To examine associations between occupation and respiratory health in a large, population-based cohort of adults in the United States.
Data from 15,273 participants, aged 45-64 years, in the Atherosclerosis Risk in Communities (ARIC) study were used to examine associations of current or most recent job held with the prevalence of self-reported chronic cough, chronic bronchitis, wheeze, asthma, and measures of lung function collected by spirometry.
Eleven percent of participants reported wheeze and 9% were classified as having airway obstruction. Compared to individuals in managerial and administrative jobs, increased prevalences of respiratory outcomes were observed among participants in selected occupations, including construction and extractive trades (wheeze: prevalence ratio [PR]: 1.92, 95% confidence interval [CI]: 1.35, 2.73; airway obstruction: PR: 1.31, 95% CI: 1.05, 1.65).
Specific occupations are associated with adverse respiratory health.
ARIC study; epidemiology; occupation; respiratory tract disease
Studies have indicated that children delivered by cesarean section are at an increased risk of developing wheezing and asthma. This could be the result of an altered immune system development due to delayed gut colonization or of increased neonatal respiratory morbidity. The authors examined the associations between delivery by cesarean section and the development of wheezing, asthma, and recurrent lower respiratory tract infections in children up to 36 months of age among 37,171 children in the Norwegian Mother and Child Cohort Study. Generalized linear models were used in the multivariable analysis. Children delivered by cesarean section had an increased likelihood of current asthma at 36 months of age (relative risk = 1.17, 95% confidence interval: 1.03, 1.32), and the association was stronger among children of nonatopic mothers (relative risk = 1.33, 95% confidence interval: 1.12, 1.58). No increased risk of wheezing or recurrent lower respiratory tract infections was seen among children delivered by cesarean section. Findings were similar among children delivered by acute and elective cesarean section. In conclusion, children delivered by cesarean section may have an increased risk of current asthma at 36 months, but residual confounding cannot be excluded. In future prospective studies, investigators should reexamine this association in different age groups.
asthma; cesarean section; respiratory sounds; respiratory tract infections
Traffic exposure is a major contributor to ambient air pollution for people living close to busy roads. The relationship between traffic exposure and lung function remains inconclusive in adults.
A cross‐sectional study was conducted to investigate the association between traffic exposure and lung function in the Atherosclerosis Risk in Communities (ARIC) study, a community based cohort of 15 792 middle aged men and women. Traffic density and distance to major roads were used as measures of traffic exposure.
After controlling for potential confounders including demographic factors, personal and neighbourhood level socioeconomic characteristics, cigarette smoking and background air pollution, higher traffic density was significantly associated with lower forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in women. Relative to the lowest quartile of traffic density, the adjusted differences across increasing quartiles were 5.1, −15.4 and −21.5 ml for FEV1 (p value of linear trend across the quartiles = 0.041) and 1.2, −23.4 and −34.8 ml for FVC (p trend = 0.010). Using distance from major roads as a simpler index of traffic related air pollution exposure, the FEV1 was −15.7 ml (95% CI −34.4 to 2.9) lower and the FVC was −24.2 ml (95% CI −46.2 to −2.3) lower for women living within 150 m compared with subjects living further away. There was no significant effect of traffic density or distance to major roads on lung function in men. The FEV1/FVC ratio was not significantly associated with traffic exposure in either men or women.
This is the largest published study of traffic exposure and pulmonary function in adults to date. These results add to growing evidence that chronic exposure to traffic related air pollution may adversely affect respiratory health.
To examine the validity of: 1) maternal questionnaire report of children's use of anti-asthmatics using a prescription database as the reference standard, 2) dispensed anti-asthmatics as a measure of asthma using maternal report of children's asthma as the reference standard.
Study Design and Setting
3394 children in the Norwegian Mother and Child Cohort Study (MoBa) aged seven were linked to the Norwegian Prescription Database (NorPD). Maternal report of both children's use of anti-asthmatics during the preceding year and of the presence of asthma was compared with data on dispensed anti-asthmatics.
2056 mothers responded and reported use of anti-asthmatics the previous year in 125 of 147 children who had been dispensed anti-asthmatics (sensitivity 85.0%). Of 1909 children with no dispensed anti-asthmatics, 1848 had no maternal report of anti-asthmatic use (specificity 96.8%). Mothers reported current asthma in 133 (6.5% of 2056) children, including 122 (5.9%) reported as verified by a doctor. Of these 122, 98 had been dispensed anti-asthmatics during the preceding year (sensitivity 80.3%). Only 1.2% of the children without reported asthma were dispensed anti-asthmatics.
Mother-reported use of anti-asthmatics during the previous year among 7 year old children is highly valid. Dispensed anti-asthmatics would be a useful proxy for the presence of current asthma when disease data are not available.
asthma; children; mother-reported; pharmacoepidemiology; prescription database; validity
Oral contraceptive pills (OCPs) are often used soon before, and sometimes during, pregnancy. A few studies have suggested that OCP use before pregnancy may increase risks for childhood respiratory outcomes, but data are inconclusive. No studies have analyzed the two types of OCPs, estrogen-progestin combined pills and progestin-only pills, separately. In the Norwegian Mother and Child Cohort Study (MoBa), we prospectively examined associations of OCP use before pregnancy, by type, with lower respiratory tract infections in 60,225 children followed to 6 months old, lower respiratory tract infections and wheezing in 42,520 children followed to 18 months old, and asthma in 24,472 children followed to 36 months old. We used logistic regression to estimate odds ratios and their 95% confidence intervals crudely and with adjustment for a wide range of potential confounders. Combined pills were used much more commonly than progestin-only pills. Taking combined pills before pregnancy was not associated with lower respiratory tract infections, wheezing, or asthma. Progestin-only pill use in the year before pregnancy had a slight positive association with wheezing at 6–8 months old [adjusted odds ratio (95% confidence interval)=1.19 (1.05–1.34)]. Our finding that combined pill use before pregnancy was not related to respiratory outcomes should provide reassurance to the vast majority of mothers using OCPs before becoming pregnant. The small association with progestin-only pill use and early respiratory outcomes may reflect uncontrolled confounding or other bias but does suggest that these two types of pills should be examined separately in future analyses of respiratory and other childhood outcomes.
Farmer's lung, or hypersensitivity pneumonitis, is an important contributor to respiratory morbidity among farmers.
Using the 1993–7 enrolment data from the Agricultural Health Study, we conducted a cross‐sectional study of occupational risk factors for farmer's lung among ∼50 000 farmers and farm spouses in Iowa and North Carolina using hierarchical logistic regression controlling for age, state, and smoking status. Participants provided information on agricultural exposures, demographic characteristics, and medical history via self‐administered questionnaires. Approximately 2% of farmers (n = 481) and 0.2% of spouses (n = 51) reported doctor‐diagnosed farmer's lung during their lifetime. We assessed farmers and spouses separately due to different information on occupational exposure history. Only pesticide exposures represented lifetime exposure history, all other farm exposures represented current activities at enrolment.
Among farmers, handling silage (OR = 1.41, 95% CI 1.10 to 1.82), high pesticide exposure events (OR = 1.75, 95% CI 1.39 to 2.21), and ever use of organochlorine (OR = 1.34, 95% CI 1.04 to 1.74) and carbamate pesticides (OR = 1.32, 95% CI 1.03 to 1.68) were associated with farmer's lung in mutually‐adjusted models. The insecticides DDT, lindane, and aldicarb were positively associated with farmer's lung among farmers. Current animal exposures, while not statistically significant, were positively associated with farmer's lung, particularly for poultry houses (OR = 1.55, 95% CI 0.93 to 2.58) and dairy cattle (OR = 1.28, 95% CI 0.86 to 1.89). The occupational data were more limited for spouses; however, we saw similar associations for dairy cattle (OR = 1.50, 95% CI 0.72 to 3.14) and organochlorine pesticides (OR = 1.29, 95% CI 0.64 to 2.59).
While historic farm exposures may contribute to the observed associations with pesticides, these results suggest that organochlorine and carbamate pesticides should be further evaluated as potential risk factors for farmer's lung.
Although previous investigations have indicated a role for genetic factors in smoking initiation, the underlying genetic mechanisms are still unknown. In 2,339 adolescents from a Chinese Han population in the Wuhan Smoking Prevention Trial (Wuhan, China, 1998–1999), the authors explored the association of 57 genes in the dopamine pathway with smoking initiation. Using a conservative approach for declaring significance, positive findings were further examined in an independent sample of 603 Caucasian adolescents followed for up to 10 years as part of the Children's Health Study (Southern California, 1993–2009). The authors identified 1 single nucleotide polymorphism (rs2298122) in the calcyon neuron-specific vesicular protein gene (CALY) that was positively associated with smoking initiation in females (odds ratio = 2.21, 95% confidence interval: 1.49, 3.27; P = 8.4 × 10−5) in the Wuhan Smoking Prevention Trial cohort, and they replicated the association in females from the Children's Health Study cohort (hazard rate ratio = 2.05, 95% confidence interval: 1.27, 3.31; P = 0.003). These results suggest that the CALY gene may influence smoking initiation in adolescents, although the potential roles of underlying psychological characteristics that may be components of the smoking-initiation phenotype, such as impulsivity or novelty-seeking, remain to be explored.
adolescent; dopamine; genetic association studies; smoking
Two recent case-control studies in Italy reported that long-term exposure to particulate air pollution or living near major traffic roads was associated with an increased risk of deep vein thrombosis (DVT). No prospective evidence exists about long-term traffic-related air pollution and incident venous thromboembolism (VTE).
To examine the association between long-term traffic exposure and incident VTE in a population-based prospective cohort study.
We studied 13,143 middle-aged men and women in the Atherosclerosis Risk in Communities Study without history of DVT or pulmonary embolus (PE) at baseline examination (1987-1989). Geographical Information System (GIS)-mapped traffic density and distance to major roads in the four study communities served as measures of traffic exposure. We examined the association between traffic exposure and incident VTE using proportional hazards regression models.
405 subjects developed VTE through 2005. Traffic density was not significantly associated with VTE. Relative to those in the lowest quartile of traffic density, the adjusted hazard ratios across increasing quartiles were 1.18 (95%CI 0.88-1.57), 0.99 (95%CI 0.74-1.34) and 1.14 (95%CI 0.86-1.51) (p for trend across quartiles = 0.64). For residents living within 150 meters of major roads compared to subjects living further away, the adjusted hazard ratio was 1.16 (95%CI 0.95-1.42, p=0.14).
This first prospective study in the general population does not support an association between air pollution exposure or traffic proximity and risk of DVT. More data may be needed to clarify whether traffic or air pollution influences the risk of VTE.
traffic exposure; VTE; air pollution; cohort
Specific occupations are associated with adverse respiratory health. Inhalation exposures encountered in these jobs may place workers at risk of new-onset respiratory disease.
We analyzed data from 8,967 participants from the Atherosclerosis Risk in Communities (ARIC) study, a longitudinal cohort study. Participants included in this analysis were free of chronic cough and phlegm, wheezing, asthma, chronic bronchitis, emphysema, and other chronic lung conditions at the baseline examination, when they were aged 45-64 years. Using data collected in the baseline and first follow-up examination, we evaluated associations between occupation and the three-year incidence of cough, phlegm, wheezing, and airway obstruction and changes in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured by spirometry. All associations were adjusted for age, cigarettes per day, race, smoking status, and study center.
During the approximately three-year follow-up, the percentage of participants developing chronic cough was 3%; chronic phlegm, 3%; wheezing, 3%; and airway obstruction, defined as FEV1 < lower limit of normal (LLN) and FEV1/FVC < LLN, 2%. The average annual declines in FEV1 and FVC were 56 mL and 66 mL, respectively, among men and 40 mL and 52 mL, respectively, among women. Relative to a referent category of managerial and administrative support occupations, elevated risks of new-onset chronic cough and chronic phlegm were observed for mechanics and repairers (chronic cough: RR: 1.81, 95% CI: 1.02, 3.21; chronic phlegm: RR: 2.10, 95% CI: 1.23, 3.57) and cleaning and building service workers (chronic cough: RR: 1.85, 95% CI: 1.01, 3.37; chronic phlegm: RR: 2.28, 95% CI: 1.27, 4.08). Despite the elevated risk of new-onset symptoms, employment in cleaning and building services was associated with attenuated lung function decline, particularly among men, who averaged annual declines in FEV1 and FVC of 14 mL and 23 mL, respectively, less than the declines observed in the referent population.
Employment in mechanic and repair jobs and cleaning and building service occupations are associated with increased incidence of respiratory symptoms. Specific occupations affect the respiratory health of adults without pre-existing respiratory health symptoms and conditions, though long-term health consequences of inhalation exposures in these jobs remain largely unexplored.
ARIC study; epidemiology; occupation; respiratory tract disease
Allergic conditions and biochemical measures are both used to characterize atopy. To assess questionnaires’ ability to predict biochemical measures of atopy, the authors used data on 5 allergic conditions (allergy, hay fever, eczema, rhinitis, and itchy rash) and serum-specific immunoglobulin E (IgE) levels from the 2005–2006 National Health and Nutrition Examination Survey. Atopy was defined as 1 or more positive specific IgEs (≥0.35 kU/L). Questionnaire responses were assessed for sensitivity, specificity, and positive and negative predictive values for atopy. In this population-based US sample, 44% of participants were specific IgE-positive and 53% reported at least 1 allergic condition. Discordance between atopy and allergic conditions was considerable; 37% of persons with atopy reported no allergic condition, and 48% of persons who reported an allergic condition were not atopic. Thus, no combination of self-reported allergic conditions achieved both high sensitivity and high specificity for IgE. The positive predictive value of reported allergic conditions for atopy ranged from 50% for eczema to 72% for hay fever, while the negative predictive value ranged from 57% for eczema to 65% for any condition. Given the high proportion of asymptomatic participants who were specific IgE-positive and persons who reported allergic conditions but were specific IgE-negative, it is unlikely that questionnaires will ever capture the same participants as those found to be atopic by biochemical measures.
hypersensitivity; immunoglobulin E; questionnaires; sensitivity and specificity
Meta-analyses of genome-wide association studies are often based on imputed single nucleotide polymorphism (SNP) data, because component studies were genotyped using different platforms. One would like to include case-parent triad studies along with case-control studies in such meta-analyses. However, there are no published methods for estimating relative risks from imputed data for case-parent triad studies. The authors propose a method for estimating the relative risk for a variant SNP allele based on a log-additive model. Their simulations first confirm that the proposed method performs well with genotyped SNP data. As an empirical test of the method's behavior with imputed SNPs, the authors then apply it to chromosome 22 data from the Mexico City Childhood Asthma Study (1998–2003). For chromosome 22, the authors had data on 7,293 SNPs that were both genotyped and imputed using the software MACH, which relies on linkage disequilibrium with nearby SNPs. Correlation between estimated relative risks based on the actual genotypes and those based on the imputed genotypes was remarkably high (r2 = 0.95), validating this method of relative risk estimation for the case-parent study design. This method should be useful to investigators who wish to conduct meta-analyses using imputed SNP data from both case-parent triad and case-control studies.
epidemiologic methods; genome-wide association study; genotype; imputation; meta-analysis; risk
There is growing interest in the study of gene-environment interactions in the context of genome-wide association studies (GWASs). These studies will likely require meta-analytic approaches to have sufficient power.
We describe an approach for meta-analysis of a joint test for genetic main effects and gene-environment interaction effects. Using simulation studies based on a meta-analysis of five studies (total n = 10,161), we compare the power of this test to the meta-analysis of marginal test of genetic association and the meta-analysis of standard 1 d.f. interaction tests across a broad range of genetic main effects and gene-environment interaction effects.
We show that the joint meta-analysis is valid and can be more powerful than classical meta-analytic approaches, with a potential gain of power over 50% compared to the marginal test. The standard interaction test had less than 1% power in almost all the situations we considered. We also show that regardless of the test used, sample sizes far exceeding those of a typical individual GWAS will be needed to reliably detect genes with subtle gene-environment interaction patterns.
The joint meta-analysis is an attractive approach to discover markers which may have been missed by initial GWASs focusing on marginal marker-trait associations.
Gene-environment interaction; Genome-wide scan; Meta-analysis; Case-control association analysis; Complex disease
Comparing agricultural cohorts with the general population is challenging because the general healthiness of farmers may mask potential adverse health effects of farming. Using data from the Agricultural Health Study, a cohort of 89,656 pesticide applicators and their spouses (N = 89, 656) in North Carolina and Iowa, the authors computed standardized mortality ratios (SMRs) comparing deaths from time of the enrollment (1993–1997) through 2007 to state-specific rates. To compensate for the cohort's overall healthiness, relative SMRs were estimated by calculating the SMR for each cause relative to the SMR for all other causes. In 1,198,129 person-years of follow-up, 6,419 deaths were observed. The all-cause mortality rate was less than expected (SMRapplicators = 0.54, 95% confidence interval (CI): 0.52, 0.55; SMRspouses = 0.52, 95% CI: 0.50, 0.55). SMRs for all cancers, heart disease, and diabetes were significantly below 1.0. In contrast, applicators experienced elevated numbers of machine-related deaths (SMR = 4.15, 95% CI: 3.18, 5.31), motor vehicle nontraffic accidents (SMR = 2.80, 95% CI: 1.81, 4.14), and collisions with objects (SMR = 2.12, 95% CI: 1.25, 3.34). In the relative SMR analysis for applicators, the relative mortality ratio was elevated for lymphohematopoietic cancers, melanoma, and digestive system, prostate, kidney, and brain cancers. Among spouses, relative SMRs exceeded 1.0 for lymphohematopoietic cancers and malignancies of the digestive system, brain, breast, and ovary. Unintentional fatal injuries remain an important risk for farmers; mortality ratios from several cancers were elevated relative to other causes.
agriculture; healthy worker effect; mortality; neoplasms; pesticides; wounds and injuries
For most of the world, human genome structure at a population level is shaped by interplay between ancient geographic isolation and more recent demographic shifts, factors that are captured by the concepts of biogeographic ancestry and admixture, respectively. The ancestry of non-admixed individuals can often be traced to a specific population in a precise region, but current approaches for studying admixed individuals generally yield coarse information in which genome ancestry proportions are identified according to continent of origin. Here we introduce a new analytic strategy for this problem that allows fine-grained characterization of admixed individuals with respect to both geographic and genomic coordinates. Ancestry segments from different continents, identified with a probabilistic model, are used to construct and study “virtual genomes” of admixed individuals. We apply this approach to a cohort of 492 parent–offspring trios from Mexico City. The relative contributions from the three continental-level ancestral populations—Africa, Europe, and America—vary substantially between individuals, and the distribution of haplotype block length suggests an admixing time of 10–15 generations. The European and Indigenous American virtual genomes of each Mexican individual can be traced to precise regions within each continent, and they reveal a gradient of Amerindian ancestry between indigenous people of southwestern Mexico and Mayans of the Yucatan Peninsula. This contrasts sharply with the African roots of African Americans, which have been characterized by a uniform mixing of multiple West African populations. We also use the virtual European and Indigenous American genomes to search for the signatures of selection in the ancestral populations, and we identify previously known targets of selection in other populations, as well as new candidate loci. The ability to infer precise ancestral components of admixed genomes will facilitate studies of disease-related phenotypes and will allow new insight into the adaptive and demographic history of indigenous people.
Admixed individuals, such as African Americans and Latinos, arise from mating between individuals from different continents. Detailed knowledge about the ancestral origin of an admixed population not only provides insight regarding the history of the population itself, but also affords opportunities to study the evolutionary biology of the ancestral populations. Applying novel statistical methods, we analyzed the high-density genotype data of nearly 1,500 Mexican individuals from Mexico City, who are admixed among Indigenous Americans, Europeans, and Africans. The relative contributions from the three continental-level ancestral populations vary substantially between individuals. The European ancestors of these Mexican individuals genetically resemble Southern Europeans, such as the Spaniard and the Portuguese. The Indigenous American ancestry of the Mexicans in our study is largely attributed to the indigenous groups residing in the southwestern region of Mexico, although some individuals have inherited varying degrees of ancestry from the Mayans of the Yucatan Peninsula and other indigenous American populations. A search for signatures of selection, focusing on the parts of the genomes derived from an ancestral population (e.g. Indigenous American), identifies regions in which a genetic variant may have been favored by natural selection in that ancestral population.
Current genome-wide association studies (GWAS) often involve populations that have experienced recent genetic admixture. Genotype data generated from these studies can be used to test for association directly, as in a non-admixed population. As an alternative, these data can be used to infer chromosomal ancestry, and thus allow for admixture mapping. We quantify the contribution of allele-based and ancestry-based association testing under a family-design, and demonstrate that the two tests can provide non-redundant information. We propose a joint testing procedure, which efficiently integrates the two sources information. The efficiencies of the allele, ancestry and combined tests are compared in the context of a GWAS. We discuss the impact of population history and provide guidelines for future design and analysis of GWAS in admixed populations.
This is the first study to examine measured folate levels in pregnancy in relation to respiratory outcomes in the children. Higher pregnancy levels of folate were associated with increased risk of asthma at age 3.
Asthma; Case-Control Studies; Child; preschool; Cohort Studies; folate; folic acid; Norway; Plasma; Pregnancy
The environment is suspected to play an important role in the development of childhood asthma. Cohort studies are a powerful observational design for studying exposure–response relationships, but their power depends in part upon the accuracy of the exposure assessment.
The purpose of this paper is to summarize and discuss issues that make accurate exposure assessment a challenge and to suggest strategies for improving exposure assessment in longitudinal cohort studies of childhood asthma and allergies.
Exposures of interest need to be prioritized, because a single study cannot measure all potentially relevant exposures. Hypotheses need to be based on proposed mechanisms, critical time windows for effects, prior knowledge of physical, physiologic, and immunologic development, as well as genetic pathways potentially influenced by the exposures. Modifiable exposures are most important from the public health perspective. Given the interest in evaluating gene–environment interactions, large cohort sizes are required, and planning for data pooling across independent studies is critical. Collection of additional samples, possibly through subject participation, will permit secondary analyses. Models combining air quality, environmental, and dose data provide exposure estimates across large cohorts but can still be improved.
Exposure is best characterized through a combination of information sources. Improving exposure assessment is critical for reducing measurement error and increasing power, which increase confidence in characterization of children at risk, leading to improved health outcomes.
childhood asthma; cohort studies; exposure assessment
Epidemiologic studies have clearly shown that air pollution is associated with a range of respiratory effects. Recent research has identified oxidative stress as a major biologic pathway underlying the toxic effect of air pollutants. Genetic susceptibility is likely to play a role in response to air pollution. Genes involved in oxidative stress and inflammatory pathways are logical candidates for the study of the interaction with air pollutants. In this article we use the example of asthma, a genetically complex disease, to address the issue of gene by environment interaction with air pollution. The majority of studies have focused on the genes GSTM1, GSTP1, NQO1, and TNF, but the inconsistency of the results prevents the drawing of firm conclusions. The limited sample size of most studies to date make them underpowered for the study of gene by gene interactions. Large consortia of studies with repeated measurements of environmental exposures and clear phenotypic assessments may help determine special environmental triggers and the window of susceptibility in the development of atopy and asthma. The role of gene by gene interactions and epigenetic mechanisms needs to be considered along with gene by environment interactions.
ozone; particulate; gene by environment interaction; oxidative stress; asthma
Over two hundred asthma candidate genes have been examined in human association studies or identified with knockout mouse approaches. However, many have not been systematically replicated in human populations, especially those containing a large number of tagging single nucleotide polymorphisms (SNPs).
We comprehensively evaluated the association of previously implicated asthma candidate genes with childhood asthma in a Mexico City population.
We identified, from the literature, candidate genes with at least one positive report of association with asthma phenotypes in humans or implicated in asthma pathogenesis by knockout mouse experiments. We performed a genome-wide association study in 492 asthmatic children aged 5 to 17 years and both parents using the Illumina HumanHap 550v3 BeadChip. Separate candidate gene analyses were performed for 2,933 autosomal SNPs in the 237 selected genes using the log-linear method with a log-additive risk model.
Sixty-one of the 237 genes had at least one SNP with p < 0.05 for association with asthma. The nine most significant results were observed for rs2241715 in TGFB1 (p=3.3×10−5), rs13431828 and rs1041973 in IL1RL1 (p=2×10−4 and 3.5×10−4), five SNPs in DPP10 (p=1.6×10−4 to 4.5×10−4), and rs17599222 in CYFIP2 (p=4.1×10−4). False discovery rates were <0.1 for all 9 SNPs. Multimarker analysis identified TGFB1, IL1RL1, IL18R1, and DPP10 as the genes most significantly associated with asthma.
This comprehensive analysis of literature-based candidate genes suggests that SNPs in several candidate genes including TGFB1, IL1RL1, IL18R1 and DPP10 may contribute to childhood asthma susceptibility in a Mexican population.
Allergy; asthma; genetic predisposition to disease; genome-wide association study (GWAS); single nucleotide polymorphism (SNP)
To explore associations between acute otitis media in early childhood and prenatal and postnatal tobacco smoke exposure.
Subjects were 32,077 children born 2000 – 2005 in the Norwegian Mother and Child Study with questionnaire data on tobacco smoke exposure and acute otitis media up to 18 months of age. Multivariate regression models were used to obtain adjusted relative risks for acute otitis media.
Acute otitis media was slightly more common in children exposed to parental smoking. The incidence from 0–6 months was 4.7% in unexposed children, and 6.0% in children exposed both pre-and postnatally. After adjusting for postnatal exposure and covariates, the relative risk for acute otitis media 0–6 months when exposed to maternal smoking in pregnancy was 1.34, 95% confidence interval: 1.06–1.69. Maternal smoking in pregnancy was associated with acute otitis media up to 12 months of age. Compared to non-exposed children, there was a slightly increased risk of recurrent acute otitis media for children exposed both pre- and postnatally with a relative risk of 1.24, 95% confidence interval: 1.01–1.52,.
Even in a cohort with relatively low exposure levels of parental smoking, maternal smoking in pregnancy was associated with an increased risk of acute otitis media in early childhood.
Acute otitis media; Smoking; Pregnancy; Norway; Cohort studies
Obesity and asthma prevalence have both risen among children over the last several decades, and research efforts increasingly suggest that obesity is associated with asthma. Some, but not all, studies have shown that the effect of obesity on asthma is stronger among non-atopic individuals than among those with atopy. Systemic inflammation may be a factor in this relationship.
To examine the association of obesity with atopic and non-atopic asthma among U.S. children and to assess the role of C-reactive protein.
Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) were used to examine the relationship of weight to current asthma using logistic regression. Overweight was defined as ≥ 85th percentile of BMI-for-age and obesity was defined as ≥ 95% percentile of BMI-for-age. The presence of at least one positive allergen-specific IgE was used to stratify the relationship by atopic status in 2005-2006 data (n=3,387).
Setting and Participants
Stratified, multi-stage probability sampling was used to identify survey participants. This analysis includes children age 2-19 (n=16,074) from the 1999-2006 NHANES who have information on BMI and current asthma.
Main Outcome Measure
Self-report of doctor-diagnosed current asthma.
Obesity was significantly related to current asthma among children and adolescents (OR: 1.68, 95% CI: 1.33, 2.12). The association was stronger in non-atopic children (OR: 2.46, 95% CI: 1.21, 5.02) than in atopic children (OR: 1.34, 95% CI: 0.70, 2.57)(interaction p-value=0.09). C-reactive protein levels were associated with current asthma in non-atopic children, but not after adjusting for BMI.
Excess weight in children is associated with higher rates of asthma, especially asthma that is not accompanied by allergic disease.
Atopy; Obesity; Asthma; BMI
Previous experimental and laboratory studies have implicated antibodies against Hu proteins (anti-Hu) as a potential marker for small cell lung cancer (SCLC); there are no estimates of the association between anti-Hu and SCLC using a population-based design.
We used stored plasma specimens to evaluate anti-Hu reactivity in relationship to small cell lung cancer in a population-based case-control study. Using Western Blot analysis, we measured anti-Hu reactivity against recombinant Hu family member, HuD, in plasma samples from forty-one (41) SCLC cases and seventy-nine (79) controls individually matched for age, race, sex, and smoking status (never, past, current). We analyzed the association between anti-Hu reactivity and SCLC using conditional logistic regression.
Anti-Hu reactivity was associated with SCLC, both before and after adjustment for amount of smoking. We observed a smoking-adjusted odds ratio of 3.2 (95 % confidence interval from 0.98 to 13.4) comparing subjects above 1800 units (the lower limit of the second tertile of the distribution among antibody positive controls) to subjects with lower reactivity. We also found suggestive evidence in follow-up of our cases that anti-Hu above 1800 units was related to longer-term survival from SCLC. The present research is the first report of anti-Hu reactivity and SCLC in a population-based study.
Given the suggestive evidence in this study, prospective analyses to examine whether anti-Hu reactivity might predict risk of developing SCLC, or whether anti-Hu reactivity could serve as an early marker for SCLC, may be warranted.
carcinoma; small cell; Hu paraneoplastic encephalomyelitis antigens; HuD antigen; autoantibodies; case-control studies; survival
Longitudinal studies provide an important tool for analyzing traits that change over time depending on the individual characteristics and the environmental exposures. Complex quantitative traits, such as lung function, may change over time and appear to depend on both genetic and environmental factors, as well as on potential gene-environment interactions. There is a growing interest in modeling both marginal genetic effects and gene-environment interactions. In an admixed population, the use of traditional statistical models may fail to adjust for confounding by ethnicity, leading to bias in the genetic effect estimates. A variety of methods have been developed to account for genetic substructure of human populations. Family-based designs provide an important resource for avoiding confounding due to admixture. However to date, most genetic analyses have been applied to cross-sectional designs. In this paper we propose a methodology which aims to improve the assessment of main and gene-environment interaction effects by combining the advantages of both longitudinal studies for continuous phenotypes, and the family-based designs. This approach is based on an extension of Ordinary Linear Mixed Models for quantitative phenotypes which incorporates information from a case-parent design.
Our results indicate that using this method permit both main genetic and gene-environment interaction effects to be estimated without bias, even in the presence of population substructure.
gene-environment interaction; longitudinal phenotypes; power; bias; population substructure
To estimate the effect of baby swimming the first six months of life on respiratory diseases from 6 to 18 months.
We used data from The Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health in children born 1999 – 2005 followed from birth to the age of 18 months (n = 30,870). Health outcomes: lower respiratory tract infections (LRTI), wheeze and otitis media between 6 and 18 months of age. Exposure: baby swimming at age 6 months. The effect of baby swimming was estimated by logistic regression analysis adjusting for potential confounders.
About 25% of the children participated in baby swimming. The prevalence of LRTI was 13.3%, wheeze 40.0% and otitis media 30.4%. Children who were baby swimming were not more likely to have LRTI, to wheeze or to have otitis media. However, children with atopic mothers who attended baby swimming had an increased risk of wheeze, aOR 1.24 (95% CI 1.11, 1.39), but not LRTI or otitis media. This was also the case for children without respiratory diseases before 6 months aOR 1.08 (95%CI 1.02–1.15).
Baby swimming may be related to later wheeze. However, these findings warrant further investigation.
Baby swimming; respiratory health
Insulin-like growth factor–I (IGF-I) and insulin stimulate cell proliferation in uterine leiomyoma (fibroid) tissue. We hypothesized that circulating levels of these proteins would be associated with increased prevalence and size of uterine fibroids.
Participants were 35–49-year-old, randomly selected members of an urban health plan who were enrolled in 1996–1999. Premenopausal participants were screened for fibroids with ultrasound. Fasting blood samples were collected. Associations between fibroids and diabetes, plasma IGF-I, IGF binding protein 3 (BP3), and insulin were evaluated for blacks (n = 585) and whites (n = 403) by using multiple logistic regression.
IGF-I showed no association with fibroids in blacks, but in whites the adjusted odds ratios (aORs) for both mid and upper tertiles compared with the lowest tertile were 0.6 (95% confidence intervals [CI] = 0.3–1.0 and 0.4–1.1, respectively). Insulin and diabetes both tended to be inversely associated with fibroids in blacks. The insulin association was with large fibroids; aOR for the upper insulin tertile relative to the lowest was 0.4 (0.2–0.9). The aOR for diabetes was 0.5 (0.2–1.0). Associations of insulin and diabetes with fibroids were weak for whites. BP3 showed no association with fibroids.
Contrary to our hypothesis, high circulating IGF-I and insulin were not related to increased fibroid prevalence. Instead, there was suggestion of the opposite. The inverse association with diabetes, although based on small numbers, is consistent with previously reported findings. Future studies might investigate vascular dysfunction as a mediator between hyperinsulinemia or diabetes and possible reduced risk of fibroids.