Mass spectrometry-based metabolomics for the discovery of candidate markers of flavonoid and polyphenolic intake in adults.

Robust biological markers of dietary exposure are essential in improving the understanding of the link between diet and health outcomes. Polyphenolic compounds, including flavonoids, have been proposed to mitigate the risk of chronic diseases where oxidative stress and inflammation play a central role. Biomarkers can provide objective measurement of the levels of polyphenolic compounds. In this study, we provide methodology to identify potential candidate markers of polyphenol intake in human serum. Seventeen participants from the UK arm of the Global Allergy and Asthma Network of Excellence (GA2LEN) had their dietary intake estimated using a validated food frequency questionnaire, and serum samples were assessed using mass spectrometry to identify potential candidate markers. 144 features were assigned identities, of these we identified four biologically relevant compounds (rhamnazin 3-rutinoside, 2-galloyl-1,4-galactarolactone methyl ester, 2″,32″-di-O-p-coumaroylafzelin and cyclocommunin), which were significantly increased in the serum of participants with high predicted level of fruit and vegetable intake. 2-galloyl-1,4-galactarolactone methyl ester was strongly correlated with total flavonoids (r = 0.62; P = 0.005), flavan-3-ols (r = 0.67; P = 0.002) as well as with other four subclasses. Rhamnazin 3-rutinoside showed strong correlation with pro-anthocyanidins (r = 0.68; P = 0.001), flavones (r = 0.62; P = 0.005). Our results suggest that serum profiling for these compounds might be an effective way of establishing the relative intake of flavonoids and could contribute to improve the accuracy of epidemiological methods to ascertain flavonoid intake.

Age at menopause and lung function: a Mendelian randomisation study.

In observational studies, early menopause is associated with lower forced vital capacity (FVC) and a higher risk of spirometric restriction, but not airflow obstruction. It is, however, unclear if this association is causal. We therefore used a Mendelian randomisation (MR) approach, which is not affected by classical confounding, to assess the effect of age at natural menopause on lung function.We included 94 742 naturally post-menopausal women from the UK Biobank and performed MR analyses on the effect of age at menopause on forced expiratory volume in 1 s (FEV1), FVC, FEV1/FVC, spirometric restriction (FVC

Dietary patterns derived from principal component analysis (PCA) and risk of colorectal cancer: a systematic review and meta-analysis.

BACKGROUND AND AIM: Colorectal cancer (CRC) is highly prevalent worldwide, with dietary habits being a major risk factor. We systematically reviewed and meta-analysed the observational evidence on the association between CRC and dietary patterns (DP) derived from principal component analysis. DESIGN: PRISMA guidelines were followed. Web of Science, Medline/PubMed, EMBASE, and The Cochrane Library were searched to identify all eligible papers published up to the 31st July 2017. Any pre-defined cancer of the colon was included, namely colon-rectal cancer (CRC), colon cancer (CC), rectal cancer (RC), or proximal and distal CC, if available. Western (WDP) and prudent (PDP) dietary patterns were compared as a proxy to estimate "unhealthy" (Rich in meat and processed foods) and "healthy" diets (containing fruits or vegetables), respectively. Meta-analyses were carried out using random effects model to calculate overall risk estimates. Relative risks (RR) and 95% confidence intervals were estimated comparing the highest versus the lowest categories of dietary patterns for any of the forms of colon cancer studied. RESULTS: 28 studies were meta-analysed. A WDP was associated with increased risk of CRC (RR 1.25; 95% CI 1.11, 1.40), and of CC (RR 1.30; 95% CI 1.11, 1.52). A PDP was negatively associated with CRC (RR 0.81; 95% CI 0.73, 0.91). Sensitivity analyses showed that individuals from North-and South-American countries had a significantly higher risk of CRC than those from other continents. CONCLUSION: A PDP might reduce the risk of CRC. Conversely, a WDP is associated with a higher risk of disease.

Dietary Intake of Flavonoids and Ventilatory Function in European Adults: A GA²LEN Study.

BACKGROUND: Flavonoids exert anti-inflammatory properties and modulate oxidative stress in vitro, suggesting a protective effect on lung function, but epidemiological studies examining this association are scarce. METHODS: A stratified random sample was drawn from the GA²LEN screening survey, in which 55,000 adults aged 15 to 75 answered a questionnaire on respiratory symptoms. Post-bronchodilator spirometry was obtained from 2850 subjects. Forced vital capacity (FVC), the ratio between the forced exhaled volume in 1 second (FEV1) and FVC (FEV1/FVC), FVC below lower limit of normal (FVC < LLN), and FEV1/FVC < LLN were calculated. Intake of the six main subclasses of flavonoids was estimated using the GA²LEN Food Frequency Questionnaire. Adjusted associations between outcomes and each subclass of flavonoids were examined with multivariate regressions. Simes' procedure was used to test for multiple comparisons. RESULTS: A total of 2599 subjects had valid lung function and dietary data. A lower prevalence of FVC < LLN (airway restriction) was observed in those with higher total flavonoid (adjusted odds ratio (aOR), higher vs. lowest quintile intake 0.58; 95% Confidence Interval (CI) 0.36, 0.94), and pro-anthocyanidin intakes (aOR 0.47; 95% CI 0.27, 0.81). A higher FEV1/FVC was associated with higher intakes of total flavonoids and pro-anthocyanidins (adjusted correlation coefficient (a ß-coeff 0.33; 0.10, 0.57 and a ß-coeff 0.44; 95% CI 0.19, 0.69, respectively). After Simes' procedure, the statistical significance of each of these associations was attenuated but remained below 0.05, with the exception of total flavonoids and airway restriction. CONCLUSIONS: This population-based study in European adults provides cross-sectional evidence of a positive association of total flavonoid intake and pro-anthocyanidins and ventilatory function, and a negative association with spirometric restriction in European adults.

Dietary antioxidants and 10-year lung function decline in adults from the ECRHS survey.

The relationship between lung function decline and dietary antioxidants over 10 years in adults from three European countries was investigated.In 2002, adults from three participating countries of the European Community Respiratory Health Survey (ECRHS) answered a questionnaire and underwent spirometry (forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)), which were repeated 10 years later. Dietary intake was estimated at baseline with food frequency questionnaires (FFQ). Associations between annual lung function decline (mL) and diet (tertiles) were examined with multivariable analyses. Simes' procedure was applied to control for multiple testing.A total of 680 individuals (baseline mean age 43.8±6.6 years) were included. A per-tertile increase in apple and banana intake was associated with a 3.59 mL·year-1 (95% CI 0.40, 7.68) and 3.69 mL·year-1 (95% CI 0.25, 7.14) slower decline in FEV1 and FVC, respectively. Tomato intake was also associated with a slower decline in FVC (4.5 mL·year-1; 95% CI 1.28, 8.02). Only the association with tomato intake remained statistically significant after the Simes' procedure was performed. Subgroup analyses showed that apple, banana and tomato intake were all associated with a slower decline in FVC in ex-smokers.Intake of fruits and tomatoes might delay lung function decline in adults, particularly in ex-smokers.

Is fruit and vegetable intake associated with asthma or chronic rhino-sinusitis in European adults? Results from the Global Allergy and Asthma Network of Excellence (GA2LEN) Survey.

BACKGROUND: Fruits and vegetables are rich in compounds with proposed antioxidant, anti-allergic and anti-inflammatory properties, which could contribute to reduce the prevalence of asthma and allergic diseases. OBJECTIVE: We investigated the association between asthma, and chronic rhino-sinusitis (CRS) with intake of fruits and vegetables in European adults. METHODS: A stratified random sample was drawn from the Global Allergy and Asthma Network of Excellence (GA2LEN) screening survey, in which 55,000 adults aged 15-75 answered a questionnaire on respiratory symptoms. Asthma score (derived from self-reported asthma symptoms) and CRS were the outcomes of interest. Dietary intake of 22 subgroups of fruits and vegetables was ascertained using the internationally validated GA2LEN Food Frequency Questionnaire. Adjusted associations were examined with negative binomial and multiple regressions. Simes procedure was used to control for multiple testing. RESULTS: A total of 3206 individuals had valid data on asthma and dietary exposures of interest. 22.8% reported having at least 1 asthma symptom (asthma score ≥1), whilst 19.5% had CRS. After adjustment for potential confounders, asthma score was negatively associated with intake of dried fruits (ß-coefficient -2.34; 95% confidence interval [CI] -4.09, -0.59), whilst CRS was statistically negatively associated with total intake of fruits (OR 0.73; 95% CI 0.55, 0.97). Conversely, a positive association was observed between asthma score and alliums vegetables (adjusted ß-coefficient 0.23; 95% CI 0.06, 0.40). None of these associations remained statistically significant after controlling for multiple testing. CONCLUSION AND CLINICAL RELEVANCE: There was no consistent evidence for an association of asthma or CRS with fruit and vegetable intake in this representative sample of European adults.

Changes in symptoms of asthma and rhinitis by sensitization status over ten years in a cohort of young Chilean adults.

BACKGROUND: We investigated the net changes in prevalence of symptoms of asthma and rhinitis over 10 years in a cohort of young by baseline sensitization status. METHODS: One thousand one hundred ninety three Chilean adults subjects aged 22-28 living in a semi-rural area of central Chile answered a lifestyle and the European Community Respiratory Health Survey (ECRHS) questionnaires. Bronchial hyper-responsiveness (BHR) and skin prick test (SPT) to eight allergens were measured at baseline in 2001. Ten years later, 772 participants completed the questionnaires again. Estimates of adjusted net changes in prevalence of symptoms by sensitization status at baseline and association between sensitization status at baseline and respiratory symptoms ten years later were assessed. RESULTS: A quarter of the participants were sensitized to at least one allergen in 2001. Prevalence of wheeze had a net change per year of -0.37 % (95 % Confidence Interval -0.71 to 0.02 %; p = 0.067). Self-reported nasal allergies in the last 12 months increased by 0.83 % per year (95 % CI 0.49 to 1.17 %; p < 0.001). Those sensitized to either cat fur (OR 1.76; CI 1.01 to 3.05), cockroach, (OR 2.09; 1.13 to 3.86) blend of grass and pollens (1.78; 95 % CI 1.08 to 2.92), or weeds (OR 1.77; 95 % CI 1.01 to 3.12) in 2001 were more likely to have wheeze in the last 12 months 10 years later. CONCLUSION: Symptoms of asthma remained stable or slightly changed over 10 years in adults, whilst rhinitis and nasal allergies greatly increased. Being sensitized to at least one allergen is a risk factor for persistent symptoms of asthma and rhinitis, but not for determining net changes of symptoms over time. The underlying causes for the contrasting trends between asthma and nasal allergy are unknown.

Indoor risk factors for cough and their relation to wheeze and sensitization in Chilean young adults.

OBJECTIVES: We assessed the effects of indoor risk factors, including smoking, on different types of cough and on cough and wheeze in combination. METHODS: Our sample was composed of 1232 men and women residing in a semirural area of Chile. We used a standardized questionnaire, sensitization to 8 allergens, and bronchial hyperresponsiveness to methacholine to assess cough and wheeze characteristics. Information was gathered on dampness, mold, ventilation, heating, housing quality, smoking, and environmental tobacco smoke exposure. RESULTS: Most exposures were associated with cough alone or cough in combination with wheeze. Smoking, past smoking, and environmental tobacco smoke exposure were strongly associated with dry cough and wheeze. The use of coal for heating was associated with dry cough. Leaks, mold, and lack of kitchen ventilation were associated with cough and wheeze. Nocturnal cough and productive cough were associated with specific types of sensitization, but dry cough was not. Productive cough was associated with hyperresponsiveness to methacholine. CONCLUSIONS: Several different types of indoor exposures, including environmental tobacco smoke exposure, are important contributors to morbidity associated with cough and wheeze. A vigorous preventive strategy designed to lower exposures to indoor risk factors would lower rates of respiratory morbidity.

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.