible with invasive tests (eg, bronchoscopy). In airway inflammation, NO is not merely a marker but may have anti-inflammatory and proinflammatory effects. Nasal NO measurement may be used in the noninvasive diagnosis and monitoring of nasal disease. This review was compiled by speakers who gave presentations on NO at the annual meeting of the American Academy of Allergy, Asthma, and Immunology in 1999 on exhaled and nasal NO, in vitro studies of NO, the chemistry of airway NO formation, and standardized measurement of exhaled mediators. (J Allergy Clin Immunol 2000;105:438-48.)

Section snippets

NONINVASIVE METHODS TO ASSESS AIRWAY INFLAMMATION

Asthma is characterized by bronchial hyperresponsiveness, airway epithelial shedding, and inflammation. Currently the only direct methods for assessing airway inflammation, bronchial biopsy specimens, and bronchoalveolar lavage fluid (BALF) are invasive. Noninvasive tests are needed, and candidates include induced sputum analysis and measurement of exhaled mediators. Of the volatile mediators, exhaled1 and nasal NO2 have been studied the most extensively, but studies of other exhaled gases (eg,

Nitric oxide synthases in the lung

De novo synthesis of nitrogen oxides (NOx) in the lung requires at least one isoform of NOS, enzyme substrates (ie, oxygen, reduced nicotinamide adenine dinucleotide phosphate, and L -arginine), and cofactors (tetrahydrobiopterin and flavoproteins).4 All NOS isoforms are active in the lung.5, 6, 7 Types I and III NOS (Table I) are classically activated by mediator-signaled calcium fluxes leading to calmodulin binding and are present primarily in subepithelial neurons (type I) and vascular

Assessment of NO production

Gaseous NO in exhaled breath can be measured by diverse techniques, most commonly chemiluminescence (see last section). Similarly, NO gas can be detected in the headspace above lung epithelial cell cultures.21 However, NO is unstable in the presence of oxygen and rapidly auto-oxidizes to a variety of NOx. Therefore one strategy is to use NOx, including NO2, NO3, OONO, and nitrosothiols to indicate NO formation. NO and oxygen react to form NO2; NO2 accumulation in cell culture supernatant

Proinflammatory effects of NO in allergic inflammation

Eosinophilia is a hallmark of asthma, and the infiltration of eosinophils correlates with airway hyperresponsiveness. Treatment with corticosteroids modestly decreases airway hyperresponsiveness as well as eosinophilia; the latter correlates with FENO levels.42 In addition, NO is chemotactic to eosinophils, neutrophils, and monocytes.43, 44 Direct chemotaxis assays performed with use of a modified Boyden’s chamber showed a significant decrease in eosinophil chemotaxis after administration of

J. O. N. Lundberg, MD, PhD

The presence of NO in human exhalate was first demonstrated by Gustafsson et al1 in 1991, and subsequently Alving et al65 showed that nasal air contained considerable amounts of NO. Later studies clearly showed that in freely exhaling healthy control subjects, a major proportion of NO found in exhaled air originated from the upper airways with only a minor contribution from the lower respiratory tract.2, 66

The exact origin of the NO found in nasal air and the relative contribution from

P. E. Silkoff

Exhaled and nasal NO measurement has been hampered by the variety of techniques used to measure FENO, resulting in widely varying values. A European Respiratory Society task force published guidelines in 1997,87 and an American Thoracic Society workshop, held in Toronto in 1998, has reached consensus on preferred methods to be used in the measurement of exhaled and nasal NO in adults and children.88

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    Reprint requests: P. E. Silkoff, MD, National Jewish Medical and Research Center, Denver, CO 80206.

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