Autoinhalation of nitric oxide after endogenous synthesis in nasopharynx

doi:10.1016/S0140-6736(94)91465-6

The Lancet

Volume 343, Issue 8896, 26 February 1994, Pages 518-519

https://doi.org/10.1016/S0140-6736(94)91465-6 Get rights and content

Abstract

Exogenous nitric oxide (NO) reduces pulmonary vascular resistance after low-dose inhalation in patients. To estimate endogenous NO synthesis in the upper respiratory tract, we measured inhaled and exhaled NO in volunteers and patients during spontaneous or controlled ventilation, respectively. 20·3 nmol per min NO was synthesised in the nasopharnyx of non-smoking volunteers, leading to autoinhalation of 0·07-0·13 NO parts per million during inspiration; smokers had reduced NO synthesis. In volunteers, 50-70% of the NO was resorbed by the lungs; ventilated patients were deprived of NO autoinhalation. Bacteria in the nose may take part in endogenous NO synthesis.

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The simultaneous detection of fractional exhaled nitric oxide (FeNO) and end-tidal carbon dioxide (ETCO₂) is of great importance for the distinguishing and diagnosis of asthma and chronic obstructive pulmonary disease (COPD), providing more comprehensive information on respiratory disorders. This work demonstrates a simultaneous ETCO₂ and FeNO detection system based on quantum cascade laser absorption spectroscopy (QCLAS) technology was presented. The system employs wavelength modulation spectroscopy (WMS) technology and the Herriott multi-pass cell, achieving a detection limit of 2.82 ppb for nitric oxide (NO) and 0.05 % for carbon dioxide (CO₂). Real-time exhalation measurements were performed on volunteers with varying ETCO₂ and FeNO levels, and the results of the test can accurately distinguish whether the corresponding volunteer was healthy, had asthma or COPD. The effect of exhalation flow rate on the concentration of the two gases was explored. A range of expiratory flow rates were tested in the flow rate interval from 1 to 4 L/min, and there was always an inverse relationship between expiratory flow rate and FeNO concentration, but flow rate changes did not affect ETCO₂ concentration. The results indicate that this detection system can simultaneously and effectively measure ETCO₂ and FeNO concentrations in real-time.
Exhaled nitric oxide levels are associated with the severity of chronic epipharyngitis and decreased via epipharyngeal abrasion
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The author previously demonstrated that the levels of oral exhaled nitric oxide (NO) were reduced by repeated epipharyngeal abrasive therapy (EAT) for chronic epipharyngitis along with the patients’ symptoms, suggesting that exhaled NO may be a useful outcome parameter of repeated EAT. This study aimed to investigate whether the levels of oral exhaled NO indicate the severity of epipharyngitis and whether an epipharyngeal abrasion immediately influences the amount of exhaled NO.
Participants visited the author's clinic for the diagnosis and treatment of chronic epipharyngitis from November 2020 to March 2021. NO levels were measured orally before EAT, after nasal anesthesia and EAT without zinc chloride (ZnCl₂), and after EAT with ZnCl₂. The correlation between the endoscopic finding scores in conventional light and black spots and the cobblestone appearance with granular changes in band-limited light as well as the exhaled NO levels were determined.
The study included 102 patients (30 males, 72 females; median age, 45.7 years). NO levels were significantly lower (p < 0.01) in EAT without ZnCl₂ (17.0 [11.0–25.3]) and even lower with ZnCl₂ (12.0 [8.0–21.0]) than before EAT (21.5 [15.8–35.0]). NO was significantly higher (p <0.01) in chronic epipharyngitis with the cobblestone appearance with granular changes (23.5 [17.0–37.8]) than without it (19.0 [15.0–23.5]). The total number of endoscopic finding scores and the exhaled NO levels showed a positive correlation (r = 0.251; p = 0.015). Additionally, the cobblestone appearance with granular changes and exhaled NO levels showed a positive correlation (r = 0.256; p = 0.013).
EAT decreased immediately exhaled NO levels with or without ZnCl₂, suggesting that physical stimulation with a cotton swab without ZnCl₂ is therapeutic, and ZnCl₂ may increase this effect. The endoscopic scores were significantly associated with the exhaled NO levels, suggesting that the exhaled NO levels represent the severity of epipharyngitis. The cobblestone appearance with granular changes, which indicates that pathologic ciliated epithelium, was significantly correlated and increased exhaled NO levels, suggesting that NO may be exhaled from ciliated epithelia. These results indicated that exhaled NO levels may be useful as an objective parameter to express the severity of epipharyngitis as well as the outcomes of repeated EAT.
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and has seriously threatened public health by causing significant morbidity and mortality. Patients with coronavirus disease (COVID-19) with preexisting endothelial dysfunction caused by aging, diabetes, hypertension, and obesity are at high risk for life-threatening thromboembolic complications. This suggests a possibility that reduced endothelial nitric oxide (NO) production and NO bioavailability could be a common underlying pathology for the progression of COVID-19. Increasingly, evidence from experimental and clinical studies of SARS-CoV-2 infection shows that NO inhibits the pathogenesis of COVID-19, including virus entry into host cells, viral replication, host immune response, and subsequent thromboembolic complications. Restoring NO bioavailability may have the potential to be a preventive or early-treatment option for COVID-19. This review aims to provide in-depth discussion of NO bioavailability to prevent SARS-CoV-2 infection, particularly by focusing on lifestyle factors such as nitrate-rich diets, physical exercise, and nasal breathing, which could be easily performed on a daily basis to boost NO bioavailability.
Sinusology
2016, European Annals of Otorhinolaryngology, Head and Neck Diseases
This paper presents a brief history of the successive anatomical, physiological and pathophysiological concepts about the paranasal sinuses. Sinusology, the science of the paranasal sinuses, is founded on scientific work on the production of nitric oxide (NO) by the sinuses and on the evo-devo theory of their formation. The paranasal sinuses seem to develop after regression of the erythropoietic marrow in the maxillary, frontal and sphenoid bones and its replacement by cavities filled with gas, which escapes into the nasal fossae through the ostium. The sinus epithelium synthesizes NO continuously. The paranasal sinus cavities form a compartmentalized reservoir of NO, which is released discontinuously in boli after an opening of the ostium. Ostium opening can be induced by sound vibration, either internal (humming) or external (an acoustic vibration added to the in-breath). NO plays the role of an “aerocrine” messenger between the upper and lower respiratory tracts, reducing pulmonary vascular resistance and facilitating alveolar oxygen transfer into the bloodstream. Its physiological role in arterial blood oxygenation could be involved in speech and singing or be activated by physiological snoring during sleep. Rhinology, the science of the nose, in which the evo-devo concept distinguishes the respiratory and the olfactory nose, is now backed up by sinusology.
Sinusology
2016, Annales Francaises d'Oto-Rhino-Laryngologie et de Pathologie Cervico-Faciale
Cet article propose une mise au point concernant les conceptions chronologiques de l’anatomie, de la physiologie et physiopathologie des sinus. La sinusologie, science des sinus paranasaux, pourrait acquérir ses lettres de noblesse grâce aux travaux sur le monoxyde d’azote ou oxyde nitrique (NO) et à la théorie évo–dévo de leur formation. Les sinus paranasaux pourraient se former par dégénérescence de la moelle érythropoïétique des os maxillaires, frontaux et sphénoïdaux laissant place à des cavités remplies d’un gaz qui s’échapperait dans les fosses nasales à travers l’ostium. L’épithélium sinusien synthétise en permanence du monoxyde d’azote (NO). Les sinus se présentent comme un réservoir pluri-compartimenté de NO qui est libéré de manière discontinue sous forme de bolus lors des ouvertures ostiales. L’ouverture ostiale est déclenchée par des vibrations sonores d’origine interne (ronronnement) ou externes (inspiration nasale additionnée d’un son). Le NO est un messager aérocrine entre les voies aériennes supérieures et inférieures qui réduit les résistances vasculaires pulmonaires et facilite les transferts alvéolaires de dioxygène vers le compartiment sanguin. Son rôle physiologique dans l’oxygénation du sang artériel pourrait intervenir dans la parole, le chant ou lors des ronflements physiologiques du sommeil. La rhinologie, science du nez dans laquelle la théorie évo–dévo individualise les nez olfactif et respiratoire, est aujourd’hui épaulée par la sinusologie.
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Autoinhalation of nitric oxide after endogenous synthesis in nasopharynx

Abstract

Biochem Biophys Res Commun

Curr Opin Immunol

J Biol Chem