Alveolar Nitric Oxide Concentration Research Articles

Alveolar nitric oxide concentration plays an important role in identifying cough variant asthma and assessing asthma control in children

Objective To study the value of alveolar nitric oxide concentration (CaNO) in the identification and disease control of cough variant asthma. Methods A retrospective study was conducted on cough variant asthma (CVA-Group), nonasthmatic cough (NAC-Group) and healthy control children (C-Group) aged 5–12 years. The exhaled nitric oxide and spirometry test results of the three groups were collected and compared. Results A total of 410 children were included in this study, including 190 in the CVA-Group, 183 in the NAC-Group, and 37 in the C-Group. The CaNO values of the CVA-Group [11.40 ppb (8.48–14.25)] were significantly higher than those of the NAC-Group and C-Group (all p values <.05). The MMEF %pred values of the CVA-Group [63.65 (56.28–73.58)] were significantly lower than those of the NAC-Group and C-Group (all p values <.05). FeNO50, JawNO and other spirometry indices (FVC %pred, FEV1%pred, FEV1/FVC %pred) showed no significant difference among the three groups. ROC curve analysis showed that the optimal cutoff point value of CaNO was 9.45 ppb, corresponding to 0.816 sensitivity and 0.736 specificity. Spearman correlation analysis showed a significant negative correlation between the CaNO measurement and CVA control score. Conclusions CaNO can not only help identify CVA early in children aged 5–12 years with chronic cough but is also significantly negatively correlated with the CVA control score.

Alveolar nitric oxide concentration has a potential value in the diagnosis and differential diagnosis of interstitial lung diseases

To investigate the value of exhaled nitric oxide (eNO) in the diagnosis and differential diagnosis of interstitial lung disease (ILD). This study was conducted among 45 patients with interstitial lung disease, including 18 with connective tissue disease-related ILD (CTD-ILD) and 27 with non-CTD-ILD, with 68 healthy subjects as the control group. According to European Respiratory Association Guidelines, alveolar nitric oxide (CaNO) concentration and fractional exhaled nitric oxide (FeNO) level were measured at the flow rates of 50 and 200 mL/s. The predictive level of CaNO was analyzed using receiver-operating characteristic curve (ROC), and the correlations between CaNO and pulmonary function indicators were examined in the patients with ILD. CaNO, FeNO50, and FeNO200 levels were significantly higher in patients with ILD than in the healthy controls. Logistic regression analysis showed that lowered levels of CaNO and FeNO200 were risk factors for ILD. ROC curve analysis showed that the area under the curve (AUC) of CaNO combined with FeNO200 was 0.829 (95% CI: 0.752-0.906) for the diagnosis of ILD. In patients with ILD, CaNO levels were negatively correlated with DLCO%pred (r=-0.471, P < 0.05). Subgroup comparison showed a significantly higher CaNO level in CTD-ILD group than in non-CTD-ILD group. The AUC for CaNO to discriminate CTD-ILD from non-CTD-ILD was 0.725 (95% CI: 0.576 to 0.875). CaNO has a potential value in the diagnosis of ILD and differential diagnosis of CTD-ILD.

Clinical implications of the concentration of alveolar nitric oxide in non-small cell lung cancer.

Clinical implications of the concentration of alveolar nitric oxide in non-small cell lung cancer.

Distal Lung Inflammation Assessed by Alveolar Concentration of Nitric Oxide Is an Individualised Biomarker of Severe COVID-19 Pneumonia.

Pulmonary sequelae as assessed by pulmonary function tests (PFTs) are often reported in patients infected by SARS-CoV-2 during the post-COVID-19 period. Little is known, however, about the status of pulmonary inflammation during clinical recovery after patients’ discharge from the hospitals. We prospectively measured PFTs coupled with the exhaled nitric oxide (NO) stemming from the proximal airways (FeNO) and the distal lung (CaNO) in 169 consecutive patients with varying degrees of the severity of COVID-19 six weeks to one year after acute infection by SARS-CoV-2. The proportions of patients with abnormal PFTs, defined as the presence of either obstructive/restrictive patterns or impaired lung gas transfer, or both, increased with the severity of the initial lung disease (15, 30, and 52% in patients with mild, moderate, and severe COVID-19). FeNO values remained within normal ranges and did not differ between the three groups of patients. CaNO, however, was significantly higher in patients with severe or critical COVID-19, compared with patients with milder forms of the disease. There was also an inverse relationship between CaNO and DLCO. We conclude that the residual inflammation of the distal lung is still present in the post-COVID-19 follow-up period, in particular, in those patients with an initially severe form of COVID-19. This long-lasting alveolar inflammation might contribute to the long-term development of pulmonary fibrosis and warrants the regular monitoring of exhaled NO together with PFTs in patients with COVID-19.

Significance of alveolar nitric oxide concentration in the airway of patients with organizing pneumonia after allogeneic hematopoietic stem cell transplantation.

Organizing pneumonia (OP) is a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a manifestation of peripheral airway/alveolar inflammation. Recently, alveolar nitric oxide concentration (Calv) has been revealed as a noninvasive marker of peripheral airway inflammation; however, whether Calv levels are associated with OP and peripheral airway in patients after allo-HSCT remains unclear. Herein, we evaluated whether Calv levels could reflect the presence of OP and structural airway changes in patients after allo-HSCT. We measured the eNO levels of 38 patients (6 with OP and 32 without OP) who underwent allo-HSCT. Three-dimensional computed tomography (CT) analysis of the airway was performed in 19 patients. We found that in patients with OP, Calv levels were significantly higher than in those without OP (10.6 vs. 5.5ppb, p < 0.01). Receiver-operating characteristic analyses revealed a Calv cut-off value for OP detection of 10.2ppb. No significant differences in the patient characteristics, except for the presence of OP (p < 0.01), were noted between the two groups stratified by the Calv cut-off value. Three-dimensional CT images of the airway revealed gradually increasing positive correlations between Calv levels and airway wall area of the third-, fourth-, and fifth-generation bronchi (r = 0.20, 0.31, 0.38; p = 0.42, 0.19, 0.038, respectively), indicating that Calv levels are strongly correlated with the wall thickness of the distal bronchi. Our results suggest that the Calv level may be a useful noninvasive detectable marker for OP after an allo-HSCT.

Improved prediction of asthma exacerbations by measuring distal airway inflammation.

IntroductionPartitioning parameters measured from exhaled nitric oxide, such as the alveolar concentration of nitric oxide (CalvNO), may provide better predictors of future asthma exacerbation than exhaled nitric oxide fraction at an expiratory flow rate of 50 mL·s−1(FENO50). We aimed to determine whether any partitioned nitric oxide parameters were more closely associated thanFENO50with subsequent asthma exacerbations.Methods68 asthmatic children (mean±sdage 9.0±2.4 years) were followed prospectively (134 visits) and exacerbations were recorded. Childhood Asthma Control Test (cACT), spirometry,FENO50,CalvNO, bronchial flux of nitric oxide (JawNO), transfer factor of nitric oxide (DawNO) and airway wall concentration of nitric oxide (CawNO) were measured.ResultsNo exacerbation was recorded in 99 visits (Group 1) and an exacerbation was recorded in 35 visits (Group 2). The median (range)FENO50,JawNO,CalvNO,DawNOandCawNOof Group 1versusGroup 2: 12.7 (4–209)versus13.5 (3.8–149.9) ppb, 715 (10–12 799)versus438 (40–7457) pL·s−1, 3.4 (0.2–10.8)versus5.2 (1.7–23.6) ppb, 38.3 (0.2–113.3)versus38 (1.3–144.5) pL·s−1·ppb−1and 26.8 (4.1–2163)versus29.9 (5.5–3054) ppb, respectively. Other than forCalvNO(p&lt;0.001), there was no difference between the two groups.CalvNO&gt;7 ppb predicted asthma exacerbation with specificity 90.9% and positive likelihood ratio (LR) 3.1. Conversely,CalvNO&lt;4 ppb excluded an exacerbation with sensitivity 71.4% and negative LR 0.48. An increase ofCalvNOby 0.5 ppb between visits could also predict an exacerbation with sensitivity 92%, specificity 92%, positive LR 11.8 and negative LR 0.08.ConclusionsAssessment ofCalvNOimproved prediction of subsequent exacerbation, highlighting the importance of distal inflammation in asthma outcomes in children.

Is small airway dysfunction an abnormal phenomenon for patients with normal forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity?

BackgroundThe clinical significance of small airway dysfunction (SAD) determined with spirometry in patients with normal forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) is controversial. ObjectiveTo determine whether SAD presents histologic abnormalities in the setting of normal computed tomography (CT) imaging and FEV1 and FEV1/FVC. MethodsA cross-sectional study was performed in 64 patients undergoing thoracotomy for pulmonary nodules. Thoracic high-resolution CT (HRCT), bronchodilation test, and fractional exhaled nitric oxide (FENO) and its alveolar component (nitric oxide alveolar concentration [CANO]) were obtained before surgery. Lung pathology and levels of cytokines in lung tissue were measured. The patients were divided into SAD and small airway normal function groups according to forced expiratory flow at 75% and 50% of the FVC (maximal expiratory flow [MEF] 25, MEF50) and maximum midexpiratory flow. ResultsThe MEF50, MEF25, and maximum midexpiratory flow were strongly negatively correlated with CANO (r, –0.42, –0.42, –0.40, respectively; P ≤ .001 for all). The MEFs were mildly negatively correlated with interleukin (IL)-6 and macrophages in lung tissue (r < –0.25, P < .001 for all). The CANO (P < .001), airspace size (mean linear intercept) (P = .02), macrophages (P = .003), IL-6 (P = .003), and IL-8 (P = .008) in lung tissue were higher in patients with SAD (n = 35) than those with small airway normal function (n = 29). A total of 8 patients (22.86%) with SAD and 2 (6.90%) without SAD had pneumatoceles (P = .10). ConclusionPatients with pulmonary nodules and SAD were more likely to have abnormal inflammation and emphysematous destruction than patients without SAD. Thus, SAD indicates histologic abnormalities in patients with normal CT imaging and FEV1 and FEV1/FVC.

Effect of exhalation flow rates and level of nitric oxide output on accuracy of linear approximation of pulmonary nitric oxide dynamics

The method of Tsoukias and George (T and G) is a commonly used linear approximation of pulmonary nitric oxide (NO) dynamics that can be used to calculate bronchial NO output (JawNO) and alveolar NO concentration (CANO). We aimed to investigate how flow rate range in exhaled NO measurements and levels of pulmonary NO parameters affect the accuracy of the T and G method. This study has three parts. (a) A theoretical part demonstrating how different exhalation flow rates and NO parameter levels affect the accuracy of the T and G method, (b) testing how exhalation flow rate range affects the method in a sample of asthmatic and healthy subjects, and (c) a meta-analysis of published literature to test whether minimum flow rate has an association with the NO parameter values. We found that both the chosen exhalation flow rates and magnitude of the pulmonary NO parameters affect the accuracy of the T and G method. Underestimation of J awNO increased with lower flow rates and higher bronchial diffusion factor of NO (DawNO), while overestimation of CANO increased with higher DawNO and bronchial wall NO concentration (CawNO) and lower CANO. Of the NO parameters, CANO was the most prone to bias and high DawNO was the most significant factor causing the bias. Furthermore, we found that using 40 ml s−1 as the lowest flow rate in our sample and 50 ml s−1 in the meta-analysis compared to 100 ml s−1 resulted in higher CANO, but JawNO was not statistically significantly affected. We have provided objective evidence that not only the flow rates used but also the magnitude of NO output in the test subjects affect the accuracy of the T and G method. We suggest that flow rates below 100 ml s−1 should not be used with the T and G method to maintain accuracy.

Detection of type2 biomarkers for response in COPD

Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory lung disease. It is important to identify patients who would respond to anti-inflammatory treatment. This prospective study aims to determine how inflammatory biomarkers could be used to predict the potential effect of inhaled corticosteroids (ICS) in terms of symptoms and lung function. We evaluated the levels of blood eosinophils, exhaled nitric oxide fraction at a flow rate of 50 ml s−1 (FeNO), alveolar nitric oxide concentration (Calv), immunoglobulin E and atopy in 43 patients with symptomatic COPD and correlated these expression levels with the changes in the COPD Assessment Test (CAT) and lung function by 12 weeks of add-on therapy with ciclesonide 400 μg d−1 on bronchodilators. The mean changes in the CAT score and FEV1 were −1.4 points and +90 ml, respectively, with significant variation in the levels of change. The area under the receiver’s operating characteristic curve (AUC) for FeNO in predicting improvements in both the CAT score and FEV1 was 0.92. The AUC for Calv and blood eosinophils was 0.82 and 0.65. Two cutoffs were chosen, one corresponding to a high value of FeNO associated with certainty for response inclusion (FeNO = 35 ppb; sensitivity = 0.67, specificity = 0.94; positive predictive value = 0.80) and the other with certainty for response exclusion (FeNO = 20 ppb; sensitivity = 1.00, specificity = 0.58, negative predictive value = 1.00). Baseline FeNO values were significantly correlated with changes in FEV1 and CAT (all p < 0.0001). FeNO could be a valuable biomarker for identifying individuals who respond to steroid therapy among patients with symptomatic COPD in terms of symptoms and airflow limitation. The study was prospectively registered with the University Hospital Medical Information Network (UMIN) in Japan (protocol ID 000010711).

Alveolar concentration of nitric oxide as a prognostic biomarker in idiopathic pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disease leading to respiratory failure and death in 2–5 years from diagnosis. To date, clinical course of disease and prognosis cannot be predicted with an acceptable accuracy. Recently, alveolar concentration of nitric oxide (CaNO) has been proposed as a marker of severity of IPF, but its prognostic value in this setting is unknown. Aim of the studyTo evaluate the reliability of CaNO as a prognostic biomarker in patients with IPF. MethodsIn the Siena Referral Centre for Interstitial Lung Diseases, multiple-flows exhaled nitric oxide analysis was performed to measure CaNO in a cohort of 88 patients with IPF and in 60 healthy controls. In this population, we evaluate functional disease progression and survival according to the follow-up of our Centre. Clinical, functional and radiological data were collected at baseline to investigate correlations with CaNO levels. ResultsIPF patients showed significantly higher levels of CaNO than healthy controls (p < 0.0001); CaNO was significantly correlated with many pulmonary functional parameters. Survival analysis showed that all patients with CaNO ≥6 ppb reported a significantly worse outcome. Disease progression, expressed as FVC time to decline to 10% (TTD10), occurred significantly earlier in patients with CaNO ≥ 9 ppb. ConclusionWe confirm that CaNO was significantly higher in IPF patients than in healthy controls and its correlation with functional parameters. Moreover, CaNO ≥6 and ≥9 ppb were significantly correlated with mortality and disease progression, respectively. These data suggest that CaNO, a non-invasive and reproducible biomarker, may predict disease progression and survival outcome in patients with IPF.

A suitable protocol for measuring alveolar nitric oxide in asthma with differing severity to assess peripheral airways inflammation

Objective: Extended nitric oxide (NO) analysis offers the partitioned monitoring of inflammation in central and peripheral airways. Different mathematical models are used to estimate pulmonary NO dynamics in asthma with variable results and limitations. We aimed to establish a protocol for extended NO analysis in patients with differing asthma severity. Methods: Forty patients with stable asthma and 25 matched control subjects were recruited. Exhaled NO was measured at constant flow rates between 10 and 300 mL/s. Twelve controls performed NO measurements weekly for 4 weeks. Results: The proportions of patients with technically acceptable measurements at 10–30–50–100–150–200–250–300 mL/s exhalation flow rates were 8–58–100–98–98–95–90–80%, respectively. Alveolar NO (CANO) and total flux of NO in the conducting airways (JawNO) were calculated with the linear method from NO values measured at 100–150–200–250 mL/s exhalation flows. The mean intrasubject bias for JawNO and CANO in controls was 0.16 nL/s and 0.85 ppb, respectively. Both JawNO (1.31/0.83–2.97/vs. 0.70/0.54–0.87/nL/s, p < 0.001) and CANO (4.08/2.63–7.16/vs. 2.42/1.83–2.89/ppb, p < 0.001) were increased in patients with asthma compared to controls. In patients, CANO correlated with RV/TLC (r = 0.58, p < 0.001), FEF25-75% (p = 0.02, r = –0.36) and DL,CO (r = –0.46, p = 0.004). JawNO was not related to lung function parameters. Conclusions: Calculation of alveolar NO concentration with the linear method from values obtained at medium flow rates (100–250 mL/s) is feasible even in asthmatic patients with severe airflow limitation and may provide information on small airways dysfunction in asthma.

Effects of Oral Supplementation With Nitrate-Rich Beetroot Juice in Patients With Pulmonary Arterial Hypertension—Results From BEET-PAH, an Exploratory Randomized, Double-Blind, Placebo-Controlled, Crossover Study

BackgroundThe nitrate–nitrite–nitric oxide (NO) pathway may represent a potential therapeutic target in patients with pulmonary arterial hypertension (PAH). We explored the effects of dietary nitrate supplementation, with the use of nitrate-rich beetroot juice (BRJ), in patients with PAH. Methods and ResultsWe prospectively studied 15 patients with PAH in an exploratory randomized, double-blind, placebo-controlled, crossover trial. The patients received nitrate-rich beetroot juice (∼16 mmol nitrate per day) and placebo in 2 treatment periods of 7 days each. The assessments included; exhaled NO and NO flow–independent parameters (alveolar NO and bronchial NO flux), plasma and salivary nitrate and nitrite, biomarkers and metabolites of the NO-system, N-terminal pro–B-type natriuretic peptide, echocardiography, ergospirometry, diffusing capacity of the lung for carbon monoxide, and the 6-minute walk test. Compared with placebo ingestion of BRJ resulted in increases in; fractional exhaled NO at all flow-rates, alveolar NO concentrations and bronchial NO flux, and plasma and salivary levels of nitrate and nitrite. Plasma ornithine levels decreased and indices of relative arginine availability increased after BRJ compared to placebo. A decrease in breathing frequency was observed during ergospirometry after BRJ. A tendency for an improvement in right ventricular function was observed after ingestion of BRJ. In addition a tendency for an increase in the peak power output to peak oxygen consumption ratio (W peak/VO2 peak) was observed, which became significant in patients reaching an increase of plasma nitrite >30% (responders). ConclusionsBRJ administered for 1 week increases pulmonary NO production and the relative arginine bioavailability in patients with PAH, compared with placebo. An increase in the W peak/VO2 peak ratio was observed after BRJ ingestion in plasma nitrite responders. These findings indicate that supplementation with inorganic nitrate increase NO synthase–independent NO production from the nitrate-nitrite-NO pathway.

Small airway function in children with mild to moderate asthmatic symptoms

BackgroundClinical significance of small airway obstruction in mild pediatric asthma is unclear. ObjectiveTo evaluate small airway properties in children with mild to moderate asthmatic symptoms and the association of small airway function with asthma control and exercise-induced bronchoconstriction (EIB). MethodsChildren (5-10 years old) with recurrent wheezing (n = 42) or persistent troublesome cough (n = 16) and healthy controls (n = 19) performed impulse oscillometry (IOS), spirometry, and a multiple-breath nitrogen washout (MBNW) test. Exhaled nitric oxide (NO) was measured at multiple flow rates to determine alveolar NO concentration (Calv). Asthma control was evaluated with the Childhood Asthma Control Test (C-ACT), short-acting β2-agonist (SABA) use within the past month, and asthma exacerbations within the past year. ResultsIOS, spirometry, and exhaled NO indexes that are related to small airway function differed between children with recurrent wheezing and healthy controls, whereas only forced expiratory flow at 25% to 75% of the forced vital capacity was associated with persistent cough. The MBNW indexes showed no difference between the groups. Among symptomatic children, conducting airway ventilation inhomogeneity and Calv were associated with asthma exacerbations (P = .03 and P = .002, respectively), and lung clearance index and Calv were associated with EIB (P = .04 and P = .004, respectively). None of the proposed small airway indexes was associated with the C-ACT score or SABA use. ConclusionSubtle changes were observed in the proposed small airway indexes of IOS, spirometry, and exhaled NO among children with mild to moderate recurrent wheezing. Small airway dysfunction, expressed as ventilation inhomogeneity indexes and Calv, was also associated with asthma exacerbations and EIB.

Altered levels of exhaled nitric oxide in rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is an autoimmune disorder characterized by bone and joint destruction, but other organ systems can also be involved. Recent studies have suggested that the disease may start in the lungs. Exhaled nitric oxide (FENO) is a marker of inflammation. The aims of the study were to compare the NO parameters between subjects with RA and healthy control subjects, and to examine whether the NO parameters correlated with lung function and disease activity in the subjects with RA. MethodsSubjects with RA (n = 35) were recruited during their regular outpatient visits to the rheumatology department. The nitric oxide (NO) parameters: alveolar NO concentration (CANO), airway compartment diffusing capacity of NO (DawNO), and tissue concentration of NO in the airway wall (CawNO), were algorithmically estimated. Healthy subjects (n = 35) matched by age, gender and height were used as controls. Data are given in median, (quartile 25, 75). Wilcoxon Matched Pairs test was used for group comparisons. Mann-Whitney U test was used to make comparisons between any two groups and for pairwise comparisons. Correlations were tested with Spearman rank order correlation. ResultsCANO was significantly lower in the RA subjects compared with healthy subjects; 1.1 (0.5, 1.8) ppb versus 2.4 (2.0, 3.0) ppb, (p < 0.001). CawNO was significantly lower in the RA subjects with 51 (22, 87) ppb versus 120 (76, 162) ppb in the control group. DawNO was significantly higher at 25 (15, 36) mL/s in the RA group versus the control group's 7.7 (5.3, 10.7) mL/s. ConclusionsThere are significant differences between subjects with RA and matched healthy control subjects regarding the exhaled NO parameters. It is unclear if this can be explained by the pathogenesis of RA, consequences of long-term disease, and/or due to drug treatment.

Serum surfactant protein D and exhaled nitric oxide as biomarkers of early lung damage in systemic sclerosis.

Interstitial lung disease (ILD) complicates the course of systemic sclerosis (SSc), representing the main cause of death in these patients. The identification of parameters that can predict the early onset and progression of ILD in SSc represents an unmet need in clinical practice. The study was designed to explore whether the surfactant proteins (SP) A and D may be used as noninvasive tools for the early identification of ILD in SSc. Alveolar exhaled nitric oxide (NO) was investigated as a surrogate marker of distal inflammation. Unselected consecutive subjects newly diagnosed with scleroderma and subjects free of respiratory and systemic diseases were recruited. All patients underwent clinical, lung functional, radiological and biological assessments. 15 individuals affected by SSc (M/F: 3/12), and 10 healthy subjects (M/F: 3/7) participated to the study. The serum SP-D values were 115.3±81.36 ng/mL in SSc subjects and 32±11.9 ng/mL in healthy controls (P=0.004). The concentrations of serum SP-A were not statistically different between groups. Serum SP-D inversely correlated with FEV1% predicted (rs=-0.29; P=0.004), FVC% predicted (rs=-0.20; P=0.02) and DLCO% predicted (rs=-0.36; P=0.001). Alveolar NO concentrations were significantly different between SSc and control subjects (6.5±2.9 ppb vs. 2.2±1.3 ppb, respectively; P=0.001), and positively associated with the levels of serum SP-D (r=0.60, P=0.03). These findings suggest that, in patients with scleroderma, SP-D and exhaled alveolar NO could represent novel non-invasive markers of early detection and activity of lung involvement.

PERIPHERAL ALVEOLAR NITRIC OXIDE CONCENTRATION REFLECTS MACROPHAGE INFLAMMATION OF AUTO‐IMMUNE PULMONARY ALVEOLAR PROTEINOSIS (APAP)

RespirologyVolume 22, Issue S3 p. 254-255 APSR Poster Abstracts PERIPHERAL ALVEOLAR NITRIC OXIDE CONCENTRATION REFLECTS MACROPHAGE INFLAMMATION OF AUTO-IMMUNE PULMONARY ALVEOLAR PROTEINOSIS (APAP) First published: 23 November 2017 https://doi.org/10.1111/resp.13207_448Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume22, IssueS3Supplement: 22nd Congress of the Asian Pacific Society of Respirology, International Convention Centre, Sydney, Australia, 23–26 November 2017November 2017Pages 254-255 RelatedInformation

Comparison of feasibility and estimates of central and peripheral nitric oxide parameters by different mathematical models

Introduction: Assessment of the central and peripheral nitric oxide (NO) dynamics of the lung provides information on the severity and anatomical site of pulmonary inflammation. Several mathematical methods for calculating alveolar and bronchial NO parameters have been introduced. Our aim was to compare these methods. Methods: The study included 69 healthy adults, 66 healthy children, 73 asbestos-exposed subjects and 72 subjects with chronic obstructive pulmonary disease (COPD). Exhaled NO was measured at multiple flow rates and we used five mathematical methods (Tsoukias and George, Pietropaoli, Condorelli, Högman and Meriläinen, and Silkoff) to estimate alveolar and bronchial NO parameters. Results: The Högman and Meriläinen method was less frequently feasible than the other methods but it had the highest degree of agreement with the measured data. The methods were most often feasible in healthy or asbestos-exposed adults but distinctly more infrequently in children and adults with COPD, suggesting difficulties in NO measurements in these groups. The linear methods (Tsoukias and George, Pietropaoli) yielded higher alveolar NO concentration and lower bronchial NO flux than the two non-linear methods (Högman and Meriläinen, Silkoff) and a linear method with correction for axial back-diffusion of NO (Condorelli). Conclusion: In differentiating central and peripheral NO sources we recommend using linear methods, as low flow rates are not needed and the feasibility of the methods is good. If bronchial wall NO concentration (CawNO) and diffusing capacity (DawNO) are of interest, non-linear methods are needed, and we recommend using the Högman and Meriläinen method as only three flow rates are needed. However, the agreement between the model and measured data needs to be checked in real time to ensure feasibility. If the subject has difficulties with the extremely low or high flow rates, we then recommend using the Silkoff method to improve feasibility, but more flow rates and measurements are then needed and the agreement between the model and the measured data may be poorer.

Exhaled nitric oxide measurements in patients with acute-onset interstitial lung disease

It is important to identify the underlying cause of acute-onset interstitial lung disease (ILD). This study aims to assess whether there are differences in the exhaled nitric oxide (eNO) level between different subtypes of acute-onset ILD. Forty patients with a combination of illness ≤4 weeks in duration and diffuse radiographic infiltrates were classified into groups based on the etiology. The eNO at a flow rate of 50 ml s−1 (FeNO), the alveolar nitric oxide concentration (Calv), and the systemic inflammatory markers of the groups were compared. The median FeNO value of patients with acute eosinophilic pneumonia (AEP) (48.1 ppb) was significantly higher than that of the other groups (17.4 ppb in cryptogenic organizing pneumonia, 20.5 ppb in hypersensitivity pneumonia, and 12.0 ppb for sarcoidosis) (p < 0.0005) as well as blood eosinophils (p < 0.005) and Calv levels (p < 0.005). The area under the receiver’s operating characteristic curve (AUC) for FeNO to identify AEP was 0.90 with a cut-off of 23.4 ppb. The AUC for Calv and blood eosinophils was 0.85 and 0.82, respectively. Even in patients with blood eosinophil numbers <5 × 105 cells μl−1, FeNO maintained a good diagnostic value for AEP (AUC = 0.85). eNO can be useful for differentiating AEP from other types of acute-onset ILD, regardless of the blood eosinophil levels.

Plasma Vascular Endothelial Growth Factor Concentration and Alveolar Nitric Oxide as Potential Predictors of Disease Progression and Mortality in Idiopathic Pulmonary Fibrosis.

Background: Declining lung function signifies disease progression in idiopathic pulmonary fibrosis (IPF). Vascular endothelial growth factor (VEGF) concentration is associated with declining lung function in 6 and 12-month studies. Alveolar nitric oxide concentration (CANO) is increased in patients with IPF, however its significance is unclear. This study investigated whether baseline plasma VEGF concentration and CANO are associated with disease progression or mortality in IPF. Methods: 27 IPF patients were studied (maximum follow-up 65 months). Baseline plasma VEGF concentration, CANO and pulmonary function tests (PFTs) were measured. PFTs were performed the preceding year and subsequent PFTs and data regarding mortality were collected. Disease progression was defined as one of: death, relative decrease of ≥10% in baseline forced vital capacity (FVC) % predicted, or relative decrease of ≥15% in baseline single breath diffusion capacity of carbon monoxide (TLCO-SB) % predicted. Results: Plasma VEGF concentration was not associated with progression-free survival or mortality. There was a trend towards shorter time to disease progression and death with higher CANO. CANO was significantly higher in patients with previous declining versus stable lung function. Conclusion: The role of VEGF in IPF remains uncertain. It may be of value to further investigate CANO in IPF.

The Role of Flow-Independent Exhaled Nitric Oxide Parameters in the Assessment of Airway Diseases.

Nitric oxide (NO), the first gas known to act as a biological messenger, is one of the most widely studied free radical/gas in medicine, both for its biological function and therapeutic applications. The measurement of endogenous NO in exhaled air is widely used in the evaluation of lung disorders. Partitioning of exhaled nitric oxide (eNO) is of increasing interest because of the additional information about lung pathology and distal lung inflammation that can be obtained. Specifically, measuring exhaled NO at multiple flow rates allows assessment of the flow-independent NO parameters: alveolar NO concentration (CalvNO), bronchial NO flux (JNO), bronchial wall NO concentration (CWNO), and bronchial diffusing capacity of NO (DNO). Several studies have reported that there were different patterns of those parameters in different airway diseases and/or in different severities of the same disease, mostly in asthma. Specifically, while JNO seems to provide the same information as FeNO50, alveolar NO concentration appears to be an independent parameter that is putatively associated with increased distal lung inflammation and more severe disease. However, despite much research interest in partitioning exhaled NO, clinical usefulness has yet to be established.