A stepped-wedge randomised controlled trial to assess efficacy and cost-effectiveness of a care-bundle to prevent falls in older hospitalised patients.

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.

Associations Between Dietary Patterns and Kidney Health Assessed in the Population-Based CHRIS Study Using Reduced Rank Regression.

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.

Six-minute walk distance in healthy subjects: reference standards from a general population sample.

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, age2, 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*heightcm-0.99*weightkg + 22.58*active-0.10*age2 + 222.55 for females (R squared = 0.238) and 6MWD = 26.80*age + 8.46*heightcm-0.45*weightkg-2.54*active-0.06*age2-0.13*age*heightcm-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.

The Hook Test Is More Accurate Than the Trampoline Test to Detect Foveal Tears of the Triangular Fibrocartilage Complex of the Wrist.

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.

Dietary flavonoids and respiratory diseases: a population-based multi-case-control study in Italian adults.

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.

Effect of a tailored home-based exercise program in patients with systemic sclerosis: A randomized controlled trial.

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.

Biomarkers of Oxidative Stress and Inflammation in Chronic Airway Diseases.

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.

Stability and Expression Levels of HLA-C on the Cell Membrane Modulate HIV-1 Infectivity.

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/ß2 microglobulin [ß2m]/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 ß2m/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 ß2m/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 ß2 microglobulin/peptide; the other conformation is not bound to ß2 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 ß2 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.

Dietary fats, olive oil and respiratory diseases in Italian adults: A population-based study.

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.

Determinants of fractional exhaled nitric oxide in healthy men and women from the European Community Respiratory Health Survey III.

INTRODUCTION: The fractional exhaled nitric oxide (FE NO) is a marker for type 2 inflammation used in diagnostics and management of asthma. In order to use FE NO as a reliable biomarker, it is important to investigate factors that influence FE NO in healthy individuals. Men have higher levels of FE NO than women, but it is unclear whether determinants of FE NO differ by sex. OBJECTIVE: To identify determinants of FE 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 FE 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 FE NO, compared with the lowest age quartile. Height was related to 8% higher FE NO level in men (P < 0.001) and 5% higher FE NO levels in women (P = 0.008). Men who smoked had 37% lower FE 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 FE 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. FE NO started increasing at lower age in women than in men, suggesting that interpretation of FE NO levels in adults aged over 50 years should take into account age and sex.

Health-related quality of life varies in different respiratory disorders: a multi-case control population based study.

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.

The Heterogeneity Hidden in Allergic Rhinitis and Its Impact on Co-Existing Asthma in Adults: A Population-Based Survey.

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.

Anemia and hemoglobin serum levels are associated with exercise capacity and quality of life in chronic obstructive pulmonary disease.

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.

Occupational exposures and uncontrolled adult-onset asthma in the European Community Respiratory Health Survey II.

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.

Socioeconomic inequalities in smoking habits are still increasing in Italy.

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.

Mild asthma and chronic bronchitis seem to influence functional exercise capacity: a multi-case control study.

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.

The cost of persistent asthma in Europe: an international population-based study in adults.

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.

Burden and risk factors of chronic obstructive pulmonary disease in Sub-Saharan African countries, 1990-2019: a systematic analysis for the Global Burden of disease study 2019.

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.

Non-lesional white matter in relapsing-remitting multiple sclerosis assessed by multicomponent T2 relaxation.

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.