Rachel Bonner

Applicability of the Global Lung Function Spirometry Equations in Contemporary Multiethnic Children

To the Editor: The challenges posed by a modern multiethnic society have had a marked impact on current health provision. There are established inequalities in health care provision for ethnic minorities (1–3) with asthma prevalence, severity, and access to health care varying by ethnic group (4). Recently the Centers for Disease Control and Prevention recommended that improved asthma management and reduced asthma burden among children from ethnic minorities can be achieved through promoting interventions that take cultural differences and population specific characteristics into account (4). However, until recently appropriate lung function reference equations for groups other than white Europeans have been lacking, especially for younger children (5). In an attempt to address these issues, the Global Lung Function Initiative (GLI), which was established as a European Respiratory Society Taskforce, recently published the first global, all-age (3–95 yr), multiethnic reference equations for spirometry (6). Because the Quanjer GLI-2012 reference equations were derived from various studies around the world during the past 3 decades, it is important to establish the level of agreement between these equations and contemporary spirometry data. London, United Kingdom, is an ideal environment in which to validate these equations because ethnic minorities comprise 40% of the population. The aims of this study were first, to investigate existing ethnic differences in lung function in a multiethnic population of children from London and second, to validate the GLI-2012 reference equations in this population. As part of the Size and Lung Function in Children study (www.ucl.ac.uk/slic), anthropometry and spirometry were undertaken in primary school children within a mobile laboratory or in classrooms between December 2010 and July 2012. Children were classified into four main ethnic groups (white, black, South Asian, other/mixed) on the basis of information from parental questionnaires, child self-identification, and investigator observation. As there is currently no GLI ethnic-specific equation for South Asians (i.e., those from the Indian subcontinent), the “South East Asian equation” (derived from subjects from South China, Thailand, and Taiwan) was used for this population as it is closest geographically. Spirometry was performed using either the Jaeger Masterscreen (V5.01; Carefusion, Warzburg, Germany) or the Easy-on PC (ndd, Zurich, Switzerland) spirometer, which have been shown to produce very similar spirometry results (7). All subjects performed at least three maneuvers to standard protocol and American Thoracic Society/European Respiratory Society acceptability and repeatability criteria, adjusted for children, were applied (8, 9). Results were analyzed in two ways. First, to calculate the magnitude of ethnic differences in lung function, all spirometric data were expressed as percent predicted on the basis of the GLI-2012 equations for white subjects, which adjust for age, sex, and height (6). Second, to assess how valid the GLI-2012 equations were in this population, results from each child were expressed as ethnic-specific z-scores. If the GLI-2012 equations are appropriate for this contemporary multiethnic population, the mean (SD) z-score for each outcome in each group would be expected to approximate 0 (1) (10). Differences between groups were assessed using one way analysis of variance with Bonferroni correction for multiple comparisons. None of the data collected from the SLIC study were used in the development of the GLI-2012 equations. Some of these results have been reported in the form of an abstract (11). Spirometry was attempted in 1,626 children aged 5–11 years from 14 London schools. Of these, 1,291 were asymptomatic and without any existing respiratory conditions or other chronic disease likely to affect lung function (335 were excluded for health reasons: airway obstruction on spirometry [14]; current asthma [172]; sickle cell disease [11]; preterm [70]; or symptomatic on the day of test [68]). Technically acceptable spirometry was obtained from 1,088/1,291 (84%) healthy children (Table 1). After adjustment for age and sex, black children were significantly taller (P < 0.001) and heavier (P < 0.001) and South Asian children were significantly lighter (P < 0.001) than white children. When compared with white children, FEV1 was significantly lower by a predicted mean (95% confidence interval) of 14% (12 to 17%) in black, 11% (9 to 14%) in South Asian, and 5% (2 to 8%) in other/mixed race children (Table 1). TABLE 1. GROUP CHARACTERISTICS AND LUNG FUNCTION RESULTS When data were expressed according to the GLI-2012 ethnic-specific reference equations, the mean (SD) FVC and FEV1 z-scores approximated 0 (1) across all groups, albeit being slightly elevated among those allocated to the “other” group in whom numbers were more limited (Figure 1, Table 1). Similarly, with the exception of the South Asian children, in whom predicted values were slightly under-estimated when applying the South East Asian equation, FEV1/FVC z-score was close to that expected from a healthy population in all groups. 95% of children in each group fell within the 95th limits of normality for FEV1 and FVC, suggesting that these outcomes can be reliably used to identify presence of lung disease irrespective of ethnic origin. Although similar results were observed for FEV1/FVC in the white or “other” groups (5.6 and 6.7% respectively falling below the 5th centile), 9.1% of black children and 13.8% South Asian healthy children fell below this lower limit of normal, when applying the ethnic-specific equations. However, if all FEV1/FVC data were expressed in relation to the white equation, close agreement was seen across all groups (Table 1, bottom row). Figure 1. Spirometric lung function results according to the GLI-2012 ethnic specific reference equations (6). Data from South Asian children were expressed according the “South East Asian equation.” For the purposes of this analysis the 95% limits ... These results demonstrate that although there are significant ethnic differences in FEV1 and FVC in primary school children, the magnitude of which is similar to that reported in older subjects (6), these differences can be minimized by using the GLI-2012 ethnic-specific reference equations. Furthermore, as reported previously (6), FEV1/FVC remained relatively constant across all ethnic groups. The results also indicate that these equations are valid for use in a multiethnic population of contemporary school children, as previously demonstrated in healthy Australasian subjects aged 4–80 years (12). The slightly lower z-score for FEV1/FVC in South Asian children despite similar absolute values, emphasizes the urgent need to develop ethnic-specific equations for this group (6). When compared with the other ethnic-specific coefficients, the South East Asian GLI equation provided the best precision when interpreting FEV1 and FVC results in children from the Indian sub-continent living in London (data not shown). However, predicted FEV1/FVC in these children is better reflected by that derived from white subjects until appropriate ethnic-specific equations can be developed for South Asian subjects. Results from children of other/mixed ethnic backgrounds must be interpreted with caution due to the limited numbers (13). Nevertheless, with the exception of FEV1/FVC in South Asian subjects when using the South East Asian equation, mean results for all outcomes in all groups were within ±0.5 z-scores; representing differences that are unlikely to be of clinical significance (6, 12). In conclusion, although further work is required to develop suitable reference equations for South Asians, and to validate equations for those of other/mixed race, use of the Quanjer GLI-2012 ethnic-specific reference equations appear to be valid in a multiethnic population of contemporary school children. This will facilitate diagnosis of respiratory conditions in children, irrespective of ethnic origin, by improved differentiation between health and disease.

Disparities in Pulmonary Function in Healthy Children across the Indian Urban–Rural Continuum

RATIONALE Marked socioeconomic health-care disparities are recognized in India, but lung health inequalities between urban and rural children have not been studied. OBJECTIVES We investigated whether differences exist in spirometric pulmonary function in healthy children across the Indian urban-rural continuum and compared results with those from Indian children living in the UK. METHODS Indian children aged 5 to 12 years were recruited from Indian urban, semiurban, and rural schools, and as part of the Size and Lung Function in Children study, London. Anthropometric and spirometric assessments were undertaken. MEASUREMENTS AND MAIN RESULTS Acceptable spirometric data were obtained from 728 (58% boys) children in India and 311 (50% boys) UK-Indian children. As an entire group, the India-resident children had significantly lower z FEV1 and z FVC than UK-Indian children (P < 0.0005), when expressed using Global Lung Function Initiative-2012 equations. However, when India-resident children were categorized according to residence, there were no differences in z FEV1 and z FVC between Indian-urban and UK-Indian children. There were, however, significant reductions of ∼ 0.5 z scores and 0.9 z scores in both FEV1 and FVC (with no difference in FEV1/FVC) in Indian-semiurban and Indian-rural children, respectively, when compared with Indian-urban children (P < 0.0005). z Body mass index, socioeconomic circumstances, tobacco, and biomass exposure were individually significantly associated with z FEV1 and z FVC (P < 0.0005). CONCLUSIONS The presence of an urban-rural continuum of lung function within a specific ethnic group emphasizes the impact of environmental factors on lung growth in emerging nations such as India, which must be taken into account when developing ethnic-specific reference values or designing studies to optimize lung health.

Interpretation of pediatric lung function: Impact of ethnicity

To evaluate the appropriateness of spirometric and plethysmographic reference equations in healthy young children according to ethnic origin.

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 (n = 698). 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 mass = 1.12+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.

Acceptability, Precision and Accuracy of 3D Photonic Scanning for Measurement of Body Shape in a Multi-Ethnic Sample of Children Aged 5-11 Years: The SLIC Study.

Background Information on body size and shape is used to interpret many aspects of physiology, including nutritional status, cardio-metabolic risk and lung function. Such data have traditionally been obtained through manual anthropometry, which becomes time-consuming when many measurements are required. 3D photonic scanning (3D-PS) of body surface topography represents an alternative digital technique, previously applied successfully in large studies of adults. The acceptability, precision and accuracy of 3D-PS in young children have not been assessed. Methods We attempted to obtain data on girth, width and depth of the chest and waist, and girth of the knee and calf, manually and by 3D-PS in a multi-ethnic sample of 1484 children aged 5–11 years. The rate of 3D-PS success, and reasons for failure, were documented. Precision and accuracy of 3D-PS were assessed relative to manual measurements using the methods of Bland and Altman. Results Manual measurements were successful in all cases. Although 97.4% of children agreed to undergo 3D-PS, successful scans were only obtained in 70.7% of these. Unsuccessful scans were primarily due to body movement, or inability of the software to extract shape outputs. The odds of scan failure, and the underlying reason, differed by age, size and ethnicity. 3D-PS measurements tended to be greater than those obtained manually (p<0.05), however ranking consistency was high (r2>0.90 for most outcomes). Conclusions 3D-PS is acceptable in children aged ≥5 years, though with current hardware/software, and body movement artefacts, approximately one third of scans may be unsuccessful. The technique had poorer technical success than manual measurements, and had poorer precision when the measurements were viable. Compared to manual measurements, 3D-PS showed modest average biases but acceptable limits of agreement for large surveys, and little evidence that bias varied substantially with size. Most of the issues we identified could be addressed through further technological development.

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 5–11 years in London, UK, with follow-up assessments 12 months later. Parents provided information on childrens birth data and health status. Forced expiratory volume in 1 s (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 ≥2.5 kg 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

Lung function in children in relation to ethnicity, physique and socioeconomic factors

Can ethnic differences in spirometry be attributed to differences in physique and socioeconomic factors? Assessments were undertaken in 2171 London primary schoolchildren on two occasions 1 year apart, whenever possible, as part of the Size and Lung function In Children (SLIC) study. Measurements included spirometry, detailed anthropometry, three-dimensional photonic scanning for regional body shape, body composition, information on ethnic ancestry, birth and respiratory history, socioeconomic circumstances, and tobacco smoke exposure. Technically acceptable spirometry was obtained from 1901 children (mean (range) age 8.3 (5.2–11.8) years, 46% boys, 35% White, 29% Black-African origin, 24% South-Asian, 12% Other/mixed) on 2767 test occasions. After adjusting for sex, age and height, forced expiratory volume in 1 s was 1.32, 0.89 and 0.51 z-score units lower in Black-African origin, South-Asian and Other/mixed ethnicity children, respectively, when compared with White children, with similar decrements for forced vital capacity (p<0.001 for all). Although further adjustment for sitting height and chest width reduced differences attributable to ethnicity by up to 16%, significant differences persisted after adjusting for all potential determinants, including socioeconomic circumstances. Ethnic differences in spirometric lung function persist despite adjusting for a wide range of potential determinants, including body physique and socioeconomic circumstances, emphasising the need to use ethnic-specific equations when interpreting results. Ethnic differences in spirometry cannot simply be attributed to differences in physique and socioeconomic factors http://ow.ly/R8EaR

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.

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.

S34 Lung Function in Children with Sickle Cell Disease

Introduction Sickle Cell Disease (SCD) is one of the most prevalent genetic diseases with an incidence of ∼1 in 200 Afro-Caribbean children in the UK (WHO; 2006). Since SCD can result in significant respiratory morbidity,[1] lung function tests (LFTs) could play an important role in the clinical management of children with SCD. Aim To determine the extent to which LFTs identify differences in children with SCD when compared with healthy Black children. Methods A respiratory health questionnaire was administered, and four commercially available LFTs (Impulse oscillometry (IOS), specific effective airways resistance (sReff), plethysmographic lung volumes, and spirometry) were undertaken in up to 214 healthy Black children and 85 children with SCD aged 4–12y. Results Amongst children with SCD, 50% reported cough on most days, and 25% had been reviewed by a specialist respiratory consultant within 3 months prior to the assessments. When compared with healthy children, 20% had a reduced total lung capacity (TLC), with concurrent reductions in FEV1 and FVC No differences in sReff were observed and IOS outcomes proved to be of limited value, due to poorly defined limits of normality and large between-subject variability. No significant group differences in bronchodilator responsiveness in SCD or healthy children were observed regardless of the outcome measured (Table 1). Conclusion Despite the high proportion of respiratory symptoms reported, the number of children with LFTs falling outside the limits of normal was relatively small. Results suggest a pattern of restrictive lung disease in children with SCD. Of the outcomes assessed, baseline spirometry appears to be the most useful for routine assessment of lung disease in young children with SCD. J Caboot, Curr Opin Pediatr 2008 Dencker, Clin Physiol Funct Imaging 2006 Kirkby, ERJ 2010 Kirkby, Ped Pulm 2012 Quanjer, ERJ 2012 Abstract S34 Table 1 Comparison of Lung Function: Children with SCD vs. healthy Black controls. Baseline Mean (95% CI) Diff (SCD – Health) Bronchodilator Response Mean (95% CI) Diff (SCD-Health) Resistance at 10Hz Z Score[2] –0.2 (–0.4; 0.1) 0.3 (–0.2; 0.7) sReff Z Score[3] –0.3 (–0.6; 0.1) 0.5 (0.1; 0.8) TLC Z Score[4] –0.8 (–1.1; –0.5)* FVC Z Score[5] –1.0 (–1.2; –0.7)* 0.2 (–0.1; 0.5) FEV1 Z Score[5] –1.2 (–1.5; –0.9)* 0.2 (–0.1; 0.5) * p<0.001.