Spirometry-adjusted fraction of exhaled nitric oxide increases accuracy for assessment of asthma control in children

Spirometry and exhaled nitric oxide are two important complimentary tools to identify and assess asthma control in children. We aimed to determine the ability of a new suggested spirometry-adjusted fraction of exhaled nitric oxide (NO) index in doing that. A random sample of 1602 schoolchildren were screened by a health questionnaire, skin prick tests, spirometry with bronchodilation and exhaled NO. A total of 662 children were included with median (IQR) exhaled NO 11(14) ppb. Receiver operating characteristic (ROC) curves using exhaled NO equations from Malmberg, Kovesi and Buchvald, and spirometry-adjusted fraction of exhaled NO values were applied to identify asthmatic children and uncontrolled asthma. Receiver operating characteristic (ROC) curves failed to identify asthmatic children (all AUC < 0.700). Spirometry-adjusted fraction of exhaled NO/FEV1 (AUC = 0.712; P = .010) and NO/FEF25%-75% (AUC = 0.735 P = .004) had a fair and increased ability to identify uncontrolled disease compared with exhaled NO (AUC = 0.707; P = .011) or the Malmberg equation (AUC = 0.701; P = .014). Sensitivity and specificity identifying non-controlled asthma were 59% and 81%, respectively, for the cut-off value of 9.7 ppb/L for exhaled NO/FEV1 , and 40% and 100% for 15.7 ppb/L/s for exhaled NO/FEF25%-75% . Exhaled NO did not allow to identify childhood asthma. Spirometry-adjusted fraction of exhaled NO performed better-assessing asthma control in children. Thus, although more validation studies are needed, we suggest its use in epidemiological studies to assess asthma control.Health, Comfort and Energy in the Built Environment (HEBE), Grant/Award Number: NORTE-01-0145-FEDER-000010; Programa Operacional Regional do Norte, Grant/Award Number: NORTE2020; Fundo Europeu de Desenvolvimento Regional (FEDER); Foundation for Science and Technology schoolarships, Grant/Award Number: SFRH/BD/108605/2015 and SFRH/BD/112269/201

Exhaled nitric oxide levels to guide treatment for adults with asthma.

BACKGROUND: Asthma guidelines aim to guide health practitioners to optimise treatment for patients so as to minimise symptoms, improve or maintain good lung function, and prevent acute exacerbations or flare-ups. The principle of asthma guidelines is based on a step-up or step-down regimen of asthma medications to maximise good health outcomes using minimum medications. Asthma maintenance therapies reduce airway inflammation that is usually eosinophilic. Tailoring asthma medications in accordance with airway eosinophilic levels may improve asthma outcomes such as indices of control or reduce exacerbations or both. Fractional exhaled nitric oxide (FeNO) is a marker of eosinophilic inflammation, and as it is easy to measure, has an advantage over other measurements of eosinophilic inflammation (for example sputum eosinophils). OBJECTIVES: To evaluate the efficacy of tailoring asthma interventions based on exhaled nitric oxide (FeNO), in comparison to not using FeNO, that is management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines or both, for asthma-related outcomes in adults. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and reference lists of articles. The last searches were undertaken in June 2016. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing adjustment of asthma medications based on exhaled nitric oxide levels compared to not using FeNO, that is management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines or both. DATA COLLECTION AND ANALYSIS: We reviewed results of searches against predetermined criteria for inclusion. We independently selected relevant studies in duplicate. Two review authors independently assessed trial quality and extracted data. We contacted study authors for further information, receiving responses from four. MAIN RESULTS: We included seven adult studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cutoff levels used (15 to 35 ppb), the way in which FeNO was used to adjust therapy, and duration of study (4 to 12 months). Of 1700 randomised participants, 1546 completed the trials. The mean ages of the participants ranged from 28 to 54 years old. The inclusion criteria for the participants in each study varied, but all had a diagnosis of asthma and required asthma medications. In the meta-analysis, there was a significant difference in the primary outcome of asthma exacerbations between the groups, favouring the FeNO group. The number of people having one or more asthma exacerbations was significantly lower in the FeNO group compared to the control group (odds ratio (OR) 0.60, 95% confidence interval (CI) 0.43 to 0.84). The number needed to treat to benefit (NNTB) over 52 weeks was 12 (95% CI 8 to 32). Those in the FeNO group were also significantly more likely to have a lower exacerbation rate than the controls (rate ratio 0.59, 95% CI 0.45 to 0.77). However, we did not find a difference between the groups for exacerbations requiring hospitalisation (OR 0.14, 95% CI 0.01 to 2.67) or rescue oral corticosteroids (OR 0.86, 95% CI 0.50 to 1.48). There was also no significant difference between groups for any of the secondary outcomes (FEV1, FeNO levels, symptoms scores, or inhaled corticosteroid doses at final visit).We considered three included studies that had inadequate blinding to have a high risk of bias. However, when these studies were excluded from the meta-analysis, the difference between the groups for the primary outcomes (exacerbations) remained statistically significant. The GRADE quality of the evidence ranged from moderate (for the outcome 'exacerbations') to very low (for the outcome 'inhaled corticosteroid dose at final visit') based on the lack of blinding and statistical heterogeneity. Six of the seven studies were industry supported, but the company had no role in the study design or data analyses. AUTHORS' CONCLUSIONS: With new studies included since the last version of this review, which included adults and children, this updated meta-analysis in adults with asthma showed that tailoring asthma medications based on FeNO levels (compared with primarily on clinical symptoms) decreased the frequency of asthma exacerbations but did not impact on day-to-day clinical symptoms, end-of-study FeNO levels, or inhaled corticosteroid dose. Thus, the universal use of FeNO to help guide therapy in adults with asthma cannot be advocated. As the main benefit shown in the studies in this review was a reduction in asthma exacerbations, the intervention may be most useful in adults who have frequent exacerbations. Further RCTs encompassing different asthma severity, ethnic groups in less affluent settings, and taking into account different FeNO cutoffs are required

Exhaled nitric oxide levels to guide treatment for children with asthma.

BACKGROUND: Asthma guidelines aim to guide health practitioners to optimise treatment for patients to minimise symptoms, improve or maintain good lung function, and prevent acute exacerbations. The principle of asthma guidelines is based on a step-up or step-down regimen of asthma medications to maximise health using minimum doses. Fractional exhaled nitric oxide (FeNO) is a marker of eosinophilic inflammation and tailoring asthma medications in accordance to airway eosinophilic levels may improve asthma outcomes such as indices of control or reduce exacerbations, or both. OBJECTIVES: To evaluate the efficacy of tailoring asthma interventions based on fractional exhaled nitric oxide (FeNO), in comparison to not using FeNO, that is, management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma-related outcomes in children. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists of articles. The last searches were in June 2016. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing adjustment of asthma medications based on FeNO levels compared to those not using FeNO, that is, management based on clinical symptoms or asthma guidelines (or both) involving children. DATA COLLECTION AND ANALYSIS: We reviewed results of searches against predetermined criteria for inclusion. Two review authors independently selected relevant studies, assessed trial quality and extracted data. We contacted study authors for further information with responses provided from three. MAIN RESULTS: The review included nine studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut-off levels used (12 parts per billion (ppb) to 30 ppb), the way in which FeNO was used to adjust therapy and duration of study (6 to 12 months). Of 1426 children randomised, 1329 completed the studies. The inclusion criteria for the participants in each study varied but all had a diagnosis of asthma. There was a significant difference in the number of children having one or more asthma exacerbations over the study period, they were significantly lower in the FeNO group in comparison to the control group (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.45 to 0.75; 1279 participants; 8 studies). The number needed to treat for an additional beneficial outcome (NNTB) over 52 weeks was 9 (95% CI 6 to 15). There was no difference between the groups when comparing exacerbation rates (mean difference (MD) -0.37, 95% CI -0.8 to 0.06; 736 participants; 4 studies; I(2) = 67%). The number of children in the FeNO group requiring oral corticosteroid courses was lower in comparison to the children in the control group (OR 0.63, 95% CI 0.48 to 0.83; 1169 participants; 7 studies; I(2) = 0%). There was no statistically significant difference between the groups for exacerbations requiring hospitalisation (OR 0.75, 95% CI 0.41 to 1.36; 1110 participants; 6 studies; I(2) = 0%). There were no significant differences between the groups for any of the secondary outcomes (forced expiratory volume in one second (FEV1), FeNO levels, symptom scores or inhaled corticosteroid doses at final visit). The included studies recorded no adverse events.Three studies had inadequate blinding and were thus considered to have a high risk of bias. However, when these studies were removed in subgroup analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant. The GRADE quality of the evidence ranged from moderate (for the outcome 'Number of participants who had one or more exacerbations over the study period') to very low (for the outcome 'Exacerbation rates'), based on lack of blinding, statistical heterogeneity and imprecision. AUTHORS' CONCLUSIONS: In this updated review with five new included studies, tailoring asthma medications based on FeNO levels (in comparison with primarily guideline management) significantly decreased the number of children who had one or more exacerbations over the study period but did not impact on the day-to-day clinical symptoms or inhaled corticosteroid doses. Therefore, the use of FeNO to guide asthma therapy in children may be beneficial in a subset of children, it cannot be universally recommended for all children with asthma.Further RCTs need to be conducted and these should encompass different asthma severities, different settings including primary care and less affluent settings, and consider different FeNO cut-offs

Exhaled nitric oxide in the diagnosis of asthma in adults: a systematic review.

OBJECTIVES: To identify and synthesise evidence on the diagnostic accuracy of FE NO for asthma in adults. MATERIALS AND METHODS: Systematic searches (nine key biomedical databases and trial registers) were carried out to November 2014. Records were included if they: recruited patients with the symptoms of asthma; used a single set of inclusion criteria; measured FE NO50 in accordance with American Thoracic Society guidelines, 2005 (off-line excluded); reported/allowed calculation of true positive, true negative, false positive and false negative patients as classified against any reference standard. Study quality was assessed using QUADAS II. Meta-analysis was planned where clinical study heterogeneity allowed. Rule-in and Rule-out uses of FE NO were considered. RESULTS: 4861 records were identified originally and 1312 in an update. 27 studies were included. Heterogeneity precluded meta-analysis. Results varied even within subgroups of studies. Cut-off values for the best sum of sensitivity and specificity varied from 12ppb to 55ppb, but did not produce high accuracy. 100% sensitivity or 100% specificity were reported by some studies indicating potential use as a rule-in or rule-out strategy. CONCLUSIONS: FE NO50 had variable diagnostic accuracy even within subgroups of studies with similar characteristics. Diagnostic accuracy, optimal cut-off values and best position for FE NO50 within a pathway remain poorly evidenced. This article is protected by copyright. All rights reserved

Acorn: Developing full-chain industrial carbon capture and storage in a resource- and infrastructure-rich hydrocarbon province

Research to date has identified cost and lack of support from stakeholders as two key barriers to the development of a carbon dioxide capture and storage (CCS) industry that is capable of effectively mitigating climate change. This paper responds to these challenges through systematic evaluation of the research and development process for the Acorn CCS project, a project designed to develop a scalable, full-chain CCS project on the north-east coast of the UK. Through assessment of Acorn's publicly-available outputs, we identify strategies which may help to enhance the viability of early-stage CCS projects. Initial capital costs can be minimised by infrastructure re-use, particularly pipelines, and by re-use of data describing the subsurface acquired during oil and gas exploration activity. Also, development of the project in separate stages of activity (e.g. different phases of infrastructure re-use and investment into new infrastructure) enables cost reduction for future build-out phases. Additionally, engagement of regional-level policy makers may help to build stakeholder support by situating CCS within regional decarbonisation narratives. We argue that these insights may be translated to general objectives for any CCS project sharing similar characteristics such as legacy infrastructure, industrial clusters and an involved stakeholder-base that is engaged with the fossil fuel industry

Innere der Nikolskoi-Kirche Petersburg

[A.G. Vickers del.]Innenansicht der Kasaner Kathedrale am Newski-Prospekt in Sankt Petersburg - rechts oben Plattennr. CLXXXIII - nach: Heath's Picturesque Annual 183