RostrumEndogenous nitric oxide in allergic airway disease☆
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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Ambient PM<inf>2.5</inf> species and ultrafine particle exposure and their differential metabolomic signatures
2021, Environment InternationalCitation Excerpt :We observed perturbations in histidine and arginine metabolisms that are amino acids and have been reported to have anti-inflammatory effects. They are related to endothelial function, inflammation, and airway hyperresponsiveness, and previously have been reported to be inversely associated with elevated level of air pollution (Silkoff et al., 2000). Previous studies found that histidine was negatively associated with inflammation and oxidative stress (Liang et al., 2018; Uchida, 2003; Watanabe et al., 2008; Niu et al., 2012).
Use of high-resolution metabolomics for the identification of metabolic signals associated with traffic-related air pollution
2018, Environment InternationalCitation Excerpt :Our results involving arginine, specifically, warrant specific attention. Arginine is an α‑amino acid that produces NO endogenously in the airways via NO synthase (Silkoff et al., 2000), and has been shown to be depleted following air pollution-induced airway hyperresponsiveness, due to the augmentation of arginase (North et al., 2011). Correspondingly, in our samples, we identified plasma arginine and found it to be inversely associated with measured BC and NOx levels.
A human study model for nitric oxide research in sinonasal disease
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2012, Kendig and Chernick's Disorders of the Respiratory Tract in Children
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Reprint requests: P. E. Silkoff, MD, National Jewish Medical and Research Center, Denver, CO 80206.