Canadian Cohort Obstructive Lung Disease (CanCOLD): Fulfilling the Need for Longitudinal Observational Studies in COPD

Awareness, diagnosis and treatment of COPD, compared to other major causes of death, remains far too low. This article describes the protocol objectives, design and the approaches taken in the Canadian Chronic Obstructive Lung Disease (CanCOLD) study, an epidemiological and integrated research. The CanCOLD study aims at better understanding heterogeneity of COPD presentation and disease progression. We hypothesize that individuals with unfavourable COPD “phenotypes” and subjects at-risk (ever smokers) with unhealthy lifestyle habits, environmental/work exposure, or co-morbidities will have increased risk of lung function decline independent of their cumulative exposure to cigarette smoke. The study is a prospective multi-center cohort study (9 sites in 6 provinces) built on the Canadian COPD prevalence study “COLD.” The study plan is to include 1800 subjects at least 40 years old who were sampled from the general population and who were found to fall within 4 groups: 1) COPD moderate–severe (GOLD 2–4); 2) COPD mild (GOLD 1); 3) subjects at-risk (ever smoker); and, 4) subjects never-smoker free of airflow obstruction. Data collection is based on using strictly standardized methods involving questionnaires, pulmonary function and cardiorespiratory exercise tests, CT scans, and blood sampling. CanCOLD is a unique study that will address challenging and important research questions on COPD disease evolution and disease management and will help to define the natural history of COPD disease evolution in individuals at-risk for COPD and in those with COPD who have mild disease.     

Physical activity as a determinant of change in mobility performance: the Longitudinal Aging Study Amsterdam

OBJECTIVES: This study examined the association of (change in) physical activity and decline in mobility performance in older men and women. DESIGN: A 3-year prospective study using data of the Longitudinal Aging Study. SETTING: Netherlands. PARTICIPANTS: Two thousand one hundred nine men and women aged 55 to 85. MEASUREMENTS: Total physical activity (expressed as hours per day and kilocalories per day) and sports participation were measured using a validated, interviewer-administered questionnaire. Mobility performance was assessed using two timed tests: 6-meter walk and repeated chair stands. RESULTS: Mobility performance declined for 45.6% of the sample. At baseline, the mean time +/- standard deviation spent on total physical activity was 3.0 +/- 2.1 h/d or 719 +/- 543 kcal/d, and 56.6% of the sample participated in sports. Sports participation and a higher level of total physical activity, walking, or household activity were associated with a smaller mobility decline. After 3 years, total physical activity declined, and only 53.4% of those reporting sports at baseline continued doing so. Continuation of physical activity over time was associated with the smallest decline in mobility. The observed associations were similar for those with and without chronic disease (P> 0.3). The conclusions did not change after adjustment for potential confounders, including demographic and lifestyle variables, depression, and cognitive status. CONCLUSIONS: Physical activity, and especially a regularly active lifestyle, may slow the decline in mobility performance. A beneficial effect was observed for sports and nonsports activities, independent of the presence of chronic disease.     

The Ability of the Framingham Steatosis Index (FSI) to Predict Non-alcoholic Fatty Liver Disease (NAFLD): A Cohort Study

BackgroundThe utilization of indexes for the diagnosis of non-alcoholic fatty liver disease (NAFLD) can be valuable. This study was conducted to determine the ability of the Framingham steatosis index (FSI) to distinguish between people with NAFLD and those without and to predict people at risk of NAFLD to establish the need for lifestyle modifications in such individuals.MethodsOur study was conducted in two phases from 2009-2010 (phase I) to 2016-2017 (phase II). A total of 4670 people in northern Iran were included. NAFLD was diagnosed by ultrasound. The FSI was calculated based on age, sex, hypertension, diabetes mellitus status, liver enzyme levels and triglyceride levels. Receiver operating characteristic (ROC) analysis was conducted to determine the discriminatory and predictive abilities of the FSI. To remove the confounding effects of potential mediators, logistic regression was performed in which NAFLD was considered the outcome and the FSI as the predictor.ResultsThe odds ratios of the FSI when the outcome was the prevalence of NAFLD in phase I and when the outcome was new cases of NAFLD from 2009–2010 to 2016-2017 were 4.909 (4.243–5.681) and 2.453 (2.024–2.972), respectively (P < 0.001). The areas under the curve (AUCs) for the discriminatory and predictive abilities of the FSI were 0.8421 (95% CI: 0.8314–0.8527) and 0.7093 (95% CI: 0.6863–0.7322), respectively.ConclusionThe FSI has a strong ability to diagnose NAFLD while it has an acceptable ability to predict the occurrence of new cases of NAFLD.     

Mini-Nutritional Assessment (MNA) is Useful for Assessing the Nutritional Status of Patients with Chronic Obstructive Pulmonary Disease: A Cross-sectional Study

Malnutrition is prevalent in patients with chronic obstructive pulmonary disease (COPD) but is often neglected in clinical practice. This study examined the usefulness of the Mini Nutritional Assessment (MNA) for assessing the nutritional status of patients with COPD. We recruited 83 patients with COPD in stable condition from the pulmonary rehabilitation unit of a medical center in northern Taiwan. Each patient was interviewed with a structured questionnaire to elicit personal and health-related data, and measured for anthropometric and blood biochemical indicators. Nutritional status was rated with two Taiwanese-specific versions of the MNA, MNA-T1 and MNA-T2. Fat-free mass was measured with bioelectrical impedance analysis (BIA), and exercise capacity indicators with the 6-Minute Walk Test. The two MNA versions showed high agreement (kappa = 0.949) in predicting the nutritional risk, and both versions predicted the FFMI well (area under the curve of the Receiver Operating Characteristics = 0.804, p < 0.001 for MNA-T1; and 0.813, p < 0.001 for MNA-T2). MNA scores decreased with increasing disease severity and were highly correlated with FFMI, BMI, mid-arm circumference, calf circumference, and oxygen saturation at rest and during exercise (all p < 0.01). The MNA score was positively correlated with FEV₁, FVC and 6-minute walking distance, and negatively correlated with GOLD stages (all p < 0.05). However, the MNA score was not significantly correlated with blood biochemical indicators, perhaps due to inflammatory status associated with COPD. The MNA appears appropriate for rating the nutritional risk of patients with COPD. Routine use of the MNA may help reduce the risk of malnutrition in patients with COPD.     

IL-8 Gene Variants are Associated with Lung Function Decline and Multidimensional BODE Index in COPD Patients But Not with Disease Susceptibility: A Validation Study

Background and objective: COPD is a leading cause of dead worldwide and tobacco smoking is its major risk factor. IL8 is a proinflammatory chemokine mainly involved in the acute inflammatory reaction. The aim of this study was to test the association of IL-8, CXCR1 and CXCR2 gene variants and COPD susceptibility as part of a replication study and explore the effect of these variations in disease progression. Methods: 9 tagSNPs were genotyped in 728 Caucasian individuals (196 COPD patients, 80 smokers and 452 non-smoking controls). Pulmonary compromise was evaluated using spirometry and clinical parameters at baseline and annually over a 2 years period. We also determined plasma levels of TNF-α, IL-6, IL-8 and IL-16 in COPD patients. Results: There was a lack of association between gene variants or haplotypes with predisposition to COPD. No correlation was observed between the polymorphisms and cytokines levels. Interestingly, significant associations were found between carriers of the rs4073A (OR = 3.53, CI 1.34-9.35, p = 0.01), rs2227306C (OR = 5.65, CI 1.75–18.88, p = 0.004) and rs2227307T (OR = 4.52, CI = 1.49–12.82, p = 0.007) alleles in the IL-8 gene and patients who scored higher in the BODE index and showed an important decrease in their FEV₁ and FVC during the 2 years follow-up period (p < 0.05). Conclusions: Despite no association was found between the studied genes and COPD susceptibility, three polymorphisms in the IL-8 gene appear to be involved in a worse progression of the disease, with an affectation beyond the pulmonary function and importantly, a reduction in lung function along the follow-up years.     

Association Between Serum Albumin Level and All-Cause Mortality in Patients With Chronic Kidney Disease: A Retrospective Cohort Study

BackgroundThe association between serum albumin and all-cause mortality (ACM) in patients with chronic kidney disease (CKD) is presently unclear.MethodsThe study subjects included 201 patients diagnosed with CKD, eliminating those with end-stage renal disease, who were admitted to our hospital from January 2014 to January 2015. The patients were divided into 4 groups according to serum albumin level (Q1: 1.60–3.88 g/dL; Q2: 3.89–4.13 g/dL; Q3: 4.14–4.43 g/dL, and Q4: 4.44–5.51 g/dL). The clinical outcome was ACM, and the difference was compared using odds ratio (OR) and 95% confidence interval (CI).ResultsAfter a median follow-up of 1480 days, 32 patients died (15.92%). The ACM was found to be 28.00%, 20.00%, 8.00%, and 7.84% in the 4 groups (P = 0.012). Pearson correlation analysis revealed a positive association between the serum albumin level and glomerular filtration rate (GFR) (r = 0.22, P = 0.001). Once the potential confounding factors were adjusted, the results indicated that decreased serum albumin was a risk factor for ACM (Q2 vs Q1: OR = 0.50, 95% CI: 0.17–1.47; Q3 vs Q1: OR = 0.12, 95% CI: 0.03–0.48; Q4 vs Q1: OR = 0.26, 95% CI: 0.07–0.98). The receiver operating characteristic curve indicated that the optimum threshold of serum albumin to predict ACM was 4 g/dL, and the area under the curve was 0.69 (95% CI: 0.60–0.79).ConclusionsDecreased serum albumin is a risk factor for ACM in patients with CKD, with the optimal threshold being 4 g/dL.     

Resource Use and Costs up to Two Years Post Diagnosis Among Newly Diagnosed COPD Patients in the UK Primary Care Setting: A Retrospective Cohort Study

The objective of this study was to estimate the annual resource use and costs before and after COPD diagnosis and compare it across stages of airflow obstruction and levels of dyspnoea in the UK primary care setting. A retrospective cohort of newly diagnosed COPD patients (1/1/2008-31/12/2009) was identified in the UK Clinical Practice Research Datalink (CPRD). Resource use did not include medication costs and comprised of exacerbations, all cause GP interactions, and non-COPD hospitalisations, which were estimated for up to 12 months before and 24 months after COPD diagnosis. It was further stratified using baseline characteristics, Medical Research Council (MRC) dyspnoea score, and stages of airflow limitation. COPD costs were estimated using NHS reference costs. The analysis included 7881 newly diagnosed COPD patients (mean age, 67.2 years; 45% females). In the 2 years follow-up, the cohort experienced moderate and severe exacerbations, non-COPD hospitalisations, and GP surgery visits at an annual rate of 0.51, 0.13, 0.47, and 12.85, respectively. All resource components showed an upward trend with increase airflow limitation and dyspnoea. GP interactions accounted for 58.5% of annual per patient COPD management costs, estimated to be £2047 during the observation period. The annual costs doubled from patients with low levels of dyspnoea (MRC = 1; £1473) to those with high levels of dyspnoea (MRC = 5; £3243). COPD management costs in the primary care setting continued to remain high up to 2 years following initial diagnosis. The cost burden increased with high levels of dyspnoea and airflow obstruction, suggesting that both measures can identify patients requiring increased monitoring.     

Failure to Intensify Antihypertensive Treatment by Primary Care Providers: A Cohort Study in Adults with Diabetes Mellitus and Hypertension

Background Although tight blood pressure control is crucial in reducing vascular complications of diabetes, primary care providers often fail to appropriately intensify antihypertensive medications. Objective To identify novel visit-based factors associated with intensification of antihypertensive medications in adults with diabetes. Design Non-concurrent prospective cohort study. Patients A total of 254 patients with type 2 diabetes and hypertension enrolled in an academically affiliated managed care program. Over a 24-month interval (1999–2001), we identified 1,374 visits at which blood pressure was suboptimally controlled (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg). Measurements and Main Results Intensification of antihypertensive medications at each visit was the primary outcome. Primary care providers intensified antihypertensive treatment in only 176 (13%) of 1,374 visits at which blood pressure was elevated. As expected, higher mean systolic and mean diastolic blood pressures were important predictors of intensification. Treatment was also more likely to be intensified at visits that were “routine” odds ratio (OR) 2.08; 95% Confidence Interval [95% CI] 1.36–3.18), or that paired patients with their usual primary care provider (OR 1.84; 95% CI 1.11–3.06). In contrast, several factors were associated with failure to intensify treatment, including capillary glucose >150 mg/dL (OR 0.54; 95% CI 0.31–0.94) and the presence of coronary heart disease (OR 0.61; 95% CI 0.38–0.95). Co-management by a cardiologist accounted partly for this failure (OR 0.65; 95% CI 0.41–1.03). Conclusions Failure to appropriately intensify antihypertensive treatment is common in diabetes care. Clinical distractions and shortcomings in continuity and coordination of care are possible targets for improvement.     

Evolution of Functional Exercise Capacity in Lung Transplant Patients With and Without Bronchiolitis Obliterans Syndrome: A Longitudinal Case–Control Study

Introduction

Bronchiolitis Obliterans Syndrome (BOS) is a debilitating disease with limited treatment options that threatens both the quality of life and long-term survival of lung transplant (LTx) recipients. This retrospective longitudinal case–control study was performed to compare the long-term functional evolution of LTx recipients with and without BOS.

Defining Myocardial Abnormalities Across the Stages of Chronic Kidney Disease: A Cardiac Magnetic Resonance Imaging Study

ObjectivesA proof of concept cross-sectional study investigating changes in myocardial abnormalities across stages of chronic kidney disease (CKD). Characterizing noninvasive markers of myocardial fibrosis on cardiac magnetic resonance, echocardiography, and correlating with biomarkers of fibrosis, myocardial injury, and functional correlates including exercise tolerance.BackgroundCKD is associated with an increased risk of cardiovascular death. Much of the excess mortality is attributed to uremic cardiomyopathy, defined by increased left ventricular hypertrophy, myocardial dysfunction, and fibrosis. The prevalence of these abnormalities across stages of CKD and their impact on cardiovascular performance is unknown.MethodsA total of 134 nondiabetic, pre-dialysis subjects with CKD stages 2 to 5 without myocardial ischemia underwent cardiac magnetic resonance (1.5-T) including; T₁ mapping (biomarker of diffuse fibrosis), T₂ mapping (edema), late gadolinium enhancement, and assessment of aortic distensibility. Serum biomarkers including collagen turnover (P1NP, P3NP), troponin T, and N-terminal pro–B-type natriuretic peptide were measured. Cardiovascular performance was quantified by bicycle cardiopulmonary exercise testing and echocardiography.ResultsNative myocardial T₁ times increased incrementally from stage 2 to 5 (966 ± 21 ms vs. 994 ± 33 ms; p < 0.001), independent of hypertension and aortic distensibility. Left atrial volume, E/eʹ, N-terminal pro–B-type natriuretic peptide, P1NP, and P3NP increased with CKD stage (p < 0.05), while effort tolerance (% predicted VO₂Peak, %VO₂VT) decreased (p < 0.001). In multivariable linear regression models, estimated glomerular filtration rate was the strongest predictor of native myocardial T₁ time (p < 0.001). Native myocardial T₁ time, left atrial dilatation, and high-sensitivity troponin T were independent predictors of % predicted VO₂Peak (p < 0.001).ConclusionsImaging and serum biomarkers of myocardial fibrosis increase with advancing CKD independent of effects of left ventricular afterload and might be a key intermediary in the development of uremic cardiomyopathy. Further studies are needed to determine whether these changes lead to the increased rates of heart failure and death in CKD. (Left Ventricular Fibrosis in Chronic Kidney Disease [FibroCKD]; NCT03176862)