Effect of short-term exposure to ambient nitrogen dioxide and particulate matter on repeated lung function measures in infancy: A South African birth cohort.

BACKGROUND: The developing lung is highly susceptible to environmental toxicants, with both short- and long-term exposure to ambient air pollutants linked to early childhood effects. This study assessed the short-term exposure effects of nitrogen dioxide (NO2) and particulate matter (PM10) on lung function in infants aged 6 weeks, 6, 12 and 24 months, the early developmental phase of child growth. METHODS: Lung function was determined by multiple breath washout and tidal breathing measurement in non-sedated infants. Individual exposure to NO2 and PM10 was determined by hybrid land use regression and dispersion modelling, with two-week average estimates (preceding the test date). Linear mixed models were used to adjust for the repeated measures design and an age*exposure interaction was introduced to obtain effect estimates for each age group. RESULTS: There were 165 infants that had lung function testing, with 82 of them having more than one test occasion. Exposure to PM10 (µg/m3) resulted in a decline in tidal volume at 6 weeks [-0.4 ml (-0.9; 0.0), p = 0.065], 6 months [-0.5 ml (-1.0; 0.0), p = 0.046] and 12 months [-0.3 ml (-0.7; 0.0), p = 0.045]. PM10 was related to an increase in respiratory rate and minute ventilation, while a decline was observed for functional residual capacity for the same age groups, though not statistically significant for these outcomes. Such associations were however less evident for exposure to NO2, with inconsistent changes observed across measurement parameters and age groups. CONCLUSION: Our study suggests that PM10 results in acute lung function impairments among infants from a low-socioeconomic setting, while the association with NO2 is less convincing.

Maternal miRNA-146a G/C rs2910164 variation, HIV/AIDS and nitrogen oxide pollution exposure collectively affects foetal growth.

OBJECTIVE:: Nitrogen oxide (NOx) pollution and human immunodeficiency virus (HIV)/AIDS intensify inflammation during pregnancy and linked with adverse birth outcomes (ABOs). MicroRNA (miRNA)-146a plays a crucial role in regulating inflammation in the NF-κB pathway. The G/C rs2910164 dampens miRNA-146a activity and linked with inflammatory diseases. The present study investigated whether HIV/AIDS and NOx exposure throughout pregnancy further intensifies ABO in Black South African women genotyped for the rs2910164. METHODS:: Pregnant women ( n = 300) were subdivided into low, medium and high NOx exposure groups, genotyped for the miRNA-146a G/C rs2910164 using polymerase chain reaction-restriction fragment length polymorphism, and further stratified based on HIV status. RESULTS:: Unstratified data (HIV+ and HIV- mothers combined): Mothers from the high NOx group with the variant C-allele had low blood iron levels ( p = 0.0238), and had babies with reduced birthweights ( p = 0.0283). As NOx increased, the prevalence of preterm birth and low birth weight also increased in mothers with the variant C-allele versus wildtype G-allele. HIV-infected mothers: In all NOx exposure groups, mothers with the variant C-allele had higher systolic blood pressure (low: p = 0.0386, medium: p = 0.0367 and high: p = 0.0109) and had babies with lower Appearance, Pulse, Grimace, Activity and Respiration scores at 1 min (low: p = 0.0190, medium: p = 0.0301 and high: p = 0.0361). CONCLUSION:: Maternal rs2910164 variant C-allele, NOx pollution and HIV/AIDS might collectively play a role in intensifying gestational hypertension and ABO.

IL-17A[G197G]-Association between NOx and gestational age in a South African birth cohort.

Interleukin (IL-)17A, plays a role in pathogenic defence, but is implicated in chronic inflammatory diseases, and has recently been associated with variable pregnancy outcomes. We investigated the role of maternal IL-17-[G197A]-specific effects of third-trimester IL-17 mRNA expression, NOx exposure levels and other variables on gestational age, in the Mother and Child in the Environment (MACE) birth cohort in South Africa. A total of 327 participants were genotyped for IL-17-[G197A] by polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP). Quantitative real-time PCR was used to quantitate IL-17-mRNA expression in whole blood. Multivariate linear regression analysis, stratified by IL-17-[G197A] genotype, was used to test for effects of NOx , IL17A/GAPDH, haemoglobin, body mass index, HIV-1 positivity, maternal education and income level on gestational age. Lower expression was associated with the IL-17-GG versus GA in the cohort and HIV-1-negative group (p = .0007, p = .0058), while no difference was observed in the HIV-1 positives. Elevated IL-17A expression was observed in the high NOx exposure groups, within IL-17[G197G] (p = .0004). IL-17[G197G] was associated with PTB (p < .0001), and the PTB group had lower IL-17A expression compared to the full-term group (p = .0002). IL-17 expression was associated with an increase in gestational age (p = .038), and NOx was associated with a decrease in gestational age in the IL-17[G197G] model (p = .046).

IL-1ß haplotype influences the effect of NOx exposure on gestational age in the South African MACE birth cohort.

OBJECTIVE: Cytokines, molecules within the immune system that affect either a pro- or anti-inflammatory response, have previously been shown to influence birth outcomes. The maternal cytokine gene-environment interactions are thought to alter their expression, potentially influencing susceptibility to adverse birth outcomes. The aim of this study was to determine the association between the maternal interleukin-1ß (IL-1ß) haplotype and expression variation with oxides of nitrogen (NOx) levels, and thereafter investigate the IL-1ß haplotype-specific effects of NOx exposure levels, IL-1ß mRNA expression and other variables on gestational age. MATERIAL AND METHODS: Using the prospective Mother and Child in the Environment (MACE) birth cohort in Durban, South Africa, 335 participants were genotyped for the IL-1ß haplotype. Previous studies showed that three single nucleotide polymorphisms (SNPs), IL-1ß-1464G/C, -511C/T and -31C/T, constitute the IL-1ß functional haplotype. These SNPs were genotyped using a restriction fragment length polymorphism assay, while IL-1ß mRNA expression was measured using a quantitative real-time polymerase chain reaction assay. Individual estimates of NOx exposure were obtained by land use regression modelling. A multivariate linear regression analysis was employed to test for significant effects on gestational age. RESULTS: IL-1ß mRNA expression was found to possess a haplotype-dependent effect ( p = 0.0001) and its expression levels positively correlated with NOx levels ( r = 0.34; p = 0.006). In the high haplotype model, a unit increase in NOx exposure level was associated with a decrease in gestational age by 1 week ( p = 0.02). Furthermore, gestational age decreased by 0.9 weeks for every unit increase of IL-1ß mRNA expression level ( p = 0.025). HIV-1 positivity was associated with a 0.2-week decrease in gestational age ( p = 0.035) in the intermediate haplotype model and a 0.4-week decrease in the high haplotype model ( p = 0.044). CONCLUSION: These data have implications for better understanding the effect of prenatal NOx exposure on gestational age and demonstrate the role of the IL-1ß haplotype in modulating the effects of NOx exposure.

Human immunodeficiency virus and urinary tract infections in children.

This was a retrospective study of HIV-infected children aged 0-12 years attending the King Edward VIII Hospital in Durban, South Africa over a 5-year period (January 1996 to December 2001) with culture-proven urinary tract infection (UTI). UTI was defined as the presence of a single bacterial growth of >10(5) colony-forming units/ml in a clean-catch, mid-stream urine sample or >10(3) organisms/ml in a catheter or suprapubic aspirate of urine. HIV/AIDS was diagnosed in accordance with World Health Organization and/or Centers for Disease Control criteria. Comparison between HIV-positive and HIV-negative children with UTI was done using the chi2 and Wilcoxon rank sum tests. Of the 55 children recruited into the study, 29 (52.1%) were HIV-positive and 26 (47.3%) HIV-negative. Escherichia coli was isolated in 50 (87.2%) children. Clinical presentation, aetiological agents, response to therapy and renal function were similar in both groups. This study showed no significant impact of HIV/AIDS on the presentation of UTI in children.