[Show abstract][Hide abstract] ABSTRACT: Although pulmonary function testing plays a key role in the diagnosis and management of chronic pulmonary conditions in children under 6 years of age, objective physiologic assessment is limited in the clinical care of infants and children less than 6 years old, due to the challenges of measuring lung function in this age range. Ongoing research in lung function testing in infants, toddlers, and preschoolers has resulted in techniques that show promise as safe, feasible, and potentially clinically useful tests. Official American Thoracic Society workshops were convened in 2009 and 2010 to review six lung function tests based on a comprehensive review of the literature (infant raised-volume rapid thoracic compression and plethysmography, preschool spirometry, specific airway resistance, forced oscillation, the interrupter technique, and multiple-breath washout). In these proceedings, the current state of the art for each of these tests is reviewed as it applies to the clinical management of infants and children under 6 years of age with cystic fibrosis, bronchopulmonary dysplasia, and recurrent wheeze, using a standardized format that allows easy comparison between the measures. Although insufficient evidence exists to recommend incorporation of these tests into the routine diagnostic evaluation and clinical monitoring of infants and young children with cystic fibrosis, bronchopulmonary dysplasia, or recurrent wheeze, they may be valuable tools with which to address specific concerns, such as ongoing symptoms or monitoring response to treatment, and as outcome measures in clinical research studies.
[Show abstract][Hide abstract] ABSTRACT: Multi-center research studies that include pulmonary function as an objective outcome are increasingly important in pediatric respiratory medicine. The need for local controls rather than depending on published normative data for lung function remains debatable.
To compare pulmonary function in childhood controls with no respiratory symptoms from three centers in the United Kingdom and ascertain the extent to which current reference equations are appropriate for this population.
Spirometry, plethysmographic lung volumes, and specific airways resistance (sRaw) were measured within specialized pediatric laboratories in children from three geographical locations throughout the UK (London, Leicester, and Glasgow), using identical equipment, software and standard operating procedures. Results were compared between centers and in relation to recent or commonly used UK pediatric reference values.
Pulmonary function was assessed in 94 healthy children (mean (SD) age: 7.7 (0.6) years; 88% white Caucasians; ∼30 from each center). There were no significant differences in background demographics or spirometric outcomes when compared between centers. By contrast, statistically significant differences in plethysmographic lung volumes and sRaw were observed between-centers. Significant differences in relation to published reference data for white subjects were noted for FEV(1) in all three centers and occasionally for other lung function measures but the differences from predicted values were small (within ± 0.5 z-score) and not clinically significant.
After appropriate inter-laboratory standardization, spirometric measurements in children can be measured in different centers without evidence of systematic differences. However, even after extensive standardization procedures, plethysmographic measures appear more prone to inter-center differences and cannot, at present, be reliably compared across centers without incorporating controls at each location.
[Show abstract][Hide abstract] ABSTRACT: High resolution computed tomography (HRCT) is a more sensitive tool for detecting early cystic fibrosis (CF) lung disease than either spirometry or plain radiography, but its relationship to other measures of lung function has not been established in young children.
(1) To assess whether the lung clearance index (LCI) derived from multiple breath inert-gas washout (MBW) is as effective as HRCT in identifying pulmonary abnormalities; and (2) explore the relationships between abnormalities detected by HRCT and by spirometry, plethysmography and MBW (collectively, LFTs) in young children with CF.
Children with CF underwent LFTs and volumetric HRCT on the same day. Healthy age-matched controls underwent identical LFTs without HRCT. Scans were anonymised, and scored using the Brody-II CT scoring system, to assess for presence and extent of bronchiectasis, airway wall thickening, mucus plugging, and parenchymal opacities.
Assessments were undertaken in 60 children with CF (mean (SD) 7.8 (1.3 years) and 54 healthy controls (7.9 (1.2) y). Among children with CF, 84% (47/56) had abnormal LCI, 58% (27/47) abnormal plethysmographic lung volumes (FRC(pleth) or RV), 35% (21/60) abnormal sRaw and 47% (28/60) abnormal spirometry (FEV1 or FEF(25-75)); whereas HRCT scans were abnormal in 85% (51/60): median total Brody-II score: 9.5% (range 0-51%). Total CT score correlated more strongly with LCI (Spearman correlation = 0.77) than with spirometry (R = -0.43) or any other marker of lung function. Of the nine children with normal LCI, five had abnormalities on HRCT, whereas five children with normal HRCT had raised LCI.
These results suggest that while LCI and HRCT have similar sensitivity to detect CF lung disease, complimentary information may be gained in individual patients.
[Show abstract][Hide abstract] ABSTRACT: The markedly improved life expectancy of children with cystic fibrosis (CF) has created a new challenge, as traditional markers of lung disease are frequently normal in young children. This prevents identification of individuals who may benefit from more aggressive therapy and also obliges large study numbers and prolonged duration for intervention studies. There is an urgent need for alternative surrogates that detect early lung disease and track through early childhood.
This study aimed to determine whether multiple-breath washout (MBW) results at preschool age can predict subsequent abnormal lung function.
Preschool children (3-5 yr) with CF and healthy control subjects underwent spirometry and MBW with testing repeated during early school age (6-10 yr). Primary outcomes were FEV1 from spirometry and lung clearance index (LCI) from MBW.
Forty-eight children with CF and 45 healthy children completed testing. Thirty-five (73%) children with CF had abnormal LCI at preschool age, whereas only five had abnormal FEV1. The positive predictive value of preschool LCI for predicting any abnormal school-age result was 94%, with a negative predictive value of 62%. Only one child with abnormal FEV1 at school age had had a normal preschool LCI. In contrast, for preschool FEV1 the positive predictive value was 100%, but negative predictive value was only 25%.
This study demonstrates that an abnormal preschool LCI predicts subsequent lung function abnormalities, whereas a normal preschool LCI usually remains normal. MBW has potential as a clinical and research outcome in young children with CF.
American Journal of Respiratory and Critical Care Medicine 10/2010; 183(6):752-8. · 11.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Multi-center studies provide advantages in clinical research but differences between centers can introduce bias. Three specialist pediatric respiratory laboratories standardized their methodology and examined differences between centers. The specific aims were to (i) assess the variability of measurements on adults within and between centers and (ii) to exchange and cross-analyze data from children to assess the extent of agreement between centers. Each laboratory used identical equipment and software. Inter-laboratory visits were used to (i) standardize protocols for data collection and analysis and (ii) make spirometric and plethysmographic measurements on participating staff at each location. Staff also had repeat measurements in their home laboratories. Measurements from children in each laboratory were exchanged on disk, cross-analyzed, and data compared by ANOVA. There were no significant within-subject, between-center differences in FVC, FEV1, FEF50, FRCpleth, or VC. There was a slight trend for TLC and RV (P=0.07) to be higher at one center. The 95% limits of agreement within and between centers were similar for all parameters. There were no differences between centers in cross-analyzed data from 10 children. By standardizing hardware, software, and protocol, potential inter-laboratory differences can be minimized. We recommend that this approach be adopted prior to multi-center studies.
[Show abstract][Hide abstract] ABSTRACT: Sensitive measures of lung function applicable to young subjects are needed to detect early cystic fibrosis (CF) lung disease. Forty children with CF aged 2 to 5 years and 37 age-matched healthy control subjects performed multiple-breath inert gas washout, plethysmography, and spirometry. Thirty children in each group successfully completed all measures, with success on first visit being between 68 and 86% for all three measures. Children with CF had significantly higher lung clearance index (mean [95% CI] difference for CF control 2.7 [1.9, 3.6], p < 0.001) and specific airway resistance (1.65 z-scores [0.96, 2.33], p < 0.001), and significantly lower forced expired volume in 0.5 seconds (-0.49 z-scores [-0.95, -0.03], p < 0.05). Abnormal lung function results were identified in 22 (73%) of 30 children with CF by multiple-breath washout, compared with 14 (47%) of 30 by plethysmography, and 4 (13%) of 30 by spirometry. Children with CF who were infected with Pseudomonas aeruginosa had significantly higher lung clearance index, but no significant difference in other lung function measures, when compared with noninfected children. Most preschool children can perform multiple-breath washout, plethysmography, and spirometry at first attempt. Multiple-breath washout detects abnormal lung function in children with CF more readily than plethysmography or spirometry.
American Journal of Respiratory and Critical Care Medicine 03/2005; 171(3):249-56. · 11.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Multiple breath inert gas washout (MBW) has been suggested as a tool for detecting early cystic fibrosis (CF) lung disease. A study was undertaken to compare the relative sensitivity of MBW and spirometry for detecting abnormal lung function in school age children with CF and to compare MBW results obtained from healthy children in the UK with those recently reported from Sweden.
Forced expiratory volume in 1 second (FEV1) and maximal expiratory flow when 25% of forced vital capacity remains to be expired (MEF25) were compared with the lung clearance index (LCI) derived from sulphur hexafluoride MBW in 22 children with CF aged 6-16 years and in 33 healthy controls.
LCI was higher in children with CF than in healthy controls (mean difference 5.1 (95% CI of difference 4.1 to 6.1) and FEV1 and MEF25 z-scores were lower (mean difference -2.3 (95% CI -2.9 to -1.7) and -1.8 (95% CI -2.4 to -1.3), respectively; p<0.001 for all). There was a significant negative correlation between LCI and FEV1 (r2 = 0.62) and MEF25 (r2 = 0.46). However, while normal (> or =-1.96 z-scores) FEV1 and MEF25 results were seen in 11 (50%) and 12 (53%) children with CF, respectively, all but one of these children had an abnormally increased LCI. LCI was repeatable in both groups (within subject CV for three measurements 6% for CF and 5% for healthy children). In healthy subjects LCI was independent of age and virtually identical in the British and Swedish children (mean difference 0.1 (95% CI -0.1 to 0.4), p = 0.38)
MBW is reproducible between laboratories, generates normal ranges which are constant over childhood, and is more frequently abnormal than spirometry in children with CF.
[Show abstract][Hide abstract] ABSTRACT: The reliability of spirometry is dependent on strict quality control. We examined whether quality control criteria recommended for adults could be applied to children aged 2-5 years. Forty-two children with cystic fibrosis and 37 healthy children attempted spirometry during their first visit to our laboratory. Whereas 59 children (75%) were able to produce a technically satisfactory forced expiration lasting 0.5 second, only 46 (58%) could produce an expiration lasting 1 second, with the youngest children having the most difficulty. Start of test criteria for adults were inappropriate for this age group, with only 16 of 59 children producing a volume of back extrapolation as a proportion of forced vital capacity of less than 5%, whereas all but 4 could produce a volume of back extrapolation of 80 ml or less. More than 90% of children were able to produce a second forced vital capacity and a second forced expired volume in 0.75 second within 10% of their highest. Errors in the spirometry software resulted in inaccurate reporting of expiratory duration and inappropriate timed expired volumes in some children. We describe recommendations for modified start of test and repeatability criteria for this age group, and for improvements in software to facilitate better quality control.
American Journal of Respiratory and Critical Care Medicine 06/2004; 169(10):1152-9. · 11.04 Impact Factor