Paracetamol and antibiotics in childhood and subsequent development of wheezing/asthma: association or causation?
Background Several studies found an association between early administration of paracetamol and antibiotics and development of wheezing. This could be due to confounding: wheeze and asthmatic symptoms in early childhood are difficult to distinguish from respiratory tract infections that are widely treated with these drugs; in case of persistence of symptoms up to school age, this could explain the observed relationship. Methods We investigated the association between paracetamol and antibiotics use in the first year of life and wheezing phenotypes, i.e. wheezing starting in different time periods (early, persistent and late-onset) in the SIDRIA-2 study, a cross-sectional survey of 16,933 ch…
Mould/dampness exposure at home is associated with respiratory disorders in Italian children and adolescents: the SIDRIA-2 Study
Aims: To report on the relation between home mould and/or dampness exposure and respiratory disorders in a large sample of children and adolescents in Italy, accounting for age at time of exposure. Methods: 20 016 children (mean age 7 years) and 13 266 adolescents (mean age 13 years) completed questionnaires on indoor exposures and respiratory symptoms/diseases. Statistical analyses were adjusted for sex, age, questionnaire's compiler, area of residence, season of interview, parental educational status, family history of asthma, rhinitis, eczema, chronic obstructive pulmonary disease, presence of gas water heaters, passive smoking, pets, and active smoking (only for adolescents). Population…
Chronic burden of near-roadway traffic pollution in 10 European cities (APHEKOM network).
AD; International audience; Recent epidemiological research suggests that near road traffic-related pollution may cause chronic disease, as well as exacerbate related pathologies, implying that the entire “chronic disease progression” should be attributed to air pollution, no matter what the proximate cause was. We estimated the burden of childhood asthma attributable to air pollution in 10 European cities by calculating the number of cases of 1) asthma caused by near road traffic-related pollution, and 2) acute asthma events related to urban air pollution levels. We then expanded our approach to include coronary heart diseases in adults.Derivation of attributable cases required combining c…
Difference in Mortality Risk in Elderly People with Bronchial Obstruction Diagnosed Using a Fixed Cutoff or the Lower Limit of Normal of the FEV1/FVC Ratio
Background: Whether a fixed cutoff or the lower limit of normal of the FEV1/FVC ratio should be used to diagnose bronchial obstruction is still a matter of debate. This issue is particularly important for elderly people. Objectives: We used equations applicable up to 90 years of age to evaluate the mortality of elderly people diagnosed with bronchial obstruction using either a fixed cutoff of 0.7 or the lower limit of normal (LLN). Methods: Participants in the SaRA (Salute Respiratoria nell'Anziano, Italian for "Respiratory Health in the Elderly") study were grouped as follows: FEV1/FVC ≥0.7 and ≥ LLN (n = 535: F-/L-), FEV1/FVC <0.7 but ≥ LLN (n = 118: F+/L-), and FEV1/FVC <0.7 and < LLN (n…
Asthma in the Elderly
Background There is a distinct lack of information on the prognosis of asthma in the elderly. Methods In order to compare mortality rates of elderly people with and without asthma and to identify mortality risk factors in those with asthma, 1,233 ambulatory patients aged ≥ 65 years with a diagnosis of asthma (n = 210) or chronic nonrespiratory conditions (n = 1,023) were enrolled in a multicentric study. Patients underwent baseline spirometry and multidimensional assessment and were then followed up for a mean of 57.9 months (SD 16.9). We compared mortality rates in the two groups and identified predictors of death using multivariable survival analysis. Results The 5-year mortality rate in …
Mechanisms of the Development of Allergy (MeDALL) : Introducing novel concepts in allergy phenotypes
Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non–IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Q…
Air Pollution Exposure During Pregnancy and Symptoms of Attention Deficit and Hyperactivity Disorder in Children in Europe
Background: Exposure to air pollution during pregnancy may increase attention-deficit/hyperactivity disorder (ADHD) symptoms in children, but findings have been inconsistent. We aimed to study this association in a collaborative study of eight European population-based birth/child cohorts, including 29,127 mother-child pairs. Methods: Air pollution concentrations (nitrogen dioxide [NO2] and particulate matter [PM]) were estimated at the birth address by land-use regression models based on monitoring campaigns performed between 2008 and 2011. We extrapolated concentrations back in time to exact pregnancy periods. Teachers or parents assessed ADHD symptoms at 3-10 years of age. We classified …
On-line Italian register for severe/non-controlled asthma
Background Severe/Non-controlled asthma (SNCA) is a crucial challenge for physicians and a socio-economic burden for National Health Services (NHS). In Italy more than 50% of costs for asthma (1-2% of total NHS expenditure) are due to SNCA and moreover, within the European Community Respiratory Health Survey, Italy was the country with the lowest % of ICS daily use (29%) and with the highest % of subjects with uncontrolled asthma despite treatment (67% vs an overall European mean of 47%). Despite few data from very selected centers, in our country a precise estimate of the epidemiological figures and the disease related costs for SNCA is not available. Thus, we aimed at instituting of an on…
SETIL: Italian multicentric epidemiological case–control study on risk factors for childhood leukaemia, non hodgkin lymphoma and neuroblastoma: study population and prevalence of risk factors in Italy
Background Aetiology of childhood leukaemia and childhood neoplasm is poorly understood. Information on the prevalence of risk factors in the childhood population is limited. SETIL is a population based case–control study on childhood leukaemia, conducted with two companion studies on non-Hodgkin Lymphoma (NHL) and neuroblastoma. The study relies on questionnaire interviews and 50 Hz magnetic field (ELF-MF) indoor measurements. This paper discusses the SETIL study design and includes descriptive information. Methods The study was carried out in 14 Italian regions (78.3% of Italian population aged 0–10). It included leukaemia, NHL and neuroblastoma cases incident in 0–10 year olds in 1998–20…
Does early onset asthma increase childhood obesity risk? A pooled analysis of 16 European cohorts
The parallel epidemics of childhood asthma and obesity over the past few decades have spurred research into obesity as a risk factor for asthma. However, little is known regarding the role of asthma in obesity incidence. We examined whether early-onset asthma and related phenotypes are associated with the risk of developing obesity in childhood.This study includes 21 130 children born from 1990 to 2008 in Denmark, France, Germany, Greece, Italy, The Netherlands, Spain, Sweden and the UK. We followed non-obese children at 3-4 years of age for incident obesity up to 8 years of age. Physician-diagnosed asthma, wheezing and allergic rhinitis were assessed up to 3-4 years of age.Children with ph…
Alternative ways of expressing forced expiratory volume in the first second and long-term mortality in elderly patients with asthma
Abstract Background Clinical and epidemiologic evidence on asthma in the elderly is scant. There is evidence that forced expiratory volume in the first second (FEV 1 ), a commonly used indicator of overall pulmonary function, might not be an independent predictor of 5-year mortality in elderly patients with asthma. Objective To investigate the association between FEV 1 expressed using 3 alternative methods and 5-, 10-, and 15-year mortality in a population of elderly patients with asthma. Methods Participants in the Salute Respiratoria nell' Anziano study were included. Asthma was diagnosed at baseline according to spirometric and clinical data. Vital status at 15 years was assessed using d…
Childhood intermittent and persistent rhinitis prevalence and climate and vegetation: a global ecologic analysis
Abstract Background The effect of climate change and its effects on vegetation growth, and consequently on rhinitis, are uncertain. Objective To examine between- and within-country associations of climate measures and the normalized difference vegetation index with intermittent and persistent rhinitis symptoms in a global context. Methods Questionnaire data from 6- to 7-year-olds and 13- to 14-year-olds were collected in phase 3 of the International Study of Asthma and Allergies in Childhood. Associations of intermittent (>1 symptom report but not for 2 consecutive months) and persistent (symptoms for ≥2 consecutive months) rhinitis symptom prevalences with temperature, precipitation, vapor…
Impact of Low Maternal Education on Early Childhood Overweight and Obesity in Europe
BackgroundComparable evidence on adiposity inequalities in early life is lacking across a range of European countries. This study investigates whether low maternal education is associated with overweight and obesity risk in children from distinct European settings during early childhood. MethodsProspective data of 45 413 children from 11 European cohorts were used. Children's height and weight obtained at ages 4-7 years were used to assess prevalent overweight and obesity according to the International Obesity Task Force definition. The Relative/Slope Indices of Inequality (RII/SII) were estimated within each cohort and by gender to investigate adiposity risk among children born to mothers …
Alternative ways of expressing FEV1 and mortality in elderly people with and without COPD
Expressing forced expiratory volume in 1 s (FEV1) as % predicted relies on the assumption of proportional variability and generalisability of prediction equations that may be unrealistic, especially for elderly people. We evaluated the prognostic implications of alternative ways of expressing FEV1. We enrolled 318 patients with chronic obstructive pulmonary disease (COPD) and 475 controls in the Salute Respiratoria nell'Anziano (SARA) study. The risk for 5-, 10- and 15-year mortality associated with FEV1 was studied by expressing FEV1 % pred, standardised by height cubed (FEV1 · Ht(-3)) and as a multiple of the sex-specific first percentile (FEV1 quotient (FEV1Q)). In the group with COPD, t…
Road Traffic Pollution and Childhood Leukemia: A Nationwide Case-control Study in Italy
Background The association of childhood leukemia with traffic pollution was considered in a number of studies from 1989 onwards, with results not entirely consistent and little information regarding subtypes. Aim of the study We used the data of the Italian SETIL case-control on childhood leukemia to explore the risk by leukemia subtypes associated to exposure to vehicular traffic. Methods We included in the analyses 648 cases of childhood leukemia (565 Acute lymphoblastic–ALL and 80 Acute non lymphoblastic-AnLL) and 980 controls. Information on traffic exposure was collected from questionnaire interviews and from the geocoding of house addresses, for all periods of life of the children. Re…
Overweight/obesity and respiratory and allergic disease in children : international study of asthma and allergies in childhood (ISAAC) phase two
Background: Childhood obesity and asthma are increasing worldwide. A possible link between the two conditions has been postulated. Methods: Cross-sectional studies of stratified random samples of 8-12-year-old children (n=10 652) (16 centres in affluent and 8 centres in non-affluent countries) used the standardized methodology of ISAAC Phase Two. Respiratory and allergic symptoms were ascertained by parental questionnaires. Tests for allergic disease were performed. Height and weight were measured, and overweight and obesity were defined according to international definitions. Prevalence rates and prevalence odds ratios were calculated. Results: Overweight (odds ratio=1.14, 95%-confidence i…
DNA methylation in childhood asthma
Background: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. Methods: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4–5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially m…
Air Pollution During Pregnancy and Childhood Cognitive and Psychomotor Development: Six European Birth Cohorts
Background: Accumulating evidence from laboratory animal and human studies suggests that air pollution exposure during pregnancy affects cognitive and psychomotor development in childhood. Methods: We analyzed data from 6 European population-based birth cohorts-GENERATI ON R (The Netherlands), DUISBURG (Germany), EDEN (France), GASPII (Italy), RHEA (Greece), and INMA (Spain)-that recruited mother-infant pairs from 1997 to 2008. Air pollution levels-nitrogen oxides (NO2, NOx) in all regions and particulate matter (PM) with diameters of <2.5, <10, and 2.5-10 mu m (PM2.5, PM10, and PMcoarse, respectively) and PM2.5 absorbance in a subgroup-at birth addresses were estimated by land-use regressi…
Restrictive pulmonary dysfunction at spirometry and mortality in the elderly
SummaryObjectivesTo evaluate the association between pulmonary restriction and mortality in the elderly, taking into account potential confounders not considered in the past (disability, cognitive dysfunction, diabetes, and visceral obesity).DesignLongitudinal study.SettingCommunity-based.ParticipantsTwelve hundred sixty-five patients (51.9% men) aged 65–97 years old from the Salute Respiratoria nell'Anziano (SaRA) Italian multicentric study.MeasurementsParticipants were divided in 4 groups: normal spirometry (NS): FEV1/FVC≥70%, FVC≥80% of predicted; restrictive ventilatory pattern (RVP): FEV1/FVC≥70%, FVC<80%; obstructive ventilatory pattern (OVP): FEV1/FVC<70%, FVC≥80%, and mixed ventilat…
Fish and seafood consumption during pregnancy and the risk of asthma and allergic rhinitis in childhood
Background: It has been suggested that prenatal exposure to n-3 long-chain fatty acids protects against asthma and other allergy-related diseases later in childhood. The extent to which fish intake in pregnancy protects against child asthma and rhinitis symptoms remains unclear. We aimed to assess whether fish and seafood consumption in pregnancy is associated with childhood wheeze, asthma and allergic rhinitis. Methods: We pooled individual data from 60 774 mother-child pairs participating in 18 European and US birth cohort studies. Information on wheeze, asthma and allergic rhinitis prevalence was collected using validated questionnaires. The time periods of interest were: infancy (0-2 ye…
Wheeze and asthma in children: associations with body mass index, sports, television viewing, and diet.
Obesity, physical activity, and dietary habits are distinct but strongly interrelated lifestyle factors that may be relevant to the prevalence of wheeze and asthma in children. Our goal was to analyze the relationship of body mass index (BMI), regular sports participation, TV viewing, and diet with current wheezing and asthma.We investigated 20,016 children, aged 6-7 years, who were enrolled in a population-based study. Parents completed standardized questionnaires. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), while adjusting for several confounders and simultaneously considering BMI, regular sports activity, TV viewing and selected dietary …
Maternal complications and procedures in pregnancy and at birth and wheezing phenotypes in children
There is increasing interest in the potential influence of fetal and early life conditions on childhood wheezing.To investigate the associations between maternal complications and procedures in pregnancy and at birth and the risk of various wheezing phenotypes in young children.We studied 15,609 children, aged 6-7 yr, enrolled in a population-based study. Standardized questionnaires were completed by the children's mothers.Of the children, 9.5% (1,478) had transient early wheezing, 5.4% (884) had persistent wheezing, and 6.1% (948) had late-onset wheezing. Maternal hypertension or preeclampsia was associated with an increased risk of all three wheezing phenotypes (for transient early wheezi…
BODE index or geriatric multidimensional assessment for the prediction of very-long-term mortality in elderly patients with chronic obstructive pulmonary disease? A prospective cohort study
BACKGROUND a multidimensional approach-the BODE index-has been proposed for prognostic purposes in chronic obstructive pulmonary disease (COPD) and theoretically seems to be well suited for elderly people, but there is a lack of data in this population, especially with respect to long-term survival. The objective of this study is to evaluate whether the BODE index can predict both long (5 years) and very-long (10 and 15 years)-term mortality in an unselected population of elderly people with COPD better than a set of variables commonly taken into account in a geriatric multidimensional assessment (MDA). METHODS : this was a multicentre, prospective, population study. We used data from the S…
International variations in associations of allergic markers and diseases in children: ISAAC Phase Two
To cite this article: Weinmayr G, Genuneit J, Nagel G, Bjorksten B, van Hage M, Priftanji A, Cooper P, Rijkjarv M-A, von Mutius E, Tsanakas J, Forastiere F, Doekes G, Garrido JB, Suarez-Varela MM, Braback L, Strachan DP, the ISAAC Phase Two Study Group. International variations in associations of allergic markers and diseases in children: ISAAC Phase Two. Allergy 2010; 65: 766–775. Abstract Background: Circulating allergen-specific IgE (sIgE) and skin prick tests (SPT) are used to define atopy. Downregulation of local inflammatory responsiveness has been proposed to explain a low prevalence of positive SPTs in less affluent countries. We analysed the association between SPTs, total and all…
Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
AbstractThere are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of …
Discriminative and predictive properties of disease-specific and generic health status indexes in elderly COPD patients
Abstract Background The association between bronchial obstruction severity and mortality in Chronic Obstructive Pulmonary Disease (COPD) is well established, but it is unknown whether disease-specific health status measures and multidimensional assessment (MDA) have comparable prognostic value. Methods We analyzed data coming from the Salute Respiratoria nell'Anziano (Respiratory Health in the Elderly – SaRA) study, enrolling elderly people attending outpatient clinics for respiratory and non-respiratory problems. From this population we selected 449 patients with bronchial obstruction (77.3% men, mean age 73.1). We classified patients' health status using tertiles of the Saint George Respi…
Air pollution exposure during pregnancy and childhood autistic traits in four European population-based cohort studies: The ESCAPE Project
Background: Prenatal exposure to air pollutants has been suggested as a possible etiologic factor for the occurrence of autism spectrum disorder. Objectives: We aimed to assess whether prenatal air pollution exposure is associated with childhood autistic traits in the general population. Methods: Ours was a collaborative study of four European population-based birth/child cohorts—CATSS (Sweden), Generation R (the Netherlands), GASPII (Italy), and INMA (Spain). Nitrogen oxides (NO2, NOx) and particulate matter (PM) with diameters of ≤ 2.5 μm (PM2.5), ≤ 10 μm (PM10), and between 2.5 and 10 μm (PMcoarse), and PM2.5 absorbance were estimated for birth addresses by land-use regression models bas…
Fish Intake in Pregnancy and Child Growth: A Pooled Analysis of 15 European and US Birth Cohorts
Importance Maternal fish intake in pregnancy has been shown to influence fetal growth. The extent to which fish intake affects childhood growth and obesity remains unclear. Objective To examine whether fish intake in pregnancy is associated with offspring growth and the risk of childhood overweight and obesity. Design, Setting, and Participants Multicenter, population-based birth cohort study of singleton deliveries from 1996 to 2011 in Belgium, France, Greece, Ireland, Italy, the Netherlands, Norway, Poland, Portugal, Spain, and Massachusetts. A total of 26 184 pregnant women and their children were followed up at 2-year intervals until the age of 6 years. Exposures Consumption of fish dur…
Exposure to benzene and childhood leukaemia: a pilot case-control study
Objectives Main purpose To evaluate the feasibility of a measurement-based assessment of benzene exposure in case-control studies of paediatric cancer; Additional aims To identify the sources of exposure variability; to assess the performance of two benzene biomarkers; to verify the occurrence of participation bias; to check whether exposures to benzene and to 50 Hz magnetic fields were correlated, and might exert reciprocal confounding effects. Design Pilot case-control study of childhood leukaemia and exposure to benzene assessed by repeated seasonal weekly measurements in breathing zone air samples and outside the children9s dwellings, with concurrent determinations of cotinine, t-t-muco…
Prognostic significance of surrogate measures for forced vital capacity in an elderly population.
Objectives To evaluate whether measures easier to obtain than the FVC can substitute it as a prognostic marker in elderly people. Design Prospective, observational study. Setting Community. Participants Outpatients (n = 1485) aged 73.4 years (SD: 6.2 range 65–98) enrolled in the Salute Respiratoria nell'Anziano (SaRA) study. Measurements We calculated the risk for mortality associated with a reduction below 80% of the predicted FVC, of the forced expiratory volume at 6 seconds (FEV6), and of a surrogate measure for forced vital capacity (SFVC), defined as the largest volume exhaled in 2 forced maneuvers regardless of its duration and of the presence of plateau. Results Among the 907 partici…
The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three: A global synthesis
This ISAAC Phase Three synthesis provides summarised information on the main findings of the study, regional tables and figures related to the prevalence and severity of current symptoms of asthma, rhinoconjunctivitis and eczema in the main regions of the world. The large number of surveyed children (≈1,200,000), the large number of centres (233) and countries (98) that participated in ISAAC Phase Three makes this study the most comprehensive survey of these diseases ever undertaken. Globally, the prevalence for current asthma, rhinoconjunctivitis and eczema in the 13-14-year age group was 14.1%, 14.6% and 7.3%, respectively. In the 6-7-year age group the prevalence for current asthma, rhin…
A multi-centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 2
BACKGROUND: Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case-control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood. METHODS: We compared 1105 wheezing and 3137 non-wheezing children aged 8-12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-ana…