Search

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 12 months.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 ∼1 year later.Technically acceptable spirometry data on two occasions ∼1 year apart (range 9-16 months) were available in 758 children (39% boys, mean±sd age 8.1±1.6 years), 593 of whom were classified as "healthy". Mean±sd within-subject between-test variability was 0.05±0.6 z-scores, with 95% of all the children achieving a between-test variability within ±1.2 z-scores (equating to ∼13% predicted).Natural variations of up to 1.2 z-scores occur in healthy children over ∼1 year. 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., (Copyright ©ERS 2016.)

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., (Copyright ©ERS 2015.)

The impact of birth before 27 completed weeks of gestation on infant pulmonary function (PF) was explored in a multi-ethnic population in comparison to more mature preterm controls (PTC) and healthy fullterm infants. Plethysmographic lung volume (FRCpleth ) and forced expired volume (FEV0.5 ) were obtained at ∼12 months post-term age in 52 extremely preterm (EP) infants (median [range] gestational age [GA]: 26 [23-27] weeks; 40% White mothers; 79% with BPD), 41 PTC (GA:35 [30-36] weeks; 37% White mothers) and 95 fullterm infants (GA:40 [37-42] weeks; 86% White mothers). Using reference equations based on identical equipment and techniques, results were expressed as z-scores to adjust for age, sex and body size. FEV0.5 was significantly lower in EP infants when compared with PTC (mean difference [95% CI]: -1.02[-1.60; -0.44] z-scores, P < 0.001), as was forced vital capacity (FVC) but there were no significant differences in FRCpleth or FEV0.5 /FVC ratio. FEV0.5 , FVC, and FEV0.5 /FVC were significantly lower in both preterm groups when compared with fullterm controls. On multivariable analyses of the combined preterm dataset: FEV0.5 at ∼1 year was 0.11 [0.05; 0.17] z-scores higher/week GA, and 1.28 (0.49; 2.08) z-scores lower in EP infants with prior BPD. Among non-white preterm infants, FEV0.5 was 0.70 (0.17; 1.24) z-scores lower, with similar reductions in FVC, such that there were no ethnic differences in FEV0.5 /FVC. Similar ethnic differences were observed among fullterm infants. These results confirm the negative impact of preterm birth on subsequent lung development, especially following a diagnosis of BPD, and emphasize the importance of taking ethnic background into account when interpreting results during infancy as in older subjects., (© 2013 Wiley Periodicals, Inc.)

Background: Long-term benefits of newborn screening (NBS) for cystic fibrosis (CF) have been established with respect to nutritional status, but effects on pulmonary health remain unclear., Hypothesis: With early diagnosis and commencement of standardised treatment, lung function at ∼3 months of age is normal in NBS infants with CF., Methods: Lung clearance index (LCI) and functional residual capacity (FRC) using multiple breath washout (MBW), plethysmographic (pleth) FRC and forced expirations from raised lung volumes were measured in 71 infants with CF (participants in the London CF Collaboration) and 54 contemporaneous healthy controls age ∼3 months., Results: Compared with controls, and after adjustment for body size and age, LCI, FRC(MBW) and FRC(pleth) were significantly higher in infants with CF (mean difference (95% CI): 0.5 (0.1 to 0.9), p=0.02; 0.4 (0.1 to 0.7), p=0.02 and 0.9 (0.4 to 1.3), p<0.001, z-scores, respectively), while forced expiratory volume (FEV(0.5)) and flows (FEF(25-75)) were significantly lower (-0.9 (-1.3 to -0.6), p<0.001 and -0.7 (-1.1 to -0.2), p=0.004, z-scores, respectively). 21% (15/70) of infants with CF had an elevated LCI (>1.96 z-scores) and 25% (17/68) an abnormally low FEV(0.5) (below -1.96 z-scores). While only eight infants with CF had abnormalities of LCI and FEV(0.5), using both techniques identified abnormalities in 35% (24/68). Hyperinflation (FRC(pleth) >1.96 z-scores) was identified in 18% (10/56) of infants with CF and was significantly correlated with diminished FEF(25-75) (r=-0.43, p<0.001) but not with LCI or FEV(0.5)., Conclusion: Despite early diagnosis of CF by NBS and protocol-driven treatment in specialist centres, abnormal lung function, with increased ventilation inhomogeneity and hyperinflation and diminished airway function, is evident in many infants with CF diagnosed through NBS by 3 months of age.

The tidal and raised volume rapid thoracoabdominal compression techniques are increasingly used to detect diminished airway function in infancy. The aim of this study was to assess the relative ability of parameters measured by these techniques to identify diminished airway function in infants newly diagnosed with cystic fibrosis (CF) with and without clinical evidence of prior lower respiratory illness. A cross-sectional, prospective study design was used in which maximal flow at functional residual capacity (VmaxFRC) from the tidal technique and FVC, FEV0.5, FEF75, and FEF25-75 from the raised volume technique were measured in 47 infants with CF and 187 healthy infants of similar body size, sex distribution, ethnic group, and exposure to maternal smoking. Multiple linear regression was used to assess group differences and to calculate SD scores for each parameter for the infants with CF. Airway function was also compared with clinical assessments of respiratory status made by pediatric pulmonologists. FEV0.5 was significantly diminished in 13 infants with CF, of whom 4 had been identified by clinicians as having normal respiratory status. Only one infant with CF had a VmaxFRC below the estimated normal range. Airway function is diminished in infants with CF irrespective of prior lower respiratory illness and in those whose respiratory status is considered normal by pediatric pulmonologists. In infants with CF, the raised volume technique identified diminished airway function more frequently than the tidal technique.

This prospective community-based study of infants born in inner London was undertaken to examine the association between premorbid airway function and subsequent wheezing in the first year of life and to explore the influence on this association of a family history of asthma and maternal smoking during pregnancy. Healthy Caucasian term infants were recruited shortly after birth, and physician-diagnosed wheezing episodes were identified retrospectively from medical records. Specific airway conductance was determined from plethysmographic measurements of lung volume and airway resistance, before 13 wk and prior to any respiratory illness, in 101 infants, 28 of whom experienced at least one episode of wheezing during the first year. Mean (SD) specific airway conductance was significantly diminished in infants who subsequently wheezed: 2.02 (1.07) s-1. kPa-1 and 2.60 (0.93) s-1. kPa-1, respectively (p < 0.05), and in those with a first-degree relative with asthma: 1.98 (0.83) s-1. kPa-1 and 2.60 (1.0) s-1. kPa-1, respectively (p < 0.05), but not in those whose mothers smoked during pregnancy, in whom airway resistance was, however, significantly elevated (p < 0.05). The odds ratio (95% confidence interval [CI]) for wheezing was 2.1 (1.1 to 3.8) for every unit (s-1. kPa-1) decline in specific airway conductance (p = 0.02). After adjustment for premorbid airway function, the odds of wheezing were significantly increased in those with a family history of asthma (4. 3; 95% CI, 1.3 to 13.8; p = 0.016) and those exposed to maternal smoking during pregnancy (4.9; 95% CI, 1.6 to 15.0; p = 0.005). Our findings confirm previous reports that impaired premorbid airway function precedes and predicts wheezing in the first year. Among those with a genetic predisposition to asthma, alterations in airway geometry or tone may increase susceptibility to wheezing. Maternal smoking has important and potentially preventable adverse effects on somatic growth and respiratory morbidity in early life.

The liver/islet glucose transporter (GLUT2) is mainly expressed in the hepatocytes of the liver and the beta-cells of the pancreatic islets and a defect in this transporter could lead to diabetic phenotypes, such as relative hypoinsulinaemia and reduced uptake and metabolism of glucose in the liver. DNA from unrelated individuals was digested with the restriction endonucleases Bgl-I and Taq-I followed by blotting and hybridisation with a 32P-labelled GLUT2 cDNA which revealed three restriction fragment length polymorphisms (RFLPs) (B1, T1 and T2) in both Caucasian and West Indian populations. Linkage analysis between these variant sites demonstrated that the alleles of these polymorphisms were in strong linkage disequilibrium. Disease association of genetic variants at the GLUT2 locus with type 2 diabetes was examined with these RFLPs in both Caucasian (n = 54) and West Indian (n = 46) populations with type 2 diabetes. There were no significant differences in the frequency of alleles, genotypes or haplotypes between diabetic patients and non-diabetic controls. However, there were significant differences in the allele frequencies of all these three polymorphisms between Caucasian and West Indian populations.

Digestion of human genomic DNA with the restriction enzyme StuI revealed a 2-allele polymorphism with a human HepG2 glucose transporter probe. Bands of 3.2 kilobases (kb; S1 allele) and 2.6 kb (S2 allele) were observed. The genotype frequencies were investigated in 2 non-insulin-dependent diabetic populations. The genotype frequencies of S1S1, S1S2 and S2S2 were 6, 42 and 52% among Caucasian diabetic subjects (n = 48), and 11, 38 and 51% in 47 controls, respectively. In West Indian diabetic patients (n = 48), the genotype frequencies were 17, 54 and 29%, and for 36 controls they were 25, 33 and 42%, respectively. The polymorphism information content of this restriction fragment length polymorphism (RFLP) is 0.32 in Caucasians and 0.37 in West Indians, respectively. There was no significant difference of allele or genotype frequencies between the diabetic patients and non-diabetic controls in either group. Haplotype analysis of the StuI and XbaI RFLPs showed that there was also no significant difference in the frequencies of the four different haplotypes S1X1, S1X2, S2X1 and S2X2 between the patients and controls. However, there was a difference for the frequency of the S1 allele between Caucasians (controls 30%, patients 27%) and West Indians (controls 42%, patients 44%). There was also a significant difference in the frequency of haplotype S2X2 between these two racial groups (controls 48%, cases 51% for Caucasians, and controls 33%, cases 22% for West Indians).