1,721,038 research outputs found
Clinical Utility of Exhaled Nitric Oxide
No full textLower airway inflammation is generally classified as eosinophilic or neutrophilic. In conditions where eosinophilic inflammation predominates such as asthma in children, corticosteroids are usually beneficial. Traditionally, lower airway eosinophilia is measured using cellular count (through bronchoalveolar lavage or induced sputum). Both methods have limited applicability in children. When instruments to measure fractional exhaled nitric oxide (FeNO) became available, it presented an attractive option as it provided a non-invasive method of measuring eosinophilic inflammation suitable for children and adult. Not surprisingly, proposals have been made that FeNO measurement can be clinically used in many scenarios including monitoring the response to anti-inflammatory medications, to verify the adherence to treatment, and to predict upcoming asthma exacerbations.\ud
\ud
This thesis addresses the utility of FeNO levels in various scenarios, specifically in relation to asthma control and cough, a contentious aspect of the diagnosis of asthma. The thesis consists of a series of systematic reviews (related to the main question) and original studies in children. The over-arching aim of the thesis is to determine if FeNO is a clinically useful tool in the management of asthma and common asthma symptoms.\ud
\ud
The specific aims of the thesis were, to:\ud
\ud
1. Determine if children with asthma have more severe acute respiratory symptoms at presentation with an asthma exacerbation and at days 7, 10 and 14 using validated scales. We also examined if children with asthma were more likely to have a persistent cough on day 14 than children with protracted bronchitis and/or controls.\ud
\ud
2. Evaluate the efficacy of tailoring asthma interventions based on sputum analysis in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults.\ud
\ud
3. Evaluate the efficacy of tailoring asthma interventions based on exhaled nitric oxide in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults.\ud
\ud
4. Determine if adjustment of asthma medications based on FeNO levels (compared to management based on clinical symptoms) reduces severe exacerbations in children with asthma.\ud
\ud
5. Examine the relationship between FeNO and exercise induced broncho-constriction and cough in children\ud
\ud
The aims above are addressed in respective chapters and all but one has been published/submitted. A synopsis of the findings are:\ud
\ud
In study-1 (Aim 1), we found that children with protracted bronchitis had the most severe acute respiratory infection symptoms and higher percentage of respiratory morbidity at day 14 in comparison to children with asthma and healthy controls.\ud
\ud
The systematic review of study-2 (Aim 2) included 246 randomised adult participants (no children) with 221 completing the trials. In the meta-analysis, a significant reduction in number of participants who had one or more asthma exacerbations occurred when treatment was based on sputum eosinophils in comparison to clinical symptoms.\ud
\ud
In the systematic review of study-3 (Aim 3), we found no significant difference between the intervention group (treatment adjusted based on FeNO) and control group (treatment adjusted based on clinical symptoms) for the primary outcome of asthma exacerbations or for the other outcomes (clinical symptoms, FeNO level and spirometry). In post-hoc analysis, a significant reduction in mean final daily dose ICS per adult was found in the group where treatment was based on FeNO in comparison to clinical symptoms. In contrast, in the paediatric studies, there was a significant increase in ICS dose in the FeNO strategy arm.\ud
\ud
Thus, controversy remains of the benefit or otherwise of utilising exhaled nitric oxide (FeNO) in routine clinical practice. FeNO levels are dependent on atopy and none of the 7 published trials have considered atopic status in FeNO levels when medications were adjusted.\ud
\ud
In study-4 (Aim 4), 64 children with asthma were recruited. Their asthma medications were adjusted according to either FeNO levels or usual clinical care utilising a management hierarchy taking into account atopy. It was concluded that tailoring of asthma medications in accordance to FeNO levels (compared to usual management), taking into account atopy status, reduced the number of children with severe exacerbations. However, a FeNO-based strategy resulted in higher daily ICS doses and had no benefit on asthma control.\ud
\ud
In study-5 (Aim 5), 33 children with cough and 17 controls were recruited. They were randomised to undertake an exercise challenge on day 1, or dry powder mannitol challenge on day 1 (with alternative challenge being done on day 2). In addition, a 24 hour cough meter, skin prick test, capsaicin cough sensitivity test and cough diary were undertaken. The change in cough frequency post exercise was significantly increased in the children with cough. FeNO decreases post exercise regardless of whether EIB is present or not.\ud
\ud
Limitations in the studies were addressed in the respective chapters. In summary, the studies from this thesis have provided new information on:\ud
\ud
• The severity of respiratory symptoms was increased in the early phase of the asthma exacerbation but not in the later recovery phase when compared with controls.\ud
\ud
• The utility of FeNO in the management of children with asthma.\ud
\ud
• The relationship of FeNO, cough and EIB in children.\ud
\ud
• Systematic reviews on the efficacy of tailoring asthma interventions based on eosinophilic inflammatory markers (sputum analysis and FeNO) in comparison to clinical symptoms
Letter in response to : Stark P et al Amoxycillin-clavulanate for chronic wet cough in children: cautious interpretation of study findings warranted
No full textWe thank Stark and colleagues1 for comments on our paper and their interest in our recent randomised controlled trial (RCT) of amoxycillin-clavulanate compared with placebo for children with chronic wet cough,2 which as they state are a ‘group of patients that often present paediatricians with a management dilemma’ and which ‘represents a valuable contribution to the literature’. We feel it is important to clarify a few points raised.\ud
\ud
First, the criteria used for defining chronic cough in children (>3 weeks) was at the time of the study commencement the definition of chronic childhood cough. We acknowledge following the study completion (enrolment between 2004 and 2006) that the 2006 American College of Chest Physicians (ACCP) clinical practice guidelines in paediatrics changed the cough definition to >4 weeks and the reasons for this are discussed in the ACCP guidelines.3 Irrespective of this the median duration of cough in the treatment and placebo groups were 15 and 11 weeks respectively at enrolment, making a discussion of 3 versus 4 weeks of cough as inclusion criteria irrelevant.\ud
\ud
Stark and colleagues argue that the verbal category descriptive score (VCD) is not the correct outcome measure to use and that cough resolution would be more appropriate. The VCD score has been used extensively in children of all ages and has been previously validated.4 As stated in the article, and shown in figure 3 and table 2, the children who improved had a cough score of 0.0 which indicates total cough resolution. The definition of primary outcome was cough resolution defined as >75% reduction in cough score for at least 3 days. While this may be argued as incomplete resolution, our a priori definition (as previously used5) is far better than just using a reduction in cough score. Further, a VCD score of 1 represents ‘cough for one or two periods only’ without any effect on daytime function.\ud
\ud
As stated in the manuscript ‘follow-up over a period of months’ was not available in this cohort as it was not study design. Children can always have another episode of coughing illness and the issue of recurrent protracted bacterial bronchitis (PBB) should indeed be examined. We have since begun following a similar group of patients, with PBB, prospectively over a number of years and look forward to being able to shed further light on the long-term outcome of these children.\ud
\ud
We agree with Stark et al that antibiotic therapy is not without implications. This manuscript is a RCT specifically designed to assess the efficacy of short-term antibiotic therapy in children with chronic wet cough. Current therapeutic guidelines recommend antibiotic treatment based on Cochrane review, prospective6 and retrospective7 observational studies. This study is the first double-blind RCT to support these recommendations and provides the first high-level evidence for the inclusion of antibiotics in paediatric cough-specific guidelines as treatment for chronic wet cough and PBB
Exhaled nitric oxide levels to guide treatment for children with asthma.
Full text linkBACKGROUND: 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
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Randomised controlled trials utilising FENO to manage asthma: is it time to acknowledge that “one size does not fit all”? (Editorial)
No full textIn the current issue of the European Respiratory Journal, MURPHY et al. [1] report the effects of managing asthma based on fractional exhaled nitric oxide (FENO) on perinatal outcomes. They conducted a multicentre, parallel, randomised controlled trial (RCT) in six hospital antenatal clinics in Australia. They compared asthma management for expectant mothers guided by FENO to usual care.No Full Tex
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
