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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. [ABSTRACT FROM AUTHOR]

Background: In epidemiological studies, continuous measures of asthma severity should be used to catch the heterogeneity of phenotypes. This study aimed at developing and validating continuous measures of asthma severity in adult patients with ever asthma from the general population, to be used in epidemiological studies. Methods: Respiratory symptoms, anti-asthmatic treatment and lung function were measured on 520 patients with ever asthma aged 20–64 years from the general Italian population (GEIRD study; 2007/2010). The variables that represent the same dimension of asthma severity were identified through an exploratory factor analysis and were summarized through a multiple factor analysis. Results: Only respiratory symptoms and anti-asthmatic treatment were summarized in a continuous score (STS). STS ranges from 0 (no symptoms/treatment) to 10 (maximum symptom frequency and treatment intensity). STS was positively correlated with the Global Initiative for Asthma classification of asthma severity computed on the 137 cases with a doctor's diagnosis (Spearman’s coefficient = 0.61, p-value<0.0001) (concurrent validity). Furthermore, using a cohort of 1,097 European asthmatics (ECRHS II study; 1999/2002), increasing STS levels at baseline (1991/1993) were positively associated with long-term outcomes (hospitalization and lost workdays for breathing problems, asthma attack frequency and use of asthma controllers) (predictive validity). Finally, the STS scores computed from the GEIRD and ECRHS II data were comparable (Lin’s coefficient = 0.95, p-value<0.0001) (replication analysis). Conclusions: STS is a valid and replicable measure of asthma severity in adults, which could be used in association studies. [ABSTRACT FROM AUTHOR]