Mean Fractional Exhaled Nitric Oxide Level Research Articles

Diagnostic role of fractional exhaled nitric oxide in pediatric eosinophilic esophagitis, relationship with gastric and duodenal eosinophils

Eosinophilic esophagitis (EoE) is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies. A non-invasive and cost-effective alternative for management of EoE is being researched. Previous studies assessing utility of fractional exhaled nitric oxide (FeNO) in EoE were low powered. None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO. To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity. Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study. Patients on steroids and with persistent asthma requiring daily controller medication were excluded. FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer (NIOX MINO, Aerocrine, Inc.; Stockholm, Sweden) prior to endoscopy. Based on the esophageal peak eosinophil count (PEC)/high power field on biopsy, patients were classified as EoE (PEC ≥ 15) or control (PEC ≤ 14). Mean FeNO levels were correlated with presence or absence of EoE, eosinophil counts on esophageal biopsy, and abnormal downstream eosinophilia in the stomach (PEC ≥ 10) and duodenum (PEC ≥ 20). Wilcoxon rank-sum test, Spearman correlation, and logistic regression were used for analysis. P value < 0.05 was considered significant. We recruited a total of 134 patients, of which 45 were diagnosed with EoE by histopathology. The median interquartile range FeNO level was 17 parts per billion (11-37, range: 7-81) in the EoE group and 12 parts per billion (8-19, range: 5-71) in the control group. After adjusting for atopic diseases, EoE patients had significantly higher FeNO levels as compared to patients without EoE (Z = 3.33, P < 0.001). A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels (r = 0.30, P < 0.005). On subgroup analysis within the EoE cohort, higher FeNO levels were noted in patients with abnormal gastric (n = 23, 18 vs 15) and duodenal eosinophilia (n = 28, 21 vs 14); however, the difference was not statistically significant. After ruling out atopy as possible confounder, we found significantly higher FeNO levels in the EoE cohort than in the control group.

Effect of cigarette smoking on smoking biomarkers, blood pressure and blood lipid levels among Sri Lankan male smokers

Study purposeThe aim of this study was to determine the fractional exhaled nitric oxide (FeNO) levels, exhaled breath carbon monoxide (eCO) levels, blood pressure, blood lipid levels between smokers and...

Usefulness of diurnal variation of fractional exhaled nitric oxide for predicting early therapeutic response to asthma treatment

Objective Fractional exhaled nitric oxide (FeNO) is considered to be an adjunct for asthma management, although its usefulness remains controversial. Therefore, it may be necessary for new approaches to use FeNO for asthma management. We evaluated whether diurnal variations of FeNO can predict response to asthma treatment. Methods This pilot study consisted of 22 uncontrolled asthmatics and 16 healthy subjects. FeNO and peak expiratory flow (PEF) were measured by themselves twice daily at home for three weeks (asthmatics) or two weeks (healthy subjects), and daily mean and diurnal variations of FeNO and PEF levels were calculated. In uncontrolled asthmatics, treatment was intensified a week after study entry, and then control status was reevaluated after three to four weeks. Asthmatics were then divided into two groups; good or poor responders. Results Diurnal variations of FeNO levels, as well as daily mean FeNO and PEF levels, in uncontrolled asthmatics before intensive treatment were significantly higher than those in healthy subjects, regardless of treatment response (p < 0.01). Furthermore, in the good responders, diurnal variations of FeNO levels were significantly decreased in the 1st week (p < 0.05) of intensive treatment, whereas the daily mean FeNO levels significantly dropped in the 2nd week (p < 0.05). In the poor responders, no such changes were observed in FeNO levels. In terms of PEF, only the daily mean levels were significantly elevated after the initiation of intensive treatment, regardless of treatment response. Conclusions Diurnal variations of FeNO may contribute to predicting early therapeutic response to asthma treatment.

The Depiction of Lung Function and Fractional-Exhaled Nitric Oxide (FeNO) among Asthmatic Outpatients: A Preliminary Study

Background: Asthma is a heterogeneous disease manifested by airway inflammation and wheezing, dyspnea, breathlessness and cough which are varied in intensity and time accompanied with variably restricted expiratory airflow. Asthma patients experienced decreased lung function that occured during asthma attack accompanied by increased levels of fractional-exhaled nitric oxide (FeNO) caused by the pathophysiological process of asthma and the resulting ventilation problems. The study aimed to reveal the depiction of lung function using spirometry dan FeNO level among asthmatic outpatients. Methods: This was a cross sectional study involving 13 uncontrolled-moderate persistent asthmatic outpatients at Asthma Clinic of Persahabatan General Hospital during October 2019 – March2020. The involved respondents had to undergo the spirometry test and the measurement of FeNO level. Results: The uncontrolled-moderate persistent asthmatic patients were dominated by female with mean age of 48.38+12.494 years old. The mean predicted FEV1 was 70.38+20.230% of whom 61.54% patients showed moderate obstruction. The mean FEV1/FVC ratio was 72.85+12.681% of whom 53.85% patients showed obstruction inFEV1/FVC ratio. The mean FeNO level was 29.62+9.152 ppb of whom 76.92% patients had FeNO level ranging 25-50 ppb. Conclusion: The moderate persistent asthmatic patients showed a decreased lung function with reduction of FEV1, obstructive FEV1/FVC ratio as well as increasing FeNO level.

Fractional exhaled nitric oxide could identify early spirometry change in clinically suspected asthma patients without airway obstruction

Fractional exhaled nitric oxide (FeNO) has been proposed as a non-invasive biomarker for allergic inflammation seen in asthma. The aim of this study was to assess the ability of FeNO to discriminate spirometry and lung volume measurements between those with and without airway obstruction among subjects with clinically suspected asthma. A retrospective study was conducted. Diagnostic evaluations including spirometry and FeNO testing (NO electrochemical equipment: NIOX VERO; Aerocrine AB, Solna, Sweden) were performed in all subjects. Airway obstruction was defined according to the Standardization of Spirometry of the American Thoracic Society (ATS)/European Respiratory Society (ERS), and 2014 recommendations of the Chinese National Guidelines of Pulmonary Function Test. It was used the Student t test for analysis of continuous variables and the χ2 test for analysis of discrete variables including FeNO levels and lung function metrics. Of the 138 subjects with clinically suspected asthma, airway obstruction was found in 61. There was no significant difference in the mean FeNO levels among subjects with or without airway obstruction ( p = 0.241) among un-selected subjects. Likewise, there was no difference in the FeNO levels between aged (&gt;50 years) and younger subjects (⩽50 years) ( p = 0.804). A significant proportion of subjects had a normal FeNO level (&lt;25 part per billion, ppb) in spite of having airway obstruction (39/138), 25 had an elevated FeNO level (⩾25 ppb) in spite of having no airway obstruction (25/138). Additionally, the airway-obstructed subjects with increased FeNO level had comparable spirometry to those with normal FeNO level ( p &gt; 0.05). However, among subjects without airway obstruction, the forced expiratory volume in 1 s (FEV1)/predicted (pred), maximal expiratory flow at 25% of forced vital capacity (FVC) (MEF25%)/pred, maximal expiratory flow at 50% of FVC (MEF50%)/pred and maximum mid-expiratory flow (MMEF)/pred were significantly lower in the FeNO ⩾ 25 ppb group compared to those in the FeNO &lt; 25 ppb group. These analyses indicated that increased FeNO levels could help to determinate early spirometry change within clinically suspected asthma subjects without airway obstruction. It is highlighted the importance of FeNO as a phenotype associated with an increased risk of airway obstruction in some subjects in this study.

Reference Ranges and Determinant Factors for Fractional Exhaled Nitric Oxide in a Healthy Saudi Adult Population.

BackgroundFractional exhaled nitric oxide (FENO) has emerged as a promising marker in respiratory research. The aim of this study was to determine the reference range values of FENO for healthy Saudi adults and the factors associated with FENO levels.Material/MethodsThis cross-sectional study was conducted at the Department of Physiology, King Saud University, Riyadh, Saudi Arabia, from January 2016 to August 2017. A total of 429 healthy Saudi adults were initially recruited. The final selection included 412 participants, consisting of 307 men and 105 women. FENO measurements were performed according to the current recommendations of the American Thoracic Society.ResultsWe observed that the FENO levels of women were significantly lower than those of men (18.6 vs. 21.3, P=0.009). In women, the measured FENO ranged from 5.7 ppb to 42 ppb, and in men from 5.0 ppb to 55.0 ppb. The mean FENO level in the entire study population was 20.6, with a range of 5.0 ppb to 55.0 ppb. The difference became non-significant when we calculated the FENO after adjusting for body surface area by different percentile distributions. Multiple linear regression analysis showed that body surface area and weight were significant predictors of FENO levels.ConclusionsIn this study, FENO levels were significantly affected by demographic variables. Therefore, it is important to consider the factors influencing FENO values to make a valid clinical interpretation.

Clinical Features of Chronic Obstructive Pulmonary Disease with High Fractional Exhaled Nitric Oxide.

Background The fractional exhaled nitric oxide (FENO) test is useful in asthma patients. However, a few studies on its usefulness in chronic obstructive pulmonary disease (COPD) patients have been reported. We analyzed the FENO level distribution and clinical characteristics according to the FENO level in COPD patients.Methods From December 2014 to June 2019, COPD patients who underwent pulmonary function and FENO tests at Chonnam National University Hospital were retrospectively evaluated for FENO, comorbidities, asthma history, blood eosinophil, and pulmonary function test. The high FENO group was defined as those with FENO level>25 parts per billion (ppb).Results A total of 849 COPD patients (mean age, 70.3±9.4 years) were included. The mean forced expiratory volume at 1 second was 66.5±21.7% and the mean FENO level was 24.3±20.5 ppb. Patients with FENO ≤25 ppb were 572 (67.4%) and those with FENO >25 ppb were 277 (32.6%). Blood eosinophil percentage was significantly higher (4.2±4.8 vs. 2.7±2.5, p<0.001) in patients with the high FENO group than the low FENO group. The high FENO group revealed a significantly higher frequency of patients with blood eosinophil percentage >3% (46.9% vs. 34.8%, p=0.001) and asthma history (25.6% vs. 8.6%, p<0.001) than the lower FENO group. Asthma history, blood eosinophil percentage >3%, and positive bronchodilator response (BDR) were independent risk factors for the high FENO level (adjusted odds ratio [aOR], 3.85; p<0.001; aOR, 1.46; p=0.017; and aOR, 1.57, p=0.034, respectively) in the multivariable analysis.Conclusion The FENO level distribution varied in COPD patients and the mean FENO value was slightly elevated. Asthma history, eosinophil percent, and positive BDR were independent risk factors for the high FENO level.

Usefulness of Fractional Exhaled Nitric Oxide-Guided Treatment in Patients with Asthma-Chronic Obstructive Pulmonary Disease Overlap

Background: Some patients present clinical features of both asthma and chronic obstructive pulmonary disease (COPD), which has led to the recent proposal of asthma-COPD overlap (ACO) as a diagnosis. Fractional exhaled nitric oxide (FeNO) is a candidate biomarker to diagnose ACO. We assessed the effect of an add-on treatment with budesonide/formoterol (BUD/FM) combination in patients with ACO, which was diagnosed by FeNO. Methods: This was a prospective, single-arm, open-label, before and after comparison study. Subjects included 83 patients with COPD who attended outpatient clinics for routine checkups at Shizuoka General Hospital between June and November 2016. All patients fulfilled the GOLD definition of COPD and were receiving long-acting muscarinic antagonist (LAMA) or LAMA/long-acting β2 agonist (LABA) combinations. After an 8-week run-in period, BUD/FM was added to the patients with FeNO levels of ≥35 ppb, defined as having ACO. For patients receiving LAMA/LABA, BUD/FM was added after the discontinuation of LABA. The modified British Medical Research Council (mMRC) score, COPD assessment test (CAT) score, spirometric indices, forced oscillation parameters, and FeNO were assessed before and after 8 weeks of BUD/ FM add-on treatment. Results: Twenty-four patients (28.9%) had FeNO levels ≥ 35 ppb, and 17 patients completed the study (mean age: 73 years and GOLD I/II/III/IV, 5/10/1/1). The mean CAT scores significantly improved (9.2 to 5.4, p = 0.015) and 10 patients (58.8%) showed ≥2 points improvement, a minimal clinically important difference. The mean FeNO levels significantly decreased from 63.0 to 34.3 ppb (p < 0.006). However, there were no changes in mMRC scores, spirometric indices, or forced oscillation parameters. Conclusions: FeNO-guided treatment with BUD/FM improves symptoms in patients with ACO.

The clinical role of fractional exhaled nitric oxide in asthma control

BackgroundThe potential role and characteristics of fractional exhaled nitric oxide (FeNO) remain unclear in the treatment of asthma. ObjectiveTo explore the clinical role of FeNO in asthmatic treatment. MethodsWe evaluated whether the mean or change of FeNO levels in the treatment period is associated with other conventional control parameters and predicted some clinical outcomes of asthma. We retrospectively analyzed the mean and percentage change of FeNO levels in the first 5 measurements at our hospital. ResultsThe study found a significantly strong correlation between FeNO level at diagnosis and the largest changes of FeNO values from diagnosis. No significant correlations were observed between FeNO levels and other parameters (Asthma Control Test [ACT] score or forced expiratory volume in one second [FEV1]) in mean and percentage change of values under treatment of asthma; however, significant positive correlations were found between ACT scores and FEV1. The mean FeNO level revealed a significant negative correlation with an annual change in FEV1 in individuals with asthma who were followed up for more than 2 years. Both the mean ACT score and percent predicted FEV1 revealed a significant negative correlation with occasional use of systemic corticosteroids. ConclusionDuring conventional treatment of asthma, the largest changes of FeNO values from diagnosis were strongly correlated with FeNO levels at diagnosis. As for the unlikely conventional parameters, no significant associations were observed between FeNO levels and deterioration of asthma during the treatment periods. An elevated mean FeNO level may be a marker of decreased lung function in individuals with asthma.

Biomarkers of oxidative stress and antioxidants in severe asthma: A Prospective Case-Control Study

BackgroundBronchial airway inflammation is the hallmark of asthma, which may be driven by an imbalance between oxidative stress and antioxidant defenses. Antioxidants deficiency may play a role, but this has remained unconfirmed. ObjectiveTo evaluate the oxidative stress burden and antioxidants defenses in patients with increasing asthma severity. MethodsThis prospective case-control study compared fractional exhaled nitric oxide (FeNO), exhaled breath condensate nitrite/nitrate (EBC-NOx), spirometry, and serum vitamins and trace elements among patients with and without asthma. ResultsSixty participants were recruited (30 with severe asthma number; 23 women [76.7%]; mean age, 41.4 years; mean forced expiratory volume in 1 second [FEV1], 2.2 L [72.2% predicted]; mean inhaled corticosteroid dosage, 2,540 μg/d; 18/30 [60%] receiving maintenance oral corticosteroids; 15 with mild asthma; all corticosteroids naïve; 9 women [60%]; mean age, 34.6 years; mean FEV1, 3.48 L [100.5% predicted]; 15 healthy controls; 12 women [80%]; mean age, 37.6 years; and mean FEV1, 3.53 L [111.7% predicted]). The mean FeNO levels increased significantly with increasing asthma severity (P = .01), but the EBC-NOx levels did not change significantly (P = .90). Paradoxically, vitamin A and vitamin E increased with increased disease severity, with vitamin E levels increasing significantly (P = .07 and P < .001, respectively). There was no significant difference between groups in the levels of copper (P = .37), zinc (P = .97), or selenium (P = .90). ConclusionFeNO but not EBC-NOx is increased significantly with asthma severity with no evidence of vitamins or trace elements deficiency in severe asthma. Impaired oxidative stress defenses in severe asthma may be driven by factors other than vitamins or trace elements deficiency.

Fractional exhaled nitric oxide is a useful adjunctive modality for monitoring bronchial asthma.

Background and Objective:To evaluate the utility of fractional exhaled nitric oxide (FeNO) in monitoring asthma control.Materials and Methods:Steroid naïve nonsmoking asthmatics were recruited and followed for 6–8 weeks on standard treatment. Serial measurements of FeNO, peak expiratory flow rate (PEFR) variability, forced expiratory volume in 1 s (FEV1), bronchodilator reversibility (BDR), and asthma control test (ACT) score were measured at baseline and after 6–8 weeks of treatment.Results:One hundred and fifty-one patients were recruited over an 18-month period. These comprised 79 males (52.3%) with mean (standard deviation) age of 34.2 (11.6). Mean (SD) FeNO levels at baseline and after therapy were 45.4 (35.9) and 38.4 (23.7) ppb, respectively (P = 0.01). Baseline FeNO correlated strongly with FEV1 (r = −0.78, P < 0.001), ACT score (r = −0.76, P < 0.001), PEFR variability (r = −0.74, P < 0.001), and moderately with BDR (r = 0.50, P < 0.001). After treatment with inhaled steroids, the correlation remained strong with ACT score (r = −0.68, P < 0.001) but weakened with PEFR variability (r = −0.34, P = 0.01) and FEV1 (r = −0.36, P = 0.01).Conclusions:FeNO may be useful as an adjunctive noninvasive modality to assess asthma control in both steroid naïve asthmatics and asthmatics on treatment. However, the suboptimal sensitivity and specificity may limit its utility as a point-of-care single monitoring tool.

Determination of fractional exhaled nitric oxide (FENO) reference values in healthy Thai population.

Fractional exhaled nitric oxide (FENO) level is directly correlated with airway inflammation in asthma patients. The objective of this study was to define normal FENO levels in healthy Thai volunteers. This prospective cohort study was conducted in healthy Thai volunteers aged ≥5 years. Demographic and clinical data were recorded and pulmonary function test (PFT) was performed. FENO was measured using a chemiluminescence nitric oxide analyzer. Seventy-nine healthy Thai volunteers with normal lung function test were included. Mean age of participants was 13 (6-47) years and 58.2% were female. All subjects had no history of allergic respiratory diseases. Mean FENO level increased with age, and the differences between age groups were statistically significant (p=0.001). The highest mean FENO level was 13.6 ppb in the 11-15 year age group, and then the FENO level gradually declined with age. The highest mean FENO level was found in the 18-24.9 body mass index (BMI) group. Significant differences were observed for FENO levels between different height groups (p=0.005) but not between different BMI groups (p=0.46). Fair correlations between FENO levels and body weight, height, FEV1, and FVC were observed. A fair correlation between FENO level and age, FENO level and FEF25%-75% was found only in volunteers ≤15 years of age. FENO level in healthy Thais increased with age until reaching maximum level (mean FENO 13.6 ppb) in the 11-15 year age group. Significant differences were observed for FENO levels between different age groups and different height groups.

Pulmonary functions in children with inflammatory bowel disease.

To investigate fractional exhaled nitric-oxide (FeNO) levels in children with Crohn's disease (CD) and ulcerative colitis (UC) and their correlation to disease activity. Children with CD and UC (aged 8-18 years) and age-matched healthy controls without respiratory symptoms were recruited. Disease activity was assessed using validated scores. All children performed spirometry and FeNO tests and the association between intestinal disease parameters and pulmonary functions was studied. Thirty-five children with CD, nine with UC, and 24 healthy controls were enrolled. The mean FeNO level was higher in children with CD compared with the controls. Increased FeNO levels (>23 parts per billion) were more common among CD and UC compared with healthy children (46, 33, and 0%, respectively, P<0.05). Nevertheless, FeNO levels did not correlate with disease activity. There were no significant differences between CD, UC patients, and healthy controls in any of the spirometric variables. FeNO level, a marker of airway inflammation, is elevated in children with inflammatory bowel diseases irrespective of their intestinal disease activity. Increased FeNO levels are not associated with respiratory symptoms, suggesting a latent pulmonary involvement in the systemic disease.

Relationship between fractional exhaled nitric oxide and bronchopulmonary dysplasia in extremely/very low birth weight infants

Objective To investigate the relationship between fractional exhaled nitric oxide (FeNO) and bronchopulmonary dysplasia (BPD) in extremely/very low birth weight infant (ELBWI/VLBWI). Methods Thirty-five ELBWI/VLBWI (gestational age <34 weeks at birth and birth weight <1 500 g), who were admitted to neonatal intensive care unit of Peking University Third Hospital from October 2014 to March 2015 with respiratory distress soon after birth, were enrolled into the study, and divided into BPD group (n=11) and non-BPD group 1 (n=24) according to the diagnosis at discharge. One day before they left the hospital, FeNO level was determined with Exhalyzer D, an equipment for pulmonary function test. Difference of FeNO and nitric oxide (NO) production between the two groups was compared with t-test or Fisher exact test, and the value of FeNO in predicting BPD was tested by receiver-operating characteristic (ROC) curve. Results The mean gestational age at birth in BPD group was significantly less than that in non-BPD group [(29.7±1.9) vs (32.0±1.5) weeks, t=4.005, P=0.000], and the duration of invasive ventilation [(53.0±91.3) vs (15.0±30.2) h, t=1.598, P=0.002] and oxygenation was longer [(42.1±7.8) vs (8.2±6.4) d, t=13.567, P=0.000]. There were more babies required surfactant treatment, prenatal cortisone administration, and inhalation of cortisone and bronchodilator during hospital stay in BPD group than in non-BPD group[10/11 vs 38%(9/24), 11/11 vs 58%(14/24) and 11/11 vs 21%(5/24), Fisher exact test, all P<0.05]. The age and body weight of the babies at the time of FeNO determination in BPD group were older or higher than those in non-BPD group [(46.4±16.3) vs (20.9±11.7) d, t=5.278, P=0.000; (2 090±164) vs (1 892±153) g, t=3.498, P=0.001], but the corrected gestational age was similar [(36.3±3.1) vs (35.0±2.3) weeks, t=1.407, P=0.169]. Both the mean FeNO level and NO production in BPD group were significantly higher than those in non-BPD group [(13.6±6.9) vs (8.0±3.6) ppb (1 ppb=1×10-9 mol/L), (25.6±10.1) vs (18.1±9.0) nl/min, t=2.967 and 2.478, P=0.006 and 0.018]. The area under the ROC curve was 0.749 (P=0.021, 95%CI: 0.539-0.953) which implied that FeNO provided medium power for discrimination of ELBWI/VLBWI with BPD from those without, with a sensitivity of 72.7% and specificity of 75.0% at the cut-off value of 11.55 ppb. Conclusions FeNO and NO production in BPD infants are significantly higher than non-BPD infants. Measurement of FeNO for ELBWI/VLBWI through mask before discharge is a simple, safe and invasive procedure to objectively evaluate pulmonary function early after birth. Key words: Bronchopulmonary dysplasia; Respiratory function tests; Nitric oxide; Infant, very low birth weight; Infant, extremely low birth weight

Exhaled nitric oxide and inducible nitric oxide synthase gene polymorphism in Japanese asthmatics

BackgroundInducible nitric oxide synthase (iNOS) induced by inflammatory cytokines and iNOS activity in bronchial epithelial cells is a major determinant of fractional exhaled nitric oxide (FeNO) levels. The aim of this study was to investigate the association of iNOS promoter gene polymorphisms and FeNO levels in Japanese asthmatics before the introduction of asthma treatment. MethodsAsthmatics were recruited from Fukushima Medical University Hospital. Genotyping of the pentanucleotide repeat (CCTTT)n and seven previously detected single nucleotide polymorphisms (SNPs) in the iNOS promoter lesion was performed. The relationships between the genotypes and FeNO levels before the introduction of asthma treatment were compared. ResultsIn 91 asthmatics, the number of microsatellite repeats ranged from 9 to 20 and showed a bimodal distribution. According to this distribution, asthmatics were divided into two groups: genotypes with at least one long allele with more than 14 repeats (L/s or L/L) and genotypes with both short alleles with 14 or fewer repeats (s/s). No significant differences were observed in each parameter between the two groups. The mean FeNO level before treatment was significantly higher in the L/s or L/L subjects than in the s/s subjects. After treatment, the lowest FeNO level did not differ between the two groups. Three SNPs detected in the Japanese subjects were not associated with FeNO levels. ConclusionsThe number of CCTTT repeats in the iNOS promoter region was associated with FeNO levels in asthmatics before treatment, suggesting the importance of iNOS genotype in the clinical application of FeNO for asthmatics.

Clinical Utility of Fractional exhaled Nitric Oxide (FeNO) as a Biomarker to Predict Severity of Disease and Response to Inhaled Corticosteroid (ICS) in Asthma Patients.

Bronchial asthma is a common chronic inflammatory airway disease diagnosed and is based on symptomatic history and Pulmonary Function Tests (PFT). Fractional exhaled Nitric Oxide (FeNO) is exclusively a non-invasive biomarker of on-going eosinophilic airway inflammation which remains unpredictable only with PFTs. FeNO measurement is recommended in predicting asthma severity and Inhaled Corticosteroid (ICS) response but further research is required to understand its clinical utility and agreement with current recommendations in a specific population. To estimate FeNO levels in Tamilian patients with mild-to-moderate persistent asthma and to correlate with disease severity and ICS response. The study was a prospective cohort with a single group of 102 persistent asthma patients under standard ICS regimen for 8 weeks (follow-up period). PFT and FeNO were measured using portable spirometry and chemiluminescence based exhaled breath analyser, at baseline and during follow-up visits. Based on PFT and FeNO parameters, the study population was sub-grouped with respect to asthma severity (as mild, moderate and moderately severe), FeNO cut-off (> or < 50ppb) and ICS response classification (good vs poor ICS responders). Significant decrease in mean FeNO levels were found in mild, moderate and moderately severe asthmatic groups following ICS treatment (90.15±27.36, 75.74±31.98 and 77.18±32.79 ppb) compared to similar baseline FeNO levels (103.03±34.08, 91.38±37.60 and 97.90±43.84 ppb) in all the above groups. Similarly, significant decrease in mean FeNO levels was found - FeNO>50ppb, good and poor ICS responders groups, in post- ICS treatment (89.63±24.04, 77.90±31.12 and 86.49±32.57 ppb) compared to baseline levels (110.183±1.23, 97.12±42.04 and 99.68±34.71 ppb). The observed baseline FeNO values in all groups as stated above did not show significant difference to differentiate asthma severity or ICS responders groups. The present study results do not support the predictive association of baseline FeNO levels with asthma severity and future ICS response, but the decrements in FeNO levels on ICS treatment, supports its clinical utility in monitoring of ongoing airway inflammation and understanding treatment response rate.

Association between allergic sensitization and exhaled nitric oxide in children in the School Inner-City Asthma Study

Association between allergic sensitization and exhaled nitric oxide in children in the School Inner-City Asthma Study

Characterization of airway inflammation in patients with COPD using fractional exhaled nitric oxide levels: a pilot study.

ObjectiveTo characterize fractional exhaled nitric oxide (FeNO) levels that may be indicative of Th2-mediated airway inflammation in patients with chronic obstructive pulmonary disease (COPD).MethodsThis single-visit, outpatient study was conducted in 200 patients aged 40 years and older with COPD. All patients underwent spirometry and FeNO testing. COPD severity was classified according to the Global initiative for chronic Obstructive Lung Disease (GOLD) 2010 guidelines.ResultsPatients who participated in the study had a mean age of 63.9±11.3 years and a mean smoking history of 46±29 pack years. Patients had a mean forced expiratory volume in 1 second % predicted of 53.9%±22.1%. The percentage of patients classified with COPD severity Stage I, II, III, and IV was 13%, 40%, 39%, and 8%, respectively. In addition, according to current procedural terminology codes, 32% of patients were classified as mixed COPD/asthma, 26% as COPD/emphysema, and 42% as all other codes. The mean FeNO level for all patients was 15.3±17.2 parts per billion (ppb). Overall, 89% of patients had a FeNO <25 ppb, 8% had a FeNO 25–50 ppb, and 3% had a FeNO >50 ppb. The percentages of patients with FeNO in the intermediate or high ranges of FeNO were greatest among patients with mixed COPD/asthma (intermediate, 11.5%; high, 6.6%) compared with COPD/emphysema (intermediate, 8%; high, 0) and all other codes (intermediate, 6.3%; high, 1.3%).ConclusionIncreases in FeNO were identified in a subset of patients with COPD, particularly in those previously diagnosed with both COPD and asthma. Since FeNO is useful for identifying patients with airway inflammation who will have a beneficial response to treatment with an inhaled corticosteroid, these data may have important implications for the management of COPD patients.

Longitudinal Assessment of High Versus Low Levels of Fractional Exhaled Nitric Oxide Among Children with Asthma and Atopy

Fractional exhaled nitric oxide (FeNO) has emerged as an important biomarker in asthma. Increasing evidence points to atopy as a confounding factor in the interpretation of elevated FeNO. We conducted a longitudinal study to understand the clinical significance of FeNO as an inflammatory biomarker. We identified 19 children aged 13-15years at baseline with a significant elevation in FeNO≥80 parts per billion (ppb) and randomly selected a group of children of similar age with a moderate elevation (40-79ppb) and normal-to-low FeNO (<40ppb). Between November 2010 and July 2011, three additional study visits were conducted. Ninety-three children participated in the study. There were 16, 24, and 53 participants in the high, mid, and low FeNO groups. During 1.5years of follow-up, mean FeNO levels were 82.6ppb (standard deviation [SD]=65.9) for atopic asthmatics, 50.6ppb (SD=42.6) for nonasthmatic atopics, 17.0ppb (SD=10.8) for nonatopic asthmatics, and 17.8ppb (SD=13.9) for nonatopic nonasthmatics (p<0.001). FeNO levels remained stable: 63% of the high FeNO group had a FeNO≥80 across all 4 measurements and 87 % of the normal-to-low FeNO group had a FeNO of <40 across all 4 measurements. The high FeNO group also was found to have an elevation in IL-5 (p=0.04), IL-6 (p=0.003), IL-10 (p=0.002), and total serum IgE (p<0.001), after adjustment by age, sex, height, body mass index, and atopy and asthma status. An elevation of FeNO appears to indicate an atopic phenotype regardless of an asthma diagnosis, clinical symptoms, or corticosteroid use. An elevation of FeNO also is associated with a systemic elevation in inflammatory cytokines.

Relationship between alveolar nitric oxide concentration in exhaled air and small airway function in COPD

Nitrative stress is thought to be involved in the inflammatory process in COPD airways, and the alveolar nitric oxide concentration (CAlv) has been reported to be increased. However, the CAlv levels are also regulated by gas diffusion at alveolar sites. The aim of the study was to assess the relationship between the CAlv and pulmonary function in COPD patients, while taking into account the lung diffusion capacity. Twenty stable COPD patients (GOLD stage1/2/3/4 = 6/8/6/0) and 16 healthy subjects took part in this cross-sectional study. Fractional exhaled nitric oxide (FENO), CAlv, and pulmonary functions were measured. Pulmonary function, including single nitrogen washout curve (dN2) and diffusion capacity for carbon monoxide (DLCO), was also evaluated in patients with COPD. The mean FENO levels (20.7 ppb versus 16.3 ppb, p < 0.05) and the mean CAlv levels (6.4 ppb versus 4.2 ppb, p < 0.01) in COPD patients were significantly increased compared to those in HS. The CAlv level in COPD was significantly correlated with dN2, %DLCO/alveolar volume (VA). Using the standard entry method of multivariate analysis to adjust for dN2 and %DLCO/VA, dN2 (β = 0.54, p = 0.005) and %DLCO/VA (β = −0.44, p = 0.018) still showed significant correlations with the CAlv levels. These results suggest that the CAlv could be a useful marker for the small airway dysfunction in COPD. Airway inflammation, including excess nitric oxide generation in the peripheral airways, might be related to the pathophysiology of COPD.