Fractional Concentration Of Nitric Oxide Research Articles

1-Year Prospective Study of the Relationship of Serial Exhaled Nitric Oxide Level and Asthma Control.

Previous studies found that the fractional nitric oxide concentration in exhaled breath (FeNO) levels in healthy Chinese adults was higher than in White adults. More understanding of serial changes of FeNO levels with asthma control in a real-life clinical setting would be important to explore the utility of this biomarker in routine asthma management. This study assessed the FeNO levels of Chinese asthma subjects with different levels of asthma control and the serial changes with respect to the changes in asthma control over 1 year. A 12-month prospective study (subjects recruited between November 2019 and January 2021) with serial measurement of FeNO levels at baseline, 4, 8 and 12 months. Asthma control was assessed by the Global Initiative for Asthma classification, Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ). Altogether, 136 subjects (mean age 51.51±15.09 years, 46[33.8%] male) had successful baseline FeNO measurements. At baseline, the FeNO levels did not show a statistically significant difference for controlled, partly controlled and uncontrolled asthma according to GINA classification, ACT and ACQ. FeNO levels decreased with improving asthma control and stayed at similar levels with unchanged or worsening asthma control for all subjects. For subjects with baseline blood eosinophil levels ≥300 cells/µL(n=59), FeNO levels decreased with improving asthma control, stayed similar without change for asthma control and increased with worsening asthma control. Receiver operating characteristic (ROC) analysis with the highest area under curve (AUC) for changes in FeNO levels for improving asthma control was between ≤ -10 to -25 ppb at various time points in the 12-month study. Changes in FeNO levels over time were associated with changes in clinical asthma control, particularly in those with higher blood eosinophil count and are likely more useful than a single time point measurement in managing asthma.

Responsiveness of Inhaled Corticosteroid Treatment in Children with Asthma: The Role of rs242941 Polymorphism of CRHR1 Gene.

Inhaled corticosteroid (ICS) is the most widely used and effective treatment of asthma. However, some patients do not respond to ICS, which might be due to various genetic factors. Hence, understanding the genetic factors involved in the ICS response could help physicians to individualize their treatment decision and action plans for given patients. This study aimed to analyze the characteristics of corticotropin-releasing hormone receptor 1 (CRHR1) genotypes in children with asthma and the correlation between rs242941 polymorphism of CRHR1 gene and ICS responsiveness. This prospective study included children with uncontrolled asthma, assessing their eosinophil count, IgE concentration, lung function, and fractional concentration of nitric oxide in exhaled breath (FENO) and performing CRHR1 polymorphism sequencing. The level of asthma control was assessed by asthma control test (ACT); the responsiveness of asthma treatment with ICS was evaluated by measuring the change of ACT and forced expiratory volume in 1s (FEV1) after treatment versus at inclusion. In total, 107 patients were analyzed for CRHR1 at rs242941. Among these, 86 (80.3%) had homozygous wild-type GG, 20 (18.7%) had heterozygous GT genotypes, and 1 (1.0%) had a homozygous variant for TT. Children with personal and family history of atopy were more likely to have GT and TT genotypes. The severity of asthma was similar between children with asthma in the three groups of GG, GT, and TT genotypes of CRHR1 at rs242941. FENO level, total IgE concentration, and eosinophilic count in children with asthma were not significantly different between GG and GT genotypes. The patient with a TT homozygous variant genotype had a higher level of FENO. There was no correlation between CRHR1 polymorphism at rs242941 and asthma control evaluated by asthma control test and lung function parameters. TT genotype of rs242941 in the CRHR1 gene is not frequent. Clinical and functional characteristics of children with asthma with rs242941 polymorphism of CRHR1 gene remain homogeneously similar. There is no correlation between rs242941 polymorphism and ACT or FEV1.

Higher diversity of vegetable consumption is associated with less airway inflammation and prevalence of asthma in school‐aged children

A diet rich in fruits and vegetables has been suggested to counteract the oxidative stress and inflammation that characterize asthma. We aimed to assess the association between vegetable and fruit diversity consumption and asthma and its related outcomes in school-aged children. Participants included 647 children (49% females, aged 7 to 12 years) recruited from 20 public schools across the city of Porto, in Portugal. Vegetable and fruit intake were ascertained using a single self-reported 24-hour recall questionnaire. A diversity score was built taking into account the different number of individual vegetables and fruits consumed, and categorized into two groups based on the total reported median consumption , which was rounded to the nearest whole number (≤3 and >3, for vegetables, and ≤1 and >1, for fruits). A questionnaire was used to enquire about self-reported medical diagnosis of asthma and respiratory symptoms. Airway inflammation was assessed measuring exhaled fractional nitric oxide concentration (eNO) and was categorized into two groups (<35 and ≥35ppb). The association between fruit and vegetable diversity and respiratory outcomes was examined using logistic regression models, adjusting for confounders. A higher vegetable diversity consumption per day was negatively associated with having self-reported asthma (OR= 0.67, 95%CI 0.47; 0.95), while having a vegetable diversity consumption superior than 3 items per day was negatively associated with levels of eNO ≥35ppb (OR= 0.38, 95%CI 0.16; 0.88) and breathing difficulties (OR= 0.39, 95%CI 0.16; 0.97). Eating a greater variety of vegetables was associated with a lower chance of airway inflammation and prevalence of self-reported asthma in school children.

Application of exhaled nitric oxide (FeNO) in pediatric asthma.

Fractional concentration of Nitric Oxide in the exhaled air (FeNO) is a moderately good biomarker of type-2 airway inflammation, and its measurement is feasible also in children. The available evidence is still not enough to support the routine use of FeNO to diagnose or manage asthma in every patient in clinical practice. However, its role in identifying asthma with eosinophilic inflammation is of particular interest in the management of severe asthma. In healthy subjects, FeNO levels increase with age and height, particularly in males, and are also influenced by ethnicity. FeNO measurement can support asthma diagnosis and help in predicting asthma development later in life in young children with recurrent wheezing. FeNO-guided asthma management is effective in reducing asthma exacerbations but may result in a higher daily dose of inhaled corticosteroids. FeNO can also be used as a marker to evaluate adherence to asthma treatment and predict response to different biologicals, especially Omalizumab and Dupilumab. This review outlines recent data on the application of FeNO in childhood-onset asthma diagnosis and management, as well as in phenotyping subjects with severe asthma who may benefit from monoclonal antibodies administration.

Short-term responses to high-dose inhaled corticosteroid treatment in patients with chronic obstructive pulmonary disease with a fractional nitric oxide concentration over 35 parts per billion: A single-centre pre–post study

Introduction: There is currently no strategy for identifying chronic obstructive pulmonary disease (COPD) patients whose pulmonary function could benefit from inhaled corticosteroids. We investigated whether a 28-day regime of inhaled corticosteroids improved pulmonary function test results among COPD patients with a fractional exhaled nitric oxide concentration &gt; 35 parts per billion. Methods: This single-centre one-arm pre–post trial included COPD patients with a fractional exhaled nitric oxide concentration &gt; 35 parts per billion treated at our institution from September 2018 to August 2019. Patients were administered budesonide (200 μg, 8 puffs daily) for 28 days. The primary outcome measure was the difference between the forced expiratory volume in 1 s (FEV1) at baseline and after 28 days of inhaled corticosteroid treatment. Secondary outcomes included differences in COPD Assessment Test scores, %FEV1, and that between the percent forced vital capacity (%FVC) at baseline and after 28 days of treatment. Results: Twenty patients completed the 28-day inhaled corticosteroid regime. The mean difference in FEV1 between day 1 and day 28 was 340 mL (95% confidence interval: −100 to 770 mL; p = 0.122). The mean differences in secondary outcomes were: %FVC, −0.16% (95% confidence interval [CI]: −2.84 to 2.53%; p = 0.905); %FEV1, 1.63% (95%CI: −4.56 to 7.81%; p = 0.589); COPD Assessment Test score, −2.50 (95%CI: −5.72 to 0.72; p = 0.121). Conclusion: The 28-day course of inhaled corticosteroids yielded no significant difference in FEV1 for COPD patients with a fractional exhaled nitric oxide concentration &gt; 35 parts per billion. Trial registration: University Hospital Medical Information Network Center, UMIN000034005. Registered 3 September 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000038557

The use of exhaled nitric oxide and peak expiratory flow to demonstrate improved breathability and antimicrobial properties of novel face mask made with sustainable filter paper and Folium Plectranthii amboinicii oil: additional option for mask shortage during COVID-19 pandemic.

BackgroundMedical face masks are integral personal protective equipment against infectious airborne disease and become scarce during epidemic outbreaks such as COVID-19. A novel, sustainably manufactured face mask with antimicrobial and anti-inflammatory properties from oil of Folium Plectranthii amboinicii can be an effective alternative to internationally sold masks.MethodsThis prospective, randomized study assigned subjects (n=67) to either conventional surgical face mask or Lamdong Medical College (LMC) face mask for three hours. Fractional concentration of nitric oxide in exhaled breath (FENO) and peak expiratory flow (PEF) was measured before and after mask use. Subjective reporting on respiratory symptoms was also analyzed. Masks were then incubated and analyzed for microorganism growth.ResultsSubjects assigned the LMC mask had a lowered FENO (p<0.05) compared to conventional face masks after mask wearing. Subjects with LMC mask use reported higher comfortability (p<0.05), breathability (p<0.05), and lower allergy symptoms (p<0.05). The LMC mask has visually less microorganism growth in the cultured medium, measured by sterile ring radius.ConclusionsThe LMC face mask is a renewably manufactured personal protective tool with antibacterial capacity that can serve as an effective alternative to internationally sold surgical face mask during shortage of mask due to COVID-19.

Measurement of FeNO in asthma: what the hospital doctor needs to know.

Asthma is the commonest chronic lung disease. Airway inflammation is a central component of asthma but clinical symptoms of asthma and standard spirometry are insensitive in reflecting the underlying inflammatory processes. Measurement of the fractional nitric oxide concentration in exhaled breath (FeNO) is a quantitative, non-invasive and safe method of measuring airway inflammation. Advances in technology and standardization have made FeNO measurements simple, enabling their use as a biomarker alongside traditional clinical tools in the assessment and management of asthma. Specifically, it can predict responsiveness to steroids and also newer biological therapy, predict future risk of exacerbation and help highlight treatment non-adherence, making it a useful asset to personalized medicine.

Predictive Biomarkers for Asthma Therapy.

Asthma is a heterogeneous disease characterized by multiple phenotypes. Treatment of patients with severe disease can be challenging. Predictive biomarkers are measurable characteristics that reflect the underlying pathophysiology of asthma and can identify patients that are likely to respond to a given therapy. This review discusses current knowledge regarding predictive biomarkers in asthma. Recent trials evaluating biologic therapies targeting IgE, IL-5, IL-13, and IL-4 have utilized predictive biomarkers to identify patients who might benefit from treatment. Other work has suggested that using composite biomarkers may offer enhanced predictive capabilities in tailoring asthma therapy. Multiple biomarkers including sputum eosinophil count, blood eosinophil count, fractional concentration of nitric oxide in exhaled breath (FeNO), and serum periostin have been used to identify which patients will respond to targeted asthma medications. Further work is needed to integrate predictive biomarkers into clinical practice.

Bayesian estimation of physiological parameters governing a dynamic two-compartment model of exhaled nitric oxide.

The fractional concentration of nitric oxide in exhaled breath (fe NO) is a biomarker of airway inflammation with applications in clinical asthma management and environmental epidemiology. fe NO concentration depends on the expiratory flow rate. Standard fe NO is assessed at 50 mL/sec, but “extended NO analysis” uses fe NO measured at multiple different flow rates to estimate parameters quantifying proximal and distal sources of NO in the lower respiratory tract. Most approaches to modeling multiple flow fe NO assume the concentration of NO throughout the airway has achieved a “steady‐state.” In practice, this assumption demands that subjects maintain sustained flow rate exhalations, during which both fe NO and expiratory flow rate must remain constant, and the fe NO maneuver is summarized by the average fe NO concentration and average flow during a small interval. In this work, we drop the steady‐state assumption in the classic two‐compartment model. Instead, we have developed a new parameter estimation approach based on measuring and adjusting for a continuously varying flow rate over the entire fe NO maneuver. We have developed a Bayesian inference framework for the parameters of the partial differential equation underlying this model. Based on multiple flow fe NO data from the Southern California Children's Health Study, we use observed and simulated NO concentrations to demonstrate that our approach has reasonable computation time and is consistent with existing steady‐state approaches, while our inferences consistently offer greater precision than current methods.

Weekly Personal Ozone Exposure and Respiratory Health in a Panel of Greek Schoolchildren.

Background:The association of ozone exposure with respiratory outcomes has been investigated in epidemiologic studies mainly including asthmatic children. The findings reported had methodological gaps and inconsistencies.Objectives:We aimed to investigate effects of personal ozone exposure on various respiratory outcomes in school-age children generally representative of the population during their normal activities.Methods:We conducted a panel study in a representative sample of school-age children in the two major cities of Greece, Athens and Thessaloniki. We followed 188, 10- to 11-y-old, elementary school students for 5 wk spread throughout the 2013–2014 academic year, during which ozone was measured using personal samplers. At the end of each study week, spirometry was performed by trained physicians, and the fractional concentration of nitric oxide in exhaled air () was measured. Students kept a daily time–activity–symptom diary and measured PEF (peak expiratory flow) using peak flow meters. Mixed models accounting for repeated measurements were applied.Results:An increase of in weekly ozone concentration was associated with a decrease in FVC (forced vital capacity) and (forced expiratory volume in 1 s) of [95% confidence interval (CI): , ] and (95% CI: , 0.003) respectively. The same increase in exposure was associated with a 11.10% (95% CI: 4.23, 18.43) increase in and 19% (95% CI: , 42.75) increase in days with any symptom. The effect estimates were robust to adjustment. No inverse association was found between ozone exposure and PEF.Conclusions:The study provides evidence that airway inflammation and the frequency of respiratory symptoms increase, whereas lung function decreases with increased ozone exposure in schoolchildren. https://doi.org/10.1289/EHP635

Changes in breathomics from a 1-year randomized smoking cessation trial of electronic cigarettes.

Electronic cigarette (EC) use is an emerging behaviour that has been shown to help smokers to reduce cigarette consumption. The aim of this study was to illustrate long-term changes in exhaled breath measurements and respiratory symptoms in smokers invited to quit or reduce their cigarette consumption by switching to ECs. Prospective evaluation of cigarette consumption, fractional nitric oxide concentration in exhaled breath (FeNO), exhaled carbon monoxide (eCO) and symptom scores was performed in a 1-year randomized, controlled trial of 'healthy' smokers receiving 2·4% nicotine, 1·8% nicotine or no nicotine ECs. FeNO and eCO data are presented on the basis of participants' pooled continuous smoking phenotype classification (failures, reducers and quitters). A significant effect of quitting classification was found on FeNo and eCO at all time points (P < 0·0001). Among quitters, FeNO (medians and interquartile range) rose from 5·5 (4·5-6·9) ppb to 17·7 (13·3-18·9) ppb by week 52. Baseline eCO (medians and interquartile range) decreased from 17 (12-20) ppm to 3 (1-4) ppm by week 52. No significant changes in FeNO and eCO levels were observed in failures and reducers. Improvements in FeNO and eCO levels were correlated with attenuations in symptom scores. Smokers invited to switch to electronic cigarettes who completely abstained from smoking showed steady progressive improvements in their exhaled breath measurements and symptom scores. FeNo and eCO normalization is highly supportive of improved respiratory health outcomes and adds to the notion that quitting from tobacco smoking can reverse harm in the lung.

Role of eosinophilic inflammation and atopy in elderly asthmatic patients.

BackgroundAsthma in the elderly is severe and associated with poor treatment outcome. Although atopy has an important role in pathogenesis, its role in the elderly is unclear, partly due to immune senescence.ObjectiveWe aimed to examine the associations of Th2-mediated inflammation with asthma severity in the elderly.MethodsConsecutive asthmatics older than 60 years without severe exacerbation within 8 weeks were enrolled. Atopic status was determined by positive serum specific IgE or skin prick test to common aeroallergens. Serum total IgE was measured simultaneously to exhaled fractional concentration of nitric oxide (FeNO). Asthma control level was assessed by using Thai Asthma Control Test (ACT) score.ResultsTotal of 44 elderly asthmatic patients were enrolled. The mean age was 68.9 years and mean age of asthma diagnosis was 46.6 years. Seventy-seven percent of patients were female. Atopic status was found in 45.5% of patients. Uncontrolled asthma classified as ACT score < 20 was noted in 25% of elderly asthma, but its association with either high serum total IgE (≥120 IU/mL), high FeNO (≥50 ppb) or atopic status was not detected.ConclusionOne-fourth of elderly asthmatics were clinically uncontrolled, while atopy was confirmed in 45.5%. Neither high total IgE, high FeNO nor atopic status was associated with uncontrolled asthma in the elderly. Other factors might play role in asthma severity in the elderly, and has to be further investigated.

Identification of infants and preschool children at risk for asthma: predictive scores and biomarkers.

Predictive asthma scores and biomarkers are important tools that help many physicians in the identification of infants and preschool children at high risk for asthma. Our objective was to review recent data regarding this subject. Recently, two new predictive asthma scores were developed with some innovative features, such as the definition of scales of asthma risk. In a systematic review, 12 asthma-predictive models were identified with heterogeneous performance. Prospective studies have shown that elevated fractional concentration of nitric oxide (FeNO) is a strong risk factor for latter asthma among early wheezers, and a predictive asthma score with FeNO values has been proposed. Plasma cytokines and exhaled volatile organic compounds were also identified as potential asthma predictors. Predictive scores are simple, practical, and inexpensive tools to identify children at high risk for asthma at school age. Whereas some scores are better at identifying asthmatic children, others are better at excluding the diagnosis of asthma. Although promising, clear evidence for FeNO as a robust asthma predictor in comparison to clinical scores is still lacking. Specific IgE and eosinophil counts remain the most consistent biomarkers for the identification of children at risk for asthma, and further studies are necessary to clarify the role of other biomarkers.

Exhaled NO: Determinants and Clinical Application in Children With Allergic Airway Disease.

Nitric oxide (NO) is endogenously released in the airways, and the fractional concentration of NO in exhaled breath (FeNO) is now recognized as a surrogate marker of eosinophilic airway inflammation that can be measured using a noninvasive technique suitable for young children. Although FeNO levels are affected by several factors, the most important clinical determinants of increased FeNO levels are atopy, asthma, and allergic rhinitis. In addition, air pollution is an environmental determinant of FeNO that may contribute to the high prevalence of allergic disease. In this review, we discuss the mechanism for airway NO production, methods for measuring FeNO, and determinants of FeNO in children, including host and environmental factors such as air pollution. We also discuss the clinical utility of FeNO in children with asthma and allergic rhinitis and further useful directions using FeNO measurement.

PS-180 Measurement Of Fractional Nitric Oxide Concentration In Exhaled Breath In Monitoring The Paediatric Patient

<h3>Introduction</h3> Fraction of exhaled nitric oxide (FeNO) is a biomarker of eosinophilic airway inflammation, determining airway responsiveness to inhaled corticosteroid treatment and atopy. It is a non-invasive, reproducible, simple and safe method of measuring airway inflammation that provides a complementary tool to other ways of assessing airways disease, including asthma. <h3>Methods</h3> Retrospective descriptive study. The data of 99 paediatric patients attending outpatients in paediatric pneumology (from July 2012 to June 2013) with 2 consecutive measurements of FeNO was included. Characteristics of sex, age, exercise-induced asthma, prick test, FeNO, forced expiratory volume (FEV1), asthma control test (ACT) and baseline asthma treatment were analysed. The variations in FeNO, ACT, exercise-induced asthma and FEV 1 after intensifying or initiating treatment were collected. <h3>Results</h3> 99 patients, 46 men and 53 women were included. The mean age of the study population was 12.5 years (5–17) with an initial average ACT of 20.13 (10–25), FEV1 of 78% (42–132%) and an initial FeNO of 51.02 (7 -170). 95.8% had a positive prick test. 45 exercise tests were performed, in 18 (40%) of them a decrease in FEV1 &gt;10% was found. 15.2% of the patients were not taking any treatment at the first visit, 23.3% received Smart therapy (long-acting beta2- agonists and inhaled corticosteroids), 20.2% beta2- adrenergic agonist, 15% therapy Smart + montelukast, inhaled corticosteroids 13.1% and 13% other combined therapies. A statistically significant decrease in FeNO to 31.9 t = 6.594 (p = 0.000) was found after starting treatment, intensifying or modifying basic treatment. A statistically significant correlation was found between FeNO decrease and ACT improvement r = -0398 (p = 0.000) and FEV1 r = -0.260 (p = 0.01) between the first and the second visit. <h3>Conclusions</h3> The decrease in airway inflammation correlates with an increased subjective control of the disease and also with a higher forced expiratory volume. In our series of patients these results were achieved increasing Smart treatment therapy, as well as adding inhaled corticosteroid in patients not previously taking, including other treatment options. The value of FeNO also served to identify non-compliant patients.

The effect of omalizumab on small airway inflammation as measured by exhaled nitric oxide in moderate-to-severe asthmatic patients

Measurement of fractional nitric oxide concentration in exhaled breath (FENO) is a simple, noninvasive method to evaluate eosinophilic airway inflammation. Nitric oxide (NO) arising from peripheral small airways/alveoli (alveolar NO concentration [CalvNO]) can be estimated using multiple flow rates and a two-compartment model of the airways and alveoli. Omalizumab, a monoclonal anti-IgE antibody, is approved for the treatment of allergic asthma and also has been shown to decrease FENO levels. This study investigates the effects of omalizumab, when added to an inhaled corticosteroid (ICS) ± long-acting beta-adrenergic agonist (LABA) treatment, on peripheral small airway/alveolar inflammation reflected by FENO measurements at higher flow rates. We hypothesized that compared with placebo, omalizumab would decrease CalvNO levels in asthmatic patients on ICS ± LABA. Forty-two patients with moderate-to-severe asthma were randomly assigned 2:1 to either omalizumab (n = 29) or placebo treatment (n = 13) for 16 weeks. Selection criteria included moderate-to-severe asthmatic patients on an ICS ± LABA, positive skin test to one or more perennial allergen, screening FENO of >13 ppb, and a baseline IgE of 30-700 IU/mL. FENO measured at multiple flow rates was used to calculate CalvNO over the course of 16 weeks. FENO levels decrease with increasing flow rates (p < 0.05 repeated measures ANOVA) but no differences between the placebo and treatment groups in overall CalvNO levels or in the changes of CalvNO with time were found. Omalizumab did not lower the CalvNO, which could have been caused by the initial low CalvNO in this asthmatic population. The model used may not be completely sufficient and/or sensitive enough to detect small changes in CalvNO.

Revisiting the role of exhaled nitric oxide in asthma

This review focuses on the most recent studies investigating fractional nitric oxide concentration in exhaled breath (FeNO) as a useful biomarker for identifying specific phenotypes in asthma and as a tool for asthma diagnosis, monitoring and clinical decision-making. On the basis of the current literature, it has been highlighted that FeNO is a clinically relevant marker in various clinical aspects of asthma: FeNO is a predictor for developing asthma in persistent rhinitis or in infants with respiratory symptoms; FeNO contributes to identification of asthma phenotypes in both children and adults, also in relation to severity; FeNO is useful in monitoring the effectiveness of inhaled corticosteroids (including compliance) and biologic treatments like omalizumab; FeNO, in conjunction with symptom registration and lung function measurements, contributes to asthma diagnosis and optimizes asthma management. FeNO provides further information in distinguishing different phenotypes in asthma, allowing a much more appropriate control of the disease, especially in patients with difficult/severe asthma. In the future, it would be interesting to shed light on the hidden biological mechanisms responsible for low or normal FeNO values in symptomatic asthmatic patients.

Exhaled nitric oxide fraction as an add-on to ACQ-7 for not well controlled asthma detection.

BackgroundThe measurement of fractional nitric oxide concentration in exhaled breath (FeNO), a noninvasive indicator of airway inflammation, remains controversial as a tool to assess asthma control. Guidelines currently limit asthma control assessment to symptom and spirometry based appraisals such as the Asthma Control Questionnaire-7 (ACQ-7). We aimed at determining whether adding FeNO to ACQ-7 improves current asthma clinical control assessment, through enhanced detection of not well controlled asthma.MethodsAsthmatic subjects, classified as not well controlled as per ACQ-7 on regular clinical practice, were included in a prospective, multicenter fashion, and had their maintenance treatment adjusted on visit 1. On follow-up (visit 2) four weeks later, the subjects were reevaluated as controlled or not well controlled using ACQ-7 versus a combination of FeNO and ACQ-7.ResultsOut of 381 subjects enrolled, 225 (59.1%) had not well controlled asthma on visit 2 as determined by ACQ-7, and 264 (69.3%) as per combined FeNO and ACQ-7. The combination of FeNO to ACQ-7 increased by 14.8% the detection of not well controlled asthma following maintenance therapy adjustment.ConclusionsThe addition of FeNO to ACQ-7 increased the detectability of not well controlled asthma upon adjustment of maintenance therapy. Adding a measure of airway inflammation to usual symptom and spirometry based scores increases the efficacy of current asthma clinical control assessment.

Storage conditions for stability of offline measurement of fractional exhaled nitric oxide after collection for epidemiologic research

BackgroundThe measurement of fractional concentration of nitric oxide in exhaled air (FeNO) is valuable for the assessment of airway inflammation. Offline measurement of FeNO has been used in some epidemiologic studies. However, the time course of the changes in FeNO after collection has not been fully clarified. In this study, the effects of storage conditions on the stability of FeNO measurement in exhaled air after collection for epidemiologic research were examined.MethodsExhaled air samples were collected from 48 healthy adults (mean age 43.4 ± 12.1 years) in Mylar bags. FeNO levels in the bags were measured immediately after collection. The bags were then stored at 4°C or room temperature to measure FeNO levels repeatedly for up to 168 hours.ResultsIn the bags stored at room temperature after collection, FeNO levels were stable for 9 hours, but increased starting at 24 hours. FeNO levels remained stable for a long time at 4°C, and they were 99.7% ± 7.7% and 101.3% ± 15.0% relative to the baseline values at 24 and 96 hours, respectively. When the samples were stored at 4°C, FeNO levels gradually decreased with time among the subjects with FeNO ≥ 51 ppb immediately after collection, although there were almost no changes among the other subjects. FeNO levels among current smokers increased even at 4°C, although the values among ex-smokers decreased gradually, and those among nonsmokers remained stable. The rate of increase was significantly higher among current smokers than among nonsmokers and ex-smokers from 9 hours after collection onwards.ConclusionsStorage at 4°C could prolong the stability of FeNO levels after collection. This result suggests that valid measurements can be performed within several days if the samples are stored at 4°C. However, the time course of the changes in FeNO levels differed in relation to initial FeNO values and cigarette smoking.

Omalizumab Protects against Allergen- Induced Bronchoconstriction in Allergic (Immunoglobulin E-Mediated) Asthma

Background: Omalizumab has been shown to suppress responses to inhaled allergens in allergic asthma patients with pretreatment immunoglobulin E (IgE) ≤700 IU/ml. To extend current dosing tables, we evaluated the potential of high omalizumab doses to block allergen-induced bronchoconstriction in patients with higher IgE levels. Methods: Asthmatic adults (18–65 years; body weight 40–150 kg) were divided into groups according to screening IgE (group 1: 30–300 IU/ml; group 2: 700–2,000 IU/ml) and randomized 2:1 to omalizumab/placebo every 2 or 4 weeks for 12–14 weeks. Allergen bronchoprovocation (ABP) testing was performed before treatment and at weeks 8 and 16. The primary efficacy endpoint, the early-phase allergic response (EAR), was defined as the maximum percentage drop in forced expiratory volume in 1 s during the first 30 min after ABP. Serum free IgE was determined as a pharmacodynamic endpoint, and the exhaled fractional concentration of nitric oxide (FE_NO) was an exploratory endpoint. Results: Fifty patients were included in the study. Omalizumab improved EAR; at week 8, EAR was 23.1% for placebo, 9.3% in group 1 (p = 0.018 versus placebo) and 5.6% in group 2 (p < 0.001). At week 16, EAR was 20%, 11.8% (p = 0.087) and 5.1% (p < 0.001), respectively. Free IgE decreased in groups 1 and 2 and remained <50 ng/ml in all patients during weeks 6–16. Omalizumab completely suppressed FE_NO increases after ABP in both groups. Conclusions: Omalizumab blocked early asthmatic responses over a broad range of IgE/body weight combinations. Extending the dosing tables enables omalizumab to benefit a wider range of patients.