Measurement Of Nitric Oxide Research Articles

Detection of Nitric Oxide from Chickpea Using DAF Fluorescence and Chemiluminescence Methods.

The free radical nitric oxide (NO) has emerged as an important signal molecule in plants, due to its involvement in various plant growth, development, and stress responses. For elucidating the role of NO, it is very important to precisely determine, localize, and quantify NO levels. Due to a relatively short half-life and its rapid, complex reactivity with other radicals, together with its capacity to diffuse from the source of production, the quantification of NO in whole plants, tissues, organelles, and extracts is notoriously difficult. Hence, it is essential to employ sensitive procedures for precise detection of NO. Currently available methods can fulfill many requirements to precisely determine NO, but each method has several advantages and pitfalls. In this article, we describe a detailed procedure for the measurement of NO by diaminofluorescein (DAF) in cell-permeable forms (DAF-FM-DA). In this method, the tissues are immersed in DAF-FM DA, leading to their diffusion from the plasma membrane to the inside of the cell, where intracellular esterases cleave the ester bonds, leading to DAF-FM release. The resulting DAF-FM reacts with intracellularly generated NO and forms highly fluorescent triazolofluorescein (DAF-FMT), which can be localized and monitored by fluorescence or confocal microscopy, and can also be detected via fluorimetry and flow cytometry. DAF dyes are very popular as they are non-invasive, relatively easy to handle, and commercially available. Another precise and very sensitive method is chemiluminescence detection of NO, where NO reacts with ozone (O3 ), leading to emission of a quantum of light from which NO can be calculated. Using chickpea seedlings, we describe in detail the measurement of NO using DAF-FM-DA and chemiluminescence methods. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Measurement of nitric oxide from chickpea seedlings using DAF-FM DA fluorescence with fluorescence and confocal microscopy Basic Protocol 2: Chemiluminescence detection of nitric oxide from chickpea seedlings.

Interannual Variability in Methane and Nitrous Oxide Concentrations and Sea‐Air Fluxes Across the North American Arctic Ocean (2015–2019)

AbstractBetween 2015 and 2018, we collected approximately 2,000 water column measurements of methane (CH4) and nitrous oxide (N2O) concentrations in the North American Arctic Ocean during summer and early fall. We also obtained 25 measurements of CH4 and N2O concentrations in rivers along the Northwest Passage and Ellesmere Island in midsummer 2017–2019. Our results show that N2O is generated in the highly productive Bering and Chukchi Seas and transported northeastward, producing a persistent subsurface N2O peak in the Beaufort Sea. The Chukchi and Beaufort Sea sediments are a significant source of CH4 to the water column. These sedimentary sources and associated water column consumption display significant spatial gradients and interannual variability. CH4 isotope data demonstrate the importance of CH4 oxidation across the study region. We find that rivers are not a significant source of CH4 or N2O to the Arctic Ocean at the time of year sampled. The estimated annual sea‐air flux across the study region (2.3 million km2) had a median (first quartile, third quartile) of 0.009 (0.002, 0.023) Tg CH4 y−1 and −0.003 (−0.013, 0.010) Tg N y−1. These results suggest that the North American Arctic Ocean currently plays a negligible role in global CH4 and N2O budgets. Our expansive data set, with observations at many repeat stations, provides a synopsis of present‐day Arctic CH4 and N2O distributions and their range of variability, as well as a benchmark against which future climate‐dependent changes can be evaluated.

Nasal nitric oxide measurement variability to establish a standard for reliable results.

A repeatability of 10% for NO measurements obtained with the velum closed in the same or both nostrils is relevant, while measurements taken during tidal breathing should aim for a repeatability of 20% and 30%, respectively https://bit.ly/3sMnug6

Calcitriol Ameliorates Brain Injury in the Rat Model of Cerebral Ischemia-Reperfusion Through Nrf2/HO-1 Signalling Axis: An in Silico and in Vivo Study

ObjectivesCalcitriol has been revealed to exert neuroprotective effects in ischemic stroke; however, its role and the underlying mechanisms in brain injury induced by ischemia are not well known. The purpose of this study was to determine the neuroprotective effects of calcitriol pretreatment and to assess the possible neuroprotective function of nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) signalling pathway against brain ischemia/reperfusion (I/R) injury in the rat models which was followed by a bioinformatics approach. MethodsThe experimental I/R model induction was performed in male Wistar rats for 1 h followed by 23 h reperfusion. Calcitriol was administered intraperitoneally for 7 days prior to stroke. Following ischemia induction 24 h later, neurobehavioral deficits and infarction volume were examined. Oxidative stress was assessed by measurement of malondialdehyde (MDA), nitric oxide (NO) and total antioxidant capacity (TAC). The protein and mRNA expression of HO-1 and Nrf2 were determined by western blot and reverse transcription polymerase chain reaction (RT-PCR), respectively. A molecular docking approach was applied to identify the interaction value of Keap1 with calcitriol. ResultsOur data demonstrated that calcitriol significantly decreased infarction volume and ameliorated neurological deficits in brain I/R. MDA and NO levels were decreased and TAC level was elevated significantly after calcitriol pretreatment. Furthermore, calcitriol upregulated the expression of HO-1 and Nrf2 protein and mRNA in ischemic brain. Molecular modelling demonstrated that calcitriol could interact with the pocket of Keap1 by an appropriate binding energy. ConclusionsThe results indicate that calcitriol protects the brain against I/R injury. This effect may pass through inhibition of oxidative stress and Nrf2/HO-1 pathway activation and this may arise by interaction of Keap1 and calcitriol.

An international survey on nasal nitric oxide measurement practices for the diagnosis of primary ciliary dyskinesia.

Nasal nitric oxide (nNO) measurements are used in the assessment of patients suspected of having primary ciliary dyskinesia (PCD), but recommendations for performing such measurements have not focused on children and do not include all current practices. To guide the development of a European Respiratory Society-supported technical standard for nNO measurement in children, an international online survey was conducted to better understand current measurement practices among providers involved in PCD diagnostics.78 professionals responded, representing 65 centres across 18 countries, mainly in Europe and North America. Nearly all centres measured nNO in children and more than half performed measurements before 5 years of age. The test was often postponed in children with signs of acute airway infection. In Europe, the electrochemical technique was more frequently used than chemiluminescence. A similar proportion of centres performed measurements during exhalation against a resistance (49 out of 65) or during tidal breathing (50 out of 65); 15 centres used only exhalation against a resistance and 15 used only tidal breathing. The cut-off values used to discriminate PCD were consistent across centres using chemiluminescence analysers; these centres reported results as an output (nL·min−1). Cut-off values were highly variable across centres using electrochemical devices, and nNO concentrations were typically reported as ppb.This survey is the first to determine real-world use of nNO measurements globally and revealed remarkable variability in methodology, equipment and interpretation. These findings will help standardise methods and training.

Limitations of Nasal Nitric Oxide Measurement for Diagnosis of Primary Ciliary Dyskinesia with Normal Ultrastructure.

Rationale: Primary ciliary dyskinesia (PCD) is a heterogeneous, multisystem disorder characterized by defective ciliary beating. Diagnostic guidelines of the American Thoracic Society and European Respiratory Society recommend measurement of nasal nitric oxide (nNO) for PCD diagnosis. Several studies demonstrated low nNO production rates in PCD individuals, but underlying causes remain elusive. Objectives: To determine nNO production rates in a well-characterized PCD cohort, including subgroup analyses with regard to ultrastructural and ciliary beating phenotypes. Methods: This study included 301 individuals assessed according to European Respiratory Society guidelines. Diagnostic cutoffs for nNO production rates for this study cohort and subgroups with normal and abnormal ultrastructure were determined. Diagnostic accuracy was also tested for the widely used 77 nl/min cutoff in this study cohort. The relationship between nNO production rates and ciliary beat frequencies (CBFs) was evaluated. Results: The study cohort comprised 180 individuals with definite PCD diagnosis, including 160 individuals with genetic diagnosis, 16 individuals with probable PCD diagnosis, and 105 disease controls. The 77 nl/min nNO cutoff showed a test sensitivity of 0.92 and specificity of 0.86. Test sensitivity was lower (0.85) in the subgroup of 47 PCD individuals with normal ultrastructure compared with 133 PCD individuals with abnormal ultrastructure (0.95). The optimal diagnostic cutoff for the nNO production rate for the whole study cohort was 69.8 nl/min (sensitivity, 0.92; specificity, 0.89); however, it was 107.8 nl/min (sensitivity, 0.89; specificity, 0.78) for the subgroup of PCD with normal ultrastructure. PCD individuals with normal ultrastructure compared with abnormal ultrastructure showed higher ciliary motility. Consistently, PCD individuals with higher CBFs showed higher nNO production rates. In addition, laterality defects occurred less frequently in PCD with normal ultrastructure. Conclusions: Measurements of nNO below the widely used 77 nl/min cutoff are less sensitive in detecting PCD individuals with normal ultrastructure. Our findings indicate that higher nNO production in this subgroup with a higher cutoff for the nNO production rate (107.8 nl/min) and higher residual ciliary motility is dependent on the underlying molecular PCD defect. Higher nNO production rates, higher residual CBFs, and the lower prevalence of laterality defects hamper diagnosis of PCD with normal ultrastructure. Adjusting the cutoff of nNO production rate to 107.8 nl/min might promote diagnosing PCD with normal ultrastructure.

Seasonal Effect of Radon Exposure on Fractional Exhaled Nitric Oxide

Fractional exhaled nitric oxide (FeNO) measures airway inflammation, with higher levels associated with asthma exacerbations and lung function decline. Radon, an omnipresent radioactive gas, may have a role in obstructive lung disease outside its known carcinogenicity. We hypothesized that radon exposure would be associated with increased FeNO levels in inner-city children with asthma.

Exhaled Nitric Oxide Level in Pharynx Angioedema.

Airway inflammation is related to increased nitric oxide production. It can be assessed noninvasively with exhaled nitric oxide measurement. As airway inflammation was supposed to be present in chronic urticaria and angioedema patients we hypothesized increased exhaled nitric oxide in this group. Twenty-six symptomatic chronic urticaria patients with an acute episode of pharynx angioedema (17 women and 9 men, median age 35) were included in the study group. None of the patients reported a history of asthma, allergic rhinitis or cigarette smoking. The control group consisted of 29 non-smoking healthy subjects (19 women and 10 men, median age 22) without any history of atopy. Exhaled nitric oxide measurement was performed in all subjects. Exhaled nitric oxide levels in the angioedema group did not differ statistically significantly from those detected in healthy subjects (15.5 ppb and 17.0 ppb respectively). Our results indicate the lack of airway inflammation in chronic urticaria patients with pharynx angioedema.

The National Heart Lung and Blood Institute guidelines finally say “yes” to fractional exhaled nitric oxide

Exhaled nitric oxide levels were first discovered to be elevated in patients with asthma in 1993, only 2 years after the first National Heart Lung and Blood Institute (NHLBI) asthma guidelines were published. 1 Alving K Weitzberg E Lundberg JM. Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J. 1993; 6: 1368-1370 PubMed Google Scholar Since then, more than 3600 articles have been published relating to the measurement of fractional exhaled nitric oxide (FeNO) in asthma, with an average of almost 20 articles per month being published over the past 10 years. Despite our growing understanding of the use of FeNO as a tool to assist in the evaluation and management of asthma, it has seen a particularly slow uptake among practitioners in the United States, especially in comparison to its wider acceptance and uses in other parts of the world including the United Kingdom and European Union. In 2011, the American Thoracic Society published evidence-based guidelines on the clinical use of FeNO 2 Dweik RA Boggs PB Erzurum SC Irvin CG Leigh MW Lundberg JO 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 (1677) Google Scholar ; however, the regularly updated international Global Initiative for Asthma guidelines did not adopt or endorse these recommendations at that time. 3 Global Initiative for Asthma. Global strategy for asthma management and prevention. 2020. Available at: http://www.ginasthma.org. Accessed September 25, 2021. Google Scholar The lack of consensus guidelines has, in part, been responsible for the slow adoption of FeNO by practitioners as a unique, clinically meaningful, and important tool in the diagnosis and management of asthma, and this has also led to several third-party payers denying payment and citing its use as “experimental.”

Reflux-related symptoms reflect poor asthma control and the presence of airway neuronal dysfunction

BackgroundGastroesophageal reflux may be associated with the worsening of asthma by increasing cough reflex sensitivity. Hull Airway Reflux Questionnaire (HARQ) consists of 14 prevalent reflux-related symptoms. It may be useful in predicting the presence of cough reflex hypersensitivity in asthma. MethodsFrom August 2018 to July 2020, 266 asthmatic patients completed the HARQ. They underwent blood analysis, spirometry, fraction of exhaled nitric oxide (FeNO) measurement, and the capsaicin cough challenge test. Patients were considered to have reflux-related symptoms if their HARQ scores were 13 points or higher. We evaluated the association between reflux-related symptoms and clinical asthma outcomes. Finally, we performed a multivariate analysis to determine the clinical significance of the HARQ for asthma. This study was registered in the University Hospital Medical Information Network (UMIN000040732). ResultsThe mean HARQ scores were 13.1 (standard deviation 12.0). Patients in the high HARQ scores group (HARQ ≥13, n = 105) showed a lower prevalence of atopic predisposition, lower levels of FeNO, heightened capsaicin cough reflex sensitivity, poorer asthma control, and more frequent admissions due to asthma than those in the low HARQ groups (all p values < 0.05). The HARQ was useful in selecting patients with poor controlled asthma and those with severe cough when the cut-off value was set at 13. Multivariate analysis revealed that heightened capsaicin cough reflex sensitivity affected reflux-related symptoms, as well as lower levels of FeNO and younger age. ConclusionsHigher HARQ scores (≥13) may be useful in predicting not only poor asthma condition but also the presence of airway neuronal dysfunction in patients with asthma to some extent.

Factors Influencing the Concentration of Exhaled Nitric Oxide (FeNO) in School Children Aged 8-9-Years-Old in Krakow, with High FeNO Values ≥ 20 ppb.

Background and Objectives: Measurement of fractional exhaled nitric oxide (FeNO) concentration is currently used as a non-invasive biomarker to assess airway inflammation. Many factors can influence the FeNO level. However, there have been no reports concerning factors attributed to FeNO levels in different age groups of children, especially those with high FeNO values. Therefore, this study aimed to assess the influence of selected factors on nitric oxide concentration in exhaled air in children aged 8–9 attending class 3 of public primary schools in Krakow with high FeNO values ≥ 20 ppb. Materials and Methods: The population-based study covered all third-grade pupils attending primary schools in the city of Krakow. Five thousand, four hundred and sixty children participated in the first screening stage, conducted from October 2017 to January 2018. Then, 792 participants with an FeNO level ≥ 20 ppb were selected. Finally, those selected pupils were invited to participate in the second stage, diagnostic, in April 2018. Four hundred and fifty-four children completed the diagnostic stage of the study, and their data was included in the presented analysis. Results and Conclusions: Significantly higher FeNO levels were observed in children diagnosed with the following diseases: asthma, allergic rhinitis, atopic dermatitis, and allergy (p < 0.05). In addition, it was observed that a higher FeNO concentration characterised children taking antihistamines compared to children not taking those medications (p = 0.008). In multivariate models, we observed that regardless of sex, age, BMI value, home smoking, and whether they were taking medications, children who had allergic rhinitis, or atopic dermatitis, or allergies had significantly higher FeNO levels. The strongest relationship was noted with allergic diseases. The results of our study may be of importance to clinicians when interpreting FeNO results, for example, when making a therapeutic decision.

Small Airway Dysfunction in Cough Variant Asthma: Prevalence, Clinical, and Pathophysiological Features.

Introduction: Small airway dysfunction (SAD) commonly presents in patients with classic asthma, which is associated with airway inflammation, disease severity, and asthma control. However, the prevalence of SAD, its relationship with cough severity and airway inflammation, and its development after antiasthmatic treatment in patients with cough variant asthma (CVA) need to be clarified. This study aimed to investigate the prevalence of SAD and its relationship with clinical and pathophysiological characteristics in patients with CVA and the change in small airway function after antiasthmatic treatment.Methods: We retrospectively analyzed 120 corticosteroid-naïve patients with CVA who had finished a standard questionnaire and relevant tests in a specialist cough clinic, such as cough visual analog scale (VAS), differential cells in induced sputum, fractional exhaled nitric oxide (FeNO) measurement, spirometry, and airway hyper-responsiveness. Information of 1-year follow-up was recorded in a part of patients who received complete cough relief after 2 months of treatment. SAD was defined as any two parameters of maximal mid-expiratory flow (MMEF)% pred, forced expiratory flow at 50% of forced vital capacity (FEF50%) pred, and forced expiratory flow at 75% of forced vital capacity (FEF75%) pred measuring <65%.Results: SAD occurred in 73 (60.8%) patients with CVA before treatment. The patients with SAD showed a significantly longer cough duration (24.0 vs. 6.0, p = 0.031), a higher proportion of women (78.1 vs. 59.6%, p = 0.029), older mean age (41.9 vs. 35.4, p = 0.005), and significantly lower forced expiratory volume in 1 s (FEV1%) pred, FEV1/FVC, MMEF% pred, FEF50% pred, FEF75% pred, PEF% pred, and PD20 (all p < 0.01) as compared with patients without SAD. There were no significant differences in cough VAS, sputum eosinophils count, FeNO, and TIgE level between patients with SAD and those without SAD. Among 105 patients who completed 2 months of antiasthmatic treatment and repeatedly experienced spirometry measurement, 57 (54.3%) patients still had SAD, despite a significant improvement in cough VAS, sputum eosinophils, FeNO, FEF50% pred, and PEF% pred (all p < 0.01). As compared with patients without SAD, patients with SAD showed no significant differences in the relapse rate (50.0 vs. 41.9%, p = 0.483) and wheeze development rate (10.4 vs. 0%, p = 0.063) during the follow-up.Conclusions: Small airway dysfunction occurred in over half of patients with CVA and persisted after short-term antiasthmatic treatment, which showed distinctive clinical and pathophysiological features.

Measurements of nitrous oxide and ammonia emissions from diesel automobile under the real-world driving conditions using laser absorption spectrometer

Nitrous oxide (N2O) is a greenhouse gas and contributes to ozone depletion, and ammonia (NH3) contributes to the formation of secondary particulate matter. To reduce global warming and particulate matter, the real-world levels of N2O and NH3 emitted from automobiles is required to be examined. However, there are a few studies on the measurements of N2O and NH3 in automobile exhaust under the real-world conditions. In this study, we have measured the real-world emissions of N2O and NH3 from the latest diesel vehicle equipped with an urea-SCR system. N2O was measured by an on-board system using mid-IR laser spectroscopy and NH3 was measured using a sensor-based measurement technique. As a result, NH3 was not emitted, while N2O was emitted intermittently when vehicle was running.

Diverging trends of respiratory allergies and eczema in Greek schoolchildren: Six surveys during 1991-2018.

Background: The prevalence of childhood asthma, rhinoconjunctivitis, and eczema in the city of Patras, Greece, has been followed in four consecutive surveys since 1991. After a continuous rise in the prevalence of all three of these disorders, a plateau was reached for asthma between 2003 and 2008, whereas the prevalence of rhinoconjunctivitis and eczema continued to increase. Objective: To investigate these trends in the same population into the following decade. Methods: We repeated two methodologically identical cross-sectional parental questionnaire surveys in 2013 and 2018 among 8-9-year-old schoolchildren (N = 2554 and N = 2648, respectively). In 2018, spirometry and fractional exhaled nitric oxide (FeNO) measurements were also performed. Results: Current asthma (i.e., wheeze/asthma in the past 2 years) decreased from 6.9% in 2008 to 5.2% in 2013 and 4.3% in 2018 (p for trend < 0.001). The prevalence of lifetime ("ever had") rhinoconjunctivitis also declined (5.1% in 2008, 4.4% in 2013, 3.0% in 2018; p for trend < 0.001), whereas that of lifetime eczema increased (10.8%, 13.6%, and 16.1%, respectively; p for trend < 0.001). The relative risk of current asthma in children with ever-had rhinoconjundtivitis was 7.73 in 2008, 6.00 in 2013, and 6.69 in 2018, whereas the relative risk in those with ever-had eczema was 5.15, 2.80, and 2.22, respectively. Among children with asthma, those with rhinoconjunctivitis had lower forced expiratory volume in the first second of expiration and higher FeNO values than those with eczema. Conclusion: The prevalence of asthma and rhinoconjunctivitis declined during the past decade in Greek schoolchildren, whereas the prevalence of eczema continued to rise. Nevertheless, the relationship between rhinoconjunctivitis and asthma remained strong, whereas the association between eczema and asthma appears to have weakened.

Experimental Demonstration of Nitric Oxide Measurement at Elevated Temperature in the Coal-Fired Boiler Exhaust

Oxides of Nitrogen (NOx) are among the most critical pollutants, leading to a variety of environmental concerns. This paper describes the demonstrates a high-temperature Quantum Cascade Laser-based (QCL) probe-based system for in-situ measurement of the pollutants in the flue gas. The system demonstrates a sensitivity of less than one ppm and a fast system response time of 60 seconds at high temperature (>300°C) and high dust-load (70 g/m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> ) flue gas from a coal-fired boiler. The system uses a pulsed 2f wavelength modulation spectroscopy technique for the NO concentration measurement at the core. The paper also elaborates on a novel optical design using hollow-core fibres to couple the laser and launch the laser beam into the measurement zone. A unique fibre cooling mechanism was adopted to shield the fibres from excessive temperatures. The filter arrangements and shielding mechanism on the measurement chamber prevent the dust from entering the measurement zone and maintain the stoichiometry of the flue gas during measurement. The probe was tested in a lab setup at 300°C for its sensitivity, response time and linearity. Field-test demonstrates designed performance and repeatability in a coal-fired power plant at an air-preheater (APH) inlet. The gas temperature was below 350°C. In conclusion, this paper demonstrats the useof a QCL based probe for in-situ gas concentration measurement in harsh conditions.

Inhaled Corticosteroids Alone and in Combination With Long-Acting β2 Receptor Agonists to Treat Reduced Lung Function in Preterm-Born Children

Decreases in future lung function are a hallmark of preterm birth, but studies for management of decreased lung function are limited. To determine whether 12 weeks of treatment with inhaled corticosteroids (ICS) alone or in combination with long-acting β2 agonists (LABA) improves spirometry and exercise capacity in school-aged preterm-born children who had percent predicted forced expiratory volume in 1 second (%FEV1) less than or equal to 85% compared with inhaled placebo treatment. A double-blind, randomized, placebo-controlled trial was conducted to evaluate ICS and ICS/LABA against placebo. Preterm-born children (age, 7-12 years; gestation ≤34 weeks at birth) who did not have clinically significant congenital, cardiopulmonary, or neurodevelopmental abnormalities underwent spirometry, exercise testing, and measurement of fractional exhaled nitric oxide before and after treatment. A total of 144 preterm-born children at the Children's Hospital for Wales in Cardiff, UK, were identified and enrolled between July 1, 2017, and August 31, 2019. Each child was randomized to 1 of 3 cohorts: fluticasone propionate, 50 μg, with placebo; fluticasone propionate, 50 μg, with salmeterol, 25 μg; or placebo inhalers, all given as 2 puffs twice daily for 12 weeks. Children receiving preexisting ICS treatment underwent washout prior to randomization to ICS or ICS/LABA. The primary outcome was between-group differences assessed by adjusted pretreatment and posttreatment differences of %FEV1 using analysis of covariance. Intention-to-treat analysis was conducted. Of 144 preterm-born children who were identified with %FEV1 less than or equal to 85%, 53 were randomized. Treatment allocation was 20 children receiving ICS (including 5 with prerandomization ICS), 19 children receiving ICS/LABA (including 4 with prerandomization ICS), and 14 children receiving placebo. The mean (SD) age of children was 10.8 (1.2) years, and 29 of the randomized children (55%) were female. The posttreatment %FEV1 was adjusted for sex, gestation, bronchopulmonary dysplasia, intrauterine growth restriction, pretreatment corticosteroid status, treatment group, and pretreatment values. Posttreatment adjusted means for %FEV1, using analysis of covariance, were 7.7% (95% CI, -0.27% to 15.72%; P = .16) higher in the ICS group and 14.1% (95% CI, 7.3% to 21.0%; P = .002) higher in the ICS/LABA group compared with the placebo group. Active treatment decreased the fractional exhaled nitric oxide and improved postexercise bronchodilator response but did not improve exercise capacity. One child developed cough when starting inhaler treatment; no other adverse events reported during the trial could be attributed to the inhaler treatment. The results of this randomized clinical trial suggest that combined ICS/LABA treatment is beneficial for prematurity-associated lung disease in children. EudraCT number: 2015-003712-20.

Obesity May Enhance the Adverse Effects of NO2 Exposure in Urban Schools on Asthma Symptoms in Children

To evaluate relationships between inner-city classroom NO2 exposure and asthma symptoms and morbidity by BMI category.Children aged 4 to 13 (n = 271) years from 37 inner-city schools who had physician-diagnosed asthma for at least 1 year and were using daily preventive asthma medication, had wheezing within the last year, and/or had at least 1 unscheduled health care visit for asthma within the past year.This was a single-center prospective study conducted within the School Inner-City Asthma Study. Before the start of the academic year, baseline demographics, environmental factors, and asthma symptoms and medication use were obtained by questionnaire. Baseline evaluations included skin testing to common seasonal and perennial aeroallergens or by assessment serum-specific IgE to the same allergens, spirometry, and fractional exhaled nitric oxide (FeNO) measurement. BMI percentile was calculated and categorized by using CDC classifications. Classroom NO2 was measured twice during the school year, ∼6 months apart. The primary outcome was the number of days with asthma symptoms within the previous 14 days. The secondary outcomes assessed in the previous 2 weeks were the number of exacerbations (hospitalizations or unscheduled health care visits for asthma), the number of days caretakers had to change plans because of the child’s asthma symptoms, FeNO level, and pulmonary function (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]).Participants were predominantly African American and Hispanic (35% each) and impoverished (49% had an annual household income <$25 000). A total of 50% had normal BMI (fifth percentile to <85th percentile), 15% were overweight (85th percentile to <95% percentile), and 35% were obese (≥95th percentile). Most (69%) were atopic, with specific immunoglobulin E to at least 1 aeroallergen. Obese students with asthma had statistically (but likely not clinically relevant) lower pulmonary function (FEV1 and FVC but not FEV1/FVC ratio), more positive skin test results, and lower FeNO than students with normal weight. The BMI category did not affect asthma symptom days, asthma symptoms, medication use, health care use for asthma, or missed school days. Caretakers of children with normal weight changed their plans more often than those of students who were overweight or obese. For children with normal weight or those who were overweight, NO2 levels were not associated with any of the measured outcomes. However, among children who were obese, for every 10-fold increase in NO2 level there were increased odds of asthma symptom days (1.9-fold), acute asthma-related health care use (2.4-fold), a missed school day because of asthma (3.1-fold), and care takers’ plans being changed because of the child’s asthma (4.2-fold). As compared with children with normal weight, in students who were obese, every 10 parts per billion increase in classroom NO2 level increased the likelihood of an asthma symptom day (odds ratio: 1.86; 95% confidence interval: 1.15 to 3.02) and of care takers changing their plans (odds ratio: 4.24; 95% confidence interval: 2.33 to 7.70). NO2 levels did not affect other outcomes, lung function, or FeNO across BMI categories.Obesity in inner-city students with asthma appears to increase susceptibility to the adverse effects of classroom NO2.NO2 is formed by combustion of liquid or solid fossil fuels. Indoor sources include gas stoves, heaters, and poorly ventilated furnaces and fireplaces. Furthermore, outdoor levels are elevated in heavily trafficked urban areas. The Environmental Protection Agency’s standard for safe outdoor level of NO2 is ∼50 parts per billion over a 1-year averaging time and 100 parts per billion over a 1 hour averaging time. Although the authors of this study do not specifically report classroom NO2 levels, it is clear from the 2 figures in the article that levels did not exceed 30 parts per billion, hence they were nowhere near the level up to which the Environmental Protection Agency considers safe. This is a warning that “safe” might not be safe enough. I think we all recognize the multiple and varied effects that both pollution and obesity have on health. With this study, the authors suggest synergy between 2 health risk factors and indicate that, as physicians, we must address all known risk factors for disease as we provide the best preventive and prospective care we can.

Measurement of Diacetyl and Related Compounds in Coffee Roasteries and Breweries.

α-Diketones such as diacetyl (2,3-butanedione) and 2,3-pentanedione are generated during the roasting and fermentation of foods and are also used as flavoring compounds. Exposure to these compounds has been associated with obliterative bronchiolitis in workers. We report indoor air concentrations of diacetyl and 2,3-pentanedione, as well as acetoin (3-hydroxy-2-butanone), in several small coffee roasteries and breweries using standard integrated air sampling sorbent tubes followed by gas chromatography tandem mass spectrometry as well as the first use of on-site continuous real-time proton-transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS). Diacetyl and 2,3-pentanedione were detected in most of the sorbent samples at concentrations between 0.02 and 8 ppbv, and in general were higher in coffee roasteries compared with breweries. Three integrated air samples, all from the barista area at one facility, exceeded the NIOSH recommended exposure limit (REL) of 5 ppbv for diacetyl. 2,3-Pentanedione concentrations in these three samples were greater than 50% of its REL, but did not exceed it. Acetoin, a precursor to diacetyl, was also detected at concentrations between 0.03 and 5 ppbv in most sorbent tube samples, with concentrations generally higher in breweries. PTR-ToF-MS measurements exhibited similar trends and provided continuous real-time volatile organic compound data that showed episodic excursions with peak concentrations of diacetyl and 2,3-pentanedione between 15 and 20 ppbv. Examination of the time series data identified specific activities associated with peak diketone emissions, including transfer of freshly roasted coffee beans to the cooling tray, or the opening of a brew kettle. Additional indoor air quality parameters including CO2, NO2, and PM2.5 were also assessed on-site. Airway inflammation was assessed in 19 workers before and after each work shift using online measurements of fractional exhaled nitric oxide (FENO). The pre-shift mean FENO was 3.7 (95% confidence interval: -3.6, 11.0) ppbv higher and the post-shift FENO was 7.1 (-1.9, 16.1) ppbv higher for workers at coffee roasteries compared with breweries. The cross-shift change in FENO was 3.4 (-2.8, 9.6) ppbv higher for workers at coffee roasteries compared with breweries. However, none of these differences were statistically significant, and the cross-shift change in FENO was not statistically different from zero for either group of workers. The findings from this pilot study demonstrate that α-diketones and related compounds are present in the indoor air of both breweries and coffee roasteries and may exceed health protective guidelines in coffee roasteries. Additional studies are required to fully characterize worker exposures in these settings and to identify specific work activities and processes associated with high exposures. Engineering controls, including targeted exhaust ventilation and the use of low-cost sensors, are recommended as an approach to protect workers from exposure to hazardous levels of α-diketones.

Sex Differences in Baseline Risk Factors for Asthma Between Early Adolescence and Young Adulthood.

Several studies have shown sex differences in the prevalence of asthma and an association with age. The aim of the present study was to prospectively investigate the development of asthma, wheeze, rhinitis, and allergic symptoms in adolescence and adulthood. We also aimed to determine whether sex modifies the association between baseline risk factors and incidence of asthma in early adulthood. In the Screening Project Asthma in Schools (SPAIS) study, adolescents aged 12-15 years completed a standardized respiratory questionnaire (International Study of Asthma and Allergies in Childhood) and underwent measurements of fractional exhaled nitric oxide (FeNO) and lung function (FEV1) at baseline. Two follow-up assessments with similar questionnaires were performed after 4 and 16 years, with a total of 491 participants in all 3 examinations. The prevalence of asthma and wheeze were unchanged after 4 years but had increased after 16 years. However, the increase was significant only for females. The prevalence of rhinitis and allergy symptoms increased steadily, albeit with no differences between the sexes. The sex interaction analysis showed that higher FeNO (P=.01) and a family history of asthma (P=.02) increased the risk of incident asthma for males but not for females. An increased prevalence of respiratory symptoms was seen primarily between late adolescence and young adulthood; the difference was significant for females but not for males. Allergic risk factors in early adolescence for incident asthma in early adulthood were confirmed in males but not in females. Awareness of these sex differences in the development of symptoms and of the associated risk factors is important in clinical practice.

Line mixing study on the fundamental rovibrational band of nitric oxide near 5.3 [formula omitted

In this work, we report quantitative absorbance measurements of nitric oxide (NO) diluted in nitrogen between 1700 to 2000 cm−1 and present three line mixing modeling approaches for the measured spectra. Static cell measurements were taken using a narrow-linewidth, external-cavity quantum-cascade laser at temperatures of 293 K and 802 K and pressures of 20–34 atm. The measured results exhibit considerable deviations from the spectra simulated by a superposition of Lorentzian line profiles due to significant line mixing coupling effects at high-number-density conditions. Our previous work demonstrated a line mixing model based on relaxation matrix theory and the Modified Exponential Gap (MEG) law for the NO R-branch. With expanded access to the P- and Q-branches, the measured data indicated significant line mixing effects between lines of different branches in addition to those within the same branch. An empirical two-scaling-factor inter-branch MEG model is presented that delivers strong agreement across the measured spectra, with residuals less than 2% for the spectrum at 293 K and 34 atm. In addition, the Energy Corrected Sudden (ECS) scaling law is shown to produce reasonable agreement across the measured spectra, excluding the Q-branch. In the Q-branch peak, the ECS model overpredicts the measured data by about 7%. The different line mixing models presented and discussed in this work will improve NO absorption predictions vital for laser absorption applications in high-number-density gas conditions. Future studies may seek to account for inter-spin-split coupling to further improve the ECS application to NO absorption.