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Objective: While diet plays a key role in chronic kidney disease (CKD) management, the potential for diet to impact CKD prevention in the general population is less clear. Using a priori knowledge, we derived disease-related dietary patterns (DPs) through reduced rank regression (RRR) and investigated associations with kidney function, separately focusing on generally healthy individuals and those with self-reported kidney diseases, hypertension, or diabetes mellitus., Methods: Eight thousand six hundred eighty-six participants from the population-based Cooperative Health Research in South Tyrol study were split into a group free of kidney disease, hypertension and diabetes (n = 6,133) and a group with any of the 3 conditions (n = 2,553). Diet was assessed through the self-administered Global Allergy and Asthma Network of Excellence food frequency questionnaire and DPs were derived through RRR selecting food frequency questionnaire-derived sodium, potassium, phosphorus, and protein intake as mediators. Outcomes were creatinine-based estimated glomerular filtration rate, urinary albumin-to-creatinine ratio, CKD and microalbuminuria. Multiple linear and logistic models were used to assess associations between RRR-based DPs and kidney outcomes separately in the 2 analytic groups., Results: We identified 3 DPs, where high adherence reflected high levels of all nutrients (DP1), high potassium-phosphorus and low protein-sodium levels (DP2), and low potassium-sodium and high protein-phosphorus levels (DP3), respectively. We observed heterogeneous associations with kidney outcomes, varying by analytic group and sex. Kidney outcomes were much more strongly associated with DPs than with single nutrients., Conclusion: RRR is a feasible approach to estimate disease-related DPs and explore the combined effects of nutrients on kidney health. Heterogeneous associations across kidney outcomes suggest possible specificity to kidney function or damage. In individuals reporting kidney disease, hypertension or diabetes, specific dietary habits were associated with better kidney health, indicating that disease-specific dietary interventions can be effective for disease control., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The purpose of this study is to demonstrate that T2-weighted imaging with very long echo time (TE > 300 ms) can provide relevant information in neurodegenerative/inflammatory disorder. Twenty patients affected by relapsing-remitting multiple sclerosis with stable disease course underwent 1.5 T 3D FLAIR, 3D T1-weighted, and a multi-echo sequence with 32 echoes (TE = 10-320 ms). Focal lesions (FL) were identified on FLAIR. T1-images were processed to segment deep gray matter (dGM), white matter (WM), FL sub-volumes with T1 hypo-intensity (T1FL), and dGM volumes (atrophy). Clinical-radiological parameters included Expanded Disability Status Scale (EDSS), disease duration, patient age, T1FL, and dGM atrophy. Correlation analysis was performed between the mean signal intensity (SI) computed on the non-lesional dGM and WM at different TE versus the clinical-radiological parameters. Multivariable linear regressions were fitted to the data to assess the association between the dependent variable EDSS and the independent variables obtained by T1FL lesion load and the mean SI of dGM and WM at the different TE. A clear trend is observed, with a systematic strengthening of the significance of the correlation at longer TE for all the relationships with the clinical-radiological parameters, becoming significant (p < 0.05) for EDSS, T1FL volumes, and dGM atrophy. Multivariable linear regressions show that at shorter TE, the SI of the T2-weighted sequences is not relevant for describing the EDSS variability while the T1FL volumes are relevant, and vice versa, at very-long TEs (around 300 ms); the SI of the T2-weighted sequences significantly (p < 0.05) describes the EDSS variability. By very long TE, the SI primarily originates from water with a T2 longer than 250 ms and/or free water, which may be arising from the perivascular space (PVS). Very-long T2-weighting might detect dilated PVS and represent an unexplored MR approach in neurofluid imaging of neurodegenerative/inflammatory diseases., (© 2024 John Wiley & Sons Ltd.)

Purpose : The aim of the study was to compare bone mineral density (BMD) in the lumbar spine (LS BMD ) and the femoral neck (F BMD ) in male road cyclists (RC n  = 39), mountain cyclists (MC n  = 30) and controls (C n  = 27) and to determine the factors associated with BMD in the same group of participants. Methods : BMD, fat mass (FM) and fat-free mass (FFM) were measured using DXA. Calcium intake (Cal), exercise energy expenditure (EEE) and energy availability (EA) were assessed using self-reported questionnaires. Samples for circulating hormones were also obtained. VO 2max was estimated by a cycloergometric test. Results : After adjustment for body mass, in cyclists LS BMD (RC 0.98 ± 0.12; MC 0.98 ± 0.10 g/cm 2 ) was significantly lower than in C (1.11 ± 0.10; p  < .001), while F BMD resulted in no significant difference in cyclists compared to C ( p  = 0.213). EA (kcal/FFM/day) was different in cyclists and in C ( p  < .05). In C, EEE and EA were positively associated with LS BMD ( R  = 0.561, R  = 0.656, respectively, p  < .01), whereas only EA was associated with F BMD ( R  = 0.554, p  < .05); a positive association between EA and F BMD was found in MC ( R  = 0.464, p  < .05). A negative relationship between VO 2max and LS BMD in RC ( R = -0.418, p  < .05) and a positive one between EEE and LS BMD in MC were found ( R  = 0.605, p  < .001). CaI, free testosterone and cortisol were unrelated to BMD. Conclusion : Both the RC and MC had lower LS BMD than C, whereas no difference was found between the two groups of cyclists. The factors associated with BMD are manifold, vary in relation to the measurement site and are likely different in RC, MC and C.

Background: Patient accidental falls in a hospital environment are a serious problem for patient safety, and for the additional costs due to associated medical interventions., Objective: The endpoints of this study were the assessment of the fall incidence in the hospital before and after the implementation of a multidisciplinary care-bundle, along with a cost-effectiveness evaluation., Design: A stepped-wedge trial was conducted between April 2015 and December 2016 in Bologna University Hospital., Methods: Incidence rates (IRs) of falls in both the control and intervention periods were calculated. A multilevel mixed-effects generalised linear model with logit link function, adjusted for age, sex, cluster cross-over timing and patients' clinical severity was used to estimate odds ratios (OR) of fall risk of patients of the intervention group respect to the controls.Intervention costs associated with the introduction of the care-bundle intervention were spread between patients per cluster-period-group of exposure. Incremental cost-effectiveness ratio was evaluated using total costs in the intervention and control groups., Results: IRs of falls in control and intervention periods were respectively 3.15 and 2.58 for 1,000 bed-days. After adjustment, the subjects receiving the intervention had a statistically significant reduced risk of falling with respect to those who did not (OR = 0.71, 95% confidence interval: 0.60-0.84). According to the cost-effectiveness analysis, the incremental cost per fall prevented was €873.92 considering all costs, and €1644.45 excluding costs related falls., Conclusions: Care-bundle had a protective effect on patients, with a statistically significant reduction of the fall risk. This type of intervention appears cost-effective compared to routine practices., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Sub-Saharan Africa (SSA) has experienced a surge of non-communicable diseases (NCDs) including chronic obstructive pulmonary disease (COPD) over the past two decades. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), in this study we have estimated the burden and attributable risk factors of COPD across SSA countries between 1990 and 2019., Methods: COPD burden and its attributable risk factors were estimated using data from the 2019 GBD. Percentage change was estimated to show the trend of COPD estimates from 1990 to 2019. COPD estimates attributable by risk factors were also reported to ascertain the risk factor that brings the greatest burden by sex and locations (at country and regions level)., Findings: In 2019, all-age prevalent cases of COPD in SSA were estimated to be 10.3 million (95% Uncertainty Intervals (UI) 9.7 million to 10.9 million) showing an increase of 117% compared with the number of all-age COPD cases in 1990. From 1990 to 2019, SSA underwent an increased percentage change in all-age YLDs due to COPD ranging from 41% in Lesotho to 203% in Equatorial Guinea. The largest premature mortality due to COPD was reported from Central SSA accounting for 729 subjects (95% UI, 509-1078). The highest rate of DALYs attributable to COPD was observed in Lesotho. Household air pollution from solid fuel was the primary contributor of the age standardized YLDs, death rate, and DALYs rate per 100,000 population., Interpretation: The prevalence of COPD in SSA has had a steady increase over the past three decades and has progressively become a major public health burden across the region. Household air pollution from solid fuel is the primary contributor to COPD related burden, and its percentage contribution showed a similar trend to the reduction of COPD attributed age-standardized DALY rate. The methodological limitations of surveys and datapoints included in the GBD need to be considered when interpreting these associations., Funding: There are no specific fundings received for this study. The Global Burden of Disease study was supported by funding from the Bill & Melinda Gates Foundation., Competing Interests: All authors in the writing team declare no competing interests., (© 2023 The Authors.)

Nursing home (NH) residents are vulnerable subjects and highly susceptible to adverse events. Knowledge of patient safety culture (PSC) is essential for an organization to ensure patient safety. However, research on PSC in NHs, and its variability among staff, is still scarce. This study aimed to explore whether and how PSC differed among NH staff (Managers, Nurses, Direct Care Staff, Support Staff, Administrative Staff and Other Providers) in the Autonomous Province of Trento, Italy. This study employed a cross-sectional design and collected data from 1145 NH providers using the Nursing Home Survey on Patient Safety Culture (NHSPSC). Data were analyzed using linear mixed models, with each of the 12 NHSPSC domains as a response variable. The majority of the respondents (61.6%) were Direct Care Staff members. 'Feedback and Communication about Incidents' and 'Overall Perceptions of Resident Safety' were the domains with the highest proportions of positive answers (PPAs). For most staff categories, 'Staffing' was the domain with the lowest PPA. Support Staff showed significantly lower scores in the majority of domains (8/12). Shorter job tenure, fewer weekly working hours, working mostly during the day and working in highly specialized areas were associated with higher scores in several domains. Interventions to improve PSC must consider the differences between professional groups. Further research is needed to explore the relationship between job-related features and perceptions of patient safety among NH workers.

Background: Inhaled corticosteroids have been widely used for the regular treatment of asthma and chronic obstructive pulmonary diseases (COPD) over the past few decades. To date, studies investigating the effects of inhaled corticosteroids (ICS) on bone in populations including asthma and COPD patients, show conflicting results. The skeletal effects of ICS remain poorly understood. We assessed the association between ICS exposure and self-reported osteoporosis diagnosis in a European cohort study., Methods: The analysis was carried out by using clinical and questionnaire data available for subjects participating in the ECRHS III (European Community Respiratory Health Survey) with age >55 years., Results: Among the 3004 enrolled subjects, 245 were ICS users with an exposure ≥12 months. Osteoporosis was reported by 16 subjects in the ICS group (6.5%) and by 167 in the not exposed group (6.1%). The adjusted risk of osteoporosis in ICS users (≥12 months) was not greater in exposed subjects when compared with the unexposed ones (OR=1.02, 95CI%: 0.51, 2.03). The same result was observed even when considering in the analysis a longer exposure to the ICS use (≥36.5 months, the median ICS exposure for all subjects). History of COPD, use of oral corticosteroids, Body Mass Index, smoking and physical activity did not show any evidence of an association with osteoporosis., Conclusions: Our study did not show any significant association between long- term ICS use and self-reported diagnosis of osteoporosis in subjects aged >55 years. To explore the real effect of ICS on bone status, further studies are needed, especially in the long-term ICS exposure.

Objective: Whether blood eosinophils (bEOS) in chronic obstructive pulmonary disease (COPD) are associated with disease progression is a topic of debate. We aimed to evaluate whether the differential white blood cell (WBC) count, symptoms and treatment may predict lung function decline and exacerbations in COPD patients., Methods: We retrospectively examined stable COPD patients with a minimum follow-up of 3 years at our outpatients' clinic. We collected information about lung volumes (FEV1, FVC), the total and differential WBC count, acute exacerbations of COPD (number in the 12 months before the beginning of the study=AE-COPD-B, and during the follow-up=AE-COPD-F), smoking status and treatment. FEV1 decline and AE-COPD-F were described by using a generalized linear model and a 2-level random intercept negative binomial regression, respectively. The models included eosinophil and neutrophil counts as potential predictors and were adjusted by sex, age, smoking status, AE-COPD-B, treatment with bronchodilators and inhaled corticosteroids (ICS)., Results: Sixty-eight patients were considered, 36 bEOS- (<170 cells/μL, the median value) and 32 bEOS+ (≥170 cells/μL). ∆FEV1 was higher in bEOS+ than bEOS- (34.86 mL/yr vs 4.49 mL/yr, p=0.029). After adjusting for potential confounders, the eosinophil count was positively (β=19.4; CI 95% 2.8, 36.1; p=0.022) and ICS negatively (β=-57.7; CI 95% -91.5,-23.9; p=0.001) associated with lung function decline. bEOS were not found to be associated with the number of AE-COPD-F., Conclusion: In stable COPD patients, a higher level of blood eosinophils (albeit in the normal range) predicts a greater FEV1 decline, while ICS are associated with a slower progression of airflow obstruction.

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., (© 2022. The Author(s).)

Background: The coronavirus disease 2019 (COVID-19) pandemic had a devastating impact on nursing homes/long-term care facilities. This study examined the relationship between geography, size, design, organizational characteristics, and implementation of infection prevention and control (IPC) measures and the extent of COVID-19 outbreaks in nursing homes in the Autonomous Province of Trento (Italy) during the time frame of March-May 2020., Methods: The analysis included 57 nursing homes (5145 beds). The association between median cumulative incidence of COVID-19 cases among residents and characteristics of nursing homes was assessed by Mann-Whitney U test, Kruskal-Wallis test or Spearman rho. To evaluate the potential confounding of geographical area, a 2-level random intercept logistic model was fitted, with level 1 units (patients in nursing homes) nested into level 2 units (nursing homes), and "being a COVID-19 case" as the dependent variable., Results: Median cumulative incidence was not significantly associated with any of the variables, except for geographical region ( p = 0.002). COVID-19 cases clustered in the part of the province bordering the Italian region most affected by the pandemic (Lombardy) (45.2% median cumulative incidence)., Conclusions: Structural/organizational factors and standard IPC measures may not predict the epidemiology of COVID-19 outbreaks and be sufficient alone to protect nursing homes against them.

Purpose: To evaluate the accuracy of the trampoline and hook tests, used in the arthroscopic assessment of triangular fibrocartilage complex (TFCC) tears compared with arthroscopic direct visualization of the radiocarpal joint (RCJ) and of the distal radial ulnar joint (DRUJ)., Methods: In total, 135 patients (97 male, 38 female, mean age 43.5 years) were divided into 2 groups: (1) 80 patients with chronic ulnar-sided wrist pain and positive fovea sign and (2) 55 patients with other complaints. TFCC was assessed by RCJ and DRUJ arthroscopy and by the trampoline and hook tests to detect rupture of distal and proximal components of the TFCC. Accuracy, specificity, sensitivity, and likelihood ratio of the 2 diagnostic methods were measured and compared, using RCJ and DRUJ arthroscopy as reference., Results: The trampoline and the hook tests showed an overall accuracy of 70.37% and 86.67%, respectively. The accuracy of the trampoline test was similar for distal (69%), proximal (66%), and complete (73%) TFCC tears. The hook test was more accurate when evaluating proximal (97%) and complete (98%) tears, rather than distal lesions (75%). Sensitivity for the trampoline and hook tests was 75.00% and 0.00% (P < .001) for distal tears and 78.85% and 100.00% (P < .001) and 58.33% and 100.00% (P < .001) for complete or isolated proximal tears, respectively. Specificity for the trampoline and hook tests was 67.27% and 96.36% (P < .001) respectively., Conclusions: The trampoline and hook tests can assure accurate diagnosis of peripheral TFCC tear. The hook test shows greater specificity and sensitivity to recognize foveal TFCC tears. Values of positive likelihood ratio suggest a greater probability to detect foveal laceration of peripheral TFCC for the hook test than for the trampoline test. These findings suggest that DRUJ arthroscopy is not necessary to confirm foveal incompetence of the TFCC, if the hook test is positive., Level of Evidence: Level II, retrospective diagnostic trial., (Copyright © 2021 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background  Magnetic resonance imaging (MRI) has been considered the most appropriate examination for wrist ligament injuries diagnosis, but it frequently fails to assess the intrinsic ligament lesion. Therefore, wrist arthroscopy is required to enhance and define the diagnosis. Purpose  We compare the MRI imaging with wrist arthroscopy for intrinsic wrist ligaments (scapholunate [SL] and lunotriquetral [LT]) and triangular fibrocartilage complex (TFCC) injuries detection. Patients and Methods  From 2007 to 2014, 532 patients affected by suspected SL, LT, and TFCC posttraumatic ligament injury have been investigated by 1.5-Tesla MRI and wrist arthroscopy. Inclusion and exclusion criteria were adopted. Only for SL ligament injury, the arthroscopic findings of complete (stage IV) and partial (stages I-III) SL ligament injury were compared with MRI findings. Statistical analysis, including sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and the diagnostic odds ratio, was used to compare MRI with arthroscopic findings. Results  A total of 146 patients were accepted in the study. In 68 cases of arthroscopic SL ligament lesion, MRI confirmed the diagnosis only in 50% of the cases. In partial SL lesions, MRI was positive in 24.3% and in complete SL lesions, MRI was positive in 80.6% of the cases. In 10 cases of arthroscopic LT ligament lesion, MRI was positive in 30.0% of the cases. In 33 patients with arthroscopic TFCC lesion, MRI was positive in 66.7% of the cases. Conclusion  1.5-T MRI demonstrated to fail in confirming the lesion of SL, LP, and TFCC ligaments respectively in 50, 70, and 33.3% of the cases positive at arthroscopy. In complete SL ligament lesion, MRI reaches a higher sensitivity than in partial lesion. Arthroscopy remains the best method to demonstrate the ligament lesion and obtain more information regarding the extent and quality of the ligament damage. Level of Evidence  This is a Level II, retrospective comparative study., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Neurodevelopmental disorders (NDDs) have been suggested to lie on a gradient continuum, all resulting from common brain disturbances, but with different degrees of impairment severity. This case-control study aimed to assess postural stability against such hypothesis in 104 children/adolescents aged 5-17, of whom 81 had NDDs and 23 were healthy controls. Compared to healthy controls, Autism Spectrum Disorder (ASD) resulted in the most severely impaired neurodevelopmental condition, followed by Attention Deficit Hyperactive Disorder (ADHD) and Tourette Syndrome (TS). In particular, while ASD children/adolescents performed worse than healthy controls in a number of sensory conditions across all parameters, ADHD children/adolescents performed worse than healthy controls only in the sway area for the most complex sensory conditions, when their vision and somatosensory functions were both compromised, and performance in Tourette Syndrome (TS) was roughly indistinguishable from that of healthy controls. Finally, differences were also observed between clinical groups, with ASD children/adolescents, and to a much lesser extent ADHD children/adolescents, performing worse than TS children/adolescents, especially when sensory systems were not operationally accurate. Evidence from this study indicates that poor postural control may be a useful biomarker for risk assessment during neurodevelopment, in line with predictions from the gradient hypothesis.

Objective: 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)., Design: Multi-case-control study., Setting: 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., Participants: 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)., Results: 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)., Conclusions: 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.

Objective: The aim was to evaluate the effect of a home-based exercise program on functional capacity, health-related quality of life (HRQoL), and disability, in patients with systemic sclerosis (SSc)., Methods: A 6-month randomized controlled trial was conducted on SSc patients by comparing a home-based minimally supervised exercise program (exercise on a stationary cycle and strengthening of upper limbs; stretching of the hands) with usual care. At baseline and after 3 and 6 months, the patients underwent: 6 minutes walking test; hand mobility in scleroderma test; maximal exercise test on an ergocycle; strength measures (handgrip, quadriceps, and biceps). HRQoL (short-form 36 [SF-36]) and disability (health assessment questionnaire disability index [HAQ-DI]) were measured at the same time., Results: Forty-four patients participated in the study. Twenty-two were randomly assigned to the intervention group (IG, mean age 63.60 ± 10.40 years) and 22 to the control group (CG, 61.80 ± 14.40 years). At 6 months, the distance walked in 6 minutes increased by 46 m (baseline 486, 95% CI 458-513 m; 6 months 532, 95% CI 504-561 m) in IG, whereas it decreased by 5 m (baseline 464, 95% CI 431-497 m; 6 months 459, 95% CI 427-490 m) in CG with a significantly different temporal trend at the between-groups comparison (P < .001). An improvement was also observed for strength measures (handgrip, P = .003; quadriceps, P < .001; biceps, P < .001), for the SF-36 physical component score (P < .001) and for the HAQ-DI (P = .011)., Conclusions: This study indicates that in SSc patients, a minimally supervised home-based exercise program improves physical performance, quality of life, and disability in comparison with usual care., (© 2020 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

An amendment to this paper has been published and can be accessed via the original article.

Introduction: The global burden of chronic airway diseases represents an important public health concern. The role of oxidative stress and inflammation in the pathogenesis of these diseases is well known. The aim of this study is to evaluate the behavior of both inflammatory and oxidative stress biomarkers in patients with chronic bronchitis, current asthma and past asthma in the frame of a population-based study., Methods: For this purpose, data collected from the Gene Environment Interactions in Respiratory Diseases (GEIRD) Study, an Italian multicentre, multicase-control study, was evaluated. Cases and controls were identified through a two-stage screening process of individuals aged 20-65 years from the general population. Out of 16,569 subjects selected from the general population in the first stage of the survey, 2259 participated in the clinical evaluation. Oxidative stress biomarkers such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-isoprostane and glutathione and inflammatory biomarkers such as Fractional Exhaled Nitric Oxide (FENO) and white blood cells were evaluated in 1878 subjects., Results: Current asthmatics presented higher levels of FENO (23.05 ppm), leucocytes (6770 n/µL), basophils (30.75 n/µL) and eosinophils (177.80 n/µL), while subjects with chronic bronchitis showed higher levels of GSH (0.29 mg/mL) and lymphocytes (2101.6 n/µL). The multivariable multinomial logistic regression confirmed high levels of leucocytes (RRR = 1.33), basophils (RRR = 1.48), eosinophils (RRR = 2.39), lymphocytes (RRR = 1.26) and FENO (RRR = 1.42) in subjects with current asthma. Subjects with past asthma had a statistically significant higher level of eosinophils (RRR = 1.78) with respect to controls. Subjects with chronic bronchitis were characterized by increased levels of eosinophils (RRR = 2.15), lymphocytes (RRR = 1.58), GSH (RRR = 2.23) and 8-isoprostane (RRR = 1.23)., Conclusion: In our study, current asthmatics show a greater expression of the inflammatory profile compared to subjects who have had asthma in the past and chronic bronchitis. On the other hand, chronic bronchitis subjects showed a higher rate of expression of oxidative stress biomarkers compared to asthmatic subjects. In particular, inflammatory markers such as circulating inflammatory cells and FENO seem to be more specific for current asthma, while oxidative stress biomarkers such as glutathione and 8-isoprostane appear to be more specific and applicable to patients with chronic bronchitis.

Background: Inhaled corticosteroids (ICSs) are the mainstay of asthma treatment, but response to medication is variable. Patients with allergic inflammation generally show a better short-term response to ICSs; however, studies on predictors of long-term response are few., Objective: To assess whether allergic sensitization can modify the association between ICS use and lung function decline over 20 years in adult asthma., Methods: We used data from the 3 clinical examinations of the European Community Respiratory Health Survey. We measured ICS use (no use, and use for <1.3, 1.3-8, and >8 years) and FEV 1 decline among subjects with asthma over the 2 periods between consecutive examinations. We conducted a cohort study combining data of the 2 periods (906 observations from 745 subjects) to assess whether the association between ICS use and FEV 1 decline was modified by allergic sensitization (IgE > 0.35 kU/L for any of house-dust mite, timothy grass, cat, or Cladosporium)., Results: FEV 1 decline was similar for non-ICS users, as well as ICS users for less than 1.3 years, with and without allergic sensitization. However, among subjects on ICSs for a longer period, sensitization was associated with an attenuated decline (P interaction  = .006): in the group treated for more than 8 years, FEV 1 decline was on average 27 mL/y (95% CI Bonferroni-adjusted , 11-42) lower for subjects with sensitization compared with nonsensitized subjects., Conclusions: Our study suggests that biomarkers of atopy can predict a more favorable long-term response to ICSs. Randomized controlled studies are needed to confirm these findings., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A persistent low inflammatory-oxidative status and the inadequacy of the antioxidant nuclear factor-E2-related factor 2 (Nrf2) have been implicated in chronic obstructive pulmonary disease (COPD) progression. Therefore this study was aimed to assess the association between lung function decline and oxidative-inflammatory markers and Nrf2 signaling pathway expression in peripheral blood mononuclear cells (PBMCs) over time., Methods: 33 mild-moderate COPD outpatients (mean age 66.9 ± 6.9 years) were age-sex matched with 37 no-COPD subjects. A clinical evaluation, blood sampling tests and a spirometry were performed at baseline and after a mean follow-up of 49.7 ± 6.9 months., Results: In COPD, compared to no-COPD, we found a faster lung function decline at follow-up. Although similar prevalence of smoking, hypertension, diabetes and dyslipidemia, systemic markers of inflammation (hs-CRP and white blood cells, WBCs) and oxidative stress (8-isoprostane) were significantly increased in COPD at follow-up, while the antioxidant glutathione (GSH) was significantly reduced. Moreover the expression of Nrf2 and of Nrf2-related genes heme oxygenase (HO)-1 and glutamate-cysteine ligase catalytic (GCLC) subunit in PBMCS were significantly down-regulated in COPD at follow-up, whereas no changes were observed in no-COPD. The percent variation (Δ) of FEV 1 detected after the follow-up in COPD patients was directly correlated with ΔNrf2 (r = 0.826 p < 0.001), ΔHO-1 (r = 0.820, p < 0.001) and ΔGCLC (r = 0.840, p < 0.001). Moreover ΔFEV 1 was also directly correlated with ΔGSH (r = 0.595, p < 0.01) and inversely correlated with Δ8-iso (r = - 0.587, p < 0.01) and with baseline smoking history (r = - 0.39, p < 0.03). No correlation was found between ΔFEV 1 , ΔCRP and ΔWBCs. By means of hierarchical stepwise multiple linear regression, taking into account other baseline key factors related to FEV 1 , ΔNrf2, ΔHO-1and ΔGCLC were found to be significant predictors of ΔFEV 1 , explaining 89.5% of its variance., Conclusions: Although our results must be confirmed in larger trial they suggest that the down-regulation of Nrf2/ARE gene expression in PBMCs may be one of the determinants of FEV 1 decline and of COPD progression. Therefore the future possibility to counteract Nrf2 decline in COPD patients may help in reducing the negative effects of the oxidative stress-induced progression of the disease.

Background and Objectives: 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., Methods: 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., Results: 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])., Conclusions: 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., Competing Interests: The authors have declared that no competing interests exist.

Background: The research was conducted in the frame of a population-based, case control study, called Genes Environment Interaction in Respiratory Disease., Objective: To assess the association between protein intake and physical performance in a general population sample., Design: Researchers investigated the association between the participants' dietary information and their physical performance using the 6-min walking test and the distance walked in metres (6MWD) as main outcome measure. Information on dietary intake was collected using the validated European Investigation into Cancer and Nutrition food frequency questionnaires (FFQs). Then, daily intake of energy and macronutrients was estimated by means of the NAF software (nutritional analysis of FFQ). Linear regression models were used to evaluate the associations between vegetable, animal and total protein intakes and the 6MWD. The models were adjusted for socio-demographic features, total fats and available carbohydrate intakes., Results: The participants were 223 subjects (57% females) aged between 23 and 68 years. Their mean vegetable and animal proteins intake for gram/kg of body weight/day were, respectively, 0.4 and 0.7. After adjusting for all the potential confounders, there was a significant increase of 20.0 (95% CI 0.8; 39.2) m in the distance walked for an increase in 10 g/day of vegetable proteins and non-significant variations of -1.8 (95% CI -9.3; 5.7) m for an increase in 10 g/day of animal proteins and of 0.5 (95% CI -6.8; 7.7) for an increase in 10 g/day of total proteins., Discussion and Conclusions: Our result suggests a positive role of vegetable proteins on physical performance. Whether this result is related to the high protein intake itself or may be a consequence of the other properties of plant-based foods deserves further investigation., Competing Interests: The authors declare no potential conflicts of interest., (© 2019 Diana Gazzani et al.)

Introduction: The fractional exhaled nitric oxide (F E NO) is a marker for type 2 inflammation used in diagnostics and management of asthma. In order to use F E NO as a reliable biomarker, it is important to investigate factors that influence F E NO in healthy individuals. Men have higher levels of F E NO than women, but it is unclear whether determinants of F E NO differ by sex., Objective: To identify determinants of F E NO in men and women without lung diseases., Method: Fractional exhaled nitric oxide was validly measured in 3881 healthy subjects that had answered the main questionnaire of the European Community Respiratory Health Survey III without airways or lung disease., Results: Exhaled NO levels were 21.3% higher in men compared with women P < 0.001. Being in the upper age quartile (60.3-67.6 years), men had 19.2 ppb (95% CI: 18.3, 20.2) higher F E NO than subjects in the lowest age quartile (39.7-48.3 years) P = 0.02. Women in the two highest age quartiles (54.6-60.2 and 60.3-67.6 years) had 15.4 ppb (14.7, 16.2), P = 0.03 and 16.4 ppb (15.6, 17.1), P = <0.001 higher F E NO, compared with the lowest age quartile. Height was related to 8% higher F E NO level in men (P < 0.001) and 5% higher F E NO levels in women (P = 0.008). Men who smoked had 37% lower F E NO levels and women had 30% lower levels compared with never-smokers (P < 0.001 for both). Men and women sensitized to both grass and perennial allergens had higher F E NO levels compared with non-sensitized subjects 26% and 29%, P < 0.001 for both., Conclusion and Clinical Relevance: Fractional exhaled nitric oxide levels were higher in men than women. Similar effects of current smoking, height, and IgE sensitization were found in both sexes. F E NO started increasing at lower age in women than in men, suggesting that interpretation of F E NO levels in adults aged over 50 years should take into account age and sex., (© 2019 John Wiley & Sons Ltd.)

Background: Fat intake has been associated with respiratory diseases, with conflicting results., Objective: We studied the association between asthma and rhinitis with dietary fats, and their food sources in an Italian population., Methods: Clinical and nutritional information was collected for 871 subjects (aged 20-84) from the population-based multi-case-control study Genes Environment Interaction in Respiratory Diseases (GEIRD): 145 with current asthma (CA), 77 with past asthma (PA), 305 with rhinitis and 344 controls. Food intake was collected using the EPIC (European Investigation into Cancer and Nutrition) Food Frequency Questionnaire. The associations between fats and respiratory diseases were estimated by multinomial models. Fats and their dietary sources were analysed both as continuous variables and as quartiles., Results: Monounsaturated fatty acids and oleic acid were associated with a reduced risk of CA in both continuous (RRR = 0.68, 95%CI: 0.48; 0.96; RRR = 0.69; 95%CI: 0.49; 0.97, per 10 g, respectively) and per-quartile analyses (p for trend = 0.028 and 0.024, respectively). Olive oil was associated with a decreased risk of CA (RRR = 0.80; 95%CI: 0.65; 0.98 per 10 g). An increased risk of rhinitis was associated with moderate total fat and SFA intake., Conclusions: High dietary intakes of oleic acid and of olive oil are associated with a lower risk of asthma but not of rhinitis., (© 2019 John Wiley & Sons Ltd.)

Background and Objective: Health-related quality of life (HRQL) in respiratory diseases has been generally investigated in clinical settings, focusing on a single disorder. In this study on a general population sample, we assessed the relationship between HRQL and several respiratory diseases studied simultaneously (COPD, current (CA) and past (PA) asthma, allergic (AR) and non-allergic (NAR) rhinitis and chronic bronchitis (CB)., Methods: Controls (n = 328) and cases of NAR (n = 95), AR (n = 163), CB (n = 48), CA (n = 224), PA (n = 126) and COPD (n = 28) were recruited in the centre of Verona in the frame of the Italian multi-case control GEIRD (Gene Environment Interactions in Respiratory Diseases) study; HRQL was measured through the SF-36 questionnaire. The relationships between HRQL (in terms of Physical (PCS) and Mental Component Scores (MCS)), respiratory diseases, and covariates were evaluated., Results: With respect to controls, the adjusted PCS median score was worse in subjects suffering from current asthma (- 1.7; 95%CI:-2.8;-0.6), CB (- 3.8; 95%CI:-5.7;-1.9), and COPD (- 5.6; 95%CI:-8.1;-3.1). MCS was worse in current asthmatics (- 2.2; 95%CI:-4.1;-0.3), CB (- 5.5; 95%CI:-8.7;-2.2), and COPD cases (- 4.6; 95%CI:-8.8;-0.5) as well., Conclusions: To our knowledge, this is the first study in the general population that analyzed HRQL performing a simultaneous comparison of HRLQ in several respiratory disorders. We found that subjects suffering from COPD, CA, and CB had the poorest HRQL. Clinicians should carefully consider the possible impact of respiratory disorders as CB and not only that of CA and COPD.

Asthma often remains uncontrolled, despite the fact that the pharmacological treatment has undergone large changes. We studied changes in the treatment of asthma over a 20-year period and identified factors associated with the regular use of inhaled corticosteroid (ICS) treatment. Changes in the use of medication were determined in 4617 randomly selected subjects, while changes in adults with persistent asthma were analysed in 369 participants. The study compares data from three surveys in 24 centres in 11 countries. The use of ICSs increased from 1.7% to 5.9% in the general population and the regular use of ICSs increased from 19% to 34% among persistent asthmatic subjects. The proportion of asthmatic subjects reporting asthma attacks in the last 12 months decreased, while the proportion that had seen a doctor in the last 12 months remained unchanged (42%). Subjects with asthma who had experienced attacks or had seen a doctor were more likely to use ICSs on a regular basis. Although ICS use has increased, only one-third of subjects with persistent asthma take ICSs on a regular basis. Less than half had seen a doctor during the last year. This indicates that underuse of ICSs and lack of regular healthcare contacts remains a problem in the management of asthma., Competing Interests: Conflict of interest: J.A. Gullón has nothing to disclose. Conflict of interest: R. Jogi reports receiving Estonian Research Council Personal Research Grant 562 during the conduct of the study; consultancy and lecture fees from GSK, Boehringer and Novartis, and travel, accommodation and meeting expenses from GSK and Boehringer. Conflict of interest: A. Johannessen has nothing to disclose. Conflict of interest: V. Bellisario has nothing to disclose. Conflict of interest: C. Janson reports receiving personal fees for lectures and advisory boards from AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis and Teva, and for advisory boards from GSK, outside the submitted work. Conflict of interest: D. Jarvis reports receiving grants from Medical Research Council, during the conduct of the study. Conflict of interest: D. Gislason has nothing to disclose. Conflict of interest: I. Pin reports receiving travel grants from MSD, presentation fees from Teva, and both from AstraZeneca, outside the submitted work. Conflict of interest: J.L. Sánchez-Ramos has nothing to disclose. Conflict of interest: Isa Cerveri has nothing to disclose. Conflict of interest: S. Accordini has nothing to disclose. Conflict of interest: J.J. Weyler has nothing to disclose. Conflict of interest: R. Nielsen reports receiving grants from Boehringer Ingelheim and Novartis, personal fees from AstraZeneca, and grants and personal fees from GSK, outside the submitted work. Conflict of interest: L. Cazzoletti has nothing to disclose. Conflict of interest: J. Garcia-Aymerich has nothing to disclose. Conflict of interest: M. Holm has nothing to disclose. Conflict of interest: J. Martinez-Moratalla Rovira has nothing to disclose. Conflict of interest: V. Siroux reports receiving speakers’ honoraria from AstraZeneca, Novartis and Teva, outside the submitted work. Conflict of interest: A. Corsico has nothing to disclose. Conflict of interest: A. Marcon has nothing to disclose. Conflict of interest: S. Chanoine reports personal fees for board membership from AstraZeneca, and travel, accommodation and meeting expenses from Boehringer Ingelheim, Actelion Pharmaceuticals and MSD, outside the submitted work. Conflict of interest: J. Quint reports receiving grants from The Health Foundation, the MRC, the British Lung Foundation and IQVIA, grants and advisory board fees from GSK, Boehringer Ingelheim and AstraZeneca, travel fees from Chiesi and Teva, grants and speaking fees from Insmed, grants and consultancy fees from Bayer, outside the submitted work. Conflict of interest: D.S. Ferreira reports receiving grants from the Asthma Foundation of Victoria, Allen and Hanburys, and the National Health and Medical Research Council during the conduct of the study. Conflict of interest: D. Nowak has nothing to disclose. Conflict of interest: A. Malinovschi has nothing to disclose. Conflict of interest: K.A. Franklin has nothing to disclose. Conflict of interest: J. Heinrich has nothing to disclose.

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., Competing Interests: The previous principal investigator of the GEIRD study Prof. Roberto de Marco (deceased 2015) received a research grant from the “Chiesi Farmaceutici SpA”. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The “Chiesi Farmaceutici SpA”had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. All the authors of this manuscript have no competing interests.

The positive association between overweight, obesity, and cardiovascular and all-cause mortality is well established, even though this relation is typically U shaped with an increased risk also in low-weight subjects. However, being overweight or obese has been associated with a better prognosis in subjects suffering from chronic diseases, id est the "obesity paradox". In both community-dwelling and hospitalized patients with COPD, several studies have reported a significant protective effect of obesity on all-cause mortality, indicating that also in obstructive pulmonary diseases, an obesity paradox may be present. Interestingly, the "paradox" is more evident for subjects with severe bronchial obstruction (i.e., a lower FEV1), while in mild-moderate conditions, the weight-related mortality shows a behavior similar to that observed in the general population. Several factors may confound the relation between COPD, obesity and mortality. The lower FEV1 found in obese people may be linked to a restrictive defect rather than to an obstructive one. Due to the modified chest wall mechanical properties-related to increased fat mass-obese COPD patients may present, respect to their lean counterpart, a lower lung hyperinflation which is associated with higher mortality. The traditional classification of COPD attributes to obese "blue bloaters" a low-grade emphysema in opposition to lean "pink puffers"; the fact that emphysema extent is related to mortality may bias the relationship between weight and survival. It is also to underline that the majority of the studies, consider BMI rather than body composition (a better predictor of mortality) when studying the intriguing relation between weight, COPD, and mortality. Reverse bias has also to be taken into account, hypothesizing that an unintentional weight loss may be the deleterious factor related to mortality, rather than considering obesity a protective one. Further prospective studies are needed to shed light on the complexity of this emerging issue., Level of Evidence: Level V: Narrative Review.

HLA-C expression is associated with a differential ability to control HIV-1 infection. Higher HLA-C levels may lead to better control of HIV-1 infection through both a higher efficiency of antigen presentation to cytotoxic T lymphocytes and the triggering of activating killer immunoglobulin-like receptors on NK cells, whereas lower levels may provide poor HIV-1 control and rapid progression to AIDS. We characterized the relative amounts of HLA-C heterotrimers (heavy chain/β 2 microglobulin [β 2 m]/peptide) and HLA-C free heavy chains on peripheral blood mononuclear cells (PBMCs) from healthy blood donors harboring both alleles with stable or unstable binding to β 2 m/peptide. We analyzed the stability of HLA-C heterotrimers of different allotypes and the infectivity of HIV-1 virions produced by PBMCs with various allotypes. We observed significant differences in HLA-C heterotrimer stability and in expression levels. We found that R5 HIV-1 virions produced by PBMCs harboring unstable HLA-C alleles were more infectious than those produced by PBMCs carrying the stable variants. We propose that HIV-1 infectivity might depend both on the amounts of HLA-C molecules and on their stability as trimeric complex. According to this model, individuals with low-expression HLA-C alleles and unstable binding to β 2 m/peptide might have worse control of HIV-1 infection and an intrinsically higher capacity to support viral replication. IMPORTANCE Following HIV-1 infection, some people advance rapidly to AIDS while others have slow disease progression. HLA-C, a molecule involved in immunity, is a key determinant of HIV-1 control. Here we reveal how HLA-C variants contribute to the modulation of viral infectivity. HLA-C is present on the cell surface in two different conformations. The immunologically active conformation is part of a complex that includes β 2 microglobulin/peptide; the other conformation is not bound to β 2 microglobulin/peptide and can associate with HIV-1, increasing its infectivity. Individuals with HLA-C variants with a predominance of immunologically active conformations would display stronger immunity to HIV-1, reduced viral infectivity and effective control of HIV-1 infection, while subjects with HLA-C variants that easily dissociate from β 2 microglobulin/peptide would have a reduced immunological response to HIV-1 and produce more infectious virions. This study provides new information that could be useful in the design of novel vaccine strategies and therapeutic approaches to HIV-1., (Copyright © 2017 Parolini et al.)

Background: Few population-based studies have assessed the prevalence and the risk factors of non-allergic rhinitis (NAR) in comparison to allergic rhinitis (AR). Moreover, epidemiologic data on rhinitis in the elderly subjects and in southern Europe are scarce., Objective: This study aimed at estimating the prevalence and at comparing the risk factor distribution of AR and NAR in a general population sample aged 20-84 years in Italy., Methods: A questionnaire on respiratory symptoms and risk factors was administered to random samples of the Italian population aged 20-44 (n = 10,494) 45-64 (n = 2167) and 65-84 (n = 1030) in the frame of the Gene Environment Interactions in Respiratory Diseases (GEIRD) study. Current AR and NAR were defined according to the self-reported presence of nasal allergies or of nasal symptoms without a cold or the flu., Results: NAR showed a significant descending pattern in females from 12.0 % (95 % CI 11.1, 13.1) in the 20-44 year age class, to 7.5 % (5.4, 10.3) in the 65-84 year age class (p = 0.0009), and a roughly stable pattern in males, from 10.2 % (9.3, 11.2) to 11.1 % (8.4, 13.9) (p = 0.5261). AR decreased from 26.6 % (25.7, 27.6) in 20-44 years age class to 15.6 % (13.3, 18.0) in the 65-84 years age class (p < 0.0001), without gender difference. Subjects living near industrial plants and ex- and current smokers had a higher risk of NAR. Current smokers had a lower risk and subjects living in a Mediterranean climate a higher risk of AR., Conclusion: AR and NAR are fairly distinct conditions, as they have a different age, gender and risk factor distribution.

Background: Studies on the prevalence of eczema and atopic dermatitis (AD), and on the factors associated with these diseases, have been mostly performed in children, whereas studies on adult populations are lacking., Objectives: To determine the prevalence of eczema and AD in the Italian adult population, and to investigate risk factors associated with the disease., Methods: A postal screening questionnaire was administered to 18 357 randomly selected subjects aged 20-44 years in the Gene-Environment Interaction in Respiratory Diseases study, which involved seven centres distributed across northern, central and southern Italy. The questionnaire included items on the occurrence of doctor-diagnosed eczema, asthma and hay fever, socio-demographic characteristics and environmental exposures., Results: In all, 10 464 (57.0%) subjects responded to the questionnaire. The prevalence of current eczema was 8.1% (95% CI: 7.6-8.7%), while the prevalence of eczema with asthma and/or hay fever (EAH), which was adopted as proxy of AD, was 3.4% (95% CI: 3.1-3.8%). About 60% of the subjects with current eczema reported the onset of the disease in adulthood. In multi-variable models, the prevalence of eczema was significantly associated with female sex, older age, living close to industrial plants, high levels of heavy traffic near home and living in central-southern Italy., Conclusions: Eczema and EAH are highly prevalent in Italian young adults, especially in women. Our results suggest that adult onset is not unusual, and that environmental factors may influence the occurrence of eczema and EAH., (© 2014 European Academy of Dermatology and Venereology.)

Background: Little is known about the relationship between hemoglobin concentrations, functional status and health related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD). Our aim was to investigate the prevalence of anemia and the association of hemoglobin with shortness of breath, exercise capacity, muscle strength and HRQL, in COPD patients., Methods: A total of 105 COPD patients (77 males, 71.6 ± 9.2 years) were studied. Patients were classified as anemic and non anemic using the WHO criteria. We used the Medical Research Council Dyspnoea scale (MRCs) to measure shortness of breath. Exercise capacity was assessed using the six minute walking distance (6MWD) and the peak of VO2 during the maximal cycle ergometer test (VO2max). We used the Quadriceps and Handgrip strength assessment to determine muscle strength. The Saint George Respiratory Questionnaire was used to investigate HRQL. The physiological/functional characteristics of the two groups were compared. Regression models adjusting for confounders examined the independent association of anemia and of hemoglobin levels with clinical and functional outcomes., Results: Anemic patients (12.3%) showed a significantly higher MRCs, a lower 6MWD, VO2max, and a worse quality of life. On the contrary, there was no difference in muscle strength between the two groups. In the regression models, hemoglobin was independently associated with reduced exercise capacity and HRQL., Conclusions: Anemia in COPD was a risk factor for poorer exercise capacity and quality of life, and these outcomes were linearly associated with hemoglobin. Our results should stimulate further research into exploring whether increasing hemoglobin has a beneficial effect on the outcomes in COPD.

Background: It has been suggested that there is some overlap between allergic rhinitis (AR), sinusitis and polyposis, but this has not been fully documented. The present study aimed to evaluate the prevalence of these co-existing diseases and their impact on bronchial asthma in the general population of Italy., Methods: Within the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study, a postal screening questionnaire including questions about self-reported symptoms of asthma, AR, AR with sinusitis without nasal polyps (AR + SsNP) and AR with sinusitis with nasal polyps (AR + SwNP) was administered. Random samples of subjects aged between 20 and 44 years (n = 5,162) answered the postal questionnaire in 4 Italian centres (Pavia, Sassari, Turin, Verona). In AR subjects, the association among AR only, AR + SsNP, AR + SwNP and bronchial asthma was estimated by the relative risk ratio (RRR) using multinomial regression models., Results: The prevalence of AR in the sample was 25.4% (95% CI 24.2-26.6). A self-reported diagnosis of AR + SsNP and AR + SwNP was reported by 5.7% (95% CI 5.0-6.3) and by 1.2% (95% CI 0.9-1.5) of the subjects, respectively. Current asthma was reported by 17.5% of the AR subjects. In the adjusted multivariate analysis, the risk of having current asthma (RRR = 2.31, 95% CI 1.29-4.15), of having at least 1 asthma attack per year (RRR = 2.30, 95% CI 1.19-4.46) and of having had an emergency department admission for respiratory diseases (RRR = 5.61, 95% CI 1.81-23.92) was higher for subjects with AR + SwNP than subjects with AR only., Conclusions: The diagnosis of AR in the epidemiological setting includes heterogeneous upper airway diseases that affect the clinical features of AR and its interactions with asthma., (© 2016 S. Karger AG, Basel.)

Background: Socioeconomic inequalities in smoking habits have stabilized in many Western countries. This study aimed at evaluating whether socioeconomic disparities in smoking habits are still enlarging in Italy and at comparing the impact of education and occupation., Methods: In the frame of the GEIRD study (Gene Environment Interactions in Respiratory Diseases) 10,494 subjects, randomly selected from the general population aged 20-44 years in seven Italian centres, answered a screening questionnaire between 2007 and 2010 (response percentage = 57.2%). In four centres a repeated cross-sectional survey was performed: smoking prevalence recorded in GEIRD was compared with prevalence recorded between 1998 and 2000 in the Italian Study of Asthma in Young Adults (ISAYA)., Results: Current smoking was twice as prevalent in people with a primary/secondary school certificate (40-43%) compared with people with an academic degree (20%), and among unemployed and workmen (39%) compared with managers and clerks (20-22%). In multivariable analysis smoking habits were more affected by education level than by occupation. From the first to the second survey the prevalence of ever smokers markedly decreased among housewives, managers, businessmen and free-lancers, while ever smoking became even more common among unemployed (time-occupation interaction: p = 0.047). At variance, the increasing trend in smoking cessation was not modified by occupation., Conclusion: Smoking prevalence has declined in Italy during the last decade among the higher socioeconomic classes, but not among the lower. This enlarging socioeconomic inequality mainly reflects a different trend in smoking initiation.

Occupational exposure is a well-recognised modifiable risk factor for asthma, but the relationship between occupational exposure and asthma control has not been studied. We aimed to study this association among working-age adults from the European Community Respiratory Health Survey (ECRHS). Data were available for 7077 participants (mean age 43 years, 45% never-smokers, 5867 without asthma and 1210 with current asthma). Associations between occupational exposure to specific asthmagens and asthma control status (33% with uncontrolled asthma, based on the Global Initiative for Asthma guidelines) were evaluated using logistic and multinomial regressions, adjusted for age, sex and smoking status, with study areas included as a random effect. Statistically significant positive associations were observed between uncontrolled adult-onset asthma and both past 12-month and 10-year exposure to any occupational asthmagens (OR (95% CI) 1.6 (1.0-2.40) and 1.7 (1.2-2.5), respectively); high (1.7 (1.0-2.8) and 1.9 (1.3-2.9), respectively) and low (1.6 (1.0-2.7) and 1.8 (1.2-2.7), respectively) molecular weight agents; and cleaning agents (2.0 (1.1-3.6) and 2.3 (1.4-3.6), respectively), with stronger associations for long-term exposures. These associations were mainly explained by the exacerbation domain of asthma control and no associations were observed between asthmagens and partly controlled asthma. These findings suggest that occupational exposure to asthmagens is associated with uncontrolled adult-onset asthma. Occupational risk factors should be quickly identified to prevent uncontrolled asthma.

Background: Only few longitudinal studies on the course of asthma among adults have been carried out., Objective: 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., Methods: 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., Results: 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., Conclusion: 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.

Lung cancer is among the most common cancers in the world. Despite advances in defining the molecular mechanisms involved in lung oncogenesis and the remarkable efforts made to improve screening programs for secondary cancer prevention, patients' prognosis remains poor. Moreover, wide international inequalities remain apparent, even among developed countries. Here we analyze and discuss the findings of the extensive work by Walters S et al., recently published in "Thorax", which aimed to clarify whether differences in stage at diagnosis might explain these divergences. A better understanding of why survival differences between different states still exist will facilitate policy design to increase lung cancer overall survival itself and to bring it up to the highest international standards. It is the first international population-based study of lung cancer survival by stage at diagnosis and includes nearly 60,000 patients. By using a well detailed and appropriate statistical approach, authors conclude that improvement in outcomes is primarily related to a proper initial disease staging and that socioeconomic international and interregional inequalities might play a relevant role in this scenario. Our review takes in consideration both the methodological and scientific issues of the paper, focusing on the potential consequences in lung cancer management and on the need, in the post genomic era, of a molecular-based epidemiologic approach.

Background: In the Genes Environment Interaction in Respiratory Diseases population-based multi-case control study, we investigated whether asthma, chronic bronchitis (CB) and rhinitis were associated with a reduced 6-minute walk distance (6MWD), and whether the 6MWD determinants were similar for subjects with/without respiratory diseases., Methods: Cases of asthma (n = 360), CB (n = 120), rhinitis (n = 203) and controls (no respiratory diseases: n = 302) were recruited. The variation in the 6MWD across the groups was analyzed by ANCOVA, adjusting for gender, age, height, weight and comorbidity. The 6MWD determinants were studied by linear regression, and heterogeneity across the cases and controls was investigated., Results: The 6MWD differed across cases and controls (p = 0.01). It was shorter for cases of asthma (-17.1, 95% CI -28.3 to -5.8 m) and CB (-20.7, 95% CI: -36.6 to -4.8 m) than for controls (604 ± 68 m on average), but not for cases of rhinitis. The negative association between age and the 6MWD was significant for cases of CB, but not for the other groups (p = 0.001)., Conclusions: Even at the level of severity found in the general population, asthma and CB could influence the 6MWD, which seems to reflect the functional exercise level for daily physical activities. The negative association between ageing and the 6MWD was particularly strong in subjects with CB. Our report adds to the mounting evidence that CB is not a trivial condition, especially in the ageing adult population, and it supports the importance of monitoring functional capacity and of physical reconditioning in mild asthma., (Copyright © 2013 S. Karger AG, Basel.)

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., (Copyright © 2012 S. Karger AG, Basel.)

The prevalence of asthma increased worldwide until the 1990s, but since then there has been no clear temporal pattern. The present study aimed to assess time trends in the prevalence of current asthma, asthma-like symptoms and allergic rhinitis in Italian adults from 1990 to 2010. The same screening questionnaire was administered by mail or phone to random samples of the general population (age 20-44 yrs) in Italy, in the frame of three multicentre studies: the European Community Respiratory Health Survey (ECRHS) (1991-1993; n = 6,031); the Italian Study on Asthma in Young Adults (ISAYA) (1998-2000; n = 18,873); and the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (2007-2010; n = 10,494). Time trends in prevalence were estimated using Poisson regression models in the centres that repeated the survey at different points in time. From 1991 to 2010, the median prevalence of current asthma, wheezing and allergic rhinitis increased from 4.1% to 6.6%, from 10.1% to 13.9% and from 16.8% to 25.8%, respectively. The prevalence of current asthma was stable during the 1990s and increased (relative risk 1.38, 95% CI 1.19-1.59) from 1998-2000 to 2007-2010, mainly in subjects who did not report allergic rhinitis. The prevalence of allergic rhinitis has increased continuously since 1991. The asthma epidemic is not over in Italy. During the past 20 yrs, asthma prevalence has increased by 38%, in parallel with a similar increase in asthma-like symptoms and allergic rhinitis.

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 1990 s 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., (Copyright © 2012 S. Karger AG, Basel.)

Increased prevalence of respiratory and irritation symptoms was found in children who live near a large wood industrial park. Proximity to the wood industries was used as indicator of exposure. This study describes a sensitivity analysis for the results of the survey. All the children (3-14 years) living in the area were surveyed through a parental questionnaire (n=3854) and their addresses were geocoded. The distances from each child's home and school to the closest industry were combined, weighted and used as an indicator of exposure. A sensitivity analysis was performed to check 1) the robustness of the results to the choice of weights used for defining the exposure indicator, 2) the effect of outliers on risk estimates and 3) the sensitivity on the functional form used for modeling the dose-response function. The choice of the weights did not influence the association between proximity to the industries and respiratory symptoms. Excluding the subjects who lived far away from the industries showed that in a radius of 5km from the industries the study did not had enough power to estimate a gradient in the dose-response function. Besides, results were sensitive to the choice of the functional form used for modeling the minimum distance. The sensitivity analyses confirmed the overall increasing trend of respiratory symptoms with proximity to the industries and pointed out that all the assumptions made for defining a proxy of exposure need to be carefully checked., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Arg/Arg homozygotes for the Gly16Arg polymorphism in the β₂-adrenoreceptor gene (ADRB2) have a reduced response to short-acting β₂-agonists but no effect has been associated with long-acting β₂-agonists (LABAs). We selected 604 subjects with current asthma from the European Community Respiratory Health Study to evaluate whether asthma control and lung function decline were associated with Gly16Arg polymorphism, and to test whether LABA or inhaled corticosteroid (ICS) use modified these effects. There was an increased risk of noncontrolled asthma (OR 1.33, 95% CI 1.01-1.75; p = 0.046) for each Arg allele. Among nonusers of ICS, the odds ratio of noncontrolled asthma among Arg/Arg versus Gly/Gly subjects was 2.73 (95% CI 1.28-5.82; p = 0.009). No increased risk of noncontrolled asthma associated with the Arg allele was observed among ICS and/or LABA users. For each Arg allele, a mean ± se decrease in decline in forced expiratory volume in 1 s of 7.7 ± 2.5 mL·yr⁻¹ was found (p-value for trend 0.003), irrespective of ICS or LABA use. Arg/Arg subjects had an increased risk of bronchial hyperresponsiveness (BHR) versus Gly/Gly subjects, with an odds ratio of 2.51 (95% CI 1.12-5.63; p = 0.025) if they did not use ICS. The Arg allele was associated with poorer asthma control, a steeper lung function decline and BHR. Absence of genotypic effects on asthma control among ICS users may be due to reversed β₂-adrenoreceptor desensitisation.

Background: Immigration usually implies a complete change of the environment where one lives. Hence, studies on immigrants may help to disentangle genetic and environmental determinants of disease. We investigated whether the incidence of allergic and respiratory symptoms differed for Italian and immigrant children living in one area of Northern Italy., Methods: In December 2006, all the children (3-14 years) living in the Viadana district were surveyed through a parental questionnaire (response rate = 99%, n = 3854). Retrospective incidences of several symptoms were compared across different ethnic groups., Results: Parental asthma, allergic rhinitis and eczema were less frequent in immigrant children than in Italian children. Wheezing and eczema incidences were lower in children born to foreign parents (especially if born abroad, incidence rate ratio (IRR) = 0.47, 95% CI: 0.26-0.82 and IRR = 0.43, 95% CI: 0.23-0.83, respectively), with respect to Italian children, while the occurrence of nasal allergies was similar among the ethnic groups. The greatest incidence of persistent cough/phlegm was observed in children born in Italy to foreign parents (IRR = 1.98, 95% CI: 1.06-3.71) and in children whose parents had chronic bronchitis (IRR = 2.57, 95% CI: 1.52-4.33)., Conclusions: Considering the distribution of parental atopic diseases and the low disease prevalence in the immigrants' countries of origin, we suggest that nasal allergies may be more sensitive than wheezing or eczema to the change in the environment related to migration. Genetic or environmental factors clustered into families seem to have a role on chronic bronchitis., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Emissions related to wood production processes are a recognized health hazard for professionally exposed subjects. The health effects of living close to wood industries are not known, particularly in the pediatric population. We aimed at investigating if living close to chipboard industries is a health hazard for the children in the Viadana district (Northern Italy). In December 2006, all the children (3-14 years) living in the Viadana district, where two big chipboard industries are located, were surveyed through a parental questionnaire (n=3854). The children were geocoded, and the distance of their houses/schools from the closest wood plant was computed. Independently of sex, age, nationality, residential area, traffic, parents' education, passive/parental smoking, questionnaire compiler and his/her environmental concern, the children living at <2 km from chipboard industries had a greater prevalence of respiratory (OR=1.33, 95%CI: 1.11, 1.60), cough/phlegm (OR=1.43, 95%CI: 1.08, 1.88), nose/throat/mouth (OR=1.47, 95%CI: 1.23, 1.75), eye (OR=1.24, 95%CI: 1.04, 1.48) symptoms, school-days lost (OR=1.24, 95%CI: 1.04, 1.48), and emergency (OR=2.14, 95%CI: 1.47, 3.11) and hospital (OR=2.21, 95%CI: 1.17, 4.18) admissions. There was an inverse dose-response relationship between the adverse health outcomes considered and the distance from the plants. The attributable fractions for the children living close to the chipboard industries were substantial, ranging from 13% (eye symptoms) to 27% (cough/phlegm). The present findings suggest that emissions from chipboard industries might have a serious impact on children's health status and should therefore be reduced and closely monitored.

Background: The identification of the factors associated with severe asthma may shed some light on its etiology and on the mechanisms of its development. We aimed to describe asthma severity using the Global Initiative for Asthma (GINA) classification and to investigate its determinants in a cross-sectional, population-based sample in Europe., Methods: In the European Community Respiratory Health Survey II (1999-2002), 1,241 adults with asthma were identified. Severity was assessed using the 2002 GINA classification (intermittent, mild persistent, moderate persistent, severe persistent) and it was related to potential determinants by a multinomial logistic model, using the intermittent group as the reference category for relative risk ratios., Results: About 30% of asthmatic subjects were affected by moderate-to-severe asthma. Sensitization to Cladosporium was associated with a more than 5-fold greater risk of having (mild, moderate or severe) persistent asthma than intermittent asthma. Persistent asthma was positively associated with sensitization to house dust mite, nonseasonal asthma, an older age at asthma onset, and chronic cough and phlegm. Sensitization to cat increased the risk of severe asthma only. Smoking was more strongly associated with asthma severity in men, while rhinitis was more strongly associated with asthma severity in women., Conclusions: One third of the asthmatic population have moderate-to-severe asthma. Sensitization to perennial indoor allergens, particularly Cladosporium, is strongly associated with asthma severity. The role of smoking and rhinitis in determining asthma severity may differ between the sexes, and it should be further investigated.