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Introduction The 6-min walking distance (6MWD) test is a useful tool to obtain a measure of functional exercise capacity. However, reference equations have been mainly based on selected populations or small samples. The purpose of this study was to determine the reference equations to predict the 6MWD in a large Italian population sample of healthy adults of a wide age range. Methods In the frame of the multi case–control population-based study Gene Environment Interaction in Respiratory Diseases (GEIRD), we studied 530 healthy subjects: 287 females ranging 21–76 and 243 males ranging 21–78 years of age. We measured 6MWD, demographic and anthropometric data and collected the reported physical activity. A multiple linear regression model for the 6MWD included age, age 2 , height, weight and physical activity for both sex equations. The two-way interaction age-height and age-weight and the quadratic terms of weight and height were also tested for inclusion separately in each model. Results The mean ± SD for 6MWD was 581.4 ± 66.5 m (range 383–800 m) for females and 608.7 ± 80.1 m (range 410–875 m) for males. The reference equations were 6MWD = 8.10*age + 1.61*height cm −0.99*weight kg  + 22.58*active−0.10*age 2  + 222.55 for females (R squared = 0.238) and 6MWD = 26.80*age + 8.46*height cm −0.45*weight kg −2.54*active−0.06*age 2 −0.13*age*height cm −890.18 for males (R squared = 0.159), where “active” is 1 when the subject is physically active, 0 otherwise. Conclusion This study is the first to describe the 6MWD in a large population sample of young, middle aged and elderly healthy Caucasian subjects, and to determine reference equations. These findings will help to improve the evaluation of Italian and European patients with diseases influencing their functional capacity.

Background The relationship between diet, respiratory diseases and the mechanisms underlying their association are still poorly understood. In an adult sample, we investigated the associations between diet quality evaluated by two dietary scores (Italian Mediterranean Index (IMI), Modified Mediterranean Score (MDS)) and asthma and rhinitis prevalence. Additionally, total and differential white blood cells count, as inflammation indicators and two markers of oxidative stress, 8-iso-prostaglandin F 2α (8-isoprostane) and 8-oxo-dihydro-deoxyguanosine (8-OHdG), were measured. Methods A total of 1183 subjects (aged 20–84) in the frame of a population-based multi-case-control study were studied: 186 with current asthma (CA), 103 with past asthma (PA), 445 with rhinitis (RN) and 449 controls. Food intake was assessed by using the EPIC Food Frequency Questionnaire. 8-OHdG and 8-isoprostane were measured on spot urine and standardized by creatinine. Results A higher adherence to IMI was associated with a lower risk of CA (RRR: 0.50; 95%CI: 0.31;0.81; p  = 0.005), but not PA or RN. In CA a higher adherence to the Mediterranean diet (MD) was associated with a lower neutrophil percentage out of total leukocytes (p for trend = 0.022 and p  = 0.014 for IMI and MDS, respectively). Urinary 8-isoprostane was not associated with the MD adherence in any of the groups. In subjects with CA, those who were highly adherent according to MDS had higher 8-OH-dG urinary concentrations than non-adherents ( p  = 0.040) and in subjects with PA, they had lower 8-isoprostane than non-adherents ( p  = 0.026). Conclusions Our findings suggest that the MD might be a protecting factor for asthma, but not for rhinitis. The link between diet and asthma is probably the reduction in chronic inflammation, whereas oxidative stress does not seem to influence this relationship.

Background: This study is aimed at providing a real-world evaluation of the economic cost of persistent asthma among European adults according to the degree of disease control [as defined by the 2006 Global Initiative for Asthma (GINA) guidelines]. Methods: A prevalence-based cost-of-illness study was carried out on 462 patients aged 30–54 years with persistent asthma (according to the 2002 GINA definition), who were identified in general population samples from 11 European countries and examined in clinical settings in the European Community Respiratory Health Survey II between 1999 and 2002. The cost estimates were computed from the societal perspective following the bottom-up approach on the basis of rates, wages and prices in 2004 (obtained at the national level from official sources), and were then converted to the 2010 values. Results: The mean total cost per patient was EUR 1,583 and was largely driven by indirect costs (i.e. lost working days and days with limited, not work-related activities 62.5%). The expected total cost in the population aged 30–54 years of the 11 European countries was EUR 4.3 billion (EUR 19.3 billion when extended to the whole European population aged from 15 to 64 years). The mean total cost per patient ranged from EUR 509 (controlled asthma) to EUR 2,281 (uncontrolled disease). Chronic cough or phlegm and having a high BMI significantly increased the individual total cost. Conclusions: Among European adults, the cost of persistent asthma drastically increases as disease control decreases. Therefore, substantial cost savings could be obtained through the proper management of adult patients in Europe.

To analyse the associations between chronic respiratory diseases and intakes of total flavonoids and their major subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, polymers and proanthocyanidins). Multi-case-control study. The analysis was conducted in the frame of the Genes Environment Interaction in Respiratory Diseases (GEIRD) study. The European Prospective Investigation into Cancer and Nutrition FFQ was used to ascertain dietary intake. Multinomial regression models adjusting for age, sex, centre, BMI, smoking habit, alcohol intake, education, total energy intake, vitamin C intake and total fruit intake were used to examine the associations between dietary exposures and the relative risk ratio (RRR) of being a case. Individuals (n 990) hierarchically defined as follows: cases with asthma (current, n 159; past, n 78), chronic bronchitis (n 47), rhinitis (allergic rhinitis, n 167; non-allergic rhinitis, n 142) and controls (n 97). An increase of 1 sd in flavanones was associated with a reduced risk of non-allergic rhinitis (adjusted RRR = 0·68, 95 % CI 0·47, 0·97); a similar result was found comparing the highest v. lowest quartile of flavanones intake (adjusted RRR = 0·24, 95 % CI 0·10, 0·59). Flavonoids contained in fruits and vegetables, especially flavanones, might reduce the risk of non-allergic rhinitis. No associations were found between other flavonoids and the considered outcomes.

Background Chronic kidney disease (CKD) is a growing public health concern, closely linked to aging and chronic conditions such as diabetes, cardiovascular disease, and hypertension. Diet is a modifiable risk factor for kidney function, but evidence on how specific dietary patterns (DPs) relate to kidney health in healthy populations remains limited. To address this, we evaluated associations between DPs and kidney function, considering sex and menstrual status. DPs were derived using both an a priori approach (DASH) and a hybrid method (RRR), capturing established dietary recommendations as well as population-specific behaviours relevant to kidney health. Methods We analysed cross-sectional data from 6133 healthy adult participants of the Cooperative Health Research In South Tyrol (CHRIS) study. Participants self-reporting previous diagnoses of any kidney disease, hypertension, or diabetes were excluded. Using self-reported food frequency questionnaire data, we derived the DASH-score and two RRR-based sex-specific DP-scores based on nine cardio-renal-metabolic parameters. We applied sex-stratified linear and non-linear models to examine associations with creatinine-based eGFR, including interaction and stratified analyses by menstrual status in females. Results In males, a DP reflecting high intake of cereals, whole grains, sugar, fruits, and legumes, and low intake of beer, red and processed meat was associated with higher eGFR levels (β = 0.75, p  = 0.0001). Similarly, higher adherence to the DASH diet was also positively associated with eGFR (β = 0.64, p  = 0.0029). In females, the associations varied by menstrual status. Among those with ceased menstruation, a DP reflecting low intake of meat, spirits, and refined grains, and high intake of whole grains and dairy products was associated with higher eGFR (β = 1.11, p  = 0.0049). In females still experiencing regular menstruation, a DP reflecting high intake of beef, nuts, beer, and legumes, and low intake of refined grains was associated with lower eGFR (β = −0.43, p  = 0.0326). No association was observed with the DASH score in females. Conclusions The DASH-style diet is associated with better kidney function in males, but not in females. Identifying sex-specific kidney function-oriented DPs using RRR provides new insights into the diet-eGFR relationship, suggesting potential effect modification by menstrual status.

Cardiovascular and respiratory diseases can frequently coexist. Understanding their link may improve disease management. We aimed at assessing the associations of chronic bronchitis (CB), asthma and rhinitis with cardiovascular diseases and risk factors in the general population. We used data collected in the Gene Environment Interactions in Respiratory Diseases study, an Italian multicentre, multicase-control study. Among 2463 participants (age 21-86, female 50%) who underwent standardized interviews, skin prick and lung function tests, we identified 254 cases of CB without airflow obstruction, 418 cases of asthma without CB, 959 cases of rhinitis alone, and 832 controls. The associations of respiratory diseases with reported cardiovascular risk factors (lifestyles, hypertension, dyslipidaemia), heart disorders (myocardial infarction, coronary thrombosis, angina, aorta or heart surgery) and intermittent claudication were estimated through relative risk ratios (RRR) by multinomial logistic regression models. Compared to controls, CB cases were more likely to be heavy smokers, alcohol consumers, physically inactive, and to suffer from hypertension or dyslipidaemia; rhinitis cases were less obese but more likely to have hypertension. Asthma was significantly associated with current smoking. After adjusting for cardiovascular risk factors, heart disorders were associated with CB (RRR[95%CI]: 1.58[1.12-2.22]) and rhinitis (1.35[0.98-1.85]) and intermittent claudication was associated with CB (3.43[2.52-4.67]), asthma (1.51[1.04-2.21]) and rhinitis (2.03[1.34-3.07]). CB, asthma and rhinitis were associated with cardiovascular risk factors and diseases. In particular, CB shared with cardiovascular diseases almost all risk factors and was strongly associated with a higher risk of heart disorders and intermittent claudication.

Introduction The purpose of the study is to investigate, by T2 relaxation, non‐lesional white matter (WM) in relapsing–remitting (RR) multiple sclerosis (MS). Methods Twenty stable RR MS patients underwent 1.5T Magnetic Resonance Imaging (MRI) with 3D Fluid‐Attenuated Inversion‐Recovery (FLAIR), 3D‐T1‐weighted, and T2‐relaxation multi‐echo sequences. The Lesion Segmentation Tool processed FLAIR images to identify focal lesions (FLs), whereas T1 images were segmented to identify WM and FL sub‐volumes with T1 hypo‐intensity. Non‐lesional WM was obtained as the segmented WM, excluding FL volumes. The multi‐echo sequence allowed decomposition into myelin water, intra‐extracellular water, and free water (Fw), which were evaluated on the segmented non‐lesional WM. Correlation analysis was performed between the non‐lesional WM relaxation parameters and Expanded Disability Status Scale (EDSS), disease duration, patient age, and T1 hypo‐intense FL volumes. Results The T1 hypo‐intense FL volumes correlated with EDSS. On the non‐lesional WM, the median Fw correlated with EDSS, disease duration, age, and T1 hypo‐intense FL volumes. Bivariate EDSS correlation of FL volumes and WM T2‐relaxation parameters did not improve significance. Conclusion T2 relaxation allowed identifying subtle WM alterations, which significantly correlated with EDSS, disease duration, and age but do not seem to be EDSS‐predictors independent from FL sub‐volumes in stable RR patients. Particularly, the increase in the Fw component is suggestive of an uninvestigated prodromal phenomenon in brain degeneration. In this study, stable relapsing−remitting MS patients were investigated by conventional imaging, WM T2−relaxation, and a fully automated post−processing. The T2−relaxation method allowed the identification of subtle alterations in non lesional WM, particularly an increase of the free water (Fw) component, which correlates with EDSS, disease duration, and patient age. Such increase in the Fw component is suggestive of an unexplored prodromal phenomenon in brain degeneration.

In this study we aimed at identifying main demographic, laboratory and environmental factors influencing the level of urinary biomarkers (DNA-derived 8-oxodG and lipid membrane-derived 8-isoprostane), and deriving their adjusted 95% reference intervals (RI) in a sample of healthy people from the general population. Data from 281 healthy subjects from the Gene Environment Interactions in Respiratory Diseases survey were used in this study. Generalized additive models for location, scale and shape (GAMLSS) were used to find determinants of the biomarkers among gender, age, season and distance from collection (DFC), and to predict their RI. The RI of the biomarkers stratified by season and adjusted for DFC showed a slight statistically significant decrease in the biomarkers at the increasing DFC in two seasons, except the 8-oxodG during the warm season: median levels at the min and max values of DFC were (ng/mgcreat) 7.0-1.1 in the cold and 3.9-3.9 in the warm seasons for 8-oxodG, 0.7-0.2 in the cold and 1.3-0.6 in the warm seasons for 8-isoprostane. Both the biomarkers should be evaluated in association with the DFC and season in large epidemiological studies. The (semi)parametric GAMLSS method is a useful and flexible technique, which makes it possible to estimate adjusted RI.

Background: The prevalence rates of smoking in subjects with asthma have frequently been reported as similar to those in the general population; however, available data are not up-to-date. There is only limited and somewhat conflicting information on the long-term effects of smoking on health outcomes among population-based cohorts of subjects with asthma. We aimed to investigate changes in smoking habits and their effects on forced expiratory volume in 1 s (FEV 1 ) in subjects with asthma in comparison with the rest of the population, focusing on the healthy smoker effect. Methods: We studied 9,092 subjects without asthma and 1,045 with asthma at baseline who participated in both the European Community Respiratory Health Survey I (20–44 years old in 1991–1993) and II (1999–2002). Results: At follow-up, smoking was significantly less frequent among subjects with asthma than in the rest of the population (26 vs. 31%; p < 0.001). Subjects with asthma who were already ex-smokers at the beginning of the follow-up in the 1990s had the highest mean asthma score (number of reported asthma-like symptoms, range 0–5), probably as a result of the healthy smoker effect (2.80 vs. 2.44 in never smokers, 2.19 in quitters and 2.24 in smokers; p < 0.001). The influence of smoking on FEV 1 decline did not depend on asthma status. Smokers had the highest proportion of subjects with chronic cough/phlegm (p < 0.01). Conclusion: One out of 4 subjects with asthma continues smoking and reports significantly more chronic cough and phlegm than never smokers and ex-smokers. This stresses the importance of smoking cessation in all patients with asthma, even in those with less severe asthma.

Only few longitudinal studies on the course of asthma among adults have been carried out. The aim of the present prospective study, carried out between 2000 and 2009 in Italy, is to assess asthma remission and control in adults with asthma, as well as their determinants. All the subjects with current asthma (21-47 years) identified in 2000 in the Italian Study on Asthma in Young Adults in 6 Italian centres were followed up. Asthma remission was assessed at follow-up in 2008-2009 (n = 214), asthma control at baseline and follow-up. Asthma remission and control were related to potential determinants by a binomial logistic and a multinomial logistic model. Separate models for remission were used for men and women. The estimate of the proportion of subjects who were in remission was 29.7% (95%CI: 14.4%;44.9%). Men who were not under control at baseline had a very low probability of being in remission at follow-up (OR = 0.06; 95%CI:0.01;0.33) when compared to women (OR = 0.40; 95%CI:0.17;0.94). The estimates of the proportion of subjects who were under control, partial control or who were not under control in our sample were 26.3% (95%CI: 21.2;31.3%), 51.6% (95%CI: 44.6;58.7%) and 22.1% (95%CI: 16.6;27.6%), respectively. Female gender, increasing age, the presence of chronic cough and phlegm and partial or absent asthma control at baseline increased the risk of uncontrolled asthma at follow-up. Asthma remission was achieved in nearly 1/3 of the subjects with active asthma in the Italian adult population, whereas the proportion of the subjects with controlled asthma among the remaining subjects was still low.