Alveolar NO Concentration Research Articles

The potential role of SP-D as an early biomarker of severity of asthma

Surfactant decreases the surface tension of peripheral airways and modulates the immunological responses of the lung. The alterations of surfactant due to the airway inflammation suggest a role in the pathogenesis of asthma. We aim to test the hypothesis that serum levels of SP-A (Surfactant Protein A) and SP-D (Surfactant Protein-D) are altered in patients with mild asthma compared to healthy controls and those alterations are related to functional abnormalities of peripheral airways, which are an early marker of progression of asthma. In this pilot study, we recruited 20 mild asthmatics and 10 healthy controls. We measured serum SP-A and SP-D and all subjects underwent clinical, lung functional and biological assessments. Serum SP-D was significantly higher in asthmatics compared to healthy controls (mean (SD) values: 7.9(4.65) vs 3.31(1.71) ng ml−1, p-value: 0.008). In the asthmatic group, serum SP-D was significantly correlated to CalvNO (alveolar NO concentration) (R-squared: 0.26; p-value: 0.014). These preliminary findings suggest that serum SP-D could be used as a lung-specific biomarker of small airways damage thus predicting the progression to the most severe forms of asthma.

Exhaled Nitric Oxide as a Surrogate Marker for Obstructive Sleep Apnea Severity Grading: An In-Hospital Population Study.

PurposeOur study aimed to evaluate the relationship between exhaled nitric oxide (eNO) markers and obstructive sleep apnea (OSA) severity and verify the changes in eNO profiles among mild, moderate, and severe OSA subgroups.MethodsThis study was a cross-sectional and in-hospital population-based study. We investigated 123 OSA patients (17 mild, 23 moderate and, 83 severe OSA) in the department of respiratory diseases. Studied data included anthropometry, respiratory polygraphy, biological markers, spirometry, and multi-flow eNO measurements. Data analysis implied linear correlation, non-parametric ANOVA, and pair-wise comparison.ResultsNo significant difference could be found among 3 OSA severity subgroups for FENO at – four sampling flow rates (50–350 mL/s). The bronchial production rate of NO (J’awNO) was proportionally increased, with median values of 11.2, 33.9, and 36.2 in mild, moderate, and severe OSA, respectively (p=0.010). The alveolar concentration of NO (CANO) changed with a non-linear pattern; it was increased in moderate (6.49) vs mild (7.79) OSA but decreased in severe OSA (5.20, p = 0.015). The only correction that could be established between OSA severity and exhaled nitric oxide markers is through J’AWNO (rho=0.25, p=0.02) and CANO (rho= 0.18, p=0.04). There was no significant correlation between FENO measured at three different flow rates and the OSA severity. We also found a weak but significant correlation between FENO 100 and averaged SpO2 (rho = 0.07, p= 0.03).ConclusionThe present study showed that J’AWNO, which represents eNO derived from the central airway, is proportionally increased in more severe OSA, while eNO from alveolar space, indicated by CANO, was also associated with OSA severity and relatively lower in the most severe OSA patients. In contrast, stand-alone FENO metrics did not show a clear difference among the three severity subgroups.

High alveolar nitric oxide is associated with steeper lung function decline in foundry workers

Occupational dust exposure induces inflammatory responses that often precede the onset of clinical disease. Inflammation in the peripheral part of the lung can be demonstrated by measuring the alveolar NO concentration (CANO) in exhaled breath. The aim of the study was to assess whether cumulative dust exposure affects the change in CANO during follow-up and whether baseline CANO can predict an impairment in lung function during follow-up in foundry workers. We examined 74 dust-exposed and 42 nonexposed foundry workers and measured CANO and lung function at baseline and after 7 years of follow-up. An increase in CANO during the follow-up period was positively associated with cumulative dust exposure in foundry work (p = 0.035). Furthermore, a higher baseline CANO was associated with an accelerated decline in the forced vital capacity (FVC) during the follow-up period (absolute decrease in FVC p = 0.021, relative decrease in FVC p = 0.017). Higher cumulative dust exposure in foundry work is associated with a greater increase in CANO during follow-up, suggesting ongoing pulmonary inflammation in these subjects. Importantly, a high baseline CANO is associated with an accelerated decline in lung function, suggesting that CANO measurements might serve as a screening tool for high-risk workers.

Extended Exhaled Nitric Oxide Analysis in Interstitial Lung Diseases: A Systematic Review.

Fractional exhaled nitric oxide (FeNO) is a well-known and widely accepted biomarker of airways inflammation that can be useful in the therapeutic management, and adherence to inhalation therapy control, in asthmatic patients. However, the multiple-flows assessment of FeNO can provide a reliable measurement of bronchial and alveolar production of NO, supporting its potential value as biomarker also in peripheral lung diseases, such as interstitial lung diseases (ILD). In this review, we first discuss the role of NO in the pathobiology of lung fibrosis and the technique currently approved for the measurement of maximum bronchial flux of NO (J’awNO) and alveolar concentration of NO (CaNO). We systematically report the published evidence regarding extended FeNO analysis in the management of patients with different ILDs, focusing on its potential role in differential diagnosis, prognostic evaluation and severity assessment of disease. The few available data concerning extended FeNO analysis, and the most common comorbidities of ILD, are explored too. In conclusion, multiple-flows FeNO analysis, and CaNO in particular, appears to be a promising tool to be implemented in the diagnostic and prognostic pathways of patients affected with ILDs.

Clinical Values of Nitric Oxide Parameters from the Respiratory System.

Fractional exhaled nitric oxide (FENO) concentration reliably reflects central airway inflammation, but it is not sensitive to changes in the NO dynamics in the lung periphery. By measuring FENO at several different flow rates one can estimate alveolar NO concentration (CANO), bronchial NO flux (JawNO), bronchial wall NO concentration (CawNO) and the bronchial diffusivity of NO (DawNO). We aimed to describe the current knowledge and clinical relevance of NO parameters in different pulmonary diseases. We conducted a systematic literature search to identify publications reporting NO parameters in subjects with pulmonary or systemic diseases affecting the respiratory tract. A narrative review was created for those with clinical relevance. Estimation of pulmonary NO parameters allows for differentiation between central and peripheral inflammation and a more precise analysis of central airway NO output. CANO seems to be a promising marker of parenchymal inflammation in interstitial lung diseases and also a marker of tissue damage and altered gas diffusion in chronic obstructive pulmonary disease and systemic diseases affecting the lung. In asthma, CANO can detect small airway involvement left undetected by ordinary FENO measurement. Additionally, CawNO and DawNO can be used in asthma to assess if FENO is increased due to enhanced inflammatory activity (increased CawNO) or tissue changes related to bronchial remodelling (altered DawNO). NO parameters may be useful for diagnosis, prediction of disease progression and prediction of treatment responses in different parenchymal lung and airway diseases. Formal trials to test the added clinical value of NO parameters are needed.

Repeatability and variation of the flow independent nitric oxide parameters

Introduction: Fractional exhaled nitric oxide (FENO) is a non-invasive marker of airway inflammation. Measuring FENO at several flow rates enables the calculation of flow independent NO-parameters (alveolar NO concentration (CANO), bronchial flux of NO (JawNO), bronchial mucosal NO concentration (CawNO) and bronchial wall NO diffusion capacity (DawNO)) that are capable of partitioning the source and release mechanism of NO from the lower respiratory tract. However, the current literature on repeatability and normal variation of the NO-parameters is deficient, and this information is needed to develop the method towards clinical use. Methods: We calculated NO-parameters in 28 healthy subjects using two different mathematical methods and used three different study protocols to investigate: (i) repeatability of two consecutive measurements of NO-parameters, (ii) within-day variation of the NO-parameters over one working day and (iii) day-to-day variation of the NO-parameters between consecutive days during course of a working week. Results: JawNO was the most repeatable among the NO-parameters, whereas DawNO and CawNO were notably least repeatable. CANO was higher during the second consecutive measurement (1.22 versus 1.57 ppb, p = 0.017). Both investigated mathematical methods yielded equally repeatable results. JawNO was slightly higher in the afternoon compared to morning (716 versus 881 pl/s, p = 0.01), but other parameters showed no diurnal variation. Upper 95% limit for the day-to-day difference in the parameters in healthy subjects was about 1.2 ppb in CANO, 400 pl/s in JawNO, 92 ppb in CawNO and 16 pl/s/ppb in DawNO. Conclusions: This is the first study assessing short-time repeatability of the NO-parameters. Repeatability of the NO-parameters was good and day-to-day variation in NO-parameters was quite low. We recommend scheduling FENO-measurements at the same time of day, if possible, and in clinical use variation in NO-parameters above the normal limits found in this study suggest changes in the disease’s activity.

Elevated Levels of Alveolar Nitric Oxide May Indicate Presence of Small Airway Inflammation in Patients with Inflammatory Bowel Disease.

Pulmonary manifestations of inflammatory bowel disease (IBD), albeit not rare, are largely overlooked in clinical practice. The role of exhaled nitric oxide (eNO) as an established biological marker of airway inflammation compels us to use it as a tool to investigate the exact nature of these manifestations. Fractional eNO (FeNO) was measured in multiple flows, and with the use of a mathematical model, alveolar concentration of NO (CANO) and bronchial flux of NO (JawNO) were assessed in 27 patients with IBD [17 with Crohn's disease (CD) and 10 with ulcerative colitis (UC)] and in 39 healthy controls. Carefully selected criteria were used to exclude patients or healthy controls that presented factors considered to be correlated with eNO measurements. Disease activity was measured in Crohn's patients using the CD activity index (CDAI) score and in UC using the partial Mayo score. CANO was significantly higher in the IBD group, compared to the control group (p < 0.0001). FeNO was significantly increased in patients with IBD (p = 0.023), while there was no statistical significance found regarding levels of JawNO in patients with IBD (p = 0.106), both compared to controls. There was no significant correlation between any eNO component and markers of disease activity. Alveolar concentration of NO is elevated in patients with IBD, regardless of disease activity. This may suggest that subclinical small airway inflammation is present in patients with IBD, even those with mild or inactive disease.

Evaluation of multiple-flows exhaled nitric oxide in idiopathic and non-idiopathic interstitial lung disease

Background: fractional exhaled nitric oxide (FeNO) is a non-invasive and reproducible marker of nitrosative stress and lung inflammation. More recently, FeNO has been proposed as a marker of severity of idiopathic pulmonary fibrosis (IPF) and systemic sclerosis associated ILD. AIM and objectives: to evaluate the role of FeNO in the diagnostic pathway of ILDs. Methods: according to ERS guidelines for exhaled biomarkers in lung diseases, FeNO at multiple flow-rates (50-100-150 and 350 ml s−1) and alveolar concentration of NO (CaNO) were collected in 60 healthy controls and 134 patients affected by ILD: 50 with IPF, 19 with fibrotic non-specific interstitial pneumonia, 19 with chronic hypersensitivitis pneumonia (cHP) and 46 with connective tissue disease related ILD (CTD–ILD). ROC curves were performed to investigate the potential role of eNO parameters in discriminating between idiopathic and non-idiopathic ILDs. Results: all ILD groups reported higher levels of FeNO 150–350 ml s−1 and CaNO than controls. Among ILDs, CTD–ILD showed more elevated FeNO 350 ml s−1 and CaNO levels than other ILD. In particular, CaNO reported the best diagnostic accuracy to discriminate CTD–ILD from idiopathic ILDs. Conclusions: patients affected by ILD reported increased FeNO 150–350 ml s−1 and CaNO in respect with healthy controls, indicating a potential role of nitrosative stress in lung fibrosis. The significant difference of CaNO levels between idiopathic ILDs and CTD–ILD is interesting and may suggest that NO is also implicated in lung inflammation associated with rheumatological disease. Further evidence is necessary to establish if CaNO is worthy of attention in the differential diagnosis of ILDs.

Comparison of inducible nitric oxide synthase mRNA expression in different airway portions and association with nitric oxide parameters from patients with asthma.

BackgroundFractional exhaled nitric oxide concentration (FeNO) is widely used to support diagnosis and monitoring of bronchial asthma (BA). Tsoukias and George proposed a two‐compartment model (2CM) for assessing the alveolar concentration of NO, referred to as CANO(2CM), while Condorelli et al proposed a model based on the trumpet shape of the airway tree and axial diffusion (TMAD), referred to as CANO(TMAD). In addition, Högman et al proposed non‐linear model, referred to as CANO(non‐linear).ObjectiveWe examined associations between the expression of inducible nitric oxide synthase (iNOS) mRNA in airway cells (ACs) by bronchoscopy and NO‐parameters calculated by the three methods and identified which of them accurately reflected expression of iNOS mRNA from different airway portions.MethodsWe retrospectively analysed data of 18 patients with stable, mild‐moderate asthma, including 10 steroid‐naïve BA (snBA) patients. Samples were obtained from airway brushings and bronchoalveolar lavage (BAL). Expressions of iNOS protein in tissue samples were evaluated by immunostaining. The iNOS mRNA in ACs was measured by qPCR. NO‐parameters calculated by the three methods above and evaluated whether they were associated with iNOS mRNA in ACs derived from proximal (2nd carina), distal (10‐15th) airways and alveolar regions.ResultsImmunostaining revealed expression of iNOS proteins mainly in epithelial cells in the airways, while it was mainly expressed in macrophages in the alveolar region in the snBA group. The iNOS mRNA expression was increased in both proximal and distal ACs in the snBA group compared with steroid‐treated BA group (stBA). CANO(2CM) negatively associated with FEV 1 (%predicted) and also associated with iNOS mRNA in distal ACs significantly. However, CANO(TMAD) and CANO(non‐linear) showed no correlation with lung function nor iNOS mRNA expression in any portions of ACs.ConclusionsThese results suggested that CANO(2CM) reflected distal airway inflammation in steroid‐naïve asthma.

Exhaled Nitric Oxide and Exhaled Breath Temperature as Potential Biomarkers in Patients with Pulmonary Hypertension.

Background Pulmonary hypertension (PH) is a progressive fatal disease thus, noninvasive prognostic tools are needed to follow these patients. The aim of our study was to evaluate fractional exhaled nitric oxide (FeNO) and exhaled breath temperature (EBT) values in patients with PH from different causes and to correlate them with respiratory functional data. Methods Twenty-four PH patients underwent spirometry, carbon monoxide diffusion (DLCO) test, transthoracic echocardiography, right-heart catheterization, and FeNO and EBT measurements. Results We studied 3 groups according to the type of PH: 10 patients with pulmonary arterial hypertension (PAH) (group A), 11 patients with PH due to chronic obstructive pulmonary disease (COPD) (group B), and 3 patients with PH associated with left heart disease (group C). Mean FeNO values tend to be higher in group B (15.0 ± 9.3ppb) compared with other groups (respectively, 9.9 ± 5.7 and 8.5 ± 5.2 ppb in groups A and C; p = 0.271) but no statistical significance has been reached. Mean values of alveolar NO concentration (CANO) were higher in groups A and B compared to group C (respectively, 16.9 ± 12.6; 13.9 ± 6.8; and 6.7 ± 2.0 ppb) (p = 0.045). EBT mean values were significantly lower in group C when compared with other groups (group C: 29.0 +- 1.3°C, groups A and B: 30.9 ± 1.3 and 31.2 ± 1.2°C, respectively: p = 0.041). EBT levels were inversely correlated to mean pulmonary artery pressure (PAPm) levels (Spearman coefficient -0.481; p = 0.017). Conclusions eNO, CANO, and EBT have been evaluated in three groups of PH patients. Interestingly EBT reduction was correlated with PAPm increase, whereas FeNO was higher in COPD patients and CANO in PAH and COPD groups. Further studies are needed to clarify EBT, FeNO, and CANO roles as biomarkers in the monitoring of patients with PH.

Influence of mouthwashes on extended exhaled nitric oxide (FENO) analysis

Fractional exhaled nitric oxide (FENO) is used to assess eosinophilic inflammation of the airways. FENO values are influenced by the expiratory flow rate and orally produced NO. We measured FENO at four different expiratory flow levels after two different mouthwashes: tap water and carbonated water. Further, we compared the alveolar NO concentration (CANO), maximum airway NO flux (J′awNO) and airway NO diffusion (DawNO) after these two mouthwashes. FENO was measured in 30 volunteers (healthy or asthmatic) with a chemiluminescence NO-analyser at flow rates of 30, 50, 100 and 300 mL/s. A mouthwash was performed before the measurement at every flow rate. The carbonated water mouthwash significantly reduced FENO compared to the tap water mouthwash at all expiratory flows: 50 mL/s (p < .001), 30 mL/s (p = .001), 100 mL/s (p < .001) and 300 mL/s (p = .004). J′awNO was also significantly reduced (p = .017), however, there were no significant differences in CANO and DawNO. In conclusion, a carbonated water mouthwash can significantly reduce oropharyngeal NO compared to a tap water mouthwash at expiratory flows of 30–300 mL/s without affecting the CANO and DawNO. Therefore, mouthwashes need to be taken into account when comparing FENO results.

The effect of bronchodilation and spirometry on fractional exhaled nitric oxide (FeNO50), bronchial NO flux (JawNO) and alveolar NO concentration (CANO) in children and young adults

ABSTRACTObjective: Fractional exhaled nitric oxide (FeNO), bronchial nitric oxide (JawNO) and alveoar nitric oxide (CANO) are biomarkers of eosinophilic inflammation, usually measured simultaneously with spirometry and bronchodilation. Our aim was to investigate the effect of bronchodilation and spirometry on FeNO, CANO and JawNO in children and young adults with well-controlled asthma and in healthy volunteers. Methods: FeNO was measured in 95 subjects (62 controls, 33 asthmatics). CANO and JawNO were assessed in 41 of the subjects (35 healthy, 6 asthmatics.) Measurements were performed before spirometry (1), right after spirometry (2), 20 min after the first spirometry and bronchodilation (3), right after the post-bronchodilation spirometry (4) and 30 min after the last spirometry (5). Results: The presence of well-controlled asthma was not associated with different pattern of reaction after spirometry and bronchodilation. A statistically significant difference was observed only between FeNO4 and FeNO5, as well as between CANO1 and CANO3 (19.14 ± 1.68 vs 20.62 ± 1.85 ppb, p = 0.001 and 4.42 ± 0.40 vs 3.09±0.32 ppb, p = 0.001, respectively). Conclusions: Spirometry and bronchodilation have an insignificant effect on FeNO and JawNO. Even if a slight change occurs in FeNO and JawNO, this does not modify clinician's decision and therapeutic strategy. CANO values (CANO1) are significantly decreased 20 min after spirometry and bronchodilation.

Optimal flow rate sampling designs for studies with extended exhaled nitric oxide analysis

Introduction. The fractional concentration of exhaled nitric oxide (FeNO) is a biomarker of airway inflammation. Repeat FeNO maneuvers at multiple fixed exhalation flow rates (extended NO analysis) can be used to estimate parameters quantifying proximal and distal sources of NO in mathematical models of lower respiratory tract NO. A growing number of studies use extended NO analysis, but there is no official standard flow rate sampling protocol. In this paper, we provide information for study planning by deriving theoretically optimal flow rate sampling designs. Methods. First, we reviewed previously published designs. Then, under a nonlinear regression framework for estimating NO parameters in the steady-state two compartment model of NO, we identified unbiased optimal four flow rate designs (within the range of 10–400 ml s−1) using theoretical derivations and simulation studies. Optimality criteria included NO parameter standard errors (SEs). A simulation study was used to estimate sample sizes required to detect associations with NO parameters estimated from studies with different designs. Results. Most designs (77%) were unbiased. NO parameter SEs were smaller for designs with: more target flows, more replicate maneuvers per target flow, and a larger range of target flows. High flows were most important for estimating alveolar NO concentration, while low flows were most important for the proximal NO parameters. The Southern California Children’s Health Study design (30, 50, 100 and 300 ml s−1) had ≥1.8 fold larger SEs and required 1.1–3.2 fold more subjects to detect the association of a determinant with each NO parameter as compared to an optimal design of 10, 50, 100 and 400 ml s−1. Conclusions. There is a class of reasonable flow rate sampling designs with good theoretical performance. In practice, designs should be selected to balance the tradeoffs between optimality and feasibility of the flow range and total number of maneuvers.

Short-Term Effects Of Airport-Associated Ultrafine Particle Exposure On Lung Function And Inflammation

Introduction: Exposure to ultrafine particles (UFP, particles with aerodynamic diameter less than 100nm) is associated with reduced pulmonary function and increased airway inflammation in asthmatics. A recent study showed that UFP number concentrations downwind of the Los Angeles International Airport (LAX) are elevated 4- to 5- fold, putting a large fraction of the population at risk. Methods: We conducted a randomized crossover study of 21 non-smoking adults with mild to moderate asthma in Nov-Dec 2014 and May-Jul 2015. Participants conducted scripted, mild walking activity for 2 hours, resting every 15 minutes, on 2 occasions, in public parks inside (exposure) and outside (control) of the LAX high UFP impact zone. Spirometry (FVC, FEV1), multiple flow exhaled nitric oxide (FeNO, at 30, 50, 100 and 300 ml/s), and blood draws for inflammatory cytokines (hsIL-6, sTNFrII, vWF, fibrinogen) were performed pre- and post- exposure. Personal UFP particle numbers (PN) and lung deposited surface area (LDSA) and stationary UFP PN, black carbon (BC), particle-bound PAHs (PB-PAH), ozone (O3), and particulate matter (PM2.5) mass were measured. Results: A high contrast of ~ 30,000 #/cm3 was achieved with mean (std) PN concentrations at the exposure and control site of 46,062 (38,932) and 17,160 (22,590) #/cm3, and LDSA of 58.6 (35.2) and 27.7 (26.2) cm2, respectively. Median particle size was 28.8nm (std 14.6) at the LAX site. The increase in hsIL-6, a pro-inflammatory cytokine, and reduction in FEV1 were larger under LAX exposure conditions. Preliminary FeNO results from the first phase (N=9) show a greater increase in distal alveolar NO concentration, CANO, in the exposure scenario compared to the control. Analyses using linear mixed effects models are underway to estimate the magnitude of the effect of UFP exposure and dose on these outcomes. Conclusions: Preliminary data suggest a relationship between airport-related UFP exposures and adverse lung effects in asthmatics.

Study of Exhaled Nitric Oxide in Subjects with Suspected Obstructive Sleep Apnea: A Pilot Study in Vietnam.

Background and Objective. The concentration of exhaled nitric oxide (eNO), reflecting the activity of inducible NO synthase in airway epithelium, has been found to increase in patients with obstructive sleep apnea (OSA). This study aimed to measure eNO concentration in patients with suspected OSA and to correlate different eNO parameters with clinical and sleep apnea characteristics. Methods. In this cross-sectional study, all patients underwent in-lab overnight polysomnography (PSG) and eNO measurement using a method of multiple flow rates before and after PSG (pre- and post-PSG). Results. According to the result of PSG, 82 persons were divided into two groups: control subjects (n = 30; 54 ± 14 years) and patients with OSA defined as apnea-hypopnea index (AHI) ≥ 5/hour (n = 52; 53 ± 12 years). Body mass index (BMI) and neck and abdomen circumferences of OSA patients were significantly higher than those from control subjects. In OSA group, post-PSG alveolar NO concentration (CANO) (5.3 ± 1.9 ppb) was significantly higher than pre-PSG CANO (4.0 ± 1.7 ppb; P < 0.001). Significant correlations have been found between CANO and AHI (P < 0.001) and between CANO and nadir SpO2 (P < 0.05). The daytime CANO value of more than 4.1 ppb can be used to screen symptomatic subjects for the presence of OSA with a high specificity of 93.3%. Conclusion. Our findings indicate CANO as a surrogate marker for OSA in persons with suggestive symptoms.

Airway and alveolar nitric oxide production, lung function, and pulmonary blood flow in sickle cell disease.

Children with sickle cell disease (SCD) often have obstructive lung function abnormalities which could be due to asthma or increased pulmonary blood volume; it is important to determine the underlying mechanism to direct appropriate treatment. In asthmatics, exhaled nitric oxide (FeNO) is elevated. FeNO, however, can also be raised due to increased alveolar production. Our aim, therefore, was to determine if airway or alveolar NO production differed between SCD children and ethnic and age-matched controls. Lung function, airway NO flux and alveolar NO production, and effective pulmonary blood flow were assessed in 18 SCD children and 18 ethnic and age-matched controls. The SCD children compared to the controls had a higher respiratory system resistance (P = 0.0008), alveolar NO production (P = 0.0224), and pulmonary blood flow (P < 0.0001), but not airway NO flux. There was no significant correlation between FeNO and respiratory system resistance in either group, but in the SCD children, there were correlations between alveolar NO production (P = 0.0006) and concentration (P < 0.0001) and pulmonary blood flow. Airway NO flux was not elevated in the SCD children nor correlated with airways obstruction, suggesting that airways obstruction, at least in some SCD children, is not due to asthma.

Extended analysis of exhaled and nasal nitric oxide for the evaluation of chronic cough

IntroductionChronic cough is usually defined as a cough that lasts for eight weeks or longer. Its etiological diagnosis is not always straightforward, and the measurement of exhaled nitric oxide (FeNO) has been proposed in patients' evaluation. No studies have assessed the usefulness of extended exhaled NO measurement for the evaluation of chronic cough. Therefore, we aimed at evaluating the usefulness of an extended exhaled NO measurement and nasal NO for an initial evaluation of chronic cough. MethodsWe studied 52 non-smoker patients with prolonged cough lasting more than eight weeks. Etiologies of cough were identified. Nasal NO and FeNO were assessed using multiple single-breath NO analysis at different constant expiratory flow-rates. From the fractional NO concentration measured at each flow-rate, the total NO flux between tissue and gas phase in the bronchial lumen (J'awNO), and the alveolar NO concentration (Cano) were extrapolated. ResultsThe patients were classified in four categories: cough variant asthma (CVA), nonasthmatic eosinophilic bronchitis (NAEB), upper airway cough syndrome (UACS) and gastro-esophageal reflux disease (GERD). Compared with UACS and GERD, both exhaled NO and J'awNO were higher in CVA and NAEB, and no differences were found in Cano and nasal NO level among the four groups. ConclusionsOur study suggests a potentially useful role for FeNO measurement in the etiological diagnosis of chronic cough. We did not find any additive value of performing exhaled NO at multiple flow-rates and nasal NO measurements.

Low alveolar and bronchial nitric oxide in severe uncomplicated obesity

Fractional concentration of exhaled nitric oxide (FeNO) is a recognized biomarker of the lower respiratory tract, where it is produced by the proximal conducting airways and the expansible peripheral bronchoalveolar compartment. We have previously shown that large increase in body mass decreases FeNO. Here we evaluated bronchial and alveolar components of the NO output of the lower respiratory tract in subjects with severe uncomplicated obesity (OB). Fifteen OB subjects (BMI 45.3 ± 5.6 kg/m(2)), 15 healthy controls (HC) (BMI 22.4 ± 2.4 kg/m(2)) and 10 obese subjects who experienced weight loss after bariatric surgery (OBS) (BMI 31.2 ± 3.4 kg/m(2)), were examined. Anthropometry and respiratory lung tests were performed. Exhaled NO was assessed using multiple single-breath NO analysis at different constant expiratory flow rates. From the fractional NO concentration measured at each flow-rate, the total NO flux between tissue and gas phase in the bronchial lumen (J'awNO), and the alveolar NO concentration (CANO) were extrapolated. Measured FeNO levels at 50 mL/s were lower in OB compared with HC and OBS (11.6 ± 2.8 ppb, 18.0 ± 4.1 ppb and 17.6 ± 2.9 ppb, respectively, p < 0.05). In OB, both J'awNO and CANO resulted significantly lower than OBS and HC values. Respiratory NO output is decreased in severe uncomplicated obesity for the reduction of both large/central airway maximal NO flux and alveolar NO concentration. The pathophysiological relevance of airway NO abnormalities in severe obese phenotype remains to be investigated.

Inflammatory Patterns in Asthmatic Children Based on Alveolar Nitric Oxide Determination

IntroductionNitric oxide (NO) levels can be measured at proximal (maximum airway NO flux [J′awNO]) and distal (alveolar NO concentration [CANO]) levels. Four inflammatory patterns have been described in asthmatic individuals, although their relevance has not been well established. The objective was to determine J′awNO and CANO in order to establish four inflammatory categories in asthmatics. Material and methodsCross-sectional study of a sample consisting of healthy and asthmatic children. Exhaled NO was determined at multiple flows. J′awNO and CANO were obtained according to the two-compartment model. The asthma control questionnaire (ACQ) and spirometry were administered to asthmatic children. Patients were categorized as type I (normal J′awNO and CANO), type II (elevated J′awNO and normal CANO), type III (elevated J′awNO and CANO) and type IV (normal J′awNO and elevated CANO). Correlation between FENO,50, J′awNO and CANO was analyzed using Spearman's R Correlation Test. Analysis of variance and paired comparisons were performed using the Bonferroni correction. ResultsOne hundred sixty-two children were studied, of whom 49 (32.23%) were healthy controls and 103 (67.76%) asthmatics. In the control subjects, FENO,50 (ppb) (median and range) was 11.5 (1.6–27.3), J′awNO (pl/s) was 516 (98.3–1470) and CANO (ppb) was 2.2 (0.1–4.5). Forty-four (42.7%) of the asthmatic participants were categorized as type I, 41 (39.8%) as type II, 14 (13.5%) as type III and 4 (3.88%) as type IV. Good correlation was observed between J′awNO and FENO,50 (r=0.97). There was no association between J′awNO and CANO. FEV1/FVC decreased significantly in type III (mean 79.8±7.5). Morbidity was significantly higher in types III and IV. ConclusionsNormal values obtained are similar to those previously reported. Asthmatics with high CANO showed higher morbidity. No correlation was found between proximal and distal inflammation.

Patrones inflamatorios en niños asmáticos basados en la determinación de óxido nítrico alveolar

IntroductionNitric oxide (NO) levels can be measured at proximal (maximum airway NO flux [J’awNO]) and distal (alveolar NO concentration [CANO]) levels. Four inflammatory patterns have been described in asthmatic individuals, although their relevance has not been well established. The objective was to determine J’awNO and CANO in order to establish four inflammatory categories in asthmatics. Material and methodsCross-sectional study of a sample consisting of healthy and asthmatic children. Exhaled NO was determined at multiple flows. J’awNO and CANO were obtained according to the two-compartment model. The asthma control questionnaire (ACQ) and spirometry were administered to asthmatic children. Patients were categorized as typei (normal J’awNO and CANO), typeii (elevated J’awNO and normal CANO), typeiii (elevated J’awNO and CANO) and typeiv (normal J’awNO and elevated CANO). Correlation between FENO,50, J’awNO and CANO was analyzed using Spearman's R Correlation Test. Analysis of variance and paired comparisons were performed using the Bonferroni correction. ResultsOne hundred sixty-two children were studied, of whom 49 (32.23%) were healthy controls and 103 (67.76%) asthmatics. In the control subjects, FENO,50 (ppb)(median and range) was 11.5 (1.6 to 27.3), J’awNO (pl/s) was 516 (98.3 to 1470) and CANO (ppb) was 2.2 (0.1 to 4.5). Forty-four (42.7%) of the asthmatic participants were categorized as typei, 41 (39.8%) as typeii, 14 (13.5%) as typeiii and 4 (3.88%) as typeiv. Good correlation was observed between J’awNO and FENO,50 (r=0.97). There was no association between J’awNO and CANO. FEV1/FVC decreased significantly in typeiii (mean 79.8±7.5). Morbidity was significantly higher in typesiii and iv. ConclusionsNormal values obtained are similar to those previously reported. Asthmatics with high CANO showed higher morbidity. No correlation was found between proximal and distal inflammation.