Inhalation of nasally derived nitric oxide modulates pulmonary function in humans

Lundberg, Jon O.; Settergren, G.; Gelinder, S.; Alving, Kjell; Weitzberg, Eddie

doi:10.1046/j.1365-201x.1996.557321000.x

Cited by 83 publications

(59 citation statements)

References 11 publications

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“…The bronchodilatatory effect of NO (in ppm concentrations) is well known [5][6][7], and recent research in animals suggests a causal relationship between airway NOS activity and bronchomotor tone in CF. In these experiments, the addition of L-arginine resulted in a significant increase of electrical field stimulated relaxation of isolated tracheas from mice deficient for the cystic fibrosis transmembrane conductance regulator (CFTR) protein but not from wild-type animals [8].…”

mentioning

confidence: 99%

Oral L-arginine supplementation in cystic fibrosis patients: a placebo-controlled study

Grasemann

Grasemann²,

Kurtz³

et al. 2005

European Respiratory Journal

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Exhaled nitric oxide (eNO) is decreased in cystic fibrosis (CF). The effect of oral Larginine, the precursor of enzymatic nitric oxide (NO) formation, on airway NO in patients with CF was studied.In a pilot study, oral L-arginine was given in a single dose of 200 mg?kg -1 body weight to eight healthy controls and eight CF patients. Subsequently, the same L-arginine dose was given to 10 patients with CF (five females) t.i.d. for 6 weeks in a randomised double-blind placebo-controlled crossover study.A single dose of oral L-arginine resulted in a 5.5-fold increase of L-arginine in plasma and a 1.3-fold increase of L-arginine in sputum after 2 h. Maximum eNO, within 3 h of L-arginine intake, increased significantly in both CF patients (5.4¡2.1 ppb versus 8.3¡3.5 ppb) and controls (18.0¡8.1 ppb versus 26.4¡12.3 ppb). Supplementation of L-arginine for 6 weeks resulted in a sustained increase in eNO compared to placebo (9.7¡5.7 ppb versus 6.3¡3.1 ppb). An effect of L-arginine supplementation on forced expiratory volume in one second was not observed.These data indicate that airway nitric oxide formation in cystic fibrosis patients can be augmented with oral L-arginine supplementation.

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confidence: 99%

Oral L-arginine supplementation in cystic fibrosis patients: a placebo-controlled study

Grasemann

Grasemann²,

Kurtz³

et al. 2005

European Respiratory Journal

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“…Autoinhalation of nasal NO occurs and has physiological effects as an airborne messenger [3,17]. Nasal breathing increases arterial oxygenation in healthy volunteers and reduces pulmonary arterial pressure in postoperative cardiac patients [18].…”

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confidence: 99%

Nasal and oral contribution to inhaled and exhaled nitric oxide: a study in tracheotomized patients

Törnberg¹,

Marteus²,

Schedin³

et al. 2002

European Respiratory Journal

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Nitric oxide (NO) is produced at different sites in the human airways and may have several physiological effects. Orally-produced NO seems to contribute to the levels found in exhaled air. Autoinhalation of nasal NO increases oxygenation and reduces pulmonary artery pressure in humans. The aim of this study was to measure the concentration and output of NO during nasal, oral and tracheal controlled exhalation and inhalation.Ten tracheotomized patients and seven healthy subjects were studied. The mean ¡ SEM fraction of exhaled NO from the nose, mouth and trachea was 56 ¡ 8, 14 ¡ 4 and 6 ¡ 1 parts per billion (ppb), respectively. During single-breath nasal, oral and tracheal inhalation the fraction of inhaled NO was 64 ¡ 14, 11 ¡ 3 and 4 ¡ 1, respectively. There was a marked flow dependency on nasal NO output in the healthy subjects, which was four-fold greater at the higher flow rates, during inhalation when compared to exhalation.There is a substantial contribution of nasal and oral nitric oxide during both inhalation and exhalation. Nasal nitric oxide output is markedly higher during inhalation, reaching levels similar to those that are found to have clinical effects in the trachea. These findings have implications for the measurement of nitric oxide in exhaled air and the physiological effects of autoinhaled endogenous nitric oxide.

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“…It may also play an important role in the regulation of ciliary function [10,11]. Pulmonary vascular resistance is decreased in humans during nasal breathing compared to that during mouth breathing, intubation or after tracheotomy [12,13]. This implies that nasally derived NO acts by autoinhalation as an aerocrine messenger to modulate the pulmonary vascular tone and to improve ventilation/perfusion matching.…”

Section: Anatomic Originmentioning

confidence: 99%

Measurement of Nasal Nitric Oxide

Corbell¹,

Hammer²

2005

Paediatric Pulmonary Function Testing

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The major part of nitric oxide (NO) in exhaled air originates from the nasal airways, with only minor contribution from the lower airways and the oral cavity. The physiological role of the very high local NO concentration in the paranasal sinuses is still unclear. The most widely used and best-standardized method to sample nasal NO in isolation from the lower respiratory tract is aspiration at a fixed flow through the nasal passages in series. Important technical considerations include the choice of the correct transnasal flow and the ability of children to perform a breath-holding manoeuvre.The effects of age and height on nasal NO values have yet to be defined in a larger population of healthy children using the recommended aspiration technique. Presently, there is no validated technique available to measure nasal NO in infants and small children.The measurement of nasal NO concentrations has evoked interest in its potential to serve as a non-invasive and simple diagnostic tool for upper and lower respiratory tract disorders. Measurements of nasal NO concentrations are helpful to screen children with clinical symptoms suggestive of primary ciliary dyskinesia and to exclude this disease in those with high nasal NO concentrations with high certainty. Nasal NO measurements are, however, of no diagnostic utility in distinguishing between other conditions such as asthma, cystic fibrosis, bronchiectasis, sinusitis or rhinitis, or in monitoring therapeutic interventions in any such disorder. Origin of Nasal Nitric OxideNitric oxide (NO) is produced endogenously within the respiratory tract and was first documented in exhaled air in humans and mammals in 1991 [1]. It was then shown that the major part of NO in exhaled air originates from the nasal airways, with only a minor contribution from the lower airways and the oral cavity [2]. NO is present in the nasal airways and paranasal sinuses in very high concentrations, close to the acute exposure levels set by occupational health guidelines for short-term exposure at the workplace [3,4]. Biochemical Pathway and Cellular OriginNO is generated from the semi-essential amino acid L-arginine by the enzyme NO synthase (NOS), which can be divided into two major categories: constitutive NOS (cNOS) and inducible NOS (iNOS). The constitutive enzyme, which according to its location may be named endothelial NOS (eNOS) or neuronal NOS (nNOS), is activated by calcium and calmodulin. It produces small amounts of NO to modulate physiological processes, and can be stimulated by bradykinin, acetylcholine, histamine, leukotrienes, and several other mediators. Calmodulin is an enzyme cofactor regulating electron transport. It is also identified in close juxtaposition to the cilia of the upper airway epithelium, and is thought to be involved in ciliary motility. The iNOS, which was first isolated in macrophages, is calciumand calmodulin-independent and activated by a variety of Hammer J, Eber E (eds): Paediatric Pulmonary Function Testing.

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Inhalation of nasally derived nitric oxide modulates pulmonary function in humans

Cited by 83 publications

References 11 publications

Oral L-arginine supplementation in cystic fibrosis patients: a placebo-controlled study

Oral L-arginine supplementation in cystic fibrosis patients: a placebo-controlled study

Nasal and oral contribution to inhaled and exhaled nitric oxide: a study in tracheotomized patients

Measurement of Nasal Nitric Oxide

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