Clinical standards for diagnosis, treatment and prevention of post-COVID-19 lung disease.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice' care for the diagnosis, treatment and prevention of post-COVID-19 lung disease.METHODS: A panel of international experts representing scientific societies, associations and groups active in post-COVID-19 lung disease was identified; 45 completed a Delphi process. A 5-point Likert scale indicated level of agreement with the draft standards. The final version was approved by consensus (with 100% agreement).RESULTS: Four clinical standards were agreed for patients with a previous history of COVID-19: Standard 1, Patients with sequelae not explained by an alternative diagnosis should be evaluated for possible post-COVID-19 lung disease; Standard 2, Patients with lung function impairment, reduced exercise tolerance, reduced quality of life (QoL) or other relevant signs or ongoing symptoms ≥4 weeks after the onset of first symptoms should be evaluated for treatment and pulmonary rehabilitation (PR); Standard 3, The PR programme should be based on feasibility, effectiveness and cost-effectiveness criteria, organised according to local health services and tailored to an individual patient's needs; and Standard 4, Each patient undergoing and completing PR should be evaluated to determine its effectiveness and have access to a counselling/health education session.CONCLUSION: This is the first consensus-based set of clinical standards for the diagnosis, treatment and prevention of post-COVID-19 lung disease. Our aim is to improve patient care and QoL by guiding clinicians, programme managers and public health officers in planning and implementing a PR programme to manage post-COVID-19 lung disease.

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.

Developing a predictive model for fine particulate matter concentrations in low socio-economic households in Durban, South Africa.

In low-resource settings, there is a need to develop models that can address contributions of household and outdoor sources to population exposures. The aim of the study was to model indoor PM2.5 using household characteristics, activities, and outdoor sources. Households belonging to participants in the Mother and Child in the Environment (MACE) birth cohort, in Durban, South Africa, were randomly selected. A structured walk-through identified variables likely to generate PM2.5 . MiniVol samplers were used to monitor PM2.5 for a period of 24 hours, followed by a post-activity questionnaire. Factor analysis was used as a variable reduction tool. Levels of PM2.5 in the south were higher than in the north of the city (P < .05); crowding and dwelling type, household emissions (incense, candles, cooking), and household smoking practices were factors associated with an increase in PM2.5 levels (P < .05), while room magnitude and natural ventilation factors were associated with a decrease in the PM2.5 levels (P < .05). A reasonably robust PM2.5 predictive model was obtained with model R2 of 50%. Recognizing the challenges in characterizing exposure in environmental epidemiological studies, particularly in resource-constrained settings, modeling provides an opportunity to reasonably estimate indoor pollutant levels in unmeasured homes.

Interaction between ambient pollutant exposure, CD14 (-159) polymorphism and respiratory outcomes among children in Kwazulu-Natal, Durban.

The objective of this study was to determine if the association between exposure to ambient air pollutants such as sulfur dioxide, nitrogen dioxde (NO2), nitrous oxide (NO), and PM10, and variation in lung function measures was modified by genotype. A validated questionnaire was administered to 71 African children to evaluate prevalence of respiratory symptoms. Atopy was evaluated by skin-prick testing and bihourly measures of lung function (spirometry) were collected. Gaseous air pollutant concentrations were monitored continuously. CD14 polymorphism was genotyped and plasma CD14 levels were measured. There was no statistically significant association between the CD14 (159) CT+TT polymorphism with any asthma-related phenotype. There was a significant association between lung function (forced expiratory volume in 1 second intraday variability) and NO2 and NO among participants carrying the CD14 CT/TT genotype for lags 1, 2, and the 5-day average. Similarly, statistically significant gene-pollutant interactions ( p < 0.05) were found with NO and CD14 CT/TT at lag 2 and for the 5-day average. While there was no association with any respiratory phenotype (as determined by symptoms), the CD14 CT/TT genotype appeared to be protective to increased exposure to NO2 and NO.

Petrol exposure and DNA integrity of peripheral lymphocytes.

PURPOSE: To determine the effect of petrol exposure on DNA integrity in peripheral blood lymphocytes among petrol attendants and a non-exposed comparison population. METHODS: This cross-sectional study included 101 fuel station employees and 50 office-based non-exposed workers in Durban, South Africa. Participants were interviewed using a validated questionnaire. Genomic DNA was extracted from peripheral lymphocytes for the benzo(a)pyrene diol epoxide (BPDE)-DNA adduct assay (ELISA), and DNA damage was determined using the comet assay and reported as percentage tail DNA. RESULTS: The exposed (n = 101) and non-exposed participants (n = 50) varied with regard to age, housing, smoking, and proximity to industry and petrol stations. Among the exposed, the mean duration of employment in the fuel industry was 5.8 years (SD = 4.6), and among those pumping fuel (n = 75), the mean metric tons of petrol pumped in the past 12 months per worker was 199.2 (SD = 88.9). The mean percentage tail DNA varied significantly between exposed and non-exposed groups: 23.8 % (SD = 13.3) and 8.1 % (SD = 1.8) (p < 0.01), respectively. A significant difference existed between the groups for BPDE-DNA adducts: 30.0 ng/ml (SD = 12.7) and 18.1 ng/ml (SD = 18.2) (p < 0.0001), respectively. Regression models, adjusting for cigarette smoking, age, and sex, showed a 16.5 greater percentage tail DNA among the exposed compared to non-exposed (95 % CI 11.8-21.1 %), while the exposed group had a 12.9 ng/ml greater increase in BPDE-DNA adducts has compared to the unexposed (95 % CI 7.2-18.7 ng/ml). Cigarette smoking resulted in almost a 3.5 % increase in percentage tail DNA. CONCLUSION: Our study adds to the literature that long-term, low-dose exposure to vehicular fuels is likely to result in altered DNA integrity and genotoxicity among petrol attendants. These results strengthen the case that these workers must be afforded appropriate protection to prevent serious adverse outcomes.

Childhood tuberculosis and exposure to indoor air pollution: a systematic review and meta-analysis.

BACKGROUND: Indoor air pollution (IAP) from environmental tobacco smoke (ETS) and biomass fuel smoke (BMS) poses respiratory health risks, with children and women bearing the major burden. OBJECTIVES: We used a systematic review and meta-analysis to investigate the relation between childhood tuberculosis (TB) and exposure to ETS and BMS. METHODS: We searched three databases for epidemiological studies that investigated the association of childhood TB with exposure to ETS and BMS. We calculated pooled estimates and heterogeneity for studies eligible for inclusion in the meta-analysis and stratified studies on ETS by outcome. RESULTS: Five case-control and three cross-sectional studies were eligible for inclusion in the meta-analysis and quality assessment. Pooled effect estimates showed that exposure to ETS is associated with tuberculous infection and TB disease (OR 1.9, 95%CI 1.4-2.9) among exposed compared to non-exposed children. TB disease in ETS studies produced a pooled OR of 2.8 (95%CI 0.9-4.8), which was higher than the OR for tuberculous infection (OR 1.9, 95%CI 0.9-2.9) for children exposed to ETS compared to non-exposed children. Studies on BMS exposure were too few and too small to permit a conclusion. CONCLUSION: Exposure to ETS increases the risk of childhood TB disease or tuberculous infection.

Oxidative stress and air pollution exposure during pregnancy: A molecular assessment.

Chronic air pollution exposure during pregnancy can cause oxidative stress leading to adverse birth outcomes. The aim of this study was to assess and compare oxidative stress response in peripheral lymphocytes isolated from pregnant women from a highly industrialized locale (south Durban (SD); n = 50) and a control with lower air pollutant levels (north Durban (ND); n = 50). Oxidative stress response was measured by quantifying malondialdehyde (MDA) levels and a SuperArray gene panel. Mitochondrial function (adenosine triphosphate (ATP) levels and mitochondrial depolarization), DNA integrity (comet assay and mitochondrial DNA (mtDNA) viability) and DNA repair (OGG1) were assessed. Antioxidant response was assessed by quantification of glutathione (GSH) and SOD2, nuclear factor erythroid 2-related factor 2 (Nrf2) and uncoupling protein 2 (UCP2) protein and messenger RNA (mRNA) expression. Levels of MDA (p = 0.9), mitochondrial depolarization (p = 0.88), ATP (1.89-fold), SOD2 (1.23-fold) and UCP2 (1.58-fold) gene expression were elevated in the SD group with significantly higher UCP2 protein levels (p = 0.05) and longer comet tail length (p = 0.0004). The expression of Nrf2 protein (p = 0.03) and mRNA levels (-1.37-fold), GSH concentration (p < 0.0001), mtDNA amplification (-2.04-fold) and OGG1 mRNA (-2.78-fold) activity were decreased in the SD group. Of the 84 oxidative stress-related genes evaluated, 26 were differentially regulated. Pregnant women exposed to higher air pollutant levels showed increased markers for oxidative stress and compromised DNA integrity and repair.

The application of subset correspondence analysis to address the problem of missing data in a study on asthma severity in childhood.

Non-response in cross-sectional data is not uncommon and requires careful handling during the analysis stage so as not to bias results. In this paper, we illustrate how subset correspondence analysis can be applied in order to manage the non-response while at the same time retaining all observed data. This variant of correspondence analysis was applied to a set of epidemiological data in which relationships between numerous environmental, genetic, behavioural and socio-economic factors and their association with asthma severity in children were explored. The application of subset correspondence analysis revealed interesting associations between the measured variables that otherwise may not have been exposed. Many of the associations found confirm established theories found in literature regarding factors that exacerbate childhood asthma. Moderate to severe asthma was found to be associated with needing neonatal care, male children, 8- to 9-year olds, exposure to tobacco smoke in vehicles and living in areas that suffer from extreme air pollution. Associations were found between mild persistent asthma and low birthweight, and being exposed to smoke in the home and living in a home with up to four people. The classification of probable asthma was associated with a group of variables that indicate low socio-economic status.

Ambient pollution and respiratory outcomes among schoolchildren in Durban, South Africa.

OBJECTIVE: To examine associations between ambient air pollutants and respiratory outcomes among schoolchildren in Durban, South Africa. METHODS: Primary schools from within each of seven communities in two regions of Durban (the highly industrialised south compared with the non-industrial north) were selected. Children from randomly selected grade 4 classrooms were invited to participate. Standardised interviews, spirometry, methacholine challenge testing and skin-prick testing were conducted. Particulate matter (PM), sulphur dioxide (SO2) and carbon monoxide were monitored at each school, while nitrogen oxides (NOx) and other pollutants were monitored at other sites. RESULTS: SO2 was significantly higher in the south than in the north, while PM concentrations were similar across the city. The prevalence of symptoms consistent with asthma of any severity was 32.1%. Covariate-adjusted prevalences were higher among children from schools in the south than among those from the north for persistent asthma (12.2% v. 9.6 %) and for marked airway hyperreactivity (AHR) (8.1% v. 2.8%), while SO2 resulted in a twofold increased risk of marked AHR (95% confidence interval 0.98 - 4.66; p=0.056). CONCLUSIONS: Schoolchildren from industrially exposed communities experienced higher covariate-adjusted prevalences of persistent asthma and marked AHR than children from communities distant from industrial sources. Our findings are strongly suggestive of industrial pollution-related adverse respiratory health effects among these children.

Pesticide safety training and practices in women working in small-scale agriculture in South Africa.

OBJECTIVES: Unregulated use of pesticides continues in developing countries in the presence of illiteracy and limited safety training and practices. This paper describes training and safety practices when mixing and spraying pesticides, and acetylcholinesterase levels among women farmers in KwaZulu-Natal, South Africa. METHODS: A cross-sectional study conducted in women working in small-scale agriculture in rural KwaZulu-Natal, South Africa in 2006 assessed pesticide training and safety practices using a questionnaire survey and measured acetylcholinesterase levels in 803 women. Three components of safety behaviour were identified through principle component analysis and described. RESULTS: The mean age of participants was 41.8 years (range 18-82 years) with a mean of 6.9 years (range 1-12 years) of education among school attendees. Among the 803 women included, 366 (45.6%) were the primary sprayers on their farm. Only 16.4% of the sprayers had ever attended a pesticide training course and only 18.0% reported ever reading pesticide labels. Of the women using some form of protective equipment, 56.7% and 54.9% reported doing so when mixing and spraying pesticides, respectively. The mean acetylcholinesterase level corrected for haemoglobin among study participants was 28.9 U/g Hb (95% CI 28.4 to 29.4). CONCLUSION: Women working in small-scale agriculture in rural KwaZulu-Natal with limited access to pesticide training observe few safety practices when mixing and spraying pesticides.

Musculoskeletal pain in women working in small-scale agriculture in South Africa.

BACKGROUND: Musculoskeletal pain is associated with demographic, occupational and physical factors. METHODS: Our study investigated the prevalence and factors associated with musculoskeletal pain in 911 women working in small-scale agriculture in rural northern KwaZulu-Natal, South Africa in 2006 using a questionnaire survey. RESULTS: In total, 67% (n = 574) of women reported any chronic musculoskeletal pain. The 12-month prevalence of pain ranged from 63.9% to 73.3% and the prevalence of specific chronic pain lasting more than 3 months ranged from 42.8% to 48.3%. Older age, carrying heavy loads, working with hands above shoulder height, and frequently squatting and kneeling were associated with chronic musculoskeletal pain. CONCLUSION: The prevalence of pain reported in our study, was similar to other developing countries, but considerably higher than in developed countries. Ergonomic interventions including improved and adapted work techniques and tools should be considered to reduce the prevalence of pain in our study population.

Organochlorine pesticides in ambient air in Durban, South Africa.

Despite the existence of numerous sources and continuing use, information regarding emissions and airborne concentrations of organochlorine pesticides in Africa is extremely limited. This paper presents results of a monitoring program conducted in Durban, South Africa that was designed to characterize levels, trends and possible sources of pesticides in both industrial and residential areas. Three monitoring sites were established, two in an industrialized area in the southern part of the city, and the third in a northern residential area. Particulate and vapor samples were sampled over the 2004-5 period and analyzed by GC/MS to estimate long-term levels of a wide range of pesticides. Based on a year of sampling, the sites had comparable levels of many pesticides with exceptions of alpha-chlordane and lindane. Levels of p,p'-DDT (42+/-27 pg m(-3)) and its derivatives were relatively high and showed an unusual mixture with high levels of p,p'-DDD (12+/-11 pg m(-3)). Other pesticides detected and quantified included aldrin, chlordanes, hexachlorobenzene and dieldrin. Potential source areas, identified using concentration patterns, local and regional gradients, compositional information and trajectory analyses, suggest that chlordane and lindane arise from both local sources as well as regional/global sources; DDT from regional sources elsewhere in South Africa, Africa and India; and most of the other long-lived pesticides detected, including gamma-nonachlor, hexachlorobenzene and toxaphene, from global sources. This monitoring results, which represent the most detailed study to date of pesticides in air in Africa, serve several purposes, including documenting the presence and use of long-banned pesticides like aldrin, aiding the understanding of the fate of persistent compounds, identifying pollutants that may contribute to health problems, and informing decision-making aimed at reducing exposures and risks.