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1.
Environ Int ; 146: 106248, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33212358

RESUMO

Air pollution has been associated with adverse health effects across the life-course. Although underlying mechanisms are unclear, several studies suggested pollutant-induced changes in transcriptomic profiles. In this meta-analysis of transcriptome-wide association studies of 656 children and adolescents from three European cohorts participating in the MeDALL Consortium, we found two differentially expressed transcript clusters (FDR p < 0.05) associated with exposure to particulate matter < 2.5 µm in diameter (PM2.5) at birth, one of them mapping to the MIR1296 gene. Further, by integrating gene expression with DNA methylation using Functional Epigenetic Modules algorithms, we identified 9 and 6 modules in relation to PM2.5 exposure at birth and at current address, respectively (including NR1I2, MAPK6, TAF8 and SCARA3). In conclusion, PM2.5 exposure at birth was linked to differential gene expression in children and adolescents. Importantly, we identified several significant interactome hotspots of gene modules of relevance for complex diseases in relation to PM2.5 exposure.

2.
Thorax ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184098

RESUMO

We aimed to determine prevalence and early-life risk factors for reversible and irreversible airflow limitation in young adults from the general population. Among young adults in their 20s, the prevalence was 5.3% for reversible airflow limitation and 2.0% for irreversible airflow limitation. While parental asthma was the only risk factor for development of reversible airflow limitation, the risk factors for development of irreversible airflow limitation were current asthma, childhood respiratory tract infections and asthma, and exposure to air pollution.

3.
Eur Respir J ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184115

RESUMO

BACKGROUND: Chronic bronchitis is associated with substantial morbidity among elderly adults, but little is known about its prevalence and risk factors in young adults. Our aim was to assess the prevalence and early life risk factors for chronic bronchitis in young adults. METHODS: Questionnaire data and clinical measures from the 24-year follow-up of the Swedish BAMSE cohort were used. We assessed chronic bronchitis (CB) as the combination of cough and mucus production in the morning during winter. Environmental and clinical data from birth and onwards were used for analyses of risk factors. RESULTS: At the 24-year follow-up, 75% (n=3064) participants completed the questionnaire and 2030 performed spirometry. The overall prevalence of CB was 5.5% (n=158) with similar estimates in males and females. Forty-nine percent of CB cases experienced more than 3 self-reported respiratory infections in the last year compared to 18% in non-CB subjects (p<0.001), and 37% of cases were current smokers (versus 19%). Statistically significant lower post-FEV1/FVC were observed in CB compared to non-CB subjects (mean z-score -0.06 versus 0.13, p=0.027). Daily smoking (adjusted Odds Ratio, aOR=3.85, p<0.001), air pollution exposure (black carbon during ages 1-4 years old, aOR=1.71 per 1 µg·m3 increase, p=0.009) and exclusive breast-feeding during four months or more (aOR=0.66, p=0.044) were associated with CB. CONCLUSION: Chronic bronchitis in young adults is associated with recurrent respiratory infections. Besides smoking, our results support role of early life exposures, such as air pollution and exclusive breast-feeding, for respiratory health later in life.

5.
Environ Res ; 192: 110249, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32980305

RESUMO

Obesity rates are increasing globally, and recent theories suggest that phthalates may contribute to obesity development. This longitudinal study aimed to investigate associations between environmental phthalate exposure during childhood and obesity, utilizing data from 100 participants from a Swedish birth cohort. The participants were followed repeatedly from birth and provided spot urine samples at 4 years. Weight and height were measured at ages 4, 8, 16 and 24 years, as well as additional anthropometric indices at 24 years. Urine samples were analysed for 10 phthalate metabolites using liquid chromatography tandem mass spectrometry. Generalized estimating equation models were performed to assess overall and age-specific associations between urinary phthalate concentrations and BMI groups; thin/normal weight vs overweight/obese. After adjustment for potential confounders, overall associations were observed for diisononyl phthalate (DiNP) metabolites mono(oxo-isononyl) phthalate (MOiNP) (OR per increase ng/ml: 1.18; 95% CI: 1.05, 1.33), mono(carboxy-isooctyl) phthalate (MCiOP) (OR: 1.06; 95% CI: 1.01, 1.11) and ∑DiNP (OR: 1.02; 95% CI:1.00, 1.04) and development of overweight/obesity up to age 24 years. Age-specific associations were observed for the same metabolites at 8, 16 and 24 years. Furthermore, linear regression analysis revealed associations between increased body fat % at age 24 years and MHiNP (ß: 2.42; 95% CI: 0.44, 4.39), MOiNP (ß: 2.32; 95% CI: 0.46, 4.18), MCiOP (ß: 2.65; 95% CI: 0.41, 4.89) and ∑DiNP (ß: 2.65; 95% CI: 0.52, 4.77). These findings suggest that DiNP exposure during preschool age may be associated with subsequent obesity, however these findings need to be corroborated by further research.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32926877

RESUMO

BACKGROUND: Whether long-term exposure air to pollution has effects on allergic sensitization is controversial. OBJECTIVE: Our aim was to investigate associations of air pollution exposure at birth and at the time of later biosampling with IgE sensitization against common food and inhalant allergens, or specific allergen molecules, in children aged up to 16 years. METHODS: A total of 6163 children from 4 European birth cohorts participating in the Mechanisms of the Development of ALLergy [MeDALL] consortium were included in this meta-analysis of the following studies: Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) (Sweden), Influences of Lifestyle-Related Factors on the Human Immune System and Development of Allergies in Childhood (LISA)/German Infant Study on the Influence of Nutrition Intervention PLUS Environmental and Genetic Influences on Allergy Development (GINIplus) (Germany), and Prevention and Incidence of Asthma and Mite Allergy (PIAMA) (The Netherlands). The following indicators were modeled by land use regression: individual residential outdoor levels of particulate matter with aerodynamic diameters less than 2.5 µm, less than 10 µm, and between 2.5 and 10 µm; PM2.5 absorbance (a measurement of the blackness of PM2.5 filters); and nitrogen oxides levels. Blood samples drawn at ages 4 to 6 (n = 5989), 8 to 10 (n = 6603), and 15 to 16 (n = 5825) years were analyzed for IgE sensitization to allergen extracts by ImmunoCAP. Additionally, IgE against 132 allergen molecules was measured by using the MedALL microarray chip (n = 1021). RESULTS: Air pollution was not consistently associated with IgE sensitization to any common allergen extract up to age 16 years. However, allergen-specific analyses suggested increased risks of sensitization to birch (odds ratio [OR] = 1.12 [95% CI = 1.01-1.25] per 10-µg/m3 increase in NO2 exposure). In a subpopulation with microarray data, IgE to the major timothy grass allergen Phleum pratense 1 (Phl p 1) and the cat allergen Felis domesticus 1 (Fel d 1) greater than 3.5 Immuno Solid-phase Allergen Chip standardized units for detection of IgE antibodies were related to PM2.5 exposure at birth (OR = 3.33 [95% CI = 1.40-7.94] and OR = 4.98 [95% CI = 1.59-15.60], respectively, per 5-µg/m3 increase in exposure). CONCLUSION: Air pollution exposure does not seem to increase the overall risk of allergic sensitization; however, sensitization to birch as well as grass pollen Phl p 1 and cat Fel d 1 allergen molecules may be related to specific pollutants.

7.
Pediatr Pulmonol ; 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32755073

RESUMO

BACKGROUND: Extremely preterm birth is a risk factor for reduced lung function later in life, and clinical follow-up from early childhood is recommended. Dynamic spirometry is the most widely used method to assess airway obstruction, but impulse oscillometry (IOS) may be an alternative method that is easier to perform in young children. The feasibility and agreement between spirometry and IOS outcome variables has not been investigated in children born extremely preterm. AIM: To determine the feasibility of and correlation between spirometry and IOS in pre-school children born extremely preterm. METHODS: Spirometry and IOS were performed in 6-year-old children born extremely preterm (n = 88) and age-matched term controls (n = 84) in Stockholm, Sweden. Correlations between spirometry and IOS outcome variables were analyzed using Pearson's partial correlation, adjusting for height. RESULTS: Success rate for spirometry (60%) was lower than for IOS (93%) but did not differ significantly between the preterm and term groups (56% and 64% for spirometry, P = .25; and 92% and 94% for IOS, P = .61). Correlations between spirometry and IOS outcomes were at best moderate (Spearman's r = -0.31 to -0.56). Normal IOS identified 69% to 90% of those with normal spirometry. A negative predictive value of 90% was found for R5-R20 versus FEV0.75 /FVC, suggesting that IOS may be used to exclude obstructive airway disease as measured by spirometry. CONCLUSION: IOS is a more feasible method than spirometry to assess lung function in young children irrespective of gestational age at birth and could be considered an alternative in children who cannot perform spirometry.

8.
PLoS Med ; 17(8): e1003182, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32810184

RESUMO

BACKGROUND: Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. METHODS AND FINDINGS: We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39-3.25] and OR 1.93 [95% CI 1.46-2.57] instead of OR 2.95 [95% CI 2.75-3.15] when reducing from ≥10 to 5-9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16-1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations. CONCLUSIONS: We observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy.


Assuntos
Pais , Obesidade Pediátrica/epidemiologia , Nascimento Prematuro/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Fumar/epidemiologia , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , América do Norte/epidemiologia , Obesidade Pediátrica/diagnóstico , Gravidez , Nascimento Prematuro/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Fatores de Risco , Fumar/tendências
10.
Acta Paediatr ; 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: covidwho-612337

RESUMO

According to the United Nations Educational, Science and Cultural Organization, 194 countries had implemented country-wide school closures by April 1st 2020 in an effort to combat the COVID-19 pandemic. It's estimated that those closures affected 91.3% of students across the globe. However, Sweden adopted a different approach to the strict lockdowns imposed elsewhere and day care centres and schools for children up to 15 years of age remained open. The strategy decision to shift schools to distance learning only for children aged 16 years and older was influenced by multiple factors, including the potential impact on school closures on the availability of the healthcare work force, the increasing evidence of mainly mild infections among children and the potential negative consequences of school closures for younger children.

11.
Allergy ; 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32512619

RESUMO

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.

13.
J Allergy Clin Immunol Pract ; 8(9): 3056-3065.e2, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32522564

RESUMO

BACKGROUND: For adolescents, asthma management can be challenging during the transition to adulthood, and changes in health care and pharmacological treatment may occur. OBJECTIVE: To investigate asthma-related health care consumption and pharmacological dispensation during the transition process. METHODS: In a Swedish birth cohort study, questionnaire and clinical data from the 16- and 24-year follow-ups were linked to national and regional registries for asthma-related health care consumption and dispensed medications during an 8-year period: 4 years before and after age 18 y, respectively. RESULTS: In the study population (n = 1808), 14% fulfilled the study definition of current asthma at the 16- and 24-year follow-up and 8% (n = 147) had persistent asthma. Among them, register data showed that in the 4-year period before their 18th birthday, 39% (58 of 147) had at least 1 consultation, similar to 37% (55 of 147) in the following 4-year period. The mean number of consultations before age 18 years was 1.6, compared with 1.0 after age 18 years (P = .02). At least 1 dispensation of any inhaled corticosteroid before age 18 years was found for 73% (107 of 147), compared with 50% (74 of 147) after age 18 years. The mean number of dispensed any inhaled corticosteroid was 3.1 before 18 years and 2.1 after 18 years (P < .01). Only 3% (5 of 147) had a regular dispensation of any inhaled corticosteroid once a year during the 8-year period. CONCLUSIONS: Health care consultations were fewer than recommended in guidelines and decreased after the transition to adult health care. Almost no one had dispensed regular asthma medications during the 8-year period.

16.
Environ Res ; 185: 109404, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32247905

RESUMO

OBJECTIVE: Increasing evidence indicates aggravation of immune-mediated diseases due to physiological and psychological stress. Noise is a stressor, however, little is known about its effects on children's respiratory health. This study investigates the association between pre- or postnatal road traffic or occupational noise exposure and asthma as well as related symptoms from infancy to adolescence. METHODS: The study was conducted in the Swedish birth cohort BAMSE, including over 4000 participants followed with repeated questionnaires and clinical tests until 16 years of age. Pre- and postnatal residential road traffic noise was assessed by estimating time-weighted average noise levels at the most exposed façade. Maternal occupational noise exposure during pregnancy was evaluated using a job-exposure-matrix. The associations between noise exposure and asthma-related outcomes were explored using logistic regression and generalised estimating equations. RESULTS: We observed non-significant associations for asthma ever up to 16 years with residential road traffic noise exposure in infancy ≥55 dBLden (adjusted OR = 1.22; 95% CI 0.90-1.65), as well as prenatal occupational noise exposure ≥80 dBLAeq,8h (1.18, 0.85-1.62). In longitudinal analyses, however, no clear associations between pre- or postnatal exposure to residential road traffic noise, or average exposure to noise since birth, were detected in relation to asthma or wheeze until 16 years. CONCLUSION: We did not find a clear overall association between exposure to noise during different time periods and asthma or wheeze up to adolescence.


Assuntos
Asma , Ruído dos Transportes , Adolescente , Asma/epidemiologia , Asma/etiologia , Criança , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Gravidez , Suécia/epidemiologia
17.
Respir Res ; 21(1): 80, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32264874

RESUMO

BACKGROUND: Adolescence is a significant period for the gender-dependent development of lung function. Prior studies have shown that DNA methylation (DNA-M) is associated with lung function and DNA-M at some cytosine-phosphate-guanine dinucleotide sites (CpGs) changes over time. This study examined whether changes of DNA-M at lung-function-related CpGs are associated with changes in lung function during adolescence for each gender, and if so, the biological significance of the detected CpGs. METHODS: Genome-scale DNA-M was measured in peripheral blood samples at ages 10 (n = 330) and 18 years (n = 476) from the Isle of Wight (IOW) birth cohort in United Kingdom, using Illumina Infinium arrays (450 K and EPIC). Spirometry was conducted at both ages. A training and testing method was used to screen 402,714 CpGs for their potential associations with lung function. Linear regressions were applied to assess the association of changes in lung function with changes of DNA-M at those CpGs potentially related to lung function. Adolescence-related and personal and family-related confounders were included in the model. The analyses were stratified by gender. Multiple testing was adjusted by controlling false discovery rate of 0.05. Findings were further examined in two independent birth cohorts, the Avon Longitudinal Study of Children and Parents (ALSPAC) and the Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) cohort. Pathway analyses were performed on genes to which the identified CpGs were mapped. RESULTS: For females, 42 CpGs showed statistically significant associations with change in FEV1/FVC, but none for change in FEV1 or FVC. No CpGs were identified for males. In replication analyses, 16 and 21 of the 42 CpGs showed the same direction of associations among the females in the ALSPAC and BAMSE cohorts, respectively, with 11 CpGs overlapping across all the three cohorts. Through pathway analyses, significant biological processes were identified that have previously been related to lung function development. CONCLUSIONS: The detected 11 CpGs in all three cohorts have the potential to serve as the candidate epigenetic markers for changes in lung function during adolescence in females.

18.
Allergy ; 75(7): 1546-1554, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32329930
19.
Allergy ; 2020 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-32277847

RESUMO

BACKGROUND: Allergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large-scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes. METHODS: Integrated transcriptomic analysis was conducted in 1233 participants with a discovery phase using gene expression data (Human Transcriptome Array 2.0) from whole blood of 786 children from three European birth cohorts (MeDALL), and a replication phase using RNA Sequencing data from an independent cohort (EVA-PR, n = 447). Allergic diseases (asthma, atopic dermatitis, rhinitis) were considered as single disease or multimorbidity (at least two diseases), and compared with no disease. RESULTS: Fifty genes were differentially expressed in allergic diseases. Thirty-two were not previously described in allergy. Eight genes were consistently overexpressed in all types of multimorbidity for asthma, dermatitis, and rhinitis (CLC, EMR4P, IL5RA, FRRS1, HRH4, SLC29A1, SIGLEC8, IL1RL1). All genes were replicated the in EVA-PR cohort. RT-qPCR validated the overexpression of selected genes. In MeDALL, 27 genes were differentially expressed in rhinitis alone, but none was significant for asthma or dermatitis alone. The multimorbidity signature was enriched in eosinophil-associated immune response and signal transduction. Protein-protein interaction network analysis identified IL5/JAK/STAT and IL33/ST2/IRAK/TRAF as key signaling pathways in multimorbid diseases. Synergistic effect of multimorbidity on gene expression levels was found. CONCLUSION: A signature of eight genes identifies multimorbidity for asthma, rhinitis, and dermatitis. Our results have clinical and mechanistic implications, and suggest that multimorbidity should be considered differently than allergic diseases occurring alone.

20.
Pediatr Allergy Immunol ; 31(5): 471-479, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32060962

RESUMO

BACKGROUND: Perinatal conditions may be associated with future allergic disease; however, data are conflicting and incomplete for childhood allergic rhinitis (AR). The aim of this study was to examine pregnancy outcome (cesarean delivery, preterm birth, low birthweight) and offspring AR as defined by national registers. METHODS: Nationwide longitudinal cohort study using prospectively recorded register data from 1 059 600 singleton livebirths born in Sweden in 2001-2012. Cox regression adjusted for infant sex and maternal factors (age at delivery, country of birth, parity, smoking, body mass index, and asthma/pulmonary disease) estimated hazard ratios (HRs) for AR during childhood. RESULTS: During the study period 2001-2013, 22 386 (2.11%) children were diagnosed with AR. AR was more common in infants born through cesarean delivery (2.34%) than in those born vaginally (2.10%) (HR = 1.12; 95% confidence interval [95% CI] = 1.08-1.16). This was equivalent to one extra case of AR in 383 children followed up in our study. AR was also associated with moderately preterm birth (≥32-36 weeks of gestation: HR = 1.12, 95% CI = 1.04-1.20), large for gestational age (HR = 1.05, 95% CI = 1.01-1.10), and low (<7) 5-minute Apgar score (HR = 1.15, 95% CI = 1.02-1.30). Similar risk estimates were obtained when we restricted the outcome to ≥2 hospital-based records of AR. No association was observed between very preterm birth, post-term birth, low birthweight, or small for gestational age and AR. CONCLUSION: Our study indicates an association between pregnancy outcomes and childhood AR, although observed effect sizes were generally modest.

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