Project description:BackgroundMain risk factor for the development of chronic obstructive pulmonary disease (COPD) is smoking, although only less than 1/3 of smokers develop clinically manifest COPD. COPD's progressive nature with high disability and mortality makes it plausible to detect it as early as possible thus allowing for an early intervention. The only tool for an early diagnosis that could be used on the global scale is spirometry, even though symptoms and deprivation of health related quality of life (HRQoL) precede relevant spirometric changes. Existing HRQoL questionnaires are too complicated or not developed for an early detection of COPD. The aim of our study was to develop a new simple HRQoL tool that will allow (alone or in combination with other markers) early detection of patients with COPD.MethodsA multicenter prospective cohort study recruiting 500 subjects at risk for COPD (smokers/ex-smokers ≥20 pack-years, 40-65 years, both sexes, with no prior diagnosis of COPD) will be carried out in two phases: (1) cross-sectional - development and validation of a new questionnaire; and (2) prospective - follow-up of a cohort of patients at risk for COPD. Subjects were recruited by 25 GPs and assessed for COPD by dedicated pulmonologists in 7 hospital centers using a predefined protocol: HRQoL, history, physical, blood sampling, exhaled breath temperature (EBT), lung function, 6-min walk test (6MWT). Patients without COPD and those in GOLD stage 1 at initial assessment will be reassessed for disease progression by the same pulmonologist after 2 and 5 years.DiscussionThis is one of the first cohort studies attempting to establish the incidence of COPD in the pre-symptomatic stage before significant end organ damage. We intend to assess the validity, predictability and discriminative power ('healthy' smokers vs. pre-symptomatic phase in newly developed COPD) of newly developed HRQoL tool alone or in combination with other markers; EBT, lung function, 6MWT, genomics, transcriptomics, proteomics). We expect that the results of this study can improve our understanding of the development of COPD, identify some new underlying pathophysiological pathways, and offer to sensitive smokers/ex-smokers new preventive and early intervention measures thus improving the management of COPD.Trial registrationClinicaltrial.gov NCT01550679 retrospectively registered February 28, 2012.
Project description:The Global Initiative for Chronic Obstructive Lung Disease (GOLD) was formed in the late 1990s to spread awareness of chronic obstructive pulmonary disease (COPD) as a major public health problem and facilitate its prevention and treatment. GOLD has since become internationally recognized for the development of evidence-based strategy documents, most notably the annual GOLD Reports, for COPD diagnosis, management, and prevention. The GOLD Reports incorporate the latest evidence and expert consensus to guide the management and prevention of COPD on a global level. Since the first GOLD Report in 2001, profound innovations have taken place regarding inhaler device options, available pharmaceuticals, knowledge regarding effective dosages and potential side effects, and the various combinations of drugs used to relieve symptoms. Concomitantly, an evolution of expert opinion on how best to apply these innovations to the care of patients with COPD has also taken place, an evolution that is nowhere more detailed or definitive than in the 20 years of annual GOLD Reports. We summarize key features and trends in inhalation therapy for stable COPD in these Reports.
Project description:BackgroundLung injury might take place before chronic obstructive pulmonary disease (COPD) occurs. A clearer definition of "pre-COPD" based on the effects of potential indicators on increasing risk of COPD development and a prediction model involving them are lacking.MethodsA total of 3526 Chinese residents without COPD aged 40 years or older derived from the national cross-sectional survey of COPD surveillance in 2014-2015 were followed up for a mean of 3.59 years. We examined the associations of chronic bronchitis, preserved ratio impaired spirometry (PRISm), low peak expiratory flow (PEF), spirometric small airway dysfunction (sSAD), low maximal mid-expiratory flow (MMEF), low forced expiratory flow 50% of pulmonary volume (FEF50), and low FEF75 with subsequent COPD and constructed a prediction model with LASSO-Cox regression.Findings235 subjects in the cohort developed COPD during the follow-up. Subjects with PRISm, low PEF, sSAD, low MMEF, low FEF50, and low FEF75 had an increased risk of developing COPD (adjusted hazard ratio [HR] ranging from 1.57 to 3.01). Only chronic bronchitis (HR 2.84 [95% CI 1.38-5.84] and 2.94 [1.43-6.04]) and sSAD/low MMEF (HR 2.74 [2.07-3.61] and 2.38 [1.65-3.43]) showed effects independent of the other indicators and their concurrence had the strongest effect (HR 5.89 and 4.80). The prediction model including age, sex, low MMEF, low FEF50, and indoor exposure to biomass had good performance both internally and temporally. The corrected C-index was 0.77 (0.72-0.81) for discrimination in internal validation. For temporal validation, the area under the receiver operating characteristic curve was 0.73 (0.63-0.83). Good calibration was indicated in plot for internal validation and by Hosmer-Lemeshow test for temporal validation.InterpretationIndividuals with concurrent chronic bronchitis and sSAD/low MMEF indicating pre-COPD optimally require more high attention from physicians. Our prediction model could serve as a multi-dimension tool to predict COPD comprehensively.FundingThe Ministry of Finance and the Ministry of Science and Technology of the People's Republic of China and the National Natural Science Foundation of China.
Project description:Gold shops in artisanal and small-scale gold mining communities represent major point sources of airborne mercury pollution. Concentrations of elemental mercury (Hg0) emitted by these shops can be determined using a portable atomic absorbance spectrometer (AAS) with Zeeman correction. These measured Hg0 concentrations can then be correlated to position as determined by a hand-held GPS unit, and the resulting data mapped using a Geographic Information System (GIS). A detailed method for obtaining and analyzing data collected near gold shops in Mazuko, Peru is provided. Maps generated using this method were employed to identify point sources of Hg0 contamination originating from gold shops in ASGM communities and were shared with local city managers to assist in urban planning.•A detailed method is provided to collect and process data, ultimately generating a map that allows for the screening of a community to identify point sources of Hg0 contamination.•Raw data is provided, as well as a video detailing data processing and mapping using a common spreadsheet program and an open-source GIS.•The generated map can be used for determining areas where people may be exposed to elevated Hg0 concentrations and/or occupational mercury vapor exposure, targeted enforcement, or outreach to limit Hg0 pollution.
Project description:BackgroundThe Acute Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Prediction Tool (ACCEPT) was developed for individualised prediction of COPD exacerbations. ACCEPT was well calibrated overall and had a high discriminatory power, but overestimated risk among individuals without recent exacerbations. The objectives of this study were to 1) fine-tune ACCEPT to make better predictions for individuals with a negative exacerbation history, 2) develop more parsimonious models, and 3) externally validate the models in a new dataset.MethodsWe recalibrated ACCEPT using data from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE, a three-year observational study, 1,803 patients, 2,117 exacerbations) study by applying non-parametric regression splines to the predicted rates. We developed three reduced versions of ACCEPT by removing symptom score and/or baseline medications as predictors. We examined the discrimination, calibration, and net benefit of ACCEPT 2·0 in the placebo arm of the Towards a Revolution in COPD Health (TORCH, a three-year randomised clinical trial of inhaled therapies in COPD, 1,091 patients, 1,064 exacerbations) study. The primary outcome for prediction was the occurrence of ≥2 moderate or ≥1 severe exacerbation in the next 12 months; the secondary outcomes were prediction of the occurrence of any moderate/severe exacerbation or any severe exacerbation.FindingsACCEPT 2·0 had an area-under-the-curve (AUC) of 0·76 for predicting the primary outcome. Exacerbation history alone (current standard of care) had an AUC of 0·68. The model was well calibrated in patients with positive or negative exacerbation histories. Changes in AUC in reduced versions were minimal for the primary outcome as well as for predicting the occurrence of any moderate/severe exacerbations (ΔAUC<0·011), but more substantial for predicting the occurrence of any severe exacerbations (ΔAUC<0·020). All versions of ACCEPT 2·0 provided positive net benefit over the use of exacerbation history alone for some range of thresholds.InterpretationACCEPT 2·0 showed good calibration regardless of exacerbation history, and predicts exacerbation risk better than current standard of care for a range of thresholds. Future studies need to investigate the utility of exacerbation prediction in various subgroups of patients.FundingThis study was funded by a team grant from the Canadian Institutes of Health Research (PHT 178432).
Project description:BackgroundThe lifetime risk of developing clinical COPD among smokers ranges from 13% to 22%. Identifying at-risk individuals who will develop overt disease in a reasonable timeframe may allow for early intervention. We hypothesised that readily available clinical and physiological variables could help identify ever-smokers at higher risk of developing chronic airflow limitation (CAL).MethodsAmong 2273 Lovelace Smokers' Cohort (LSC) participants, we included 677 (mean age 54 years) with normal spirometry at baseline and a minimum of three spirometries, each 1 year apart. Repeated spirometric measurements were used to determine incident CAL. Using logistic regression, demographics, anthropometrics, smoking history, modified Medical Research Council dyspnoea scale, St George's Respiratory Questionnaire, comorbidities and spirometry, we related variables obtained at baseline to incident CAL as defined by the Global Initiative for Chronic Obstructive Lung Disease and lower limit of normal criteria. The predictive model derived from the LSC was validated in subjects from the COPDGene study.ResultsOver 6.3 years, the incidence of CAL was 26 cases per 1000 person-years. The strongest independent predictors were forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.75, having smoked ≥30 pack-years, body mass index (BMI) ≤25 kg·m2 and symptoms of chronic bronchitis. Having all four predictors increased the risk of developing CAL over 6 years to 85% (area under the receiver operating characteristic curve (AUC ROC) 0.84, 95% CI 0.81-0.89). The prediction model showed similar results when applied to subjects in the COPDGene study with a follow-up period of 10 years (AUC ROC 0.77, 95% CI 0.72-0.81).ConclusionIn middle-aged ever-smokers, a simple predictive model with FEV1/FVC, smoking history, BMI and chronic bronchitis helps identify subjects at high risk of developing CAL.
Project description:Background:Respiratory parameters are important predictors of prognosis in the COPD population. Global Initiative for Obstructive Lung Disease (GOLD) 2017 Update resulted in a vertical shift of patients across COPD categories, with category B being the most populous and clinically heterogeneous. The aim of our study was to investigate whether respiratory parameters might be associated with increased all-cause mortality within GOLD category B patients. Methods:The data were extracted from the Czech Multicentre Research Database, a prospective, noninterventional multicenter study of COPD patients. Kaplan-Meier survival analyses were performed at different levels of respiratory parameters (partial pressure of oxygen in arterial blood [PaO2], partial pressure of arterial carbon dioxide [PaCO2] and greatest decrease of basal peripheral capillary oxygen saturation during 6-minute walking test [6-MWT]). Univariate analyses using the Cox proportional hazard model and multivariate analyses were used to identify risk factors for mortality in hypoxemic and hypercapnic individuals with COPD. Results:All-cause mortality in the cohort at 3 years of prospective follow-up reached 18.4%. Chronic hypoxemia (PaO2 <7.3 kPa), hypercapnia (PaCO2 >7.0 kPa) and oxygen desaturation during the 6-MWT were predictors of long-term mortality in COPD patients with forced expiratory volume in 1 second ?60% for the overall cohort and for GOLD B category patients. Univariate analyses confirmed the association among decreased oxemia (<7.3 kPa), increased capnemia (>7.0 kPa), oxygen desaturation during 6-MWT and mortality in the studied groups of COPD subjects. Multivariate analysis identified PaO2 <7.3 kPa as a strong independent risk factor for mortality. Conclusion:Survival analyses showed significantly increased all-cause mortality in hypoxemic and hypercapnic GOLD B subjects. More important, PaO2 <7.3 kPa was the strongest risk factor, especially in category B patients. In contrast, the majority of the tested respiratory parameters did not show a difference in mortality in the GOLD category D cohort.
Project description:BackgroundIndacaterol/glycopyrronium (IND/GLY) is approved for maintenance treatment of adult patients with COPD. This post hoc analysis explored the efficacy and safety of IND/GLY versus salmeterol/fluticasone (SFC) in symptomatic (Global Initiative for Chronic Obstructive Lung Disease [GOLD] B and GOLD D) patients with moderate-to-severe COPD.Patients and methodsData from LANTERN and ILLUMINATE studies were pooled and analyzed. In both studies, symptomatic COPD patients were randomized to once-daily IND/GLY 110 μg/50 μg or twice-daily SFC 50 μg/500 μg. End points were pre-dose trough forced expiratory volume in one second (FEV1), standardized area under the curve for FEV1 from 0 to 12 hours (FEV1 AUC0-12 hours), peak FEV1, peak forced vital capacity (FVC), pre-dose trough FVC, Transition Dyspnea Index (TDI) total score, St George's Respiratory Questionnaire total score, rescue medication use and safety.ResultsA total of 1,263 patients were classified as either GOLD B (n=809) or GOLD D (n=454). At week 26, IND/GLY demonstrated statistically significant improvement in all lung function parameters versus SFC in patients in both the GOLD B and GOLD D subgroups. TDI total score and rescue medication use were significantly improved with IND/GLY versus SFC in the overall population and in the GOLD B (TDI total score only) and GOLD D (rescue medication only) subgroups. IND/GLY also reduced the rate of exacerbations in the pooled population. Overall safety profile was comparable with a higher incidence of pneumonia in the SFC-treated group.ConclusionIn this pooled analysis, IND/GLY demonstrated superior efficacy compared with SFC in patients in the GOLD B and GOLD D subgroups and supported its use in symptomatic COPD patients.
Project description:Introducing transition metals into frustrated Lewis pair systems has attracted considerable attention in recent years. Here we report a selection of three metal-only frustrated systems based on Au(I)/Pt(0) combinations and their reactivity toward alkynes. We have inspected the activation of acetylene and phenylacetylene. The gold(I) fragments are stabilized by three bulky phosphines bearing terphenyl groups. We have observed that subtle modifications on the substituents of these ligands proved critical in controlling the regioselectivity of acetylene activation and the product distribution resulting from C(sp)-H cleavage of phenylacetylene. A mechanistic picture based on experimental observations and computational analysis is provided. As a result of the cooperative action of the two metals of the frustrated pairs, several uncommon heterobimetallic structures have been characterized.