Restricted spirometry and cardiometabolic comorbidities: Results from the international population based BOLD study

Background: Whether restricted spirometry, i.e. low Forced Vital Capacity (FVC), predicts chronic cardiometabolic disease is not definitely known. In this international population-based study, we assessed the relationship between restricted spirometry and cardiometabolic comorbidities. Methods: A total of 23,623 subjects (47.5% males, 19.0% current smokers, age: 55.1 ± 10.8 years) from five continents (33 sites in 29 countries) participating in the Burden of Obstructive Lung Disease (BOLD) study were included. Restricted spirometry was defined as post-bronchodilator FVC < 5th percentile of reference values. Self-reports of physician-diagnosed cardiovascular disease (CVD; heart disease or stroke), hypertension, and diabetes were obtained through questionnaires. Results: Overall 31.7% of participants had restricted spirometry. However, prevalence of restricted spirometry varied approximately ten-fold, and was lowest (8.5%) in Vancouver (Canada) and highest in Sri Lanka (81.3%). Crude odds ratios for the association with restricted spirometry were 1.60 (95% CI 1.37–1.86) for CVD, 1.53 (95% CI 1.40–1.66) for hypertension, and 1.98 (95% CI 1.71–2.29) for diabetes. After adjustment for age, sex, education, Body Mass Index (BMI) and smoking, the odds ratios were 1.54 (95% CI 1.33–1.79) for CVD, 1.50 (95% CI 1.39–1.63) for hypertension, and 1.86 (95% CI 1.59–2.17) for diabetes. Conclusion: In this population-based, international, multi-site study, restricted spirometry associates with cardiometabolic diseases. The magnitude of these associations appears unattenuated when cardiometabolic risk factors are taken into account

Association between lung function and dyspnoea and its variation in the multinational Burden of Obstructive Lung Disease (BOLD) study

Background: Dyspnoea is a common symptom of respiratory disease. However, data on its prevalence in general populations and its association with lung function are limited and are mainly from high-income countries. This study aimed to estimate the prevalence of dyspnoea across several world regions and to investigate the association of dyspnoea with lung function. Methods: Dyspnoea was assessed, and lung function was measured in 25,806 adult participants of the multinational Burden of Obstructive Lung Disease study. Dyspnoea was defined as ≥2 on the modified Medical Research Council (mMRC) dyspnoea scale. The prevalence of dyspnoea was estimated for each of the study sites and compared across countries and world regions. Multivariable logistic regression was used to assess the association of dyspnoea with lung function in each site. Results were then pooled using random-effects meta-analysis. Results: The prevalence of dyspnoea varied widely across sites without a clear geographical pattern. The mean prevalence of dyspnoea was 13.7 % (SD=8.2 %), ranging from 0 % in Mysore (India) to 28.8 % in Nampicuan-Talugtug (Philippines). Dyspnoea was strongly associated with both spirometry restriction (FVC<LLN: OR 2.07, 95 %CI 1.75–2.45) and spirometry airflow obstruction (FEV1/FVC<LLN: OR 3.76, 95 %CI 1.04–4.65). These associations did not significantly differ between sexes, age groups, or smoking history. The association of dyspnoea with airflow obstruction was weaker among obese participants (OR 2.20, 95 %CI 1.61–3.01). Conclusion: The prevalence of dyspnoea varies substantially across the world and is strongly associated with lung function impairment. Using the mMRC scale in epidemiological research should be discussed.info:eu-repo/semantics/publishedVersio

Statistical evaluation of a new resistance model for cold-formed stainless steel cross-sections subjected to web crippling

This paper presents a statistical evaluation according to Annex D of EN 1990 (2002) of a new resistance function for web crippling design of cold-formed stainless steel cross-sections. This resistance function was derived by Bock et al. (2013) through the use of carefully validated numerical models with the aim to propose a design expression for stainless steel sections, which are currently designed following the provisions for cold-formed carbon steel sections given in EN 1993-1-3 (2006). Although it was shown that the proposed design equation is appropriate for application to various stainless steels, the statistical uncertainties in material properties that the different types of stainless steels exhibit require an assessment of various partial safety factors. The statistical assessment showed that the proposed resistance function by Bock et al. (2013) requires adjustment to satisfy the safety level set out in EN 1993-1-4 (2006); A recalibration is performed herein. The web crippling design provisions given in EN 1993-1-3 (2006) and SEI/ASCE 8-02 (2002) American standard for application to stainless steel are also statistically evaluated herein. Comparison with test and numerical data showed that the predictions of the recalibrated resistance function are better suited and consistent than existing design provisionsResearch Fund for Coal and Stee

The association of spirometric small airways obstruction with respiratory symptoms, cardiometabolic diseases, and quality of life: Results from the Burden of Obstructive Lung Disease (BOLD) study

Background: Spirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown. Methods: Using data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF25-75) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV3/FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV1/FVC ≥ LLN). Results: Almost a fifth of the participants had spirometric SAO (19% for FEF25-75; 17% for FEV3/FVC). Using FEF25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77–2.70), chronic cough (OR = 2.56, 95% CI 2.08–3.15), chronic phlegm (OR = 2.29, 95% CI 1.77–4.05), wheeze (OR = 2.87, 95% CI 2.50–3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11–1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV3/FVC. Isolated spirometric SAO (10% for FEF25-75; 6% for FEV3/FVC), was also associated with respiratory symptoms and cardiovascular disease. Conclusion: Spirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF25-75 and FEV3/FVC, in addition to traditional spirometry parameters

Cytomegalovirus infection in pediatric rheumatic diseases: a review

Human cytomegalovirus (HCMV) is familiar to pediatric rheumatologists mainly as a cause of opportunistic disease in pharmacologically immune suppressed patients. However, HCMV also has a variety of immuno-modulatory effects, through which it may influence the course of rheumatic conditions. In this article we discuss the interplay between HCMV and the immune system, and review the clinical manifestations, diagnosis, and treatment of HCMV infection in children with rheumatic disease

Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema : Subgroup analysis of the MEAD study

Background: Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME. Methods: Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34.68 Early Treatment Diabetic Retinopathy Study letters (20/200.20/50 Snellen equivalent), and central retinal thickness (CRT) 65300 \u3bcm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was 6515-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry. Results: Baseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n=261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5 % of DEX 0.7 patients versus 11.1 % of sham had 6515-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was -126.1 \u3bcm with DEX 0.7 versus -39.0 \u3bcm with sham(P < 0.001). Cataract-related adverse events were reported in 70.3 % of baseline phakic patients in the previously treated DEX 0.7 subgroup; vision gains were restored following cataract surgery. Conclusions: DEX 0.7 significantly improved visual and anatomic outcomes in patients with DME previously treated with laser, intravitreal anti-vascular endothelial growth factor, intravitreal triamcinolone acetonide, or a combination of these therapies. The safety profile of DEX 0.7 in previously treated patients was similar to its safety profile in the total study population