Expired nitric oxide (NO) is used as a biomarker in different respiratory diseases. The recommended flow rate of 50 mL s⁻¹ (F(E)NO₀.₀₅) does not reveal from where in the lung NO production originated. Theoretical models of NO transfer from the respiratory system, linear or nonlinear approaches, have therefore been developed and applied. These models can estimate NO from distal lung (alveolar NO) and airways (bronchial flux). The aim of this study was to show the limitation in exhaled flow rate for the theoretical models of NO production in the respiratory system, linear and nonlinear models. Subjects (n = 32) exhaled at eight different flow rates between 10-350 mL s⁻¹ for the theoretical protocols. Additional subjects (n = 32) exhaled at tree flow rates (20, 100 and 350 mL s⁻¹) for the clinical protocol. When alveolar NO is calculated using high flow rates with the linear model, correction for axial back diffusion becomes negligible, -0.04 ppb and bronchial flux enhanced by 1.27. With Högman and Meriläinen algorithm (nonlinear model) the corrections factors can be understood to be embedded, and the flow rates to be used are ≤20, 100 and ≥350 mL s⁻¹. Applying these flow rates in a clinical setting any F(E)NO can be calculated necessitating fewer exhalations. Hence, measured F(E)NO₀.₀₅ 12.9 (7.2-18.7) ppb and calculated 12.9 (6.8-18.7) ppb. In conclusion, the only possibility to avoid inconsistencies between research groups is to use the measured NO values as such in modelling, and apply tight quality control to accuracies in both NO concentration and exhaled flow measurements.

The lung just like all other organs is affected by age. The lung matures by the age of 20 and age-related changes start around middle age, at 40-50 years. Exhaled nitric oxide (FNO) has been shown to be age, height and gender dependent. We hypothesize that the nitric oxide (NO) parameters alveolar NO (CNO), airway flux (JNO), airway diffusing capacity (DNO) and airway wall content (CNO) will also demonstrate this dependence. Data from healthy subjects were gathered by the current authors from their earlier publications in which healthy individuals were included as control subjects. Healthy subjects (n = 433) ranged in age from 7 to 78 years. Age-stratified reference values of the NO parameters were significantly different. Gender differences were only observed in the 20-49 age group. The results from the multiple regression models in subjects older than 20 years revealed that age, height and gender interaction together explained 6% of variation in FNO at 50 ml s (FNO), 4% in JNO, 16% in CNO, 8% in DNO and 12% in CNO. In conclusion, in this study we have generated reference values for NO parameters from an extended NO analysis of healthy subjects. This is important in order to be able to use these parameters in clinical practice.

AimThe objective of this study was to apply extended NO analysis for measurements of NO dynamics in the lung, divided into alveolar and airway contribution, in amateur runners and marathoners.MethodsThe athletes participated in either a marathon or a half marathon. The athletes self-reported their age, weight, height, training distance per week, competing distance, cardio-pulmonary health, atopic status, and use of tobacco. Measurements of exhaled NO (FENO) with estimation of alveolar NO (CANO) and airway flux (JawNO), ventilation, pulse oximetry, and peak flow were performed before, immediately after, and 1 hour after completing the race.ResultsAt baseline the alveolar NO was higher in amateur runners, 2.9 ± 1.1 ppb (p = 0.041), and marathoners, 3.6 ± 1.9 ppb (p = 0.002), than in control subjects, 1.4 ± 0.5 ppb. JawNO was higher in marathoners, 0.90 ± 0.02 nL s−1 (p = 0.044), compared with controls, 0.36 ± 0.02 nL s−1, whereas the increase in amateur runners, 0.56 ± 0.02 nL s−1, did not attain statistical significance (p = 0.165). Immediately after the race there was a decrease in FENO in both amateur runners and marathoners, whereas CANO and JawNO were decreased in marathoners only.ConclusionOur results support the view that there is an adaptation of the lung to exercise. Thus strenuous exercise increased both airway and alveolar NO, and this might in turn facilitate oxygen uptake.

Exhaled nitric oxide (F E NO) is a marker of type-2 inflammation in asthma and is used in its management. However, smokers and ex-smokers have lower F E NO values, and the clinical use of F E NO values in COPD patients is unclear. Therefore, we investigated if F E NO had a relationship to different COPD characteristics in smoking and ex-smoking subjects. Patients with COPD (n ¼ 533, 58% females) were investigated while in stable condition. Measurements of F E NO 50 , blood cell counts, IgE sensitisation and lung function were performed. Medication reconciliation was used to establish medication usage. Smokers (n ¼ 150) had lower F E NO 50 9 (8, 10) ppb (geometric mean, 95% confidence interval) than ex-smokers did (n ¼ 383) 15 (14, 16) ppb, p < 0.001. F E NO 50 was not associated with blood eosinophil or neutrophil levels in smokers, but in ex-smokers significant associations were found (r ¼ 0.23, p < 0.001) and (r ¼ -0.18, p ¼ 0.001), respectively. Lower F E NO values were associated with lower FEV 1 % predicted in both smokers (r ¼ 0.17, p ¼ 0.040) and ex-smokers (r ¼ 0.20, p < 0.001). Neither the smokers nor ex-smokers with reported asthma or IgE sensitisation were linked to an increase in F E NO 50 . Ex-smokers treated with inhaled corticosteroids (ICS) had lower F E NO 50 14 (13, 15) ppb than non-treated ex-smokers 17 (15, 19) ppb, p ¼ 0.024. This was not found in smokers (p ¼ 0.325). F E NO is associated with eosinophil inflammation and the use of ICS in ex-smoking COPD subjects, but not in smoking subjects suggesting that the value of F E NO as an inflammatory marker is more limited in smoking subjects. The association found between low F E NO values and low lung function requires further investigation.