Exhaled and Nasal Nitric Oxide - Impact for Allergic Rhinitis.

FeNO measurement is a validated non-invasive technique, which is used for diagnosis and monitoring of asthma. It would be desirable to find a reliable method to monitor allergic rhinitis (AR) via measurement of FeNO, and/or nasal nitric oxide (nNO). The aim of our study was the assessment of the efficacy of FeNO and nNO as markers in AR treatment. FeNO and nNO were measured with the portable NO analyser (NIOX MINO®) in healthy participants and in patients with AR. The patients were examined during the pollen season and out of it. The effect of local corticosteroids and antihistamine therapy was observed in patients with AR during pollen season after three weeks of therapy. There are significant differences between FeNO and nNO in patients with AR compared to healthy controls at all set points of measurements. While FeNO responded well to the treatment with both antihistamines and combined therapy, nNO decreased only after combined therapy with antihistamines and nasal corticosteroids. nNO monitoring alone is not a suitable method to monitor inflammation of the upper airways in AR and its suppression by anti-allergic treatment and should be correlated with other markers as FeNO or symptom scores.

Physiology of nitric oxide in the respiratory system.

Nitric oxide (NO) is an important endogenous neurotransmitter and mediator. It participates in regulation of physiological processes in different organ systems including airways. Therefore, it is important to clarify its role in the regulation of both airway and vascular smooth muscle, neurotransmission and neurotoxicity, mucus transport, lung development and in the. surfactant production. The bioactivity of NO is highly variable and depends on many factors: the presence and activity of NO-producing enzymes, activity of competitive enzymes (e.g. arginase), the amount of substrate for the NO production, the presence of reactive oxygen species and others. All of these can change NO primary physiological role into potentially harmful. The borderline between them is very fragile and in many cases not entirely clear. For this reason, the research focuses on a comprehensive understanding of NO synthesis and its metabolic pathways, genetic polymorphisms of NO synthesizing enzymes and related effects. Research is also motivated by frequent use of exhaled NO monitoring in the clinical manifestations of respiratory diseases. The review focuses on the latest knowledge about the production and function of this mediator and understanding the basic physiological processes in the airways.

Nasal nitric oxide in healthy adults - reference values and affecting factors.

Nitric oxide (NO) is an important endogenous mediator with significant role in the respiratory system. Many endogenous and exogenous factors influence the synthesis of NO and its level is significantly changed during the inflammation. Analysis of nasal nitric oxide (nNO) is not validated so far as the diagnostic method. There is a lack of reference values with possible identification of factors modulating the nNO levels. In healthy adult volunteers (n=141) we studied nasal NO values by NIOX MINO® (Aerocrine, Sweden) according to the recommendations of the ATS & ERS. Gender, age, height, body weight, waist-to-hip ratio, FEV1/FVC, PEF and numbers of leukocytes, eosinophils, basophils and monocytes were studied as potential variables influencing the levels of nNO. The complexity of the results allowed us to create a homogenous group for nasal NO monitoring and these data can be used further as the reference data for given variables. Because of significant correlation between nNO and exhaled NO, our results support the "one airway - one disease" concept. Reference values of nasal NO and emphasis of the individual parameters of tested young healthy population may serve as a starting point in the non-invasive monitoring of the upper airway inflammation.

The impact of hypertonic saline inhalation on mucociliary clearance and nasal nitric oxide.

Nitric oxide (NO) has an influence on airway physiology by mediation in ciliary activity, inflammation, host defence, bronchial tone, and pulmonary vascular resistance. However, the clinical relevance of the measurement of nasal NO (nNO) in different physiological and pathological conditions has yet to be established before it can be used as a diagnostic tool. The aim of our study was to establish the relation between nNO and mucociliary clearance (MCC) and the impact of hypertonic saline inhalation on these markers. We examined 43 subjects. nNO was measured in the right (RnNO) and left (LnNO) nostrils before and after inhalation of hypertonic saline (HS) using a NIOX® analyser. MCC was measured before and after inhalation of HS by saccharin test. The levels of nNO before inhalation of HS (RnNO 806 ppb, IQR-337.6; LnNO 854 ppb, IQR 295.8) were significantly lower than levels after inhalation (RnNO 841.8 ppb, IQR 342.3; LnNO 897.4 ppb, IQR 304.1) (p<0.05, Wilcoxon T-test). The difference between RnNO and LnNO before and after inhalation of HS was not statistically significant. However, the difference in MCC before inhalation (507 s, IQR 233) and after inhalation of aerosol (360 s, IQR 238) was statistically significant (p<0.0001, Wilcoxon T-test). We did not confirm a correlation between nNO and MCC. An increase in osmolarity of the airway surface increases MCC and nNO, which could help to clear accumulated secretions in the airways and prevent respiratory tract infections.

[Airway hyperreactivity]. / Hyperreaktivita dýchacích ciest.

The airway hyperreactivity (AHR) is a symptom occurring in various diseases of the respiratory system. It is defined as an abnormal bronchoconstriction response to a different spectrum of biological, chemical and pharmacological stimuli. Pathogenesis of airway hyperreactivity is not well understood. The available literature data shows that in the AHR pathogenesis is important not only genetic predisposition or influence of combination environmental and genetic factors, but also the presence and activity of various inflammatory mediators and other endogenous factors (growth factors, nuclear transcription factors). In this process is also important role of neural regulation and release of pro-inflammatory neurotransmitters. Our aim was to provide a comprehensive overview of knowledge about the symptoms--from the risk factors and pathogenesis through the clinical importance to the need for better understanding new options in therapeutic interventions.

Exhaled nitric oxide - circadian variations in healthy subjects.

OBJECTIVE: Exhaled nitric oxide (eNO) has been suggested as a marker of airway inflammatory diseases. The level of eNO is influenced by many various factor including age, sex, menstrual cycle, exercise, food, drugs, etc. The aim of our study was to investigate a potential influence of circadian variation on eNO level in healthy subjects. METHODS: Measurements were performed in 44 women and 10 men, non-smokers, without respiratory tract infection in last 2 weeks. The eNO was detected at 4-hour intervals from 6 a.m. to 10 p.m. using an NIOX analyzer. We followed the ATS/ERS guidelines for eNO measurement and analysis. RESULTS: Peak of eNO levels were observed at 10 a.m. (11.1 +/- 7.2 ppb), the lowest value was detected at 10 p.m. (10.0 +/- 5.8 ppb). The difference was statistically significant (paired t-test, P<0.001). CONCLUSIONS: The daily variations in eNO, with the peak in the morning hours, could be of importance in clinical practice regarding the choice of optimal time for monitoring eNO in patients with respiratory disease.

Bidirectional link between upper and lower airways in patients with allergic rhinitis.

OBJECTIVE: Exhaled nitric oxide has been proposed as a noninvasive marker of eosinophilic airway inflammation in lower airways. The aim of the study was to investigate the impact of atopy, pollen exposure, and pharmacological treatment on NO production in lower airways of patients with allergic rhinitis. SUBJECTS AND METHODS: Measurements of exhaled NO were performed in 79 non-asthmatic subjects with seasonal allergic rhinitis outside and in pollen season, before and after pharmacological treatment, and in 54 healthy controls. RESULTS: Patients with allergic rhinitis had significantly higher levels of exhaled NO (18.3 +/-11.0 ppb) than healthy controls (13.0 +/-7.2 ppb) measured outside the pollen season (P=;0.0024). Increased exhaled NO levels were also found in patients with allergic rhinitis in the pollen season (27.0 +/-20.0 ppb) compared with the levels outside pollen season (P=0.0001), before pharmacological treatment. In rhinitic patients treated by nasal corticosteroids and antihistamines in the pollen season, the levels of exhaled NO were significantly lower (17.0 +/-16.4 ppb; P=0.045) than those before treatment. No difference was found in NO levels in rhinitic patients outside and in pollen season after pharmacological treatment. CONCLUSIONS: This study has shown the presence of eosinophilic airway inflammation in the lower airways in allergic rhinitis patients. A significant increase of exhaled NO after pollen exposure in rhinitic patients underlies the impact of inflammation on the upper respiratory tract. A bidirectional link between upper and lower airways is confirmed by a decrease in exhaled NO in the pollen season, almost to the starting levels, after application of topic corticosteroids and antihistamines.