Background Both gastrointestinal microbiota composition and cesarean section have been linked to atopic manifestations. However, results are inconsistent, and the hypothesized intermediate role of ...the microbiota in the association between birth mode and atopic manifestations has not been studied yet. Objectives We sought to investigate the relationship between microbiota composition, mode and place of delivery, and atopic manifestations. Methods The Child, Parent and Health: Lifestyle and Genetic Constitution Birth Cohort Study included data on birth characteristics, lifestyle factors, and atopic manifestations collected through repeated questionnaires from birth until age 7 years. Fecal samples were collected at age 1 month (n = 1176) to determine microbiota composition, and blood samples were collected at ages 1 (n = 921), 2 (n = 822), and 6 to 7 (n = 384) years to determine specific IgE levels. Results Colonization by Clostridium difficile at age 1 month was associated with wheeze and eczema throughout the first 6 to 7 years of life and with asthma at age 6 to 7 years. Vaginal home delivery compared with vaginal hospital delivery was associated with a decreased risk of eczema, sensitization to food allergens, and asthma. After stratification for parental history of atopy, the decreased risk of sensitization to food allergens (adjusted odds ratio, 0.52; 95% CI, 0.35-0.77) and asthma (adjusted odds ratio, 0.47; 95% CI, 0.29-0.77) among vaginally home-born infants was only found for children with atopic parents. Mediation analysis showed that the effects of mode and place of delivery on atopic outcomes were mediated by C difficile colonization. Conclusion Mode and place of delivery affect the gastrointestinal microbiota composition, which subsequently influences the risk of atopic manifestations.
Background Metabolomics, defined as the comprehensive identification and quantification of low-molecular-weight metabolites to be found in a biological sample, has been put forward as a potential ...tool for classifying individuals according to their risk of coronary heart disease (CHD). Here, we investigated whether a single-point blood measurement of the metabolome is associated with and predictive for the risk of CHD. Methods and results We obtained proton nuclear magnetic resonance spectra in 79 cases who developed CHD during follow-up (median 8.1 years) and in 565 randomly selected individuals. In these spectra, 100 signals representing 36 metabolites were identified. Applying least absolute shrinkage and selection operator regression, we defined a weighted metabolite score consisting of 13 proton nuclear magnetic resonance signals that optimally predicted CHD. This metabolite score, including signals representing a lipid fraction, glucose, valine, ornithine, glutamate, creatinine, glycoproteins, citrate, and 1.5-anhydrosorbitol, was associated with the incidence of CHD independent of traditional risk factors (TRFs) (hazard ratio 1.50, 95% CI 1.12-2.01). Predictive performance of this metabolite score on its own was moderate ( C -index 0.75, 95% CI 0.70-0.80), but after adding age and sex, the C -index was only modestly lower than that of TRFs ( C -index 0.81, 95% CI 0.77-0.85 and C -index 0.82, 95% CI 0.78-0.87, respectively). The metabolite score was also associated with prevalent CHD independent of TRFs (odds ratio 1.59, 95% CI 1.19-2.13). Conclusion A metabolite score derived from a single-point metabolome measurement is associated with CHD, and metabolomics may be a promising tool for refining and improving the prediction of CHD.
Objective To investigate the potential effect of modification by maternal allergic status on the relationship between breast-feeding duration and infant atopic manifestations in the first 2 years of ...life. Study design Data from 2705 infants of the KOALA Birth Cohort Study (The Netherlands) were analyzed. The data were collected by repeated questionnaires at 34 weeks of gestation and 3, 7, 12, and 24 months postpartum. Total and specific immunoglobulin E measurements were performed on venous blood samples collected during home visits at age 2 years. Relationships were analyzed using logistic regression analyses. Results Longer duration of breast-feeding was associated with a lower risk for eczema in infants of mothers without allergy or asthma ( Ptrend = .01) and slightly lower risk in those of mothers with allergy but no asthma ( Ptrend = .14). There was no such association for asthmatic mothers ( Ptrend = .87). Longer breast-feeding duration decreased the risk of recurrent wheeze independent of maternal allergy ( Ptrend = .02) or asthma status ( Ptrend = .06). Conclusions Our findings show that the relationship between breast-feeding and infant eczema in the first 2 years of life is modified by maternal allergic status. The protective effect of breast-feeding on recurrent wheeze may be associated with protection against respiratory infections.
Background Perturbations in the gut microbiota have been linked to atopic diseases. However, the development of atopic diseases depends not only on environmental factors (like microbial stimulation) ...but also on genetic factors. It is likely that particularly gene-environmental interactions in early life determine the development of atopy. Objective We examine the interaction between detection of fecal Escherichia coli and genetic variations in the CD14 and Toll-like receptor 4 (TLR4) genes in relation to atopic manifestations. Methods Within the Child, Parent and Health: Lifestyle and Genetic Constitution (KOALA) Birth Cohort Study, fecal samples of 957 one-month-old infants were collected and quantitatively screened for E coli . Fourteen haplotype-tagging polymorphisms in the genes TLR4 and CD14 were genotyped in 681 of the 957 children. Atopic outcomes were parentally reported eczema in the first 2 years of life and clinically diagnosed eczema and allergic sensitization at age 2 years. Multiple logistic regression was used to evaluate a multiplicative model of interaction. Results Most of the single nucleotide polymorphisms (SNPs) showed no significant interaction with E coli exposure for both eczema and allergic sensitization. A borderline significant multiplicative interaction was found between E coli and the rs2569190 (CD14/-159) SNP regarding allergic sensitization. Furthermore, a statistically significant multiplicative interaction was found for the TLR4 SNP rs10759932 ( P for interaction = .001). E coli colonization was associated with a decreased risk of sensitization only in children with the rs10759932 TT genotype (adjusted odds ratio, 0.31; 95% CI, 0.14-0.68) and not in children with the minor C allele. This interaction remained statistically significant after controlling for multiple testing. Conclusion The current study is the first to address the potential effect-modifying role of genetic variations in the relationship between the intestinal microbiota and allergy development.
Abstract Context One potential agent to improve symptoms and quality of life (QoL) in advanced cancer patients is adenosine 5'-triphosphate (ATP). Several reports suggest that ATP may positively ...affect QoL and survival in patients with advanced non-small-cell lung cancer. Objectives To investigate the effects of ATP infusions on QoL parameters in patients with preterminal cancer of mixed tumor types. Methods Ninety-nine preterminal cancer patients were randomly allocated to receive either ATP intravenously weekly (8–10 hours/week, with maximum 50 μg/kg.minute) for eight weeks or receive no ATP (control group). QoL parameters were assessed until eight weeks and analyzed by repeated-measures analysis of covariance. Results Fifty-one patients were randomized to the ATP group and 48 to the control group. Unexpectedly, in the untreated control group, most of the outcome parameters did not deteriorate but remained stable or even significantly improved over time. Between the ATP and control groups, no statistically significant differences were observed for the large majority of outcome parameters, except for the strength of elbow flexor muscles in favor of the control group. Conclusion ATP infusions, at the dose and schedule studied, did not have a significant effect on QoL, functional status, or fatigue in preterminal cancer patients of mixed tumor types.
Abstract Purpose Oxidative stress is possibly related to prostate carcinogenesis. We constructed a dietary antioxidant score, which is a measure of combined antioxidant exposures, and an oxidative ...balance score (OBS), which is a measure of combined antioxidant and pro-oxidant exposures. We hypothesized that both scores are inversely associated with the risk of prostate cancer (PCa). Methods We conducted a case–cohort study among 58,279 men in the Netherlands Cohort Study. Cohort members completed a baseline questionnaire. From 1986 to 2003, 3451 patients with PCa were identified including 1196 advanced cancers (stage III/IV). The antioxidant score and the OBS were created by summing quartile and category scores of individual score constituents, which had an equal weight. Pro-oxidants were scored in the opposite way to antioxidants. Results Both the antioxidant score and OBS were not associated with risk of overall PCa or PCa subgroups on the basis of disease stage. Most score constituents were not associated with the risk of PCa. Total catechin intake was associated with a decreased risk of stage IV PCa (greatest vs. lowest quartile: hazard ratio, 0.76; 95% confidence interval, 0.59–0.98). Conclusions The antioxidant score and OBS were not associated with risk of overall and advanced-stage PCa.
Abstract Kool J, Bachmann S, Oesch P, Knuesel O, Ambergen T, de Bie R, van den Brandt P. Function-centered rehabilitation increases work days in patients with nonacute nonspecific low back pain: ...1-year results from a randomized controlled trial. Objective To compare the effect of function-centered treatment (FCT) and pain-centered treatment (PCT) on the number of work days, permanent disability, and the unemployment rate. Design Randomized controlled trial. Setting Inpatient rehabilitation center. Participants Patients (N=174; 79% male; mean age, 42y) with previous sick leave of 6 weeks or more. Interventions FCT (4h/d for 3wk) emphasized activity despite pain by using work simulation, strength, endurance, and cardiovascular training. PCT (2.5h/d for 3wk) emphasized pain reduction and included passive and active mobilization, stretching, strength training, and a 4-hour mini back school with education and exercise. Analysis was by intention to treat. Main Outcome Measures Work days, return to work, rate of patients receiving financial compensation for permanent disability, and unemployment rate. Effect sizes (Cohen d ) were defined as small (0.2–0.5), moderate (0.5–0.8), and large (>0.8). Results After 1 year, the FCT group had significantly more work days (mean, 118; median, 39.5; interquartile range IQR, 0−198) than the PCT group (mean, 74; median, 0; IQR, 0−160; Mann-Whitney U test, P =.011). The odds ratio of returning to work in the FCT group relative to the PCT group was 2.1 (95% confidence interval, 1.1−3.9). The differences in unemployment rates and in the numbers of patients receiving compensation for permanent disability were not significant. Conclusions FCT is more effective than PCT for increasing work days.
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