Changes in IgE sensitization and total IgE levels over 20 years of follow-up.

BACKGROUND: Cross-sectional studies have reported a lower prevalence of sensitization in older adults, but few longitudinal studies have examined whether this is an aging or a year-of-birth cohort effect. OBJECTIVE: We sought to assess changes in sensitization and total IgE levels in a cohort of European adults as they aged over a 20-year period. METHODS: Levels of serum specific IgE to common aeroallergens (house dust mite, cat, and grass) and total IgE levels were measured in 3206 adults from 25 centers in the European Community Respiratory Health Survey on 3 occasions over 20 years. Changes in sensitization and total IgE levels were analyzed by using regression analysis corrected for potential differences in laboratory equipment and by using inverse sampling probability weights to account for nonresponse. RESULTS: Over the 20-year follow-up, the prevalence of sensitization to at least 1 of the 3 allergens decreased from 29.4% to 24.8% (-4.6%; 95% CI, -7.0% to -2.1%). The prevalence of sensitization to house dust mite (-4.3%; 95% CI, -6.0% to -2.6%) and cat (-2.1%; 95% CI, -3.6% to -0.7%) decreased more than sensitization to grass (-0.6%; 95% CI, -2.5% to 1.3%). Age-specific prevalence of sensitization to house dust mite and cat did not differ between year-of-birth cohorts, but sensitization to grass was most prevalent in the most recent ones. Overall, total IgE levels decreased significantly (geometric mean ratio, 0.63; 95% CI, 0.58-0.68) at all ages in all year-of-birth cohorts. CONCLUSION: Aging was associated with lower levels of sensitization, especially to house dust mite and cat, after the age of 20 years.

The association of asthma with BMI and menarche in the 1958 British Birth Cohort.

BACKGROUND: Obesity and early menarche have been associated with asthma. In this report, we assess the association of asthma with BMI and with changes in BMI from childhood to early adulthood. In addition, we determine if, in girls, any observed association of asthma with menarche can be explained by BMI. METHODS: In a large national birth cohort, the associations of asthma at age 7, 11, 16 and 33 years with BMI, and of, asthma at age 33 years with changes in BMI from age 7 to age 33 years was assessed using logistic and mixed effects models as appropriate. Associations of asthma with age of menarche in girls were similarly assessed with and without adjustment for BMI. RESULTS: Information on asthma, BMI, onset of menarche and confounders at all assessments was available for 1968 girls and 2223 boys. Obesity was relatively uncommon (<2%) in childhood. Overweight (BMI 25+) girls had more asthma. Girls with early menarche were more likely to be overweight. At age 11 years, asthma was associated with early menarche (OR = 1.70, 95% CI 1.17-2.47, after adjustment for BMI OR = 1.60, 95% CI 1.10-2.34). Across all ages, asthma was significantly associated with BMI (OR = 1.50, 95% CI 1.18-1.90) but not with early menarche (OR = 1.24, 95% CI 0.95-1.63). CONCLUSION: Asthma is more common in overweight girls. Early menarche is more common in overweight girls but this does not explain its association with asthma at age 11 years. Early menarche is not a risk factor for asthma at age 33 years in this cohort.

Prenatal and infant acetaminophen exposure, antioxidant gene polymorphisms, and childhood asthma.

BACKGROUND: Prenatal and infant acetaminophen exposure has been associated with an increased risk of childhood asthma phenotypes. Demonstration of biologically plausible interactions between these exposures and maternal and child antioxidant gene polymorphisms would strengthen causal inference. OBJECTIVE: To explore potential interactions between prenatal and infant acetaminophen exposure and antioxidant genotypes on childhood asthma. METHODS: In the Avon Longitudinal Study of Parents and Children, we typed a functional nuclear erythroid 2 p45-related factor 2 (Nrf2) polymorphism and glutathione S-transferase (GST) M1, T1, and P1 polymorphisms. Effects of prenatal and infant acetaminophen exposure on asthma phenotypes at 7 years were stratified by genotype in >4000 mothers and >5000 children. RESULTS: Risk of asthma and wheezing associated with early gestation acetaminophen exposure was increased when maternal copies of the minor T allele of Nrf2 were present (P interactions, .02 and .04, respectively). Risk of asthma associated with late gestation exposure was higher when maternal GSTT1 genotype was present rather than absent (P interaction, .006), and risk of wheezing was increased when maternal GSTM1 was present (P interaction, .04). Although acetaminophen use in infancy was associated with an increased risk of atopy, child antioxidant genotype did not modify associations between infant acetaminophen use and asthma phenotypes. However, the increased risk of asthma and wheezing associated with late gestation acetaminophen exposure in the presence of maternal GSTM1 was further enhanced when GSTM1 was also present in the child. CONCLUSION: Maternal antioxidant gene polymorphisms may modify the relation between prenatal acetaminophen exposure and childhood asthma, strengthening evidence for a causal association. In contrast, relations between infant acetaminophen use and asthma and atopy were not modified by child genotype and may be confounded by pre-existing wheeze or allergy.

Incident gout and weight change patterns: a retrospective cohort study of US adults.

BACKGROUND: Although the relationship between obesity and incident gout has been clarified, the influence of weight changes during the transition from early adulthood to midlife and the different weight change patterns in specific age ranges on the incidence of gout in later life remain unknown. Therefore, we aimed to investigate the association between weight change patterns across adulthood and incident gout. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES), we categorized individuals into four weight change patterns: those who remained obese (stable obese), those who moved from a non-obese body mass index (BMI) to an obese BMI (gaining), those who moved from an obese BMI to a non-obese BMI (losing), and those who remained non-obese (stable non-obese). Incident gout reflected its occurrence over the 10-year follow-up from the recalled midlife weight measure to the time of this survey. Hazard ratios (HRs) and 95% confidence intervals relating weight change patterns to incident gout over the 10-year follow-up period were calculated using Cox models adjusted for covariates. The hypothetical population attributable fraction (PAF) for the weight change patterns was calculated. RESULTS: Among our sample of adults aged 40-74 years at their midlife weight measure (n = 11,079), 320 developed gout. The highest risk of incident gout was found for participants with the stable obese pattern (HR 1.84; 1.08-3.14) and not for participants who remained stable non-obese during adulthood. Moreover, gaining weight was a significant risk factor for incident gout (HR 1.65; 1.19-2.29). No significant associations were found between losing weight change patterns and the risk of gout during the study period. If participants who gained weight had become non-obese during the 10-year follow-up, an estimated 3.2% (95% CI 0-6.3) of observed gout cases could have been averted. In addition, if the population had maintained a normal BMI, 32.9% (95% CI 18.2-44.9) cases could have been prevented during the 10 years. CONCLUSIONS: Gaining weight over adulthood was associated with an increased risk of gout. These findings have highlighted that maintaining non-obese weight and weight loss across adulthood is essential for the prevention and treatment of gout in adult life.

Combined healthy lifestyle behaviours and incident disability in an elderly population: the Ohsaki Cohort 2006 Study.

BACKGROUND: The joint impact of healthy lifestyle behaviours (HLBs) on incident disability among elderly populations is still uncertain. This cohort study was conducted to estimate the population-attributable fraction (PAF) of combined HLBs for disability reduction in elderly Japanese. METHODS: We analysed 10-year follow-up data for 9910 community-dwelling elderly people (≥65 years) in a prospective cohort study. Information on lifestyle behaviours and food consumption was collected via a questionnaire in 2006. The exposure variable was defined as a healthy lifestyle index (HLI), which represented the summed number of HLBs ('never or former smoker', 'time spent walking ≥0.5 hour/day' and 'vegetable and fruit consumption volume ≥median'). Data on incident disability were retrieved from the public Long term Care Insurance database. HRs and 95% CIs were estimated by Cox proportional regression and the PAFs and their 95% CIs were estimated with the multivariate-adjusted model. RESULTS: The 10-year incidence of disability was 35.7%. An inverse dose-response relationship was observed (HR (95% CI): 0.85(0.81 to 0.90) for each one-point increase of the HLI score, p-trend <0.001). Based on multivariate-adjustment, adherence to each one additional HLB gives PAF of 10.5%(95% CI 9.0% to 12.0%) for disability reduction. The PAF would have been 25.9%(14.2% to 36.0%) if all subjects had adhered to all three HLBs. CONCLUSION: Combined HLBs may have a substantial impact on reducing the risk of incident disability among elderly people. Even having one more healthy lifestyle habit may bring considerable benefit.

Are primary care factors associated with hospital episodes for adverse drug reactions? A national observational study.

OBJECTIVE: Identification of primary care factors associated with hospital admissions for adverse drug reactions (ADRs). DESIGN AND SETTING: Cross-sectional analysis of 2010-2012 data from all National Health Service hospitals and 7664 of 8358 general practices in England. METHOD: We identified all hospital episodes with an International Classification of Diseases (ICD) 10 code indicative of an ADR, in the 2010-2012 English Hospital Episode Statistics (HES) admissions database. These episodes were linked to contemporary data describing the associated general practice, including general practitioner (GP) and patient demographics, an estimate of overall patient population morbidity, measures of primary care supply, and Quality and Outcomes Framework (QOF) quality scores. Poisson regression models were used to examine associations between primary care factors and ADR-related episode rates. RESULTS: 212,813 ADR-related HES episodes were identified. Rates of episodes were relatively high among the very young, older and female subgroups. In fully adjusted models, the following primary care factors were associated with increased likelihood of episode: higher deprivation scores (population attributable fraction (PAF)=0.084, 95% CI 0.067 to 0.100) and relatively poor glycated haemoglobin (HbA1c) control among patients with diabetes (PAF=0.372; 0.218 to 0.496). The following were associated with reduced episode likelihood: lower GP supply (PAF=-0.016; -0.026 to -0.005), a lower proportion of GPs with UK qualifications (PAF=-0.035; -0.058 to -0.012), lower total QOF achievement rates (PAF=-0.021; -0.042 to 0.000) and relatively poor blood pressure control among patients with diabetes (PAF=-0.144; -0.280 to -0.022). CONCLUSIONS: Various aspects of primary care are associated with ADR-related hospital episodes, including achievement of particular QOF indicators. Further investigation with individual level data would help develop understanding of the associations identified. Interventions in primary care could help reduce the ADR burden. ADRs are candidates for primary care sensitive conditions.

Cardiovascular disease mortality and years of life lost attributable to non-optimal systolic blood pressure and hypertension in northeastern Iran.

BACKGROUND: High blood pressure is the second most important risk factor of cardiovascular diseases (CVDs) in Iran. It is imperative to estimate the burden of CVDs that can be averted if high blood pressure is controlled at the population level. The aim of the current study was to estimate the avertable CVD mortality in the setting of Golestan Cohort Study (GCS). METHODS: Over 50,000 participants were recruited and followed for a median of 7 years. The exposures of interest in this study were non-optimal systolic blood pressure (SBP) and hypertension measured at baseline. Deaths by cause have been precisely recorded. The Population Attributable Fraction (PAF) of deaths and Years of Life Lost (YLLs) due to CVDs attributable to exposures of interest were calculated. RESULTS: Overall, 223 deaths due to ischemic heart disease (IHD), 207 deaths due to cerebrovascular accidents (CVA), and 460 deaths due to all CVDs could be averted if the SBP of all subjects in the study were optimal. Similarly, 5,560 YLLs due to IHD, 4,771 YLLs due to CVA, and 11,135 YLLs due to CVDs could be prevented if SBP were optimal. In all age groups, the avertable deaths and YLLs were higher due to IHD compared with CVA. Deaths and YLLs attributable to non-optimal SBP in women were less than men. CONCLUSIONS: A very large proportion of CVD deaths can be averted if blood pressure is controlled in Iran. Effective interventions in primary and secondary health care setting are mandatory to be implemented as early as possible.

Consequences of exposure to peri-articular injections of micro- and nano-particulate cobalt-chromium alloy.

Metal hip replacements generate both metal particles and ions. The biological effects of peri-articular exposure to nanometre and micron sized cobalt chrome (CoCr) wear particles were investigated in a mouse model. Mice received injections of two clinically relevant doses of nanoparticles (32 nm), one of micron sized (2.9 µm) CoCr particles or vehicle alone into the right knee joint at 0, 6, 12 and 18 weeks. Mice were analysed for genotoxic and immunological effects 1, 4 and 40 weeks post exposure. Nanoparticles but not micron particles progressively corroded at the injection site. Micron sized particles were physically removed. No increase of Co or Cr was seen in peripheral blood between 1 and 40 weeks post exposure to particles. No significant inflammatory changes were observed in the knee tissues including ALVAL or necrosis. DNA damage was increased in bone marrow at one and forty weeks and in cells isolated from frontal cortex at 40 weeks after injection with nanoparticles. Mice exposed to the micron sized, but not nanoparticles became immunologically sensitized to Cr(III), Cr (VI) and Ni(II) over the 40 week period as determined by lymphocyte transformation and ELISpot (IFN-γ and IL-2) assays. The data indicated that the response to the micron sized particles was Th1 driven, indicative of type IV hypersensitivity. This study adds to understanding of the potential adverse biological reactions to metal wear products.

Prenatal paracetamol exposure and asthma: further evidence against confounding.

BACKGROUND: Observational studies have reported an association between maternal use of paracetamol in pregnancy and childhood asthma, which was not explained by measured confounding factors. However, it is possible that this relation might be confounded by unmeasured behavioural factors linked to paracetamol usage; if that were the case, effects of similar magnitude of partner's paracetamol use and/or postnatal maternal use would be expected. METHODS: In the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based birth cohort, we compared the univariate effects of maternal use of paracetamol in pregnancy on risk of doctor-diagnosed asthma, wheeze and elevated immunoglobulin E (IgE) in the offspring at 7 years of age, with the univariate effects of partner's use and postnatal maternal use on these phenotypes. RESULTS: Maternal use of paracetamol in pregnancy was strongly associated with all outcomes. Partner's use was very weakly associated with asthma but not associated with wheezing or IgE. Postnatal maternal use was associated with asthma and wheezing, though less strongly than was prenatal use, and was not associated with IgE. On mutual adjustment, the effects of maternal use in pregnancy on all outcomes were not substantially attenuated, whereas the effects of partner's use on asthma, and of postnatal maternal use on asthma and wheezing, were reduced. CONCLUSIONS: These findings suggest that the relation between maternal use of paracetamol in pregnancy and childhood asthma is unlikely to be confounded by unmeasured behavioural factors linked to paracetamol use.

Randomised, double blind, placebo-controlled trial of selenium supplementation in adult asthma.

BACKGROUND: Epidemiological evidence from observational studies has suggested that blood levels and dietary intake of selenium of adults with asthma are lower than those of controls. The only previous trial of selenium supplementation in adults with asthma found no objective evidence of benefit but involved only 24 participants. METHODS: A randomised, double blind, placebo-controlled trial of selenium supplementation was performed in adults with asthma in London, UK, the majority of whom (75%) reported inhaled steroid use at baseline. 197 participants were randomised to receive either a high-selenium yeast preparation (100 microg daily, n=99) or placebo (yeast only, n=98) for 24 weeks. The primary outcome was asthma-related quality of life (QoL) score. Secondary outcomes included lung function, asthma symptom scores, peak flow and bronchodilator usage. Linear regression was used to analyse the change in outcome between the two treatment arms by "intention to treat". RESULTS: There was a 48% increase in plasma selenium between baseline and end of trial in the active treatment group but no change in the placebo group. While the QoL score improved more in the active treatment group than in the placebo group, the difference in change in score between the two groups was not significant (-0.05 (95% CI -0.19 to 0.09); p=0.47). Selenium supplementation was not associated with any significant improvement in secondary outcomes compared with placebo. CONCLUSIONS: Selenium supplementation had no clinical benefit in adults with asthma, the majority of whom were taking inhaled steroids.

Umbilical cord and maternal blood red cell fatty acids and early childhood wheezing and eczema.

BACKGROUND: Few studies have explored whether fetal exposure to n-6 and n-3 fatty acids influences the inception of atopic disease. OBJECTIVE: To assess prenatal fatty acid exposures as predictors of early childhood wheezing and eczema. METHODS: In the Avon Longitudinal Study of Parents and Children, late pregnancy maternal blood samples and umbilical cord blood samples were assayed for n-6 and n-3 fatty acids (percentage of total red cell phospholipid), and mothers were asked about wheezing and eczema in their children. We measured associations of 11 n-6 and n-3 fatty acid exposures with wheezing at 30 to 42 months, with wheezing patterns defined by presence (+) or absence (-) of wheezing during 2 periods, 0 to 6 months and 30 to 42 months (transient infant, +/-; later-onset, -/+; persistent, +/+; n=1191 and n=2764 for cord and maternal analyses, respectively), and with eczema at 18 to 30 months (n=1238 and n=2945 for cord and maternal analyses, respectively). RESULTS: In cord blood red cells, the ratio of arachidonic:eicosapentaenoic acid was positively associated with eczema (adjusted odds ratio [OR] per doubling, 1.14; 95% CI, 1.00-1.31; P=.044), the ratio of linoleic acid:alpha-linolenic acid was positively associated with later-onset wheeze (OR, 1.30; CI, 1.04-1.61; P=.019), and the ratio of alpha-linolenic acid:n-3 products was negatively associated with later-onset wheeze (OR, 0.86; CI, 0.75-0.99; P=.040). However, these associations were no longer significant after adjusting for multiple comparisons. CONCLUSIONS: It seems unlikely that fetal exposure to n-6 and n-3 fatty acids is an important determinant of early childhood wheezing and atopic disease.