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Aims: Spirometry is used by many clinicians to monitor asthma in children but relatively little is understood about its variability over time. The aim of this study was to determine the variability of forced expiratory volume in 1 s (FEV 1 ) in children with symptomatically well-controlled asthma by applying three different methods of expressing change in FEV 1 over 3-month intervals., Methods: Data from five longitudinal studies of children with asthma which measured FEV 1 at 3-month intervals over 6 or 12 months were used. We analysed paired FEV 1 measurements when asthma symptoms were controlled. The variability of FEV 1 % predicted (FEV 1 %), FEV 1 z-score (FEV 1 z) and conditional z score for change (Zc) in FEV 1 was expressed as limits of agreement., Results: A total of 881 children had 3338 FEV 1 measurements on occasions when asthma was controlled; 5184 pairs of FEV 1 measurements made at 3-month intervals were available. Each unit change in FEV 1 z score was equivalent to a Zc 1.45 and an absolute change in FEV 1 % of 11.6%. The limits of agreement for change in FEV 1 % were -20 and +21, absolute change in FEV 1 z were -1.7 and +1.7 and Zc were -2.6 and +2.1. Regression to the mean and increased variability in younger children were present for change in FEV 1 % and FEV 1 z comparisons, but not Zc., Conclusion: Given the wide limits of agreement of paired FEV 1 measurements in symptomatically well-controlled children, asthma treatment should primarily be guided by symptoms and not by a change in spirometry., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Fractional exhaled nitric oxide (Feno) levels can identify eosinophilic asthma phenotypes. We aimed to determine Feno values of healthy Aboriginal and/or Torres Strait Islander (Indigenous) Australians, differences between these Indigenous ethnic groups, and appropriateness of published cutoff values., Methods: We measured Feno levels in 1,036 Indigenous Australians (3-16 years of age). Participants were classified into healthy (ie, no asthma or atopy history) or asthmatic and/or atopic groups., Results: Median Feno values and distribution did not differ between Indigenous ethnicities. For healthy participants < 12 years of age (n = 390), 7.2% of our cohort fell into the inflammatory zone of the American Thoracic Society (ATS), National Institute for Health and Care Excellence (NICE), and British Thoracic Society (BTS)/Scottish Intercollegiate Guidelines Network (SIGN) guidelines (cutoff 35 parts per billion [ppb]), but only 3.8% fell into this category when using the Global Initiative for Asthma (GINA) guidelines (50 ppb). Similarly, when using the NICE and BTS/SIGN guidelines (40 ppb) for participants 12 to 16 years of age (n = 213), more healthy participants fell into the inflammatory zone compared with the ATS and GINA guidelines (50 ppb) (9.9% vs 4.7%, respectively)., Conclusions: Feno values for healthy Indigenous Australians children (3-16 years of age) are likely higher than published white-based values. The GINA recommended cutoff value (> 50 ppb) appears the most appropriate for identifying healthy Indigenous children but requires confirmation from a larger study., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Background: Asthma guidelines guide health practitioners to adjust treatments to the minimum level required for asthma control. As many people with asthma have an eosinophilic endotype, tailoring asthma medications based on airway eosinophilic levels (sputum eosinophils or exhaled nitric oxide, FeNO) may improve asthma outcomes., Objective: To synthesise the evidence from our updated Cochrane systematic reviews, for tailoring asthma medication based on eosinophilic inflammatory markers (sputum analysis and FeNO) for improving asthma-related outcomes in children and adults., Data Sources: Cochrane reviews with standardised searches up to February 2017., Study Selection: The Cochrane reviews included randomised controlled comparisons of tailoring asthma medications based on sputum analysis or FeNO compared with controls (primarily clinical symptoms and/or spirometry/peak flow)., Results: The 16 included studies of FeNO-based management (seven in adults) and 6 of sputum-based management (five in adults) were clinically heterogeneous. On follow-up, participants randomised to the sputum eosinophils strategy (compared with controls) were significantly less likely to have exacerbations (62 vs 82/100 participants with ≥1 exacerbation; OR 0.36, 95% CI 0.21 to 0.62). For the FeNO strategy, the respective numbers were adults OR 0.60 (95% CI 0.43 to 0.84) and children 0.58 (95% CI 0.45 to 0.75). However, there were no significant group differences for either strategy on daily inhaled corticosteroids dose (at end of study), asthma control or lung function., Conclusion: Adjusting treatment based on airway eosinophilic markers reduced the likelihood of asthma exacerbations but had no significant impact on asthma control or lung function., Competing Interests: Competing interests: HLP, and ABC have conducted a randomised controlled trial in children on this subject. Other authors have no competing interests to declare., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Chronic respiratory conditions are major causes of mortality and morbidity. Children with chronic health conditions have increased morbidity associated with their physical, emotional, and general well-being. Acute respiratory exacerbations (AREs) are common in children with chronic respiratory disease, often requiring admission to hospital. Reducing the frequency of AREs and recurrent hospitalisations is therefore an important goal in the individual and public health management of chronic respiratory illnesses in children. Discharge planning is used to decide what a person needs for transition from one level of care to another and is usually considered in the context of discharge from hospital to the home. Discharge planning from hospital for ongoing management of an illness has historically been referral to a general practitioner or allied health professional or self management by the individual and their family with limited communication between the hospital and patient once discharged. Effective discharge planning can decrease the risk of recurrent AREs requiring medical care. An individual caseworker-assigned discharge plan may further decrease exacerbations., Objectives: To evaluate the efficacy of individual caseworker-assigned discharge plans, as compared to non-caseworker-assigned plans, in preventing hospitalisation for AREs in children with chronic lung diseases such as asthma and bronchiectasis., Search Methods: We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, trials registries, and reference lists of articles. The latest searches were undertaken in November 2017., Selection Criteria: All randomised controlled trials comparing individual caseworker-assigned discharge planning compared to traditional discharge-planning approaches (including self management), and their effectiveness in reducing the subsequent need for emergency care for AREs (hospital admissions, emergency department visits, and/or unscheduled general practitioner visits) in children hospitalised with an acute exacerbation of chronic respiratory disease. We excluded studies that included children with cystic fibrosis., Data Collection and Analysis: We used standard Cochrane Review methodological approaches. Relevant studies were independently selected in duplicate. Two review authors independently assessed trial quality and extracted data. We contacted the authors of one study for further information., Main Results: We included four studies involving a total of 773 randomised participants aged between 14 months and 16 years. All four studies involved children with asthma, with the case-planning undertaken by a trained nurse educator. However, the discharge planning/education differed among the studies. We could include data from only two studies (361 children) in the meta-analysis. Two further studies enrolled children in both inpatient and outpatient settings, and one of these studies also included children with acute wheezing illness (no previous asthma diagnosis); the data specific to this review could not be obtained. For the primary outcome of exacerbations requiring hospitalisation, those in the intervention group were significantly less likely to be rehospitalised (odds ratio (OR) 0.29, 95% confidence interval (CI) 0.16 to 0.50) compared to controls. This equates to 189 (95% CI 124 to 236) fewer admissions per 1000 children. No adverse events were reported in any study. In the context of substantial statistical heterogeneity between the two studies, there were no statistically significant effects on emergency department (OR 0.37, 95% CI 0.04 to 3.05) or general practitioner (OR 0.87, 95% CI 0.22 to 3.44) presentations. There were no data on cost-effectiveness, length of stay of subsequent hospitalisations, or adherence to medications. One study reported quality of life, with no significant differences observed between the intervention and control groups.We considered three of the studies to have an unclear risk of bias, primarily due to inadequate description of the blinding of participants and investigators. The fourth study was assessed as at high risk of bias as a single unblinded investigator was used. Using the GRADE system, we assessed the quality of the evidence as moderate for the outcome of hospitalisation and low for the outcomes of emergency department visits and general practitioner consultations., Authors' Conclusions: Current evidence suggests that individual caseworker-assigned discharge plans, as compared to non-caseworker-assigned plans, may be beneficial in preventing hospital readmissions for acute exacerbations in children with asthma. There was no clear indication that the intervention reduces emergency department and general practitioner attendances for asthma, and there is an absence of data for children with other chronic respiratory conditions. Given the potential benefit and cost savings to the healthcare sector and families if hospitalisations and outpatient attendances can be reduced, there is a need for further randomised controlled trials encompassing different chronic respiratory illnesses, ethnicity, socio-economic settings, and cost-effectiveness, as well as defining the essential components of a complex intervention.

Background: Asthma severity and control can be measured both subjectively and objectively. Sputum analysis for evaluation of percentage of sputum eosinophilia directly measures airway inflammation, and is one method of objectively monitoring asthma. Using sputum analysis to adjust or tailor asthma medications is potentially superior to traditional methods based on symptoms and spirometry., Objectives: To evaluate the efficacy of tailoring asthma interventions based on sputum analysis in comparison to traditional methods (usually symptom-based with or without spirometry/peak flow) for asthma-related outcomes in children and adults., Search Methods: We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, trials' registries, and reference lists of articles. The last search was conducted in February 2017., Selection Criteria: All randomised controlled comparisons of adjustment of asthma therapy based on sputum eosinophils compared to traditional methods (primarily clinical symptoms and spirometry/peak flow)., Data Collection and Analysis: Results of searches were reviewed against pre-determined criteria for inclusion. In this update, two reviewers selected relevant studies, independently assessed trial quality and extracted the data. We contacted authors for further information when relevant. We analysed data as 'treatment received' and performed sensitivity analyses., Main Results: Three new studies were added in this update, resulting in a total of six included studies (five in adults and one involving children/adolescents). These six studies were clinically and methodologically heterogeneous (use of medications, cut-off for percentage of sputum eosinophils and definition of asthma exacerbation). Of 374 participants randomised, 333 completed the trials. In the meta-analysis, there was a significant reduction in the occurrence of any exacerbations when treatment was based on sputum eosinophil counts, compared to that based on clinical symptoms with or without lung function; pooled odds ratio (OR) was 0.57 (95% confidence interval (CI) 0.38 to 0.86). The risk of having one or more exacerbations over 16 months was 82% in the control arm and 62% (95% CI 49% to 74%) in the sputum strategy arm, resulting in a number needed to treat to benefit (NNTB) of 6 (95% CI 4 to 13).There were also differences between the groups in the rate of exacerbation (any exacerbation per year) and severity of exacerbations defined by requirement for use of oral corticosteroids and hospitalisations: the risk of one or more hospitalisations over 16 months was 24% in controls compared to 8% (95% CI 3% to 21%) in the sputum arm. Data for clinical symptoms, quality of life and spirometry were not significantly different between groups. The mean dose of inhaled corticosteroids per day was also similar in both groups. However sputum induction was not always possible. The included studies did not record any adverse events.One study was not blinded and thus was considered to have a high risk of bias. However, when this study was removed in a sensitivity analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant between groups. The GRADE quality of the evidence ranged from moderate (for the outcomes 'Occurrence of any exacerbation' and 'Hospitalisation' ) to low (for the outcome 'Mean dose of inhaled corticosteroids per person per day') due to the inconsistency in defining exacerbations and the small number of hospital admissions., Authors' Conclusions: In this updated review, tailoring asthma interventions based on sputum eosinophils is beneficial in reducing the frequency of asthma exacerbations in adults with asthma. Adults with frequent exacerbations and severe asthma may derive the greatest benefit from this additional monitoring test, although we were unable to confirm this through subgroup analysis. There is insufficient data available to assess tailoring asthma medications based on sputum eosinophilia in children.Further robust RCTs need to be undertaken and these should include participants with different underlying asthma severities and endotypes.

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 (FEV 1 ), 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.

Background: Quality of life (QoL) measures are an important patient-relevant outcome measure for clinical studies. Cough is the most common symptom that results in new medical consultations. Although adult and parent-proxy cough-specific QoL instruments have been shown to be a useful cough outcome measure, no suitable cough-specific QoL measure for children with chronic cough exists. We report on the statistical properties of a chronic cough-specific QoL (CC-QoL) questionnaire for children., Method: 130 children (median age 10 years, IQR 8-12 years; 65 girls) participated. A preliminary 37-item version was developed from conversations with children with chronic cough (>4 weeks). Children also completed generic QoL questionnaires (Pediatric QoL Inventory 4.0 (PedsQL4.0), Spence Children's Anxiety Scale (SCAS)) and cough diary scores., Results: The clinical impact method of item reduction resulted in 16 items that had excellent internal consistency (Cronbach's α=0.94) among these items and also within each domain. Evidence for construct and criterion validity was established with significant correlations between CC-QoL subscales with cough scores, PedsQL and SCAS scores. CC-QoL scores were sensitive to change following an intervention and significant differences were noted between those children coughing and those who had ceased coughing. Minimum important difference (MID) for overall and domain CC-QoL ranged from 0.37-1.36 (distribution-based approach) to 1.11-1.58 (anchor-based approach)., Conclusions: Chronic cough significantly impacts the QoL of children. The CC-QoL is a reliable, valid and sensitive to change outcome measure that assesses QoL from the child's perspective. Pending data from a confirmatory cohort, a MID for the CC-QoL of 1.1 is recommended when evaluating health status change., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

While several randomized control trials (RCTs) have evaluated the use of fractional exhaled nitric oxide (FeNO) to improve asthma outcomes, none used FeNO cut-offs adjusted for atopy, a determinant of FeNO levels. In a dual center RCT, we assessed whether a treatment strategy based on FeNO levels, adjusted for atopy, reduces asthma exacerbations compared with the symptoms-based management (controls). Children with asthma from hospital clinics of two hospitals were randomly allocated to receive an a-priori determined treatment hierarchy based on symptoms or FeNO levels. There was a 2-week run-in period and they were then reviewed 10 times over 12-months. The primary outcome was the number of children with exacerbations over 12-months. Sixty-three children were randomized (FeNO = 31, controls = 32); 55 (86%) completed the study. Although we did achieve our planned sample size, significantly fewer children in the FeNO group (6 of 27) had an asthma exacerbation compared to controls (15 of 28), P = 0.021; number to treat for benefit = 4 (95% CI 3-24). There was no difference between groups for any secondary outcomes (quality of life, symptoms, FEV1 ). The final daily inhaled corticosteroids (ICS) dose was significantly (P = 0.037) higher in the FeNO group (median 400 µg, IQR 250-600) compared to the controls (200, IQR100-400). Taking atopy into account when using FeNO to tailor asthma medications is likely beneficial in reducing the number of children with severe exacerbations at the expense of increased ICS use. However, the strategy is unlikely beneficial for improving asthma control. A larger study is required to confirm or refute our findings., (© 2014 Wiley Periodicals, Inc.)

Background: While the burden of chronic cough in children has been documented, etiologic factors across multiple settings and age have not been described. In children with chronic cough, we aimed (1) to evaluate the burden and etiologies using a standard management pathway in various settings, and (2) to determine the influence of age and setting on disease burden and etiologies and etiology on disease burden. We hypothesized that the etiology, but not the burden, of chronic cough in children is dependent on the clinical setting and age., Methods: From five major hospitals and three rural-remote clinics, 346 children (mean age 4.5 years) newly referred with chronic cough (> 4 weeks) were prospectively managed in accordance with an evidence-based cough algorithm. We used a priori definitions, timeframes, and validated outcome measures (parent-proxy cough-specific quality of life [PC-QOL], a generic QOL [pediatric quality of life (PedsQL)], and cough diary)., Results: The burden of chronic cough (PC-QOL, cough duration) significantly differed between settings (P = .014, 0.021, respectively), but was not influenced by age or etiology. PC-QOL and PedsQL did not correlate with age. The frequency of etiologies was significantly different in dissimilar settings (P = .0001); 17.6% of children had a serious underlying diagnosis (bronchiectasis, aspiration, cystic fibrosis). Except for protracted bacterial bronchitis, the frequency of other common diagnoses (asthma, bronchiectasis, resolved without specific-diagnosis) was similar across age categories., Conclusions: The high burden of cough is independent of children’s age and etiology but dependent on clinical setting. Irrespective of setting and age, children with chronic cough should be carefully evaluated and child-specific evidence-based algorithms used.

Asthma severity and control can be measured both subjectively and objectively. Traditionally asthma treatments have been individualised using symptoms and spirometry/peak flow. Increasingly treatment tailored in accordance with inflammatory markers (sputum eosinophil counts or fractional exhaled nitric oxide (FeNO) data) is advocated as an alternative strategy. The objective of this review was to evaluate the efficacy of tailoring asthma interventions based on inflammatory markers (sputum analysis and FeNO) in comparison with clinical symptoms (with or without spirometry/peak flow) for asthma-related outcomes in children and adults. Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles were searched. The last searches were in February 2009. All randomised controlled comparisons of adjustment of asthma treatment based on sputum analysis or FeNO compared with traditional methods (primarily clinical symptoms and spirometry/peak flow) were selected. Results of searches were reviewed against predetermined criteria for inclusion. Relevant studies were selected, assessed and data extracted independently by at least two people. The trial authors were contacted for further information. Data were analysed as 'intervention received' and sensitivity analyses performed. Six (2 adults and 4 children/adolescent) studies utilising FeNO and three adult studies utilising sputum eosinophils were included. These studies had a degree of clinical heterogeneity including definition of asthma exacerbations, duration of study and variations in cut-off levels for percentage of sputum eosinophils and FeNO to alter management in each study. Adults who had treatment adjusted according to sputum eosinophils had a reduced number of exacerbations compared with the control group (52 vs. 77 patients with ≥1 exacerbation in the study period; p=0.0006). There was no significant difference in exacerbations between groups for FeNO compared with controls. The daily dose of inhaled corticosteroids at the end of the study was decreased in adults whose treatment was based on FeNO in comparison with the control group (mean difference -450.03 μg, 95% CI -676.73 to -223.34; p<0.0001). However, children who had treatment adjusted according to FeNO had an increase in their mean daily dose of inhaled corticosteroids (mean difference 140.18 μg, 95% CI 28.94 to 251.42; p=0.014). It was concluded that tailoring of asthma treatment based on sputum eosinophils is effective in decreasing asthma exacerbations. However, tailoring of asthma treatment based on FeNO levels has not been shown to be effective in improving asthma outcomes in children and adults. At present, there is insufficient justification to advocate the routine use of either sputum analysis (due to technical expertise required) or FeNO in everyday clinical practice.

Background: The measurement of severity and control of asthma in both children and adults can be based on subjective or objective measures. It has been advocated that fractional exhaled nitric oxide (FeNO) can be used to monitor airway inflammation as it correlates with some markers of asthma. Interventions for asthma therapies have been traditionally based on symptoms and/or spirometry., Objectives: To 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., Search Strategy: 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 search was completed in February 2009., Selection Criteria: All randomised controlled comparisons of adjustment of asthma therapy based on exhaled nitric oxide compared to traditional methods (primarily clinical symptoms and spirometry/peak flow)., Data Collection and Analysis: Results of searches were reviewed against pre-determined criteria for inclusion. Relevant studies were independently selected in duplicate. Two authors independently assessed trial quality and extracted data. Authors were contacted for further information with response from one., Main Results: Two studies have been added for this update, which now includes six (2 adults and 4 children/adolescent) studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut off levels, the way in which FeNO was used to adjust therapy and duration of study. Of 1053 participants randomised, 1010 completed the trials. In the meta-analysis, there was no significant difference between groups for the primary outcome of asthma exacerbations or for other outcomes (clinical symptoms, FeNO level and spirometry). In post-hoc analysis, a significant reduction in mean final daily dose inhaled corticosteroid per adult was found in the group where treatment was based on FeNO in comparison to clinical symptoms, (mean difference -450 mcg; 95% CI -677 to -223 mcg budesonide equivalent/day). However, the total amount of inhaled corticosteroid used in one of the adult studies was 11% greater in the FeNO arm. In contrast, in the paediatric studies, there was a significant increase in inhaled corticosteroid dose in the FeNO strategy arm (mean difference of 140 mcg; 95% CI 29 to 251, mcg budesonide equivalent/day)., Authors' Conclusions: Tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide in comparison to clinical symptoms was carried out in different ways in the six studies and found only modest benefit at best and potentially higher doses of inhaled corticosteroids in children. The role of utilising exhaled nitric oxide to tailor the dose of inhaled corticosteroids cannot be routinely recommended for clinical practice at this stage and remains uncertain.

Background: : Viral respiratory illness triggers asthma exacerbations, but the influence of respiratory illness on the acute severity and recovery of childhood asthma is unknown. Our objective was to evaluate the impact of a concurrent acute respiratory illness (based on a clinical definition and PCR detection of a panel of respiratory viruses, Mycoplasma pneumoniae and Chlamydia pneumoniae) on the severity and resolution of symptoms in children with a nonhospitalized exacerbation of asthma., Methods: : Subjects were children aged 2 to 15 years presenting to an emergency department for an acute asthma exacerbation and not hospitalized. Acute respiratory illness (ARI) was clinically defined. Nasopharyngeal aspirates (NPA) were examined for respiratory viruses, Chlamydia and Mycoplasma using PCR. The primary outcome was quality of life (QOL) on presentation, day 7 and day 14. Secondary outcomes were acute asthma severity score, asthma diary, and cough diary scores on days 5, 7, 10, and 14., Results: : On multivariate regression, presence of ARI was statistically but not clinically significantly associated with QOL score on presentation (B = -0.36, P = 0.025). By day 7 and 14, there was no difference between groups. Asthma diary score was significantly higher in children with ARI (B = 0.41, P = 0.039) on day 5 but not on presentation or subsequent days. Respiratory viruses were detected in 54% of the 78 NPAs obtained. There was no difference in the any of the asthma outcomes of children grouped by positive or negative NPA., Conclusions: : The presence of a viral respiratory illness has a modest influence on asthma severity, and does not influence recovery from a nonhospitalized asthma exacerbation.

Aim: Acute respiratory infections (ARI) are common in children, and symptoms range from days to weeks. The aim of this study was to determine if children with asthma have more severe ARI episodes compared with children with protracted bronchitis and controls., Methods: Parents prospectively scored their child's next ARI using the Canadian acute respiratory illness and flu scale (CARIFS) and a validated cough diary (on days 1-7, 10 and 14 of illness). Children were age- and season-matched., Results: On days 10 and 14 of illness, children with protracted bronchitis had significantly higher median CARIFS when compared with children with asthma and healthy controls. On day 14, the median CARIFS were: asthma = 4.1 (interquartile range (IQR) 4.0), protracted bronchitis = 19.6 (IQR 25.8) and controls = 4.1 (IQR 5.25). The median cough score was significantly different between groups on days 1, 7, 10 and 14 (P < 0.001). A significantly higher proportion of children with protracted bronchitis (63%) were still coughing at day 14 in comparison with children with asthma (24%) and healthy controls (26%)., Conclusion: Children with protracted bronchitis had the most severe ARI symptoms and higher percentage of respiratory morbidity at day 14 in comparison with children with asthma and healthy controls.

Objective: To determine whether a 5-day course of oral prednisolone is superior to a 3-day course in reducing the 2-week morbidity of children with asthma exacerbations who are not hospitalised., Design, Setting and Participants: Double-blind randomised controlled trial of asthma outcomes following a 5-day course of oral prednisolone (1 mg/kg) compared with a 3-day course of prednisolone plus placebo for 2 days. Participants were children aged 2-15 years who presented to the emergency departments of three Queensland hospitals between March 2004 and February 2007 with an acute exacerbation of asthma, but were not hospitalised. Sample size was defined a priori for a study power of 90%., Main Outcome Measures: Difference in proportion of children who were symptom-free at Day 7, as measured by intention-to-treat (ITT) and per-protocol analysis; quality of life (QOL) on Days 7 and 14., Results: 201 children were enrolled, and there was an 82% completion rate. There was no difference between groups in the proportion of children who were symptom-free (observed difference, 0.04 [95% CI, - 0.09 to 0.18] by ITT analysis; 0.04 [95% CI, - 0.17 to 0.09] by per-protocol analysis). There was also no difference between groups in QOL (P = 0.42). The difference between groups for the primary outcome was within the equivalence range calculated post priori., Conclusion: A 5-day course of oral prednisolone confers no advantage over a 3-day course for children with asthma exacerbations who are not hospitalised., Trial Registration: Australian Clinical Trials Registry ACTRN012605000305628.

Background: The measurement of severity and control of asthma in both children and adults can be based on subjective or objective measures. It has been advocated that fractional exhaled nitric oxide (FeNO) can be used to monitor airway inflammation as it correlates with some markers of asthma. Interventions for asthma therapies have been traditionally based on symptoms and/or spirometry., Objectives: To 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., Search Strategy: 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 search was completed in December 2006., Selection Criteria: All randomised controlled comparisons of adjustment of asthma therapy based on exhaled nitric oxide compared to traditional methods (primarily clinical symptoms and spirometry/peak flow)., Data Collection and Analysis: Results of searches were reviewed against pre-determined criteria for inclusion. Relevant studies were independently selected in duplicate. Two authors independently assessed trial quality and extracted data. Authors were contacted for further information but none were received. Data was analysed as "intervention received" and sensitivity analyses performed., Main Results: Four (2 adult and 2 paediatric) studies were included; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut off levels and duration of study. Of 356 participants randomised, 324 completed the trials. In the meta-analysis, there was no difference between groups for the primary outcome of asthma exacerbations or for other outcomes (clinical symptoms, FeNO level and spirometry). In post-hoc analysis, a significant reduction in mean final daily dose inhaled corticosteroid per adult was found in the group where treatment was based on FeNO in comparison to clinical symptoms; WMD -282.46 (95% CI -422.08 to -142.84). There was no difference in ICS dose between the groups in the overall daily dose in the adult studies or in the paediatric studies., Authors' Conclusions: Tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide in comparison to clinical symptoms was carried out in different ways in the four studies that were found, and the results show only modest differences. The role of utilising exhaled nitric oxide to tailor the dose of inhaled corticosteroids is currently uncertain.

Background: Asthma severity and control can be measured both subjectively and objectively. Sputum analysis for evaluation of percentage of sputum eosinophilia directly measures airway inflammation, and is one method of objectively monitoring asthma. Interventions for asthma therapies have been traditionally based on symptoms and spirometry., Objectives: To 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., Search Strategy: 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 search was on 31 October 2006., Selection Criteria: All randomised controlled comparisons of adjustment of asthma therapy based on sputum eosinophils compared to traditional methods (primarily clinical symptoms and spirometry/peak flow)., Data Collection and Analysis: Results of searches were reviewed against pre-determined criteria for inclusion. Three sets of reviewers selected relevant studies. Two review authors independently assessed trial quality extracted data. Authors were contacted for further information but none were received. Data was analysed as "treatment received" and sensitivity analyses performed., Main Results: Three adult studies were included; these studies were clinically and methodologically heterogenous (use of medications, cut off for percentage of sputum eosinophils and definition of asthma exacerbation). There were no eligible paediatric studies. Of 246 participants randomised, 221 completed 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; pooled odds ratio (OR) was 0.49 (95% CI 0.28 to 0.87); number needed to treat to benefit (NNTB) was 6 (95% CI 4 to 32). There were also differences between groups in the rate of exacerbation (any exacerbation per year) and severity of exacerbations defined by requirement for use of oral corticosteroids but the reduction in hospitalisations was not statistically significant. Data for clinical symptoms, quality of life and spirometry were not significantly different between groups. The mean dose of inhaled corticosteroids per day was similar in both groups and no adverse events were reported. However sputum induction was not always possible., Authors' Conclusions: Tailored asthma interventions based on sputum eosinophils is beneficial in reducing the frequency of asthma exacerbations in adults with asthma. This review supports the use of sputum eosinophils to tailor asthma therapy for adults with frequent exacerbations and severe asthma. Further studies need to be undertaken to strengthen these results and no conclusion can be drawn for children with asthma.