Fractional Concentration Of Exhaled Nitric Oxide Research Articles

Pulmonary Function should be the Surveillance Tool in Obese Children to Prevent Asthma

ObjectiveTo investigate the important mediator linking from obesity to childhood asthmaIntroductionThe mediating pathways in the obesity-asthma link are largely unknown. We aimed to investigate the mediating pathways and to search for the most prominent pathological mechanism between central obesity and childhood asthma.MethodsIn Taiwan Children Health Study, we collected data on an open cohort of children ranged from 9 to 13 years old. Children's respiratory outcomes, atopic conditions, obesity measures, and pulmonary function were surveyed annually between 2010 and 2012. Fractional exhaled nitric oxide concentrations were recorded in 2012. Generalized estimating equations and general linear models were used to examine the associations among central obesity, possible mediators, and asthma. Structural equation models were applied to investigate the pathways that mediate the link between central obesity and asthma.ResultsCentral obesity (waist-to-hip ratio) most accurately predicted childhood asthma. In the model of active asthma, the percentage of mediation was 28.6% for pulmonary function, 18.1% for atopy, and 5.7% for airway inflammation. The percentage of mediation for pulmonary function was 40.2% in the model of lifetime wheeze. Pulmonary function was responsible for the greatest percentage of mediation among the three mediators in both models.ConclusionsDecline in pulmonary function is the most important pathway in central obesity–related asthma. Pulmonary function surveillance should be applied to obese children for asthma risk prediction.

Fractional exhaled nitric oxide in preterm‐born subjects: A systematic review and meta‐analysis

BackgroundDecreased lung function is common in preterm‐born survivors. Increased fractional exhaled nitric oxide (FeNO) appears to be a reliable test for eosinophillic airway inflammation especially in asthma. We, systematically, reviewed the literature to compare FeNO levels in preterm‐born children and adults who did or did not have chronic lung disease of prematurity (CLD) in infancy with term‐born controls.MethodsWe searched eight databases up to February 2018. Studies comparing FeNO levels in preterm‐born subjects (<37 weeks’ gestation) in childhood and adulthood with and without (CLD) with term‐born subjects were identified and extracted by two reviewers. Data were analysed using Review Manager v5.3.ResultsFrom 6042 article titles, 183 full articles were screened for inclusion. Nineteen studies met the inclusion criteria. Seventeen studies compared FeNO levels in preterm‐ and term‐born children and adults; 11 studies (preterm n = 640 and term n = 4005) were included in a meta‐analysis. The mean FeNO concentration difference between the preterm‐born and term‐born group was −0.74 (95% CI −1.88 to 0.41) ppb. For the six studies reporting data on CLD (preterm n = 204 and term n = 211) the mean difference for FeNO levels was −2.82 (95% CI −5.87 to 0.22) ppb between the preterm‐born CLD and term‐born groups.ConclusionsOur data suggest that preterm born children with and without CLD have similar FeNO levels to term‐born children suggesting an alternative mechanism to eosinophilic inflammation for symptoms of wheezing and airway obstruction observed in preterm‐born subjects.

New asthma testing enhances the care of respiratory patients

New asthma testing enhances the care of respiratory patients

Usefulness of measurement of nitric oxide in exhaled air in diagnostics and treatment of allergic rhinitis and asthma in children and adolescents

StreszczenieTlenek azotu, powstający przy udziale enzymów z grupy syntaz tlenku azotu, spełnia w organizmie człowieka szereg istotnych funkcji, ale produkowany w nadmiarze wykazuje działanie prozapalne. Pomiary stężenia tlenku azotu w powietrzu wydychanym znajdują zastosowanie w diagnostyce i monitorowaniu nasilenia stanu zapalnego dróg oddechowych o podłożu eozynofilowym, nie powinny być jednak wykorzystywane jako samodzielny parametr w diagnozowaniu astmy lub monitorowaniu jej leczenia. Ocena stężeń tlenku azotu w powietrzu wydychanym znajduje również zastosowanie w ustalaniu patogenezy objawów u pacjentów z nieżytem nosa. Jest także pomocna w wykrywaniu i monitorowaniu współistniejącego eozynofilowego stanu zapalnego w dolnych drogach oddechowych u tych chorych. Wartości tlenku azotu w powietrzu wydychanym mogą być nieprawidłowe (zarówno obniżone, jak i podwyższone) w innych chorobach przewlekłych takich jak: mukowiscydoza, pierwotna dyskineza rzęsek oraz nieswoiste zapalenia jelit. Na wartości pomiaru wpływają liczne czynniki, takie jak: atopia, polimorfizmy genów syntaz tlenku azotu i parametry przemiany lipidowej organizmu. Oprócz pomiarów tlenku azotu w powietrzu wydychanym przydatne są także pomiary nosowego tlenku azotu, które znalazły zastosowanie w ocenie występowania oraz nasilenia zapalenia eozynofilowego w górnych drogach oddechowych.

Effect of tralokinumab, an interleukin-13 neutralising monoclonal antibody, on eosinophilic airway inflammation in uncontrolled moderate-to-severe asthma (MESOS): a multicentre, double-blind, randomised, placebo-controlled phase 2 trial

The role of interleukin 13 in airway inflammation and remodelling in asthma is unclear. Tralokinumab is a human monoclonal antibody that neutralises interleukin 13. We aimed to evaluate whether tralokinumab would have an effect on airway eosinophilic infiltration, blood and sputum eosinophil concentrations, eosinophil activation, and airway remodelling. We did a multicentre, double-blind, randomised, placebo-controlled phase 2 trial at 15 centres across the UK, Denmark, and Canada. We enrolled participants of either sex aged 18-75 years with inadequately controlled moderate-to-severe asthma for 12 months or more, requiring treatment with inhaled corticosteroids at a stable dose. We randomly assigned participants (1:1) to receive tralokinumab (300 mg) or placebo by an interactive web-based system or voice response system. Participants and study personnel were masked to treatment allocation. Both tralokinumab and placebo were administered subcutaneously every 2 weeks. The primary outcome measure was change from baseline to week 12 in bronchial biopsy eosinophil count. Secondary outcome measures included change in blood and sputum eosinophil counts. Exploratory outcomes included fractional exhaled nitric oxide (FENO) and blood IgE concentrations. Safety analyses were carried out in all participants who received study drug. This trial is registered with ClinicalTrials.gov, number NCT02449473, and with the European Clinical Trials Database, EudraCT 2015-000857-19. Between Sept 25, 2015, and June 21, 2017, 224 participants were enrolled and screened. Of these participants, 79 were randomly assigned to receive tralokinumab (n=39) or placebo (n=40). Tralokinumab did not significantly affect bronchial eosinophil count compared with placebo at week 12 (treatment effect ratio 1·43, 95% CI 0·63-3·27; p=0·39). Compared with placebo, tralokinumab did not significantly affect blood eosinophil count (treatment effect ratio 1·21, 95% CI 1·00-1·48; p=0·055) or sputum eosinophil count (0·57, 0·06-6·00; p=0·63), but FENO concentration (0·78, 0·63-0·96; p=0·023) and total blood IgE concentration (0·86, 0·77-0·97; p=0·014) were significantly reduced. 33 (85%) of 39 patients receiving tralokinumab and 32 (80%) of 40 receiving placebo reported at least one adverse event during the treatment period. No deaths in either treatment group were observed. Treatment-related adverse events occurred more frequently in the tralokinumab group than in the placebo group (11 [28%] of 39 vs seven [18%] of 40). Tralokinumab did not significantly affect eosinophilic inflammation in bronchial submucosa, blood, or sputum compared with placebo, but did reduce FENO and IgE concentrations. These results suggest interleukin 13 is not crucial for eosinophilic airway inflammation control in moderate-to-severe asthma. AstraZeneca.

Exhaled Nitric Oxide is Not a Biomarker for Pulmonary Tuberculosis

.To reduce transmission of tuberculosis (TB) in resource-limited countries where TB remains a major cause of mortality, novel diagnostic tools are urgently needed. We evaluated the fractional concentration of exhaled nitric oxide (FeNO) as an easily measured, noninvasive potential biomarker for diagnosis and monitoring of treatment response in participants with pulmonary TB including multidrug resistant–TB in Lima, Peru. In a longitudinal study however, we found no differences in baseline median FeNO levels between 38 TB participants and 93 age-matched controls (13 parts per billion [ppb] [interquartile range (IQR) = 8–26] versus 15 ppb [IQR = 12–24]), and there was no change over 60 days of treatment (15 ppb [IQR = 10–19] at day 60). Taking this and previous evidence together, we conclude FeNO is not of value in either the diagnosis of pulmonary TB or as a marker of treatment response.

Relationship between upper airway diseases, exhaled nitric oxide, and bronchial hyperresponsiveness to methacholine

ABSTRACTObjective: The “united airway disease” concept is based on the bidirectional interaction between asthma and rhinitis. The aim of this study was to determine the relationship between upper airway diseases and bronchial hyperresponsiveness (BHR), as well as their association with the fractional concentration of exhaled nitric oxide (FeNO) and atopy in patients with persistent symptoms suggestive of asthma requiring methacholine challenge testing (MCT) to confirm asthma diagnosis. Methods: A cross-sectional prospective study was carried out in adult patients with persistent asthma-like symptoms and negative bronchodilator testing. FeNO and MCT were performed in all patients. Asthma was confirmed based on the presence of suggestive symptoms and MCT results. Associated upper airway diseases included allergic rhinitis, nonallergic rhinitis, chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD). Results: The study included 575 patients; asthma was confirmed in 32.3%, and FeNO values ≥ 50 ppb were found in 27% of the patients. Elevated FeNO was significantly associated to AERD. The prevalence of atopy in asthma patients was 86.6%. Atopy was present in 90.4% of patients with asthma and FeNO levels ≥ 50 ppb. A significant association was found between AERD, asthma, and FeNO ≥ 50 ppb. Conclusions: Patients with symptoms suggestive of asthma but negative bronchodilator testing are commonly seen in usual practice. In this population, the association of high FeNO levels and BHR to atopy, as well as to AERD, suggests the presence eosinophilic inflammation in both the upper and lower airways and supports the “one airway” hypothesis.

Significance of Measurment of the Fractional Exhaled Nitric Oxide Concentrations in Patients with Eosinophilic Chronic Rhinosinusitis

Significance of Measurment of the Fractional Exhaled Nitric Oxide Concentrations in Patients with Eosinophilic Chronic Rhinosinusitis

Characterizing patients with asthma who received Global Initiative for Asthma steps 4-5 therapy and managed in a specialty care setting.

Severe asthma is recognized in the European Respiratory Society/American Thoracic Society guidelines as a major unmet need in the management of asthma. The study objective was to describe the clinical burden of Global Initiative for Asthma (GINA) steps 4-5 asthma for patients treated by specialists in the U.S. community setting. Patients, ages ≥12 years, with asthma who received GINA step 4 or 5 treatment and were treated at a large U.S. allergy practice network between January 1, 2010, and April 30, 2016, were retrospectively identified by using electronic health records. Clinical outcomes included lung function (forced expiratory volume in one second of expiration [FEV1] and FEV1% predicted), symptom control (Asthma Control Test [ACT]), the fractional exhaled nitric oxide (FeNO) value (FeNO ≥25 ppb indicates airway inflammation), and asthma medication use. The change in outcomes from baseline to 12 and 24 months after the index date was calculated. Of 120,116 patients with asthma, 12,922 (10.8%) had severe asthma, 68% (n = 8751) while on step 4 therapy. The mean baseline prebronchodilation FEV1% predicted was 79.7%, and the mean baseline ACT score was 17.0. With uncontrolled asthma defined as an ACT score of ≤19 and/or an FEV1 value of <80% predicted and/or oral corticosteroid use of ≥2 bursts, 52.5% and 57.7% of patients on step 4 and step 5 therapy, respectively, had uncontrolled asthma at baseline. Of a subset of patients, 40.9% had an eosinophil count of ≥300 cells/mm3 and 44% had an FeNO concentration of ≥25 ppb. Small increases in the FEV1 value were observed from baseline to 12 months (n = 4022) and 24 months (n = 2326) postindex (0.07 and 0.04 L, respectively). A considerable proportion of patients had uncontrolled asthma while on current GINA steps 4-5 treatment, which indicated that additional therapies may be required to reduce the clinical burden of severe asthma.

Decreased expression of indolamine 2,3-dioxygenase in childhood allergic asthma and its inverse correlation with fractional concentration of exhaled nitric oxide

BackgroundThe tryptophan metabolic pathway mediated by indolamine 2,3-dioxygenase (IDO), a tryptophan-degrading enzyme, plays an important role in controlling the development of allergic inflammation. The fractional concentration of exhaled nitric oxide (FeNO) is closely associated with the allergic state and is extensively used for the clinical evaluation of airway allergic inflammation. Clinical trials have rarely assessed the expression of IDO in childhood allergic asthma and its correlation with FeNO. ObjectiveTo evaluate the IDO level in children with childhood allergic asthma and the relation between IDO levels and FeNO. MethodsThirty children older than 5 years who were diagnosed the first time with allergic asthma were selected from the pediatric outpatient department. Another 30 healthy children were selected as controls. The subjects were evaluated by complete medical history, pulmonary function test results, skin prick test reaction, FeNO concentration test result, eosinophil count, and a disease severity score. Peripheral venous blood and induced sputum were obtained to measure the concentrations of IDO metabolites (ie, tryptophan and kynurenine). ResultsThe IDO levels in the peripheral blood and induced sputum were significantly lower in patients with childhood allergic asthma than in children in the control group. The IDO level was negatively correlated with FeNO but was not significantly correlated with age, sex, blood eosinophil count, or disease severity scale. ConclusionThe expression of IDO was significantly lower in childhood allergic asthma, particularly in children with high FeNO levels. There was no significant relation between IDO levels and asthma severity. Trial RegistrationChinese Clinical Trial Register (www.chictr.org.cn) Identifier: ChiCTR-COC-15006080.

Evaluation on exposures to particulate matter at a junior secondary school: a comprehensive study on health risks and effective inflammatory responses in Northwestern China.

Air pollutant measurement and respiratory inflammatory tests were conducted at a junior secondary school in Xi'an, Northwestern China. Hazardous substances including particulate matters (PMs), black carbon(BC) and particle-bounded polycyclic aromatic hydrocarbons (PAHs) were quantified both indoors and outdoors of the school. Source characterization with organic tracers and particle-size distribution demonstrated that the school's air was mostly polluted by combustion emissions from the surrounding environment. The evaluation of health assessment related to air quality was conducted by two methods, including potential risk estimation of air pollutants and direct respiratory inflammatory test. The incremental lifetime cancer risks associated with PAHs were estimated and were 1.62×10-6 and 2.34×10-6, respectively, for indoor and outdoor fine PMs. Both the values exceeded the threshold value of 1×10-6, demonstrating that the carcinogenic PAHs are a health threat to the students. Respiratory inflammatory responses of 50 students who studied in the sample classroom were examined with a fractional exhaled nitric oxide (FeNO) test, with the aid of health questionnaires. The average FeNO concentration was 17.4±8.5ppb, which was slightly lower than the recommended level of 20ppb established by the American Thoracic Society for children. However, a wide distribution and 6% of the values were >35ppb, suggesting that the potentials were still high for eosinophilic inflammation and responsiveness to corticosteroids. A preliminary interpretation of the relationship between air toxins and respiratory inflammatory response demonstrated the high exposure cancer risks and inflammatory responses of the students to PMs in the city.

Comparison of fractional exhaled nitric oxide levels measured using the NIOX VERO and NOA 280i

Fractional exhaled nitric oxide (FeNO) is a type 2 biomarker of eosinophilic airway inflammation and predicts the likelihood of corticosteroid responsiveness in patients with eosinophilic asthma. 1 Dweik R.A. Boggs P.B. Erzurum S.C. et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011; 184: 602-615 Crossref PubMed Scopus (1805) Google Scholar , 2 Robinson D. Humbert M. Buhl R. et al. Revisiting type 2-high and type 2-low airway inflammation in asthma: current knowledge and therapeutic implications. Clin Exp Allergy. 2017; 47: 161-175 Crossref PubMed Scopus (247) Google Scholar Several devices are available to measure FeNO levels for research purposes or in clinical practice worldwide, including the Sievers Nitric Oxide Analyzer (NOA 280i; GE Analytical Instruments, Boulder, Colorado), a stationary chemiluminescence analyzer, and the NIOX VERO (Aerocrine AB, Solna, Sweden), a portable electrochemical analyzer. The NIOX VERO is a new FeNO measurement device that is intended to replace the NIOX MINO, a previous portable electrochemical analyzer from the same manufacturer. [3] National Institute for Health and Care Excellence. Measuring fractional exhaled nitric oxide concentration in asthma. NICE diagnostics guidance 12. www.nice.org.uk/dg12. Accessed August 24, 2017. Google Scholar Some reports have compared the NOA 280i with the NIOX MINO. 4 Kim S.H. Moon J.Y. Kwak H.J. et al. Comparison of two exhaled nitric oxide analyzers: the NIOX MINO hand-held electrochemical analyzer and the NOA280i stationary chemiluminescence analyzer. Respirology. 2012; 17: 830-834 Crossref PubMed Scopus (33) Google Scholar , 5 Maniscalco M. de Laurentiis G. Weitzberg E. et al. Validation study of nasal nitric oxide measurements using a hand-held electrochemical analyser. Eur J Clin Invest. 2008; 38: 197-200 Crossref PubMed Scopus (41) Google Scholar However, potential differences between the NOA 280i and NIOX VERO remain unclear. In this cross-sectional study, we compared FeNO levels measured using the NOA 280i and NIOX VERO.

Lower Airway Inflammation in Eosinophilic Chronic Rhinosinusitis as Determined by Exhaled Nitric Oxide

Background: Chronic rhinosinusitis (CRS) is classified into eosinophilic CRS (ECRS) and non-ECRS. The objectives of this study were to evaluate lower airway inflammation by measuring the fractional concentration of exhaled nitric oxide (FeNO) and to examine the effects of endoscopic sinus surgery (ESS) on FeNO in patients with ECRS compared to non-ECRS. Methods: CRS patients with nasal polyps (23 with ECRS and 22 with non-ECRS) were enrolled into this study. ECRS was diagnosed based on the definition proposed by the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) study group. Several clinical markers including blood eosinophil counts, percent of eosinophils in white blood cells (WBC), number of eosinophils in nasal polyps, JESREC scores, total IgE, FeNO, and Lund-Mackay paranasal sinus CT scores were compared between ECRS and non-ECRS. These markers were also tested before and 2 months after ESS. Results: FeNO was significantly higher in patients with ECRS than in non-ECRS patients. When all CRS patients were tested, a significant correlation was found between FeNO and eosinophilic markers including blood eosinophil counts, percent of eosinophils in WBC, number of eosinophils in nasal polyps, and JESREC scores. FeNO showed a significant correlation with Lund-Mackay scores only in ECRS patients. Blood eosinophil counts, percent of eosinophils in WBC, and FeNO decreased after ESS only in ECRS patients. Conclusions: ECRS patients had lower airway inflammation as revealed by an elevated FeNO, which was parallel to the Lund-Mackay CT scores. ESS decreased the blood eosinophils and FeNO, leading to an improvement of the occult pulmonary dysfunction in ECRS patients.

Genetic and epigenetic susceptibility of airway inflammation to PM2.5 in school children: new insights from quantile regression

BackgroundThe fractional concentration of exhaled nitric oxide (FeNO) is a biomarker of airway inflammation that has proved to be useful in investigations of genetic and epigenetic airway susceptibility to ambient air pollutants. For example, susceptibility to airway inflammation from exposure to particulate matter with aerodynamic diameter < =2.5 μm (PM2.5) varies by haplotypes and promoter region methylation in inducible nitric oxide synthase (iNOS encoded by NOS2). We hypothesized that PM2.5 susceptibility associated with these epigenetic and genetic variants may be greater in children with high FeNO from inflamed airways. In this study, we investigated genetic and epigenetic susceptibility to airborne particulate matter by examining whether the joint effects of PM2.5, NOS2 haplotypes and iNOS promoter methylation significantly vary across the distribution of FeNO in school children.MethodsThe study included 940 school children in the southern California Children’s Health Study who provided concurrent buccal samples and FeNO measurements. We used quantile regression to examine susceptibility by estimating the quantile-specific joint effects of PM2.5, NOS2 haplotype and methylation on FeNO.ResultsWe discovered striking differences in susceptibility to PM2.5 in school children. The joint effects of short-term PM2.5 exposure, NOS2 haplotypes and methylation across the FeNO distribution were significantly larger in the upper tail of the FeNO distribution, with little association in its lower tail, especially among children with asthma and Hispanic white children.ConclusionSchool-aged children with higher FeNO have greater genetic and epigenetic susceptibility to PM2.5, highlighting the importance of investigating effects across the entire distribution of FeNO.

The effect of sleep duration on exhaled nitric oxide levels in U.S. adults.

Poor sleep quality and duration are associated with systemic endothelial dysfunction. However, an association between poor sleep and pulmonary endothelial dysfunction has not been elucidated. We sought to determine if there is a relationship between sleep duration and fractional exhaled nitric oxide (FeNO) concentrations as a surrogate for pulmonary endothelial function. We used three National Health and Nutrition Examination Survey (NHANES) cycles (2007-2012). Linear regression models were built with and without adjustment for age, sex, race, BMI, asthma/bronchitis, CRP, smoking, folate, renal function, respiratory infections, and steroid use. To examine a non-linear relationship, we introduced a spline, with single knot at mean sleep duration (7h). Of 13,173 participants (50.8% male, 44.2% Caucasian), 78% slept 6-8hours (h). FeNO was significantly higher in the group sleeping 6-8h (17.3±14.9ppb) than in the other two groups (16.0±13.0ppb, 15.9±12.7ppb for <6 and >8hrespectively; P<0.001). In unadjusted linear regression, FeNO increased by 1.1ppb for each hour increase in sleep up to 7h (P<0.001). Increased sleep duration beyond 7h saw a 0.96ppb decrease in FeNO (P<0.001). After adjustment for confounders, FeNO increased by 1.09ppb for each hour of sleep up to 7h (P=0.001) and decreased by 0.71ppb for each hour after (P=0.02). Sleeping less or more than 7h is associated with pulmonary endothelial dysfunction as measured by FeNO. Further study is needed to evaluate mechanism(s) of this association and validity of FeNO as a marker of endothelial function.

Polymorphisms of asthma susceptibility gene ORMDL3 in infantile wheezing

Objective To discuss the polymorphisms of asthma susceptibility gene ORMDL3 in infantile wheezing, in order to provide a theoretical basis for early diagnosis of asthma. Methods One hundred and fifty whee-zing infants were recruited and divided into 2 groups as asthma predictive index(API) positive group(n=80) and ne-gative group(n=70). Taqman probe was applied to detect the genotypes of 2 single nucleotide polymorphisms (SNPs) in childhood asthma susceptibility gene ORMDL3, which were rs4794820 and rs7216389.The genotype distributions were analyzed and compared between 2 groups, and the correlations among genotype distribution and tidal breath pulmonary function, fractional exhaled nitric oxide (FeNO) concentration, percentage of eosinophils (EOS%), serum immune globulin E (total IgE) levels respectively were also analyzed, respectively. Results (1) The frequencies of rs4794820 AG and rs7216389 TC heterozygotes in the API positive group were the highest, which were significantly higher than those in the negative group(58.75% vs.31.42%, 56.25% vs.32.86% respectively, all P<0.01). The frequencies of GG and TT homozygotes in the API negative group were the highest, which were significantly higher than those in the positive group (58.57% vs.30.00%, 57.14% vs.31.25% respectively, all P<0.01). (2)The time to reach the peak expiratory flow in tidal breathing over the total expiratory time (TPTEF/TE) and the volume to reach the peak expiratory flow in tidal breathing over the total expiratory volume (VPEF/VE) of the infants in the API positive group were less than those in the API negative group(16.87±5.31 vs.20.12±5.23, 20.87±5.92 vs.25.56±6.77, respectively), and the FeNO concentration was higher than that in the API negative group[(22.44±9.77) ppb vs.(13.23±7.90) ppb], and the differences were significant(t=-3.776, -4.490, 6.377, respectively; all P<0.01). (3)In the API positive group, the TPTEF/TE and VPEF/VE of the infants who expressed AG/TC genotype were lower than those who expressed GG/TT genotype(14.55±4.83 vs.19.91±4.17, 18.85±4.26 vs.25.20±7.06, respectively, t=-4.727, -3.976, all P<0.01); while the FeNO concentrations, EOS% and total IgE levels were higher than those who expressed GG/TT genotype[(25.02±8.77)ppb vs.(18.39±6.56)ppb, 7.16±2.62 vs.5.50±1.34, (366 727±275 533) IU/L vs.(166 826±62 865) IU/L, respectively](t=3.484, 3.409, 4.589 respectively; all P<0.01). Conclusions Childhood asthma susceptibility gene ORMDL3 SNPs rs4794820 AG and rs7216389 TC heterozygotes are the risk factors for API positive infantile wheezing.The pulmonary function damage and airway inflammation of the infants who expressed AG/TC genotype are more serious than those who expressed GG/TT genotype, and more likely to develop persistent asthma. Key words: Infantile wheezing; Asthma; Gene polymorphisms; ORMDL3; Asthma predictive index

Fractional Exhaled Nitric Oxide: A Potential Biomarker in Allergic Rhinitis?

Background: The fractional concentration of exhaled nitric oxide (FeNO) is a surrogate biomarker for Th2-dependent bronchial inflammation. The present study investigated whether FeNO may characterize allergic rhinitis (AR) patients. Methods: A total of 553 AR patients (497 males, mean age 28.8 years) were evaluated. Those patients with a high FeNO underwent a 2-year follow-up. Results: Increased FeNO was associated with a significantly longer AR duration, impaired lung function, more severe symptoms, and more frequent bronchial hyperresponsiveness (BHR). At follow-up, 22 out of 82 patients (26.8%) with high FeNO levels (>50 ppb) developed asthma. Conclusions: AR patients may frequently have high FeNO values, exceeding 50 ppb. This might be associated with an initial impaired lung function, BHR, a perceived worsening of respiratory symptoms, and potential progression to asthma.

Study of nasal exhaled nitric oxide levels in diagnosis of allergic rhinitis in subjects with and without asthma.

BackgroundThe measure of fractional exhaled nitric oxide (FENO) in the airways is a useful tool to guide the diagnosis and titration of inhaled corticosteroids in patients with asthma. However, its role in diagnosis of allergic rhinitis (AR), especially in subjects with asthma, is not well established.ObjectiveTo study the cutoff of nasal FENO in the diagnosis of subjects with AR and AR-asthma compared to age-matched subjects without AR or asthma and its correlations with the clinical and functional characteristics.MethodsThe study was cross sectional and descriptive. Subjects were grouped into control subjects, AR, and AR-asthma, based on the inclusion criteria. Exhaled NO (nasal FENO, bronchial FENO, and alveolar concentration of NO) was measured by multiple flow electro-luminescence device.ResultsSix hundred twenty-eight subjects were included: 217 control subjects (children: n=98, 10±4 years; adults: n=119, 50±16 years), 168 subjects with AR (children: n=54, 10±3 years; adults: n=114, 49±15 years), and 243 subjects with AR-asthma (children: n=115, 10±3 years; adults: n=128, 51±14 years). Nasal peak inspiratory flow and peak expiratory flow were lower in subjects with AR and AR-asthma than in control subjects (P<0.01 and P<0.01; and P<0.05 and P<0.01, respectively). Nasal FENO levels were significantly higher in subjects with AR and AR-asthma than in control subjects (1614±629 and 1686±614 ppb vs 582±161 ppb; P<0.001 and P<0.001, respectively). In subjects with AR non-asthma, the cutoffs of nasal FENO for those diagnosed with AR were 775 ppb in children, 799 ppb in adults, and 799 in the general population (sensitivity: 92.68%, 92.63%, and 92.65%, respectively; specificity: 91.67%, 95.00%, and 96.87%, respectively). In subjects with AR-asthma, the cutoffs of nasal FENO were higher, especially in asthma children (1458 ppb; sensitivity: 72.97% and specificity: 95.83%).ConclusionNasal FENO measurement is a useful technique for the diagnosis of AR in subjects with and without asthma.

A Novel Method of Measuring Fractional Exhaled Nitric Oxide in Tracheostomized Ventilator-Dependent Children.

The lower airway concentration of fractional exhaled nitric oxide (FENO) is unknown in children with chronic lung disease of infancy who have tracheostomy for long-term mechanical ventilation. We aimed to evaluate an online method of measuring FENO in a cohort of ventilator-dependent children with a tracheostomy and to explore the relationship between the peak FENO concentration (FENO peak) and the degree of respiratory support using the respiratory severity score. We conducted a prospective cross-sectional study in 31 subjects who were receiving long-term respiratory support through a tracheostomy. We measured the FENO peak and FENO plateau concentration from the tip of the tracheostomy tube using a nitric oxide analyzer in subjects during a quiet state while being mechanically ventilated. We obtained 2 consecutive 2-min duration measurements from each subject. The FENO peak, exhaled NO output (equal to the FENO peak × minute ventilation), and pulmonary NO excretion (exhaled NO output/weight) were calculated and correlated with the respiratory severity score. The median FENO peak was 2.69 ppb, and the median FENO plateau was 1.57 ppb. The coefficients of repeatability between the 2 consecutive measurements for FENO peak and FENO plateau were 0.74 and 0.59, respectively. The intraclass coefficient between subjects within the cohort was 0.988 (95% CI 0.975-0.994, P < .001) for FENO peak and 0.991 (95% CI 0.982-0.996, P < .001) for FENO plateau. We found that the FENO peak was directly correlated with minute ventilation, but we did not find a direct relationship between the FENO peak concentration, exhaled NO output, or pulmonary NO excretion and respiratory severity score. FENO peak and plateau concentration can be measured online easily with a high degree of reliability and repeatability in infants and young children with a tracheostomy. FENO peak concentration from the lower airway is low and influenced by minute ventilation in children receiving mechanical ventilation.

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.