Nitric Oxide Concentration In Exhaled Breath Research Articles

NO and hypoxia: Taking nitrate to new heights

Residents of the Tibetan plateau appear to produce more nitric oxide (NO) compared to lowlanders as indicated by enhanced NO concentrations in exhaled breath and elevated levels of NO metabolites (incl. nitrite, nitrate and nitroso species) in their blood. This adaptation may help offset the consequences of life-long exposure to reduced atmospheric oxygen at high altitude by improving oxygen delivery and/or utilization and thus hypoxic tolerance. Recently, lowland participants of two independent research expeditions to Nepal have been demonstrated to also respond to environmental hypoxia with enhanced NO formation, suggesting this to be an integral part of human physiology that contributes to the process of acclimatization to reduced oxygen availability. Furthermore, dietary nitrate has been demonstrated to reduce the oxygen cost of exercise by improving mitochondrial efficiency at sea level and suggested to be sequentially reduced to nitrite and NO in hypoxia. This pathway could theoretically complement NOS-mediated l -arginine oxidation by providing an alternative source of NO under conditions of reduced oxygen availability. We hypothesized, therefore, that dietary nitrate administration may improve oxygen efficiency at high altitude, and this rationale has been tested in a randomized, double-blind field study carried out during summer 2010 at the Margherita Hut at 4,559 m ( Xtreme Alps ). This presentation will highlight some of the key results of this study and discuss their potential implications for the treatment of patients suffering from hypoxemia during critical illness.

Spectroscopic monitoring of NO traces in plants and human breath: applications and perspectives

Optical methods based on quantum cascade lasers (QCLs) are becoming popular in many life science ap- plications. We report on two trace gas detection schemes based on continuous wave QCLs for on-line detection of nitric oxide (NO) at the sub-part-per-billion level by vol- ume (ppbv, 1 : 10 −9 ), using wavelength modulation spec- troscopy (WMS) and Faraday rotation spectroscopy (FRS) at 1894 cm −1 and 1875.73 cm −1 , respectively. Several tech- nical incremental steps are discussed to further improve the sensitivity of these methods. Examples are included to demonstrate the merits of WMS-based sensor: direct mon- itoring of NO concentrations in exhaled breath, and from plants under pathogen attack. A simple hand-held breath sampling device that allows single breath collection at var- ious exhalation flows (15, 50, 100 and 300 mL/s, respec- tively) is developed for off-line measurements and validated in combination with the WMS-based sensor. Additionally, the capability of plants to remove environmental NO is pre-

Mouse Models of Asthma: Can They Give Us Mechanistic Insights into the Role of Nitric oxide?

New clinical practice guidelines for patients with asthma include the recommendation to monitor exhaled breath nitric oxide (NO) levels. NO concentrations in exhaled breath are increased in asthmatics and increased NO levels correlate with worsening airway inflammation and asthma symptoms. The multiple roles of NO in the lung have not been delineated clearly. Clinical trials are being performed presently that test the apparently conflicting hypotheses that either donors or inhibitors of NO in the lung are effective strategies for treating asthma. These strategies evolved, in part, from results of pre-clinical studies performed in mice and other animal models. This review evaluates the existing literature with regard to mouse models of asthma and explores the often conflicting data on the role of NO, the nitric oxide synthase (NOS) enzymes, and the arginase enzymes in allergic airway inflammation. While we will emphasize the ovalbumin exposure mouse model, we will also examine other models. Where inconsistencies are identified among the studies, we attempt to determine whether such inconsistencies arise from methodological differences or alternative mechanisms. Ultimately, we address whether the allergen-exposed mouse is a suitable model for identifying promising new drugs for the treatment of human asthma. While a consensus is building that NO is beneficial or protective in subsets of asthmatics, results from studies using mouse models to investigate the individual roles of NO and the NOS enzymes in airway inflammation are often contradictory. Further research efforts with this model will allow us to distinguish which asthma patients may benefit best from NO donors and which may benefit from NO inhibitors.

Quantum cascade laser-based integrated cavity output spectroscopy of exhaled nitric oxide

A nitric oxide (NO) sensor employing a thermoelectrically cooled, continuous-wave, distributed feedback quantum cascade laser operating at 5.47 μm (1828 cm-1) and off-axis integrated cavity output spectroscopy was used to measure NO concentrations in exhaled breath. A minimum measurable concentration (3σ) of 3.6 parts-per-billion by volume (ppbv) of NO with a data-acquisition time of 4 s was demonstrated. Five prepared gas mixtures and 15 exhaled breath samples were measured with both the NO sensor and for intercomparison with a chemiluminescence-based NO analyzer and were found to be in agreement within 0.6 ppbv. Exhaled NO flow-independent parameters, which may provide diagnostic and therapeutic information in respiratory diseases where single-breath measurements are equivocal, were estimated from end-tidal NO concentration measurements collected at various flow rates. The results of this work indicate that a laser-based exhaled NO sensor can be used to measure exhaled nitric oxide at a range of exhalation flow rates to determine flow-independent parameters in human clinical trials.

Exhaled nitric oxide decreases upon acute exposure to high-altitude hypoxia

Nitric oxide (NO) is a vasodilator that plays a role in blood flow and oxygen delivery. Acute hypoxia down regulates NO synthesis, a response that may exacerbate hypoxic stress by decreasing blood flow. This study was designed to test the hypotheses that pulmonary NO decreases upon acute exposure to high-altitude hypoxia and that relatively low levels of NO at altitude are associated with greater stress as reflected in more symptoms of acute mountain sickness (AMS). A sample of 47 healthy, adult, nonsmoking, sea-level residents provided measurements at sea level, at 2,800 m, and at 0-, 2-, and 3-h exposure times at 4,200 m altitude on Mauna Kea, Hawaii. Measurements were made of exhaled NO, oxygen saturation of hemoglobin, heart rate, and reported symptoms of AMS. The partial pressure of NO concentration in exhaled breath decreased significantly from a sea level mean of 4.2 nmHg to 3.8 nmHg at 2,800 m and 3.4 nmHg at 4,200 m. NO concentration in exhaled breath did not change significantly over a 3-h exposure at 4,200 m and recovered to pre-exposure baseline upon return to sea level. There was no significant association between the level of NO exhaled and the number of self-reported symptoms of AMS during this brief exposure.