Vassiliki Bountziouka

The impact of switching to the new global lung function initiative equations on spirometry results in the UK CF Registry

BACKGROUNDnThe Quanjer et al. Global Lung Function Initiative (GLI)-2012 multi-ethnic all-age reference equations for spirometry are endorsed by all major respiratory societies and are the new gold standard. Before the GLI equations are implemented for use in CF patients, the impact of changing equations from those currently used needs to be better understood.nnnMETHODSnAnnual review data submitted to the UK CF Trust Registry between 2007 and 2011 were used to calculate %predicted FEV1, FVC and FEV1/FVC using three widely used reference equations (Wang-Hankinson and Knudson) and the new GLI-2012 equations.nnnRESULTSnOverall, Knudson and Wang equations overestimated %predicted values in paediatric patients, such that a greater proportion of patients had lung function values in the normal range. Within individual patients, the impact of switching equations varied greatly depending on the patients age, and which equations were used.nnnCONCLUSIONSnA unified approach to interpreting spirometric lung function measurements would help facilitate more appropriate comparison both within and between centres and countries. Interpretation of longitudinal measurements using a continuous reference equation across all-ages, like the GLI, may further improve our understanding of CF lung disease.

Ethnic Variability in Body Size, Proportions and Composition in Children Aged 5 to 11 Years: Is Ethnic-Specific Calibration of Bioelectrical Impedance Required?

Background Bioelectrical Impedance Analysis (BIA) has the potential to be used widely as a method of assessing body fatness and composition, both in clinical and community settings. BIA provides bioelectrical properties, such as whole-body impedance which ideally needs to be calibrated against a gold-standard method in order to provide accurate estimates of fat-free mass. UK studies in older children and adolescents have shown that, when used in multi-ethnic populations, calibration equations need to include ethnic-specific terms, but whether this holds true for younger children remains to be elucidated. The aims of this study were to examine ethnic differences in body size, proportions and composition in children aged 5 to 11 years, and to establish the extent to which such differences could influence BIA calibration. Methods In a multi-ethnic population of 2171 London primary school-children (47% boys; 34% White, 29% Black African/Caribbean, 25% South Asian, 12% Other) detailed anthropometric measurements were performed and ethnic differences in body size and proportion were assessed. Ethnic differences in fat-free mass, derived by deuterium dilution, were further evaluated in a subsample of the population (nu200a=u200a698). Multiple linear regression models were used to calibrate BIA against deuterium dilution. Results In children <11 years of age, Black African/Caribbean children were significantly taller, heavier and had larger body size than children of other ethnicities. They also had larger waist and limb girths and relatively longer legs. Despite these differences, ethnic-specific terms did not contribute significantly to the BIA calibration equation (Fat-free massu200a=u200a1.12+0.71*(height2/impedance)+0.18*weight). Conclusion Although clear ethnic differences in body size, proportions and composition were evident in this population of young children aged 5 to 11 years, an ethnic-specific BIA calibration equation was not required.

New reference ranges for interpreting forced expiratory manoeuvres in infants and implications for clinical interpretation: a multicentre collaboration

The raised volume rapid thoracoabdominal compression (RVRTC) technique is commonly used to obtain full forced expiratory manoeuvres from infants, but reference equations derived from ‘in-house’ equipment have been shown to be inappropriate for current commercially available devices. Aim To explore the impact of equipment differences on RVRTC outcomes, derive robust equipment-specific RVRTC reference ranges and investigate their potential clinical impact on data interpretation. Method RVRTC data from healthy subjects using Jaeger BabyBody or the ‘Respiratory Analysis Software Program, RASP’ systems were collated from four centres internationally. Data were excluded if gestational age <37u2005weeks or birth weight <2.5u2005kg. Reference equations for RVRTC outcomes were constructed using the LMS (lambda–mu–sigma) method, and compared with published equations using data from newborn screened infants with cystic fibrosis (CF). Results RVRTC data from 429 healthy infants (50.3% boys; 88% white infants) on 639 occasions aged 4–118u2005weeks were available. When plotted against length, flows were significantly higher with RASP than Jaeger, requiring construction of separate equipment-specific regression equations. When comparing results derived from the new equations with those from widely used published equations based on different equipments, discrepancies in forced expiratory volumes and flows of up to 2.5 z-scores were observed, the magnitude of which increased with age. According to published equations, 25% of infants with CF fell below the 95% limits of normal for FEV0.5, compared with only 10% when using the new equations. Conclusions Use of equipment-specific prediction equations for RVRTC outcomes will enhance interpretation of infant lung function results; particularly during longitudinal follow-up.

How “healthy” should children be when selecting reference samples for spirometry?

How “healthy” do children need to be when selecting reference samples for spirometry? Anthropometry and spirometry were measured in an unselected, multi-ethnic population of school children aged 5–11u2005years in London, UK, with follow-up assessments 12u2005months later. Parents provided information on childrens birth data and health status. Forced expiratory volume in 1u2005s (FEV1) and forced vital capacity (FVC) were adjusted for sex, age, height and ethnicity using the 2012 Global Lungs Initiative equations, and the effects of potential exclusion criteria on the z-score distributions were examined. After exclusions for current and chronic lung disease, acceptable data were available for 1901 children on 2767 occasions. Healthy children were defined as those without prior asthma or hospitalisation for respiratory problems, who were born at full-term with a birthweight ≥2.5u2005kg and who were asymptomatic at testing. Mean±sd z-scores for FEV1 and FVC approximated 0±1, indicating the 2012 Global Lungs Initiative equations were appropriate for this healthy population. However, if children born preterm or with low birthweight, children with prior asthma or children mildly symptomatic at testing were included in the reference, overall results were similar to those for healthy children, while increasing the sample size by 25%. With the exception of clear-cut factors, such as current and chronic respiratory disease, paediatric reference samples for spirometry can be relatively inclusive and hence more generalisable to the target population. Population samples for childrens lung function can be relatively inclusive http://ow.ly/I0Jkw

Assessing pubertal status in multi-ethnic primary schoolchildren.

Pubertal status is related to childhood growth and independently associated with health outcomes such as lung function, blood pressure and mental health (1). However, self-assessment of pubertal status is difficult in young children as relevant questions may either be too difficult for young children, especially boys, to answer reliably or perceived to be culturally inappropriate (1–5). This is especially true for overweight children (6). The Size and Lung function In Children (SLIC) study was designed to explore ethnic differences in lung function and body physique in a multi-ethnic population of London schoolchildren (7). As part of this study, we collected both self-reports and parental reports of pubertal status in children aged eight to 11xa0years, both to investigate the feasibility of assessing the attainment of secondary sex characteristics, as a proxy for pubertal status in this population, and to explore any ethnic differences in rates of pubertal attainment.

Challenges in Collating Spirometry Reference Data for South-Asian Children: An Observational Study

Availability of sophisticated statistical modelling for developing robust reference equations has improved interpretation of lung function results. In 2012, the Global Lung function Initiative(GLI) published the first global all-age, multi-ethnic reference equations for spirometry but these lacked equations for those originating from the Indian subcontinent (South-Asians). The aims of this study were to assess the extent to which existing GLI-ethnic adjustments might fit South-Asian paediatric spirometry data, assess any similarities and discrepancies between South-Asian datasets and explore the feasibility of deriving a suitable South-Asian GLI-adjustment. Methods Spirometry datasets from South-Asian children were collated from four centres in India and five within the UK. Records with transcription errors, missing values for height or spirometry, and implausible values were excluded(n = 110). Results Following exclusions, cross-sectional data were available from 8,124 children (56.3% male; 5–17 years). When compared with GLI-predicted values from White Europeans, forced expired volume in 1s (FEV1) and forced vital capacity (FVC) in South-Asian children were on average 15% lower, ranging from 4–19% between centres. By contrast, proportional reductions in FEV1 and FVC within all but two datasets meant that the FEV1/FVC ratio remained independent of ethnicity. The ‘GLI-Other’ equation fitted data from North India reasonably well while ‘GLI-Black’ equations provided a better approximation for South-Asian data than the ‘GLI-White’ equation. However, marked discrepancies in the mean lung function z-scores between centres especially when examined according to socio-economic conditions precluded derivation of a single South-Asian GLI-adjustment. Conclusion Until improved and more robust prediction equations can be derived, we recommend the use of ‘GLI-Black’ equations for interpreting most South-Asian data, although ‘GLI-Other’ may be more appropriate for North Indian data. Prospective data collection using standardised protocols to explore potential sources of variation due to socio-economic circumstances, secular changes in growth/predictors of lung function and ethnicities within the South-Asian classification are urgently required.

Birth data accessibility via primary care health records to classify health status in a multi-ethnic population of children: an observational study.

Background:Access to reliable birth data (birthweight (BW) and gestational age (GA)) is essential for the identification of individuals who are at subsequent health risk.Aims:This study aimed to explore the feasibility of retrospectively collecting birth data for schoolchildren from parental questionnaires (PQ) and general practitioners (GPs) in primary care clinics, in inner city neighbourhoods with high density of ethnic minority and disadvantaged populations.Methods:Attempts were made to obtain birth data from parents and GPs for 2,171 London primary schoolchildren (34% White, 29% Black African origin, 25% South Asians, 12% Other) as part of a larger study of respiratory health.Results:Information on BW and/or GA were obtained from parents for 2,052 (95%) children. Almost all parents (2,045) gave consent to access their children’s health records held by GPs. On the basis of parental information, GPs of 1,785 children were successfully contacted, and GPs of 1,202 children responded. Birth data were retrieved for only 482 children (22% of 2,052). Missing birth data from GPs were associated with non-white ethnicity, non-UK born, English not the dominant language at home or socioeconomic disadvantage. Paired data were available in 376 children for BW and in 407 children for GA. No significant difference in BW or GA was observed between PQ and GP data, with <5% difference between sources regardless of normal or low birth weight, or term or preterm status.Conclusions:Parental recall of birth data for primary schoolchildren yields high quality and rapid return of data, and it should be considered as a viable alternative in which there is limited access to birth records. It provides the potential to include children with an increased risk of health problems within epidemiological studies.

Natural variability of lung function in young healthy school children

Knowledge about long-term variability of lung function in healthy children is essential when monitoring and treating those with respiratory disease over time. The aim of this study was to define the natural variability in spirometry in young children after an interval of 12u2005months. The Size and Lung function In Children study was a prospective study designed to assess spirometry and body size, shape and composition in a multi-ethnic population of London school children. 14 schools with a wide range of socioeconomic circumstances were recruited. Spirometric and anthropometric assessments and parental questionnaires pertaining to respiratory symptoms, previous medical history, pubertal status and socioeconomic circumstances were completed at baseline and ∼1u2005year later. Technically acceptable spirometry data on two occasions ∼1u2005year apart (range 9–16u2005months) were available in 758 children (39% boys, mean±sd age 8.1±1.6u2005years), 593 of whom were classified as “healthy”. Mean±sd within-subject between-test variability was 0.05±0.6u2005z-scores, with 95% of all the children achieving a between-test variability within ±1.2u2005z-scores (equating to ∼13% predicted). Natural variations of up to 1.2u2005z-scores occur in healthy children over ∼1u2005year. These must be considered when interpreting results from annual reviews in those with lung disease who are otherwise stable, if unnecessary further investigations or changes in treatment are to be avoided. Spirometry can vary by up to 1.2u2005z-scores over the course of 1u2005year in children without any overt lung disease http://ow.ly/YZ7mT

Additional file 1: of A comparison of the quality of image acquisition between the incident dark field and sidestream dark field video-microscopes

Two examples of images obtained using the sidestream dark field video-microscope. (PNG 1188 kb)

S11 Feasibility of conducting complex physiological measurements in london primary schools: the Size & Lung function in children (SLIC) Study

Despite recognised ethnic differences in lung function, most reference ranges are based on White subjects. Ethnic minorities comprise 40% of the London population, which impacts on healthcare provision. Even when available, selection of appropriate equations is complicated by the increase in admixed populations and complexities of defining ‘ethnicity’. As part of the Wellcome Trust SLIC study (www.ucl.ac.uk/slic) to determine the extent to which body shape, size and composition contributes to ethnic differences in lung function, we examined the feasibility of conducting complex physiological measurements in a multi-ethnic population of London primary school children. Methods 14 London schools participated in the study. Science workshops were presented one week prior to commencing assessments. Consent forms and information packs were distributed to all children. All children with parental consent were eligible and were categorised into 4 broad ethnic groups: White; Black; South-Asian (Indian subcontinent) and Other/mixed. Assessments were performed at school in 5 11 year-old children and included detailed anthropometry, 3D phototonic scan for body shape; body composition; spirometry and saliva samples (cotinine and DNA analysis). Results Parental consent for anthropometry and spirometry was obtained in 54% of those approached. Amongst these, 88% and 96% provided specific consent for DNA samples and access to GP records respectively (Table 1). Assessments were performed in 2175 children (mean (SD)age: 8.22(1.63); 34%White; 29%Black; 25%South-Asian; 12%Other/mixed ethnicities), 1045(48%) of whom had follow-up assessments a year later. Preliminary analysis indicates: 18% had chronic respiratory illness or acute symptoms at time of test. 12% children had a diagnosis of ‘asthma ever’, with 6% having current asthma (Table 1). Acceptable spirometry1 was obtained from 1574(72%) healthy children. Abstract S11 Table 1. Consent, asthma status &spirometry success rates of study population White Black S-Asian Other/mixed Total Tested (% boys) 742 (49.7%) 629 (43.6%) 540 (48.7%) 264 (46.6%) DNA consent 89.3% 84.0% 85.8% 92.2% GP record access consent 97.1% 93.8% 93.6% 97.4% Asthma: ever 11.6% 11.1% 8.9% 19.7% Asthma: current 5.5% 4.6% 5.6% 7.2% Totalspirometrya 533 (71.8%) 435 (69.2%) 411 (76.1%) 195 (73.9%) Data presented as %. Abbreviations: DNA: Deoxyribonucleic acid (for genetic ancestry); GP: General Practitioner; Current asthma: defined as those having symptoms and/or asthma medication over the past 12 months; a based on data from healthy children and after exclusions from poor health and poor performance. Summary Conducting a field study to undertake complex physiological measurements is feasible even in young children. However, the relatively high prevalence of chronic or acute respiratory disease at time of testing in this age group, combined with exclusions due to technically unsatisfactory spirometry means that results from ~30% of children may be excluded if analysis of results is to be based on a ‘healthy’ population. Such factors must be accounted for when designing respiratory field studies to ensure adequate sample size to reach definitive conclusions. Reference Kirkby et al. Pediatr Pulmonol 2008.