Leslie Elliott

Prospective study of breast-feeding in relation to wheeze, atopy, and bronchial hyperresponsiveness in the Avon Longitudinal Study of Parents and Children (ALSPAC)

BACKGROUND Breast-feeding clearly protects against early wheezing, but recent data suggest that it might increase later risk of atopic disease and asthma. OBJECTIVE We sought to examine the relationship between breast-feeding and later asthma and allergy outcomes by using data from the Avon Longitudinal Study of Parents and Children, a large birth cohort in the United Kingdom. METHODS We used adjusted logistic regression models to evaluate the association between breast-feeding and atopy at age 7 years, bronchial responsiveness to methacholine at age 8 years, and wheeze at ages 3 and 7 1/2 years. Bayesian methods were used to assess the possibility of bias caused by an influence of early wheezing on the duration of breast-feeding, as well as selection bias. RESULTS Breast-feeding was protective for wheeze in the first 3 years of life (odds ratio [OR] of 0.80 [95% CI, 0.70-0.90] for > or = 6 months relative to never) but not wheeze (OR, 0.98; 95% CI, 0.79-1.22), atopy (OR, 1.12; 95% CI, 0.92-1.35), or bronchial hyperresponsiveness (OR, 1.07; 95% CI, 0.82-1.40) at ages 7 to 8 years. Bayesian models adjusting for the longer duration of breast-feeding among children with wheezing in early infancy produced virtually identical results. CONCLUSIONS We did not find consistent evidence for either a deleterious effect or a protective effect of breast-feeding on later risk of allergic disease in a large prospective birth cohort of children with objective outcome measures and extensive data on potential confounders and effect modifiers. Neither reverse causation nor loss to follow-up appears to have materially biased our results.

Poisson regression analysis of ungrouped data

Background: Poisson regression is routinely used for analysis of epidemiological data from studies of large occupational cohorts. It is typically implemented as a grouped method of data analysis in which all exposure and covariate information is categorised and person-time and events are tabulated. Aims: To describe an alternative approach to Poisson regression analysis using single units of person-time without grouping. Methods: Data for simulated and empirical cohorts were analysed by Poisson regression. In analyses of simulated data, effect estimates derived via Poisson regression without grouping were compared to those obtained under proportional hazards regression. Analyses of empirical data for a cohort of 138 900 electrical workers were used to illustrate how the ungrouped approach may be applied in analyses of actual occupational cohorts. Results: Using simulated data, Poisson regression analyses of ungrouped person-time data yield results equivalent to those obtained via proportional hazards regression: the results of both methods gave unbiased estimates of the “true” association specified for the simulation. Analyses of empirical data confirm that grouped and ungrouped analyses provide identical results when the same models are specified. However, bias may arise when exposure-response trends are estimated via Poisson regression analyses in which exposure scores, such as category means or midpoints, are assigned to grouped data. Conclusions: Poisson regression analysis of ungrouped person-time data is a useful tool that can avoid bias associated with categorising exposure data and assigning exposure scores, and facilitate direct assessment of the consequences of exposure categorisation and score assignment on regression results.

Incidence of allergy and allergy symptoms among workers exposed to laboratory animals

Background and Aims: Few studies have described relations between exposure to laboratory animals and the incidence of laboratory animal allergy (LAA). Studies that have found exposure-response relations have been cross sectional in design or have focused on exposure to rats and mice. This study used longitudinal data collected over a 12 year period to describe the relations between indices of exposure to laboratory animals and the development of LAA and LAA symptoms. Methods: Data were obtained from questionnaires and serological laboratory results from a dynamic cohort of workers exposed to a variety of laboratory animals in a pharmaceutical manufacturing company. Poisson regression was used to model the incidence rate ratios of species specific and general LAA and LAA symptoms at different levels of exposure. Results: The 12 year incidence rates of LAA symptoms and LAA for all workers were 2.26 (95% CI 1.61 to 2.91) and 1.32 (95% CI 0.76 to 1.87) per 100 person-years, respectively. Higher rate ratios were seen with increasing reported hours of exposure to tasks that required working with animal cages or with many animals at one time. The most common symptoms were related to rhinitis rather than to asthma. Conclusions: This study suggests that the risk of LAA increases with duration of exposure to animals and work in animal related tasks. Incidence might be reduced by limiting hours per week of exposure to laboratory animals.

Volatile organic compounds and pulmonary function in the Third National Health and Nutrition Examination Survey, 1988-1994.

Background Volatile organic compounds (VOCs) are present in much higher concentrations indoors, where people spend most of their time, than outdoors and may have adverse health effects. VOCs have been associated with respiratory symptoms, but few studies address objective respiratory end points such as pulmonary function. Blood levels of VOCs may be more indicative of personal exposures than are air concentrations; no studies have addressed their relationship with respiratory outcomes. Objective We examined whether concentrations of 11 VOCs that were commonly identified in blood from a sample of the U.S. population were associated with pulmonary function. Methods We used data from 953 adult participants (20–59 years of age) in the Third National Health and Nutrition Examination Survey (1988–1994) who had VOC blood measures as well as pulmonary function measures. Linear regression models were used to evaluate the relationship between 11 VOCs and measures of pulmonary function. Results After adjustment for smoking, only 1,4-dichlorobenzene (1,4-DCB) was associated with reduced pulmonary function. Participants in the highest decile of 1,4-DCB concentration had decrements of −153 mL [95% confidence interval (CI), −297 to −8] in forced expiratory volume in 1 sec and −346 mL/sec (95% CI, −667 to −24) in maximum mid-expiratory flow rate, compared with participants in the lowest decile. Conclusions Exposure to 1,4-DCB, a VOC related to the use of air fresheners, toilet bowl deodorants, and mothballs, at levels found in the U.S. general population, may result in reduced pulmonary function. This common exposure may have long-term adverse effects on respiratory health.

Dust Weight and Asthma Prevalence in the National Survey of Lead and Allergens in Housing (NSLAH)

Background Settled dust has been used in studies to assess exposures to allergens and other biologically active components, but it has not been considered in the aggregate in relation to respiratory health outcomes in the general population. Objective We addressed whether total house dust weight, an index of total dust exposure, was associated with respiratory health outcomes in the National Survey of Lead and Allergens in Housing (1998–1999) (NSLAH). Methods NSLAH was a cross-sectional survey designed to represent permanently occupied housing units in the United States. In each household, a questionnaire was administered and settled dust was vacuumed from five locations. Linear regression models were used to identify predictors of dust weight; logistic regression models were used to examine the relationship between dust weight and asthma and wheeze. Results Dust weight samples were available for 829 households, and survey information was available for 2,456 participants (children and adults). Lower income, older homes, household pets, having a smoker in the house, and less frequent cleaning predicted higher dust weight levels in U.S. households. Higher levels of dust weight were associated with greater odds of current asthma and wheeze. The strongest associations were seen for wheeze [adjusted odds ratio (OR) = 1.99; 95% confidence interval (CI), 1.21–3.28 for bedroom bed dust; OR = 2.81; 95% CI, 1.52–5.21 for upholstery dust). These associations persisted when adjusting for allergen and endotoxin exposures. Conclusions Dust weight, an index of total dust exposure in the home, may contribute to respiratory outcomes independently of the exposure to specific components.

Increased lung cancer mortality among chrysotile asbestos textile workers is more strongly associated with exposure to long thin fibres.

Background Animal data and physical models suggest that the carcinogenicity of asbestos fibres is related to their size and shape. Objectives To investigate the influence of fibre length and diameter on lung cancer risk in workers at asbestos textile mills in North Carolina and South Carolina, USA. Methods Men and women (n=6136) who worked ≥30 days in production and were employed between 1940 and 1973 were enumerated and followed for vital status through 2003. A matrix of fibre size-specific exposure estimates was constructed using determinations of fibre numbers and dimensions through analysis of 160 historical dust samples by transmission electron microscopy. Associations of lung cancer mortality with metrics of fibre exposure were estimated by Poisson regression with adjustment for age, sex, race and calendar year. Results Exposure to fibres throughout the range of length and diameter was significantly associated with increased risk of lung cancer. Models for fibres >5 μm long and <0.25 μm in diameter provided the best fit to the data, while fibres 5–10 μm long and <0.25 μm in diameter were associated most strongly with lung cancer mortality (log rate about 4% per IQR, p<0.001). When indicators of mean fibre length and diameter were modelled simultaneously, lung cancer risk increased as fibre length increased and diameter decreased. Conclusions The findings support the hypothesis that the occurrence of lung cancer is associated most strongly with exposure to long thin asbestos fibres. The relationship of cancer risk and fibre dimensions should be examined in cohorts exposed to other types of fibres.

Case-control Study of a Gastroschisis Cluster in Nevada

OBJECTIVE To identify potential risk factors associated with a sudden increase in gastroschisis cases in northern Nevada. DESIGN Case-control study. SETTING Medical centers and a pregnancy care center in Reno, Nevada. PARTICIPANTS Participants (n = 14) were women who gave birth to infants with gastroschisis at either of the 2 medical centers in Reno, Nevada, from April 5, 2007, through April 4, 2008. Controls (n = 57) were selected from the same pregnancy center providing perinatal care to the cases and were matched 4:1 to the case mothers by maternal date of birth within 1 year. MAIN EXPOSURES Environmental exposures and illnesses during pregnancy. OUTCOME MEASURES Association of gastroschisis with illnesses, medications, or environmental exposures. RESULTS Gastroschisis was associated with the use of methamphetamine (odds ratio [OR], 7.15; 95% confidence interval [CI], 1.35-37.99) or any vasoconstrictive recreational drug (methamphetamine, amphetamine, cocaine, ecstasy) (OR, 4.46; 95% CI, 1.21-16.44) before pregnancy. When we limited self-reported illnesses to those occurring during the first trimester of pregnancy, chest colds (OR, 16.77; 95% CI, 1.88-150.27) and sore throats (OR, 12.72; 95% CI, 1.32-122.52) were associated with gastroschisis. CONCLUSIONS These findings add strength to the hypothesis that use of methamphetamine and related drugs is a risk factor for gastroschisis and raise questions about the risks associated with infections.

Ecological associations between asthma prevalence and potential exposure to farming

Farming and exposure to livestock have been proposed as protective against the development of asthma in children. An ecological study was conducted to examine the support for these relationships in the USA. County-specific aggregate measures were used to examine the relationship between the prevalence of asthma and wheeze in 7th and 8th grade school children (aged 12–14 yrs) and selected measures of potential exposure to farming in the state of North Carolina. Binomial regression models were fitted to quantify these relationships, with adjustments for parental smoking, socioeconomic status, sex and race. Regression coefficients were reported for an increment of one interquartile range (IQR) in each indicator of exposure. The prevalence of asthma showed decreasing trends for most indicators of farm exposure. Regression results suggested that the largest decreases in asthma prevalence were associated with the number of farms (−5.0% per IQR increment), acreage of hay (−7.2% per IQR increment) and beef cattle (−7.8% per IQR increment). The pattern of results was similar for wheezing. In conclusion, the findings of this study are consistent with the hypothesis that certain farm exposures are protective against childhood asthma. Further research with individual-level data is needed to identify the specific protective exposures.

Lung cancer mortality in North Carolina and South Carolina chrysotile asbestos textile workers

Objectives Studies of workers in two US cohorts of asbestos textile workers exposed to chrysotile (North Carolina (NC) and South Carolina (SC)) found increasing risk of lung cancer mortality with cumulative fibre exposure. However, the risk appeared to increase more steeply in SC, possibly due to differences in study methods. The authors conducted pooled analyses of the cohorts and investigated the exposure-disease relationship using uniform cohort inclusion criteria and statistical methods. Methods Workers were included after 30 days of employment in a production job during qualifying years, and vital status ascertained through 2003 (2001 for SC). Poisson regression was used to estimate the exposure-response relationship between asbestos and lung cancer, using both exponential and linear relative rate models adjusted for age, sex, race, birth cohort and decade of follow-up. Results The cohort included 6136 workers, contributing 218 631 person-years of observation and 3356 deaths. Cumulative exposures at the four study facilities varied considerably. The pooled relative rate for lung cancer, comparing 100 f-yr/ml to 0 f-yr/ml, was 1.11 (95% CI 1.06 to 1.16) for the combined cohort, with different effects in the NC cohort (RR=1.10, 95% CI 1.03 to 1.16) and the SC cohort (RR=1.67, 95% CI 1.44 to 1.93). Conclusions Increased rates of lung cancer were significantly associated with cumulative fibre exposure overall and in both the Carolina asbestos-textile cohorts. Previously reported differences in exposure-response between the cohorts do not appear to be related to inclusion criteria or analytical methods.

COPD in farmers: what have we learnt?

Farming is a complex occupation, comprising a spectrum of activities that range from small-scale hobby farms to large-scale corporate farms. The activities, and thus the occupational exposures, on a farm are dictated by the type and size of the farm, as well as cultivation practices [1]. The farmers themselves are also diverse, living and working on farms alone or with family members or employees, working seasonally, or working at nonfarming occupations but returning home to farms that demand their labour. With heterogeneity on so many levels, it is no wonder that characterising exposures and identifying occupational hazards for agricultural workers has been daunting. Even more difficult has been measuring the burden of disease in farming populations when a specific hazard has been identified. Challenges in studying COPD prevalence in farmers: definition, diagnosis and choice of reference population http://ow.ly/V3XUq