Does lung function change in the months after an asthma exacerbation in children?

BACKGROUND: There are limited data describing lung function changes in children after an asthma exacerbation. Our hypothesis was that lung function does not fully recover in children in the months following an asthma exacerbation. METHODS: We used a data set of children with asthma where lung function (including FEV1 , FEV1 /FVC ratio and FEF25-75 ) was measured at 3-month intervals over a year. Mixed-level models compared spirometry measured on two occasions 3 months apart before a single exacerbation (assessments 1 and 2) with measurements made on two occasions after the exacerbation (assessments 3 and 4), with adjustment for covariates. Changes in spirometry over a year were also analysed across those with exacerbations in no, one or more than one 3-month periods. RESULTS: For the 113 children who had a single exacerbation, spirometry measured at assessments 1 or 2 did not differ from measurements at assessments 3 or 4 when the whole population was considered. When stratified into tertiles by change in %FEV1 between assessments 2 and 3, those with the greater reduction were more likely to be treated with long-acting beta-agonist, but in this category, %FEV1 at assessment 4 had returned to the value at assessment 1. %FEV1 did not change over a 12-month period within and between the three exacerbation categories (n = 809). CONCLUSION: One or more asthma exacerbation was not associated with a fall in lung function for the whole population. In a subset of individuals, lung function does fall after an exacerbation but returns to pre-exacerbation values after a period of months.

Does treatment guided by exhaled nitric oxide fraction improve outcomes in subgroups of children with asthma?

INTRODUCTION: Exhaled nitric oxide fraction (F ENO), a biomarker of eosinophilic airway inflammation, may be useful to guide asthma treatment. F ENO-guided treatment may be more effective in certain subgroups for improving asthma outcomes compared to standard treatment. METHODS: An individual patient data analysis was performed using data from seven randomised clinical trials (RCTs) which used F ENO to guide asthma treatment. The incidence of an asthma exacerbation and loss of control, and the time to first exacerbation and loss of control were described between five subgroups of RCT participants. RESULTS: Data were available in 1112 RCT participants. Among those not treated with leukotriene receptor antagonists (LTRA), but not among those who were treated with LTRA, F ENO-guided treatment was associated with reduced exacerbation risk (OR 0.68, 95% CI 0.49-0.94), longer time to first exacerbation (hazard ratio (HR) 0.76, 95% CI 0.57-0.99) and borderline reduced risk for loss of control (OR 0.70, 95% CI 0.49-1.00). Nonobese children, compared to obese children, were less likely to lose asthma control when treatment was guided by F ENO (OR 0.69, 95% CI 0.48-0.99) and time to loss of control was longer (HR 0.77, 95% CI 0.61-0.99). CONCLUSIONS: Asthma treatment guided by F ENO may be more effective in achieving better asthma outcomes for patients who are not treated with LTRA and who are not obese, compared to standard practice.

What is a clinically meaningful change in exhaled nitric oxide for children with asthma?

INTRODUCTION: Fractional exhaled nitric oxide (FE NO) may be a useful objective measurement to guide asthma treatment. What remains uncertain is what change in FE NO is clinically significant. METHODS: An individual patient data analysis was performed using data from seven randomized clinical trials which used FE NO to guide asthma treatment. The absolute and percentage intra-subject change in FE NO measurements over "stable" and also "unstable" 3-month periods were described. RESULTS: Data were available in 1112 randomized controlled trial participants and ≥1 stable period was present for 665 individuals. The interquartile range (IQR) and limits of agreement (LoA) for change in absolute FE NO among individuals whose initial FE NO was <50 parts per billion (ppb) were -7 to +9 ppb and -43 to +50 ppb, and for those with initial FE NO ≥50 ppb IQR was -29 to +17 ppb and LoA was -80 to +76 ppb. For percentage change in FE NO, the IQR and LoA for individuals whose initial FE NO was <50 ppb were -33% to +51% and -157% to +215%, and for those with initial FE NO ≥50 ppb were -33% to +35% and -159% to +192%. The variation in FE NO values for a stable period was similar irrespective of whether it was followed by a stable or unstable period. CONCLUSIONS: Over a 3-month period where FE NO is initially <50 ppb, a rise of <10 ppb or of <50% (based on IQR) is unlikely to be related to asthma. When FE NO is initially ≥50 ppb an percentage change of <50% (based on IQR) is unlikely to be asthma-related.

Change in FEV1 and Feno Measurements as Predictors of Future Asthma Outcomes in Children.

BACKGROUND: Repeated measurements of spirometry and fractional exhaled nitric oxide (Feno) are recommended as part of the management of childhood asthma, but the evidence base for such recommendations is small. We tested the hypothesis that reducing spirometric indices or increasing Feno will predict poor future asthma outcomes. METHODS: A one-stage individual patient data meta-analysis used data from seven randomized controlled trials in which Feno was used to guide asthma treatment; spirometric indices were also measured. Change in %FEV1 and % change in Feno between baseline and 3 months were related to having poor asthma control and to having an asthma exacerbation between 3 and 6 months after baseline. RESULTS: Data were available from 1,112 children (mean age, 12.6 years; mean %FEV1, 94%). A 10% reduction in %FEV1 between baseline and 3 months was associated with 28% increased odds for asthma exacerbation (95% CI, 3-58) and with 21% increased odds for having poor asthma control (95% CI, 0-45) 6 months after baseline. A 50% increase in Feno between baseline and 3 months was associated with 11% increase in odds for poor asthma control 6 months after baseline (95% CI, 0-16). Baseline Feno and %FEV1 were not related to asthma outcomes at 3 months. CONCLUSIONS: Repeated measurements of %FEV1 that are typically within the "normal" range add to clinical risk assessment of future asthma outcomes in children. The role of repeated Feno measurements is less certain because large changes were associated with small changes in outcome risk.