A common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults.

BACKGROUND: Exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation in the airways and for responsiveness to corticosteroids in asthmatics. OBJECTIVE: We sought to identify in adults the genetic determinants of fractional exhaled nitric oxide (FeNO) levels and to assess whether environmental and disease-related factors influence these associations. METHODS: We performed a genome-wide association study of FeNO through meta-analysis of two independent discovery samples of European ancestry: the outbred EGEA study (French Epidemiological study on the Genetics and Environment of Asthma, N = 610 adults) and the Hutterites (N = 601 adults), a founder population living on communal farms. Replication of main findings was assessed in adults from an isolated village in Sardinia (Talana study, N = 450). We then investigated the influence of asthma, atopy and tobacco smoke exposure on these genetic associations, and whether they were also associated with FeNO values in children of the EAGLE (EArly Genetics & Lifecourse Epidemiology, N = 8858) consortium. RESULTS: We detected a common variant in RAB27A (rs2444043) associated with FeNO that reached the genome-wide significant level (P = 1.6 × 10(-7) ) in the combined discovery and replication adult data sets. This SNP belongs to member of RAS oncogene family (RAB27A) and was associated with an expression quantitative trait locus for RAB27A in lymphoblastoid cell lines from asthmatics. A second suggestive locus (rs2194437, P = 8.9 × 10(-7) ) located nearby the sodium/calcium exchanger 1 (SLC8A1) was mainly detected in atopic subjects and influenced by inhaled corticosteroid use. These two loci were not associated with childhood FeNO values. CONCLUSIONS AND CLINICAL RELEVANCE: This study identified a common variant located in RAB27A gene influencing FeNO levels specifically in adults and with a biological relevance to the regulation of FeNO levels. This study provides new insight into the biological mechanisms underlying FeNO levels in adults.

Probing the factor structure of metabolic syndrome in Sardinian genetic isolates.

BACKGROUND AND AIMS: Owing to the multiplicity of the key components of metabolic syndrome (MetS), its diagnosis is very complex. The lack of a unique definition is responsible for the prevalence variability observed among studies; therefore, a definition based on continuous variables was recommended. The aim of this study was to compare competing models of the MetS factor structure for selecting the one that explains the best clustering pattern and to propose an algorithm for computing MetS as a continuous variable. METHODS AND RESULTS: Data were from isolated Sardinian populations (n = 8102). Confirmatory factor analysis (CFA) and two-group CFA by gender were performed to evaluate the sex-specific factor structure of MetS. After selecting the best model, an algorithm was obtained using factor loadings/residual variances. The quality of the MetS score was evaluated by the receiver operating characteristics curve and the area under the curve. Cross-validation was performed to validate the score and to determine the best cut point. The best fit model was a bifactor one with a general factor (MetS) and three specific factors (f1: obesity/adiposity trait; f2: hypertension/blood pressure trait; and f3: lipid trait). Gender-specific algorithms were implemented to obtain MetS scores showing a good diagnostic performance (0.80 specificity and 0.80 sensitivity for the cut point). Furthermore, cross-validation confirmed these results. CONCLUSION: These analyses suggested that the bifactor model was the most representative one. In addition, they provided a score and a cut point that are both clinically accessible and interpretable measures for MetS diagnosis and likely useful for evaluating the association with adverse cardiovascular disease and diabetes and for investigating the MetS genetic component.

The Effect of Crackers Enriched with Camelina Sativa Oil on Omega-3 Serum Fatty Acid Composition in Older Adults: A Randomized Placebo-Controlled Pilot Trial.

BACKGROUND: Camelina sativa oil is one of the richest dietary sources of omega-3, with polyunsaturated fatty acids amounts of over 50%, linolenic acid content of around 40-45%, and linoleic acid of about 15%. Moreover, this oil is a valuable source of antioxidants which provide oxidative stability. All those features raise interest in considering Camelina oil as an alternative and sustainable oil source providing stable omega-3-rich emulsions for functional food production. OBJECTIVES: The present study aimed to investigate the effects of Camelina oil-enriched crackers on serum omega-3 concentration, inflammatory markers and serum lipid profile. DESIGN: Randomized placebo-controlled pilot trial. SETTING: Research and Development Center (Complife Italia s.r.l.). PARTICIPANTS: Sixty-six free-living older volunteers (aged≥65 years). INTERVENTION: Older adults were enrolled and randomly assigned to one of two groups: the camelina group or the placebo group. Subjects consumed daily 35 g of crackers (Camelina enriched crackers or placebo ones) twice daily for 12 weeks. MEASUREMENTS: Serum polyunsaturated fatty acid profile, inflammatory status and serum lipid panel parameters were recorded pre and post-intervention. RESULTS: In the camelina group, alpha-linolenic acid serum concentration was significantly higher (p<0.01) compared to the placebo group at the end of the study. Concerning inflammatory plasma markers, a significant mean pro-inflammatory interleukin-18 plasma concentration decrease in the placebo group compared to the camelina one was observed (p<0.05). No significant differences in other mean inflammatory markers concentrations post-intervention were noted in either group. Lastly, examining the change in lipid profile, it is noteworthy that a higher reduction of total cholesterol, low-density lipoprotein and triglycerides in the camelina group post-intervention, despite the lack of statistical significance. CONCLUSION: Camelina oil significantly elevated the serum alpha-linolenic acid concentration with no significant changes in inflammatory markers and lipid profile.

Epicardial fat thickness: threshold values and lifestyle association in male adolescents.

BACKGROUND: Obese adolescents with high proportion of visceral fat are at higher risk of developing the metabolic syndrome. OBJECTIVES: The study aims to investigate if echocardiographic epicardial fat thickness (EF) could be predictive of visceral obesity (VO) early in life and to provide EF threshold values specific for male adolescents. Further aim was to investigate the association between EF, lifestyle and metabolic disease familiarity. METHODS: Anthropometric data were collected from 102 normal weight and overweight, healthy male adolescents (mean age: 14.91 ± 1.98 years); bioelectrical impedance analysis and transthoracic echocardiogram were performed in the same sample. Each participant fulfilled a validated self-administered lifestyle questionnaire. RESULTS: We found higher EF values in sedentary adolescents (P < 0.05), in those who never eat fruit and vegetables (P < 0.05), and in those with overweight mothers (P < 0.05). The strongest independent predictor of EF was waist circumference (P < 0.0001). Using the waist to height ratio as a marker of VO, logistic regression analysis revealed that 1 mm EF gain is responsible for seven times higher VO risk (P < 0.0001). Receiver Operating Characteristic (ROC) analysis showed that the optimal cut-off for EF thickness associated to youth VO is 3.2 mm. CONCLUSION: Ultrasonography EF measurement might be a second-level assessment tool, useful to detect early cardiometabolic damage stage.

Reliability of a dietary questionnaire on food habits, eating behaviour and nutritional knowledge of adolescents.

OBJECTIVE: To develop a dietary questionnaire on food habits, eating behaviour and nutrition knowledge of adolescents and to examine its reliability. DESIGN: A cross-sectional baseline survey. The questionnaire was self-administered to study participants twice with 7 days between each administration. SETTING: A school community in Pavia, Italy. SUBJECTS: A group of students (n=72, aged 14-17 y, both sexes) studying in a secondary school in the second year of the course were invited to compile a dietary questionnaire during school time. Informed written consent was obtained from each subject and their parents. Subjects were initially recruited for a nutrition intervention; recruitment was opportunistic and school based. STATISTICAL ANALYSES: Reliability was assessed using the Cronbach's alpha and the Pearson correlation coefficients. RESULTS: Cronbach's alpha ranges from a minimum of 0.55 to a maximum of 0.75, indicating that only two sections have a poor internal consistency. The Pearson correlation coefficients range from a minimum of 0.78 to a maximum of 0.88, indicating a very good temporal stability of the questionnaire. All the Pearson correlation coefficients are statistically significant with P<0.01. CONCLUSIONS: The present questionnaire has the potential to measure the effects of nutrition interventions on adolescents because of its stability in making comparisons over time. The instruments is low in cost and easy to administer and analyse; moreover, it could be modified appropriately to fit the needs of other populations as well.

Is a modest weight loss significant in the improvement of dyslipidemic patients lipid profile.

AIM: The aim of the present study was to evaluate serum lipid abnormalities and the relationship with various factors in overweight and obese patients and to assess lipid profile modifications subsequent to weight loss in a subgroup of patients. METHODS: A sample of 110 obese out-patients first and a subgroup of 34 subjects afterwards, was selected at the Human Nutrition Research Centre of the University of Pavia for a retrospective analysis. The subjects recruited were all dyslipidemic, according to the American Clinical Guidelines for the assessment of cardiovascular risk. Differences in lipid profiles in subjects with different life habits were evaluated and in a subgroup of 34 subjects compared before and after a short-term moderate hypocaloric diet. RESULTS: Sample's mean age was 46.8+/-12.6 with a mean body mass index (BMI) of 32.1+/-4.8 kg/m2 (no difference with gender). The correlation analyses showed that total cholesterol (TC) concentrations were highly correlated with age (p<0.001); no correlation was found between TC and BMI, waist hip ratio (WHR), % body fat (BF%). Triglycerides (TG) concentrations were not related to age or BMI, however there was a significant correlation between TG and WHR and with waist circumference (WC) (p<0.001). The 34 subjects selected to take part in a dietary regimen, without significant changes in life habits, lost 5.1% of their initial weight and presented a significant improvement (p<0.001) in lipid profile. CONCLUSIONS: The high correlation between lipid profile and anthropometric measurements implies further longitudinal evaluation of the validity of the anthropometric indexes in the dyslipidemic patient management. Indeed, the results suggest that modest weight loss is sufficient to obtain a significant improvement in fasting serum lipid profile of dyslipidemic overweight patients.

Evaluation of the efficacy of the Italian guidelines on COPD: a cluster randomized trial.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a profoundly disabling disease managed predominantly by General Practitioners (GPs). We planned this prospective trial to evaluate the applicability of Italian GP-directed guidelines in routine practice and whether adherence to them improves treatment efficacy, with respect to decreased exacerbations, hospital admissions, drug use, and out-patient appointments and improved quality of life (QoL). METHODS: In a cluster randomised trial, 22 GPs were randomly put into two groups: one group was asked to follow the guidelines (YES-GL), the other to continue normal clinical practice (NO-GL). These GPs enrolled 123 patients with COPD and followed them for one year. RESULTS: Patients managed by the YES-GL GPs had more outpatient appointments and specialist consultations and a higher probability of being classified as having severe COPD. The QoL was fairly low in both groups, and all other clinical outcomes taken into consideration, were not affected by application of the guidelines. CONCLUSION: The guidelines did not substantially alter the clinical evolution of COPD patients, even though some facets of management improved.

ECRHS screening questionnaire scoring: a methodological suggestion for asthma assessment. European Community Health Survey.

Univocal definition and classification of Asthma have always been a matter of discussion, and that is reflected in the difficulty of constructing a measure of pathology severity. The European Community Health Survey is a multinational survey designed to compare the prevalence of asthma in subjects, aged 20 to 44 years, in several European areas. In each participating center a sample of 3000 adults filled a self-administered screening questionnaire composed by 9 dichotomous items. Aim of the present study is to investigate unidimensionality of the ECRHS screening questionnaire and to determine and validate a scoring of asthma-like symptoms seriousness. Dimensionality and scoring was determined through a Homogeneity Analysis by Alternating Least Square; while scoring validation was assessed by a cross validation technique. This study found the existence of a sole dimension underlying the screening questionnaire; furthermore a scoring of asthma-like symptoms seriousness was determined with the indication of a cut-off in order to distinguish between asthma symptomatic and non symptomatic subjects.