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Male sex, early life chemical exposure and the brain aromatase enzyme have been implicated in autism spectrum disorder (ASD). In the Barwon Infant Study birth cohort (n = 1074), higher prenatal maternal bisphenol A (BPA) levels are associated with higher ASD symptoms at age 2 and diagnosis at age 9 only in males with low aromatase genetic pathway activity scores. Higher prenatal BPA levels are predictive of higher cord blood methylation across the CYP19A1 brain promoter I.f region (P = 0.009) and aromatase gene methylation mediates (P = 0.01) the link between higher prenatal BPA and brain-derived neurotrophic factor methylation, with independent cohort replication. BPA suppressed aromatase expression in vitro and in vivo. Male mice exposed to mid-gestation BPA or with aromatase knockout have ASD-like behaviors with structural and functional brain changes. 10-hydroxy-2-decenoic acid (10HDA), an estrogenic fatty acid alleviated these features and reversed detrimental neurodevelopmental gene expression. Here we demonstrate that prenatal BPA exposure is associated with impaired brain aromatase function and ASD-related behaviors and brain abnormalities in males that may be reversible through postnatal 10HDA intervention.
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Aromatasa , Trastorno del Espectro Autista , Compuestos de Bencidrilo , Encéfalo , Metilación de ADN , Ratones Noqueados , Fenoles , Efectos Tardíos de la Exposición Prenatal , Animales , Aromatasa/metabolismo , Aromatasa/genética , Masculino , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/inducido químicamente , Compuestos de Bencidrilo/toxicidad , Femenino , Fenoles/toxicidad , Embarazo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Ratones , Humanos , Metilación de ADN/efectos de los fármacos , Fenotipo , Modelos Animales de Enfermedad , Regiones Promotoras Genéticas , PreescolarRESUMEN
BACKGROUND: Several techniques can be used to assess bronchodilator response (BDR) in preschool-aged children, including spirometry, respiratory oscillometry, the interrupter technique, and specific airway resistance. However, there has not been a systematic comparison of BDR thresholds across studies yet. METHODS: A systematic review was performed on all studies up to May 2023 measuring a bronchodilator effect in children 2-6 years old using one of these techniques (PROSPERO CRD42021264659). Studies were identified using MEDLINE, Cochrane, EMBASE, CINAHL via EBSCO, Web of Science databases, and reference lists of relevant manuscripts. RESULTS: Of 1224 screened studies, 43 were included. Over 85% were from predominantly European ancestry populations, and only 22 studies (51.2%) calculated a BDR cutoff based on a healthy control group. Five studies included triplicate testing with a placebo to account for the within-subject intrasession repeatability. A relative BDR was most consistently reported by the included studies (95%) but varied widely across all techniques. Various statistical methods were used to define a BDR, with six studies using receiver operating characteristic analyses to measure the discriminative power to distinguish healthy from wheezy and asthmatic children. CONCLUSION: A BDR in 2- to 6-year-olds cannot be universally defined based on the reviewed literature due to inconsistent methodology and cutoff calculations. Further studies incorporating robust methods using either distribution-based or clinical anchor-based approaches to define BDR are required.
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Electronic waste (e-waste) contains numerous metals and organic pollutants that have detrimental impacts on human health. We studied 199 e-waste recycling workers and 104 non-exposed workers; analyzed blood, urine, and hair samples to measure heavy metals, hormonal, liver, and renal function. We used quantile regression models to evaluate the impact of Pb, Cd, and Hg on hormonal, liver and renal function, and the role of DNA oxidative damage in mediating the relationship between exposures and outcomes. Exposed workers had higher blood lead (Pb) (median 11.89 vs 3.63⯵g/dL), similar blood cadmium (Cd) (1.04 vs 0.99⯵g/L) and lower total mercury (Hg) in hair (0.38 vs 0.57â¯ppm) than non-exposed group. Exposed workers also had elevated median concentrations of total triiodothyronine (TT3), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urinary albumin, albumin creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were significantly higher than non-exposed group (p≤0.05). Sex hormones including luteinizing hormone, follicle stimulating hormone, estrogen, progesterone and testosterone concentrations were not significantly different between exposed and non-exposed (all p≥0.05). The median concentration of ALT was 4.00 (95% CI: 0.23, 7.77), urinary albumin was 0.09 (95% CI: 0.06, 0.12) and ACR was 1.31 (95% CI: 0.57, 2.05) units higher in the exposed group compared to non-exposed group. Pb was associated with a 3.67 unit increase in the ALP (95% CI: 1.53, 5.80), 0.01 unit increase in urinary albumin (95% CI: 0.002, 0.01), and 0.07 unit increase in ACR (95% CI: 0.01, 0.13). However, no hormonal, renal, and hepatic parameters were associated with Cd or Hg. Oxidative DNA damage did not mediate exposure-outcome relationships (p≥0.05). Our data indicate e-waste exposure impairs liver and renal functions secondary to elevated Pb levels. Continuous monitoring, longitudinal studies to evaluate the dose-response relationship and effective control measure are required to protect workers from e-waste exposure.
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Residuos Electrónicos , Riñón , Exposición Profesional , Humanos , Residuos Electrónicos/efectos adversos , Adulto , Masculino , Exposición Profesional/efectos adversos , Exposición Profesional/análisis , Femenino , Bangladesh/epidemiología , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/fisiopatología , Hígado/efectos de los fármacos , Hígado/metabolismo , Persona de Mediana Edad , Metales Pesados/orina , Metales Pesados/sangre , Metales Pesados/toxicidad , Reciclaje , Adulto Joven , Cadmio/sangre , Cadmio/orina , Cadmio/toxicidad , Cabello/química , Plomo/sangre , Plomo/toxicidad , Hormonas/sangre , Daño del ADNRESUMEN
There is an urgent need to develop sensitive, non-invasive biomarkers that can track airway inflammatory activity for patients with cystic fibrosis (CF). Urinary glutathione sulfonamide (GSA) levels correlate well with GSA levels in BAL samples and other markers of neutrophilic inflammation, suggesting that this biomarker may be suitable for tracking disease activity in this population. We recruited 102 children (median 11.5 years-old) and 64 adults (median 32.5 years-old) who were admitted to hospital for management of an acute pulmonary exacerbation and/or eradication of infectious agents such as Pseudomonas aeruginosa or Staphylococcus aureus. Our aim was to explore how urinary GSA levels changed across admission timepoints. Urine samples were collected at admission and discharge, and GSA measured by liquid chromatography with mass spectrometry. Paired admission-discharge results were compared using Wilcoxon signed-rank test. Paired admission-discharge samples were available for 53 children and 60 adults. A statistically significant difference was observed between admission-discharge for children and adults. Spearman's correlation analysis identified a correlation between urinary GSA levels and sex and S. aureus infection for children only. Our preliminary findings suggest that urinary GSA is responsive to the resolution of an acute pulmonary exacerbation and therefore warrants further studies in this population.
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BACKGROUND: COMBAT-CF showed that children aged 0-3 years treated with azithromycin did clinically better than placebo but there was no effect on CT-scores. We reanalysed CTs using an automatic bronchus-artery (BA) analysis. METHOD: Inspiratory and expiratory CTs at 12 and 36 months were analysed. BA-analysis measures BA-diameters: bronchial outer wall (Bout), bronchial inner wall (Bin), artery (A), and bronchial wall thickness (Bwt) and computes BA-ratios: Bout/A and Bin/A for bronchial widening, Bwt/A and Bwa/Boa (bronchial wall area/bronchial outer area) for bronchial wall thickening. Low attenuation regions (LAR) were analysed using an automatic method. Mixed-effect model was used to compare BA-outcomes at 36 months between treatment groups. RESULTS: 228 CTs (59 placebo; 66 azithromycin) were analysed. The azithromycin group had lower Bwa/Boa (p = 0.0034) and higher Bin/A (p = 0.001) relative to placebo. Bout/A (p = 0.0088) was higher because of a reduction in artery diameters which correlated to a reduction in LAR. CONCLUSION: Azithromycin-treated infants with CF show a reduction in bronchial wall thickness and possibly a positive effect on lung perfusion.
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BACKGROUND: Longitudinal measurements of intrabreath respiratory impedance (Zrs) in preschool-aged children may be able to distinguish abnormal lung function trajectories in children with a history of wheezing compared to healthy ones. METHODS: Children from a prospective, longitudinal community-based cohort performed annual intrabreath oscillometry (IB-OSC) measurements from age 3- to 7-years. IB-OSC was performed using a single 10 Hz sinusoid while clinically asymptomatic. Linear mixed-effects models were developed to explore the effects of wheezing phenotypes, growth, and sex on seven IB-OSC outcome variables over time: resistance at end-expiration (ReE), resistance at end-inspiration (ReI), the tidal change in resistance (∆R=ReE-ReI), reactance at end-expiration (XeE), reactance at end-inspiration (XeI), the tidal change in reactance (∆X=XeE-XeI), and ∆X normalized by tidal volume (∆X/VT). RESULTS: Eighty-five children produced 374 acceptable IB-OSC measurements. Subjects were classified into one of three wheeze groups: never (n = 36), transient (n = 34), or persistent (n = 15). After adjusting for height, children with persistent wheezing, compared to those who never wheezed, had +0.814 hPa s L-1 ReE (95% confidence interval [CI] +0.178 to +1.451, p = 0.015), -0.792 hPa s L-1 XeE (95% CI -1.203 to -0.381, p = 0.003), -0.538 hPa s L-1 ∆X (95% CI -0.834 to -0.242, p = 0.007) and -1.672 hPa s L-2 ∆X/VT (95% CI -2.567 to -0.777, p < 0.001). Increasing height had a significant effect on all IB-OSC resistance and reactance variables when adjusted for the effect of preschool wheezing. CONCLUSIONS: IB-OSC is feasible for tracking lung function growth in preschool-aged children and may allow abnormal lung function to be identified early in asymptomatic preschoolers with a history of persistent wheezing.
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Ruidos Respiratorios , Humanos , Masculino , Preescolar , Femenino , Estudios Prospectivos , Ruidos Respiratorios/fisiopatología , Estudios Longitudinales , Niño , Oscilometría/métodos , Resistencia de las Vías Respiratorias/fisiología , Pruebas de Función Respiratoria/métodos , Volumen de Ventilación Pulmonar/fisiologíaRESUMEN
BACKGROUND: Early life is a key period that determines long-term health. Lung development in childhood predicts lung function attained in adulthood and morbidity and mortality across the life course. We aimed to assess the effect of early-life lower respiratory tract infection (LRTI) and associated risk factors on lung development from birth to school age in a South African birth cohort. METHODS: We prospectively followed children enrolled in a population-based cohort from birth (between March 5, 2012 and March 31, 2015) to age 5 years with annual lung function assessment. Data on multiple early-life exposures, including LRTI, were collected. The effect of early-life risk factors on lung function development from birth to age 5 years was assessed using the Generalised Additive Models for Location, Scale and Shape and Interrupted Time Series approach. FINDINGS: 966 children (475 [49·2%] female, 491 [50·8%] male) had lung function measured with oscillometry, tidal flow volume loops, and multiple breath washout. LRTI occurred in 484 (50·1%) children, with a median of 2·0 LRTI episodes (IQR 1·0-3·0) per child. LRTI was independently associated with altered lung function, as evidenced by lower compliance (0·959 [95% CI 0·941-0·978]), higher resistance (1·028 [1·016-1·041]), and higher respiratory rate (1·018 [1·063-1·029]) over 5 years. Additional impact on lung function parameters occurred with each subsequent LRTI. Respiratory syncytial virus (RSV) LRTI was associated with lower expiratory flow ratio (0·97 [0·95-0·99]) compared with non-RSV LRTI. Maternal factors including allergy, smoking, and HIV infection were also associated with altered lung development, as was preterm birth, low birthweight, female sex, and coming from a less wealthy household. INTERPRETATION: Public health interventions targeting LRTI prevention, with RSV a priority, are vital, particularly in low-income and middle-income settings. FUNDING: UK Medical Research Council Grant, The Wellcome Trust, The Bill & Melinda Gates Foundation, US National Institutes of Health Human Heredity and Health in Africa, South African Medical Research Council, Hungarian Scientific Research Fund, and European Respiratory Society.
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Pulmón , Pruebas de Función Respiratoria , Humanos , Femenino , Sudáfrica/epidemiología , Masculino , Preescolar , Pulmón/fisiopatología , Lactante , Recién Nacido , Factores de Riesgo , Infecciones del Sistema Respiratorio/epidemiología , Estudios Prospectivos , Análisis de Series de Tiempo Interrumpido , Cohorte de NacimientoRESUMEN
BACKGROUND: Fetal exposure to tobacco smoking throughout pregnancy is associated with wheezing in infancy. We investigated the influence of in utero smoking exposure on lung ventilation homogeneity and the relationship between lung ventilation inhomogeneity at 7 weeks of age and wheezing in the first year of life. METHODS: Maternal smoking was defined as self-reported smoking of tobacco or validated by exhaled (e)CO > 6 ppm. Lung function data from healthy infants (age 5-9 weeks) born to asthmatic mothers and parent-reported respiratory questionnaire data aged 12 months were collected in the Breathing for Life Trial (BLT) birth cohort. Tidal breathing analysis and SF6-based Multiple Breath Washout testing were performed in quiet sleep. Descriptive statistics and regression analysis were used to assess associations. RESULTS: Data were collected on 423 participants. Infants born to women who self-reported smoking during pregnancy (n = 42) had higher lung clearance index (LCI) than those born to nonsmoking mothers (7.90 vs. 7.64; p = .030). Adjusted regression analyzes revealed interactions between self-reported smoking and LCI (RR: 1.98, 95% CI: 1.07-3.63, 0.028, for each unit increase in LCI) and between eCO > 6 ppm and LCI (RR: 2.25, 95% CI: 1.13-4.50, 0.022) for the risk of wheeze in the first year of life. CONCLUSION: In utero tobacco smoke exposure induces lung ventilation inhomogeneities. Furthermore, an interaction between smoke exposure and lung ventilation inhomogeneities increases the risk of having a wheeze in the first year of life.
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Efectos Tardíos de la Exposición Prenatal , Ruidos Respiratorios , Humanos , Ruidos Respiratorios/etiología , Femenino , Embarazo , Lactante , Masculino , Fumar/efectos adversos , Pulmón/fisiopatología , Asma/etiología , Asma/epidemiología , Adulto , Factores de Riesgo , Pruebas de Función Respiratoria , Contaminación por Humo de Tabaco/efectos adversosRESUMEN
Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion transporter required for epithelial homeostasis in the lung and other organs, with CFTR mutations leading to the autosomal recessive genetic disease CF. Apart from excessive mucus accumulation and dysregulated inflammation in the airways, people with CF (pwCF) exhibit defective innate immune responses and are susceptible to bacterial respiratory pathogens such as Pseudomonas aeruginosa. Here, we investigated the role of CFTR in macrophage antimicrobial responses, including the zinc toxicity response that is used by these innate immune cells against intracellular bacteria. Using both pharmacological approaches, as well as cells derived from pwCF, we show that CFTR is required for uptake and clearance of pathogenic Escherichia coli by CSF-1-derived primary human macrophages. CFTR was also required for E. coli-induced zinc accumulation and zinc vesicle formation in these cells, and E. coli residing in macrophages exhibited reduced zinc stress in the absence of CFTR function. Accordingly, CFTR was essential for reducing the intramacrophage survival of a zinc-sensitive E. coli mutant compared to wild-type E. coli. Ectopic expression of the zinc transporter SLC30A1 or treatment with exogenous zinc was sufficient to restore antimicrobial responses against E. coli in human macrophages. Zinc supplementation also restored bacterial killing in GM-CSF-derived primary human macrophages responding to P. aeruginosa, used as an in vitro macrophage model relevant to CF. Thus, restoration of the zinc toxicity response could be pursued as a therapeutic strategy to restore innate immune function and effective host defense in pwCF.
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Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Macrófagos , Humanos , Antibacterianos/uso terapéutico , Fibrosis Quística/microbiología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Macrófagos/metabolismo , Macrófagos/microbiología , Zinc/metabolismoRESUMEN
BACKGROUND: Electronic waste (e-waste) recycling activities release toxic metals, which pose substantial hazard to the environment and human health. We evaluated metal concentrations in biological and environmental samples, and examined the associations between biological lead (Pb), cadmium (Cd), and mercury (Hg) with soil and dust metals, and other possible determinants, among populations exposed and non-exposed to e-waste in Bangladesh. METHODS: A total of 199 e-waste workers and 104 non-exposed individuals were recruited. We measured blood Pb (BPb) and Cd (BCd) concentrations and total Hg (THg) from hair samples. Data were collected on occupational, and behavioral factors. We fitted an elastic net regression (ENET) to model the relationship between a set of influencing factors and metals as outcome variables while controlling for potential covariates. RESULTS: The median concentrations of BPb (11.89 µg/dL) and BCd (1.04 µg/L) among exposed workers were higher than those of non-exposed workers (BPb: 3.63 µg/dL and BCd: 0.83 µg/L respectively). A 100 ppm increment in soil Pb level was associated with an increase in ln-Pb (transformed) in blood (ß = 0.002; 95% CI = 0.00, 0.02). Similarly, ln-BCd level increased (ß = 0.02; 95% CI = 0.001, 0.07) with every ppm increase in dust Cd level. The number of years worked in e-waste activities was associated with elevated ln-BPb (ß = 0.01; 95% CI = 0.01, 0.02) and ln-BCd levels (ß = 0.003; 95% CI = 0.00, 0.05). Smoking significantly contributed to elevated levels of ln-BCd (ß = 0.46; 95% CI = 0.43, 0.73). An increment of 100 kg of e-waste handling per week led to an increase in ln-BPb levels (ß = 0.002; 95% CI = 0.00, 0.01), while respondents knowledge about adverse impact on e-waste reduced the ln-BPb level (ß = -0.14; 95% CI = -0.31, -0.03). Fish consumption frequency had a positive association with THg in hair. CONCLUSIONS: Our data show the need for workplace controls to reduce exposure to Pb and Cd with a broader view of exposure source taken.
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Residuos Electrónicos , Mercurio , Humanos , Cadmio , Plomo , Polvo/análisis , Bangladesh , Reciclaje , Cabello/químicaRESUMEN
Background: The United Nations has declared that humans have a right to clean air. Despite this, many deaths and disability-adjusted life years are attributed to air pollution exposure each year. We face both challenges to air quality and opportunities to improve, but several areas need to be addressed with urgency. Objective: This paper summarises the recent research presented at the Pacific Basin Consortium for Environment and Health Symposium and focuses on three key areas of air pollution that are important to human health and require more research. Findings and conclusion: Indoor spaces are commonly places of exposure to poor air quality and are difficult to monitor and regulate. Global climate change risks worsening air quality in a bi-directional fashion. The rising use of electric vehicles may offer opportunities to improve air quality, but it also presents new challenges. Government policies and initiatives could lead to improved air and environmental justice. Several populations, such as older people and children, face increased harm from air pollution and should become priority groups for action.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , Contaminación del Aire , Niño , Humanos , Anciano , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Cambio Climático , Contaminantes Atmosféricos/análisisRESUMEN
Exposure to indoor air pollution (IAP) is a leading environmental risk for respiratory diseases. We investigated the relationship between respiratory symptoms and polluting indoor activities such as smoking, cooking and contact with pets among children in Ho Chi Minh City (HCMC), Vietnam. A cross-sectional survey applied a multistage sampling method in 24 randomly selected secondary schools across the city. Approximately 15,000 students completed self-administrated questionnaires on risk factors and respiratory health outcomes within the preceding 12 months. Data were analyzed using a multivariable logistic regression model with robust standard errors. Wheeze was the most common respiratory symptom (39.5 %) reported, followed by sneezing and runny nose (28.3 %). A small percentage of students self-reported asthma (8.6 %). Approximately 56 % of participants lived with family members who smoked. A positive association between exposure to indoor secondhand smoke and respiratory symptoms was observed, with adjusted odds ratios (aOR) of 1.41 (95 % CI: 1.25-1.60, p < 0.001) for wheezing and 1.64 (95 % CI: 1.43-1.87, p < 0.001) for sneezing and runny nose, respectively. Using an open stove fuelled by coal, wood, or kerosene for cooking was associated with wheeze (aOR: 1.36, CI 95 %: 1.10-1.68, p = 0.01) and sneezing and runny nose (aOR: 1.36, CI 95 %: 1.09-1.69, p = 0.01). In the present study, IAP was associated with adverse health outcomes, as evidenced by an increase in respiratory symptoms reported within the previous 12 months.
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Contaminación del Aire Interior , Contaminación del Aire , Contaminación por Humo de Tabaco , Niño , Humanos , Contaminación del Aire Interior/efectos adversos , Estudios Transversales , Estornudo , Vietnam/epidemiología , Rinorrea , Culinaria , Factores de RiesgoRESUMEN
The association of air pollution and greenspace with respiratory pathogen acquisition and respiratory health was investigated in a community-based birth-cohort of 158 Australian children. Weekly nasal swabs and daily symptom-diaries were collected for 2-years, with annual reviews from ages 3-7-years. Annual exposure to fine-particulate-matter (PM2.5), nitrogen-dioxide (NO2), and normalised-difference-vegetation-index (NDVI) was estimated for pregnancy and the first 2-years-of-life. We examined rhinovirus, any respiratory virus, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae detections in the first 3-months-of-life, age at initial pathogen detection, wheezing in the first 2-years, and asthma at ages 5-7-years. Our findings suggest that higher NDVI was associated with fewer viral and M. catarrhalis detections in the first 3-months, while increased PM2.5 and NO2 were linked to earlier symptomatic rhinovirus and H. influenzae detections, respectively. However, no associations were observed with wheezing or asthma. Early-life exposure to air pollution and greenspace may influence early-life respiratory pathogen acquisition and illness. .
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BACKGROUND: Azithromycin (AZM) is widely being used for treating patients with cystic fibrosis (pwCF) following clinical trials demonstrating improved lung function and fewer incidents of pulmonary exacerba-tions. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammatory M2 macrophage polarization in CF. This study systematically analyzed the effect of AZM on the functions of unpolarized and M1/M2 polarized macrophages in CF. METHODS: Monocytes, isolated from the venous blood of patients with CF (pwCF) and healthy controls (HCs), were differentiated into monocyte-derived macrophages (MDMs) and subsequently infected with P. aeruginosa. P. aeruginosa uptake and killing by MDMs in the presence or absence of AZM was studied. M1 and M2 macrophage polarizations were induced and their functions and cytokine release were analyzed. RESULTS: Following AZM treatment, both HC and CF MDMs exhibited a significant increase in P. aeruginosa uptake and killing, however, lysosomal acidification remained unchanged. AZM treatment led to higher activation of ERK1/2 in both HC and CF MDMs. Pharmacological inhibition of ERK1/2 using U0126 significantly reduced P. aeruginosa uptake in HC MDMs. M1 macrophage polarization remained unaffected; however, AZM treatment led to increased IL-6 and IL-10 release in both HC and CF M1 macrophages. AZM also significantly increased the phagocytic index for both pHrodo E. coli and S. aureus in CF M1 macrophages. In CF, AZM treatment promoted anti-inflammatory M2 macrophage polarization, with an increased percentage of CD209+ M2 macrophages, induction of the M2 gene CCL18, along with its secretion in the culture supernatant. However, AZM d'd not restore endocytosis in CF, another essential feature of M2 macrophages. CONCLUSIONS: This study highlights the cellular functions and molecular targets of AZM which may involve an improved uptake of both Gram-positive and Gram-negative bacteria, restored anti-inflammatory macrophage polarization in CF. This may in turn shape the reduced lung inflammation observed in clinical trials. In addition, we confirmed the role of ERK1/2 activation for bacterial uptake.
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Azitromicina , Fibrosis Quística , Humanos , Azitromicina/farmacología , Bacterias Gramnegativas , Antibacterianos/farmacología , Fibrosis Quística/tratamiento farmacológico , Escherichia coli , Staphylococcus aureus , Bacterias Grampositivas , Macrófagos , Antiinflamatorios/farmacologíaRESUMEN
Exposure to endocrine-disrupting plasticisers (EDPs), such as phthalates and bisphenols, has been associated with reduced lung function in children and adolescents. However, the existing literature yields conflicting results. This systematic review and meta-analysis aimed to assess the epidemiologic evidence investigating the association between EDP exposure and lung function in children and adolescents. A comprehensive search of five databases identified 25 relevant studies. We employed a random-effects meta-analysis on spirometry measures. The effect size of interest was the change in lung function in standard deviation (SD) units resulting from a two-fold increase in exposure levels. We found that certain phthalates marginally reduced lung function in children. Forced expiratory volume in 1 s (FEV1) was reduced by a two-fold increase in mono-benzyl phthalate (MBzP) (ß = -0.025 SD, 95%CI: 0.042, -0.008), mono-ethyl-oxo-hexyl phthalate (MEOHP) (ß = -0.035 SD, 95%CI: 0.057, -0.014) and mono-carboxy-nonyl phthalate (MCNP) (ß = -0.024 SD, 95%CI: 0.05, -0.003). Forced vital capacity (FVC) was decreased by a two-fold increase in MBzP (ß = -0.022 SD, 95%CI: 0.036, -0.008) and MEOHP (ß = -0.035 SD, 95%CI: 0.057, -0.014) levels. A two-fold increase in MCNP levels was associated with lower FEV1/FVC (ß = -0.023 SD, 95%CI: 0.045, -0.001). Furthermore, a two-fold increase in MEOHP levels reduced forced mid-expiratory flow (FEF25-75) (ß = -0.030 SD, 95%CI: 0.055, -0.005) and peak expiratory flow (PEF) (ß = -0.056 SD, 95%CI: 0.098, -0.014). Notably, associations were more pronounced in males. Given the potential for reverse causation bias, the association between childhood exposure to EDPs and lung function remains uncertain. Overall, our meta-analysis showed small reductions in lung function with higher phthalate exposure. However, future studies are warranted in younger age groups.
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Contaminantes Ambientales , Ácidos Ftálicos , Masculino , Niño , Humanos , Adolescente , Exposición a Riesgos Ambientales/análisis , Ácidos Ftálicos/toxicidad , Capacidad Vital , Pulmón/química , Contaminantes Ambientales/toxicidad , Contaminantes Ambientales/análisisRESUMEN
BACKGROUND: Rhinovirus (RV) positive bronchiolitis episodes in infancy confer a higher risk to develop asthma in later childhood with associated lung function impairments. We aimed to investigate the association between the type of virus causing a bronchiolitis hospitalization episode and lung ventilation inhomogeneities at preschool age. METHODS: Infants hospitalized with a clinical diagnosis of moderate (ward admission) or severe (pediatric intensive care ward admission) bronchiolitis were prospectively followed-up at preschool age to assess nitrogen (N2 ) multiple breath washout (MBW). Lung clearance index (LCI), functional residual capacity (FRC), and concentration normalized phase III slope analysis (SnIII ) indices were reported from ≥2 technically acceptable trials. Differences between groups were calculated using logistic and linear regression and adjusted for confounders (sex, age at bronchiolitis admission, height at visit, maternal asthma, and doctor-diagnosed asthma, including interaction terms between the latter three). An interaction term was included in a regression model to test for an interaction between RV bronchiolitis severity and MBW parameters at preschool age. RESULTS: One hundred and thirty-nine subjects attended preschool follow-up, of which 84 out of 103 (82%) performing MBW had technically acceptable data. Children with a history of RV positive bronchiolitis (n = 39) had increased LCI (adjusted ß-coefficient [aß] = 0.33, 95% confidence interval [CI] 0.02-0.65, p = 0.040) and conductive airways ventilation inhomogeneity [Scond ] (aß = 0.016, CI 0.004-0.028, p = 0.011) when compared with those with a RV negative bronchiolitis history (n = 45). In addition, we found a statistical interaction between RV bronchiolitis and bronchiolitis severity strengthening the association with LCI (aß = 0.93, CI 0.20-1.58, p = 0.006). CONCLUSION: Children with a history of hospital admission for RV positive bronchiolitis in infancy might be at a higher risk of lung ventilation inhomogeneities at preschool age, arising from the peripheral conducting airways.
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Asma , Bronquiolitis , Niño , Lactante , Humanos , Preescolar , Pulmón , Bronquiolitis/complicaciones , Asma/epidemiología , Hospitalización , HospitalesRESUMEN
INTRODUCTION: Several psychosocial factors, such as maternal mental health and parents' financial hardship, are associated with asthma symptoms among children. So, we aim to investigate the changing patterns of important psychosocial environmental factors and their associations with asthma symptom trajectories among children in Australia. METHODS: We considered asthma symptoms as wheezing (outcome) and psychosocial environmental factors (exposures) from 0/1 year to 14/15 years of the participants from the "Longitudinal Study of Australian Children (LSAC)" for this study. We used group-based trajectory modeling to identify the trajectory groups for both exposure and outcome variables. Associations between psychosocial factors and three distinct asthma symptom trajectories were assessed by multivariable logistic regression. RESULTS: We included 3917 children from the LSAC birth cohort in our study. We identified distinct trajectories for maternal depression, parents' financial hardship, parents' stressful life events and parents' availability to their children from birth to 14/15 years of age. Compared to the "low/no" asthma symptom trajectory group, children exposed to a "moderate & increasing" maternal depression, "moderate & declining" parents' financial hardship, and "moderate & increasing" parents' stressful life events were significantly associated (relative risk ratio [RRR]: 1.55, 95% confidence interval [CI]: 1.27, 1.91; RRR: 1.40, 95%; CI: 1.15, 1.70; RRR: 1.77, 95%; CI: 1.45, 2.16) with "persistent high" asthma symptom trajectory. CONCLUSION: Several psychosocial factors that are potential stressors for mental health increase the risk of having an adverse asthma symptom trajectory during childhood. Further attention should be given to reducing exposure to maternal depression, parents' financial hardship, and parents' stressful live events for long-term asthma control in children.
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Asma , Niño , Humanos , Estudios Longitudinales , Australia/epidemiología , Asma/epidemiología , Asma/etiología , Padres/psicología , Modelos LogísticosRESUMEN
BACKGROUND: Prenatal alcohol exposure (PAE) is a known risk factor for a range of adverse outcomes, such as facial dysmorphism, adverse birth outcomes, and neurodevelopmental changes. Preclinical research shows that PAE also inhibits lung development, lowers surfactant protein expression, has detrimental effects on alveolar macrophages, and decreases both T and B cell numbers. However, clinical evidence of respiratory impacts from PAE is limited. This study explored whether lung function, wheeze, and incidence of respiratory infections differ in children with PAE compared with unexposed children. METHODS: Data from the Barwon Infant Study (n = 1074) were examined. PAE data were extracted from maternal questionnaires at trimesters 1 and 2 (combined), and trimester 3, and included as "total standard drinks" during each trimester and total pregnancy intake, a binary yes/no for PAE, and binge drinking (>5 standard drinks in one session). Respiratory outcomes were parent-reported wheeze, lung function (measured by multiple breath washout), and parent report and medical record indicators of health service attendances for respiratory conditions. Linear and logistic regressions were performed to quantify relationships between PAE and respiratory outcomes, controlling for socioeconomic status, birthweight, sex, gestational age, and maternal smoking. RESULTS: Binge drinking was associated with increased health service attendance for respiratory condition(s) in the first 12 months of life (OR = 5.0, 95% CI (1.7, 20.7), p = 0.008). We did not find a relationship between binary PAE and binge drinking with lung function at 4 weeks of age or wheeze at 12 months. The number of standard drinks consumed in trimester two was associated with a lower lung clearance index (ß = -0.011 turnovers, 95% CI (-0.0200, -0.0013), p = 0.03), and a small increase in functional residual capacity (ß = 0.34 mL, 95% CI (0.02, 0.66), p = 0.04). CONCLUSIONS: We found an association between binge drinking and health service utilization for respiratory conditions in infancy, but no evidence that low-level PAE was associated with adverse respiratory outcomes.
RESUMEN
The association between air pollution and adverse health outcomes has been extensively studied, and while oxidative stress in likely to be involved, the underlying mechanism(s) remain unclear. Recent studies propose environmentally persistent free radicals (EPFRs) as the missing connection between air pollution and detrimental health impacts. However, the indoor environment is rarely considered in EPFR research. We measured EPFRs in household dust from two locations in Australia and investigated household characteristics associated with EPFRs. Random forest models were built to identify important household characteristics through variable importance plots and the associations were analysed using Spearman's rho test. We found that age of house, type of garage, house outer wall material, heating method used in home, frequency of extractor fan use when cooking, traffic related air pollution, frequency of cleaning and major house renovation were important household characteristics associated with EPFRs in Australian homes. The direction of association between household characteristics and EPFRs differ between the locations. Hence, further research is warranted to determine the generalisability of our results.