Health Outcomes Associated with Lung Function Decline and Respiratory Symptoms and Disease in a Community Cohort

Background: In workplace respiratory disease prevention, a thorough understanding is needed of the relative contributions of lung function loss and respiratory symptoms in predicting adverse health outcomes. Methods: Copenhagen City Heart Study respiratory data collected at 4 examinations (1976–2003) and morbidity and mortality data were used to investigate these relationships. With 15 or more years of follow-up for a hospital diagnosis of chronic obstructive pulmonary disease (COPD) morbidity, COPD or coronary heart disease (CHD) mortality, and all-cause mortality, risks for these outcomes were estimated in relation to asthma, chronic bronchitis, shortness of breath, and lung function level at examination 2 (1981–1983) or lung function decline established from examinations 1 (1976–1978) to 2 using 4 measures (FEV₁ slope, FEV₁ relative slope, American College of Occupational and Environmental Medicine's Longitudinal Normal Limit [LNL], or a limit of 90 milliliters per year [ml/yr]). These risks were estimated by hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age, height-adjusted baseline forced expiratory volume in 1 second (FEV₁/height²), and height. Results: For COPD morbidity, the increasing trend in the HR (95% CI) by quartiles of the FEV₁ slope reached a maximum of 3.77 (2.76–5.15) for males, 6.12 (4.63–8.10) for females, and 4.14 (1.57–10.90) for never-smokers. Significant increasing trends were also observed for mortality, with females at higher risk. Conclusion: Lung function decline was associated with increased risk of COPD morbidity and mortality emphasizing the need to monitor lung function change over time in at-risk occupational populations.     

Exercise Ventilatory Inefficiency Adds to Lung Function in Predicting Mortality in COPD

Severity of resting functional impairment only partially predicts the increased risk of death in chronic obstructive pulmonary disease (COPD). Increased ventilation during exercise is associated with markers of disease progression and poor prognosis, including emphysema extension and pulmonary vascular impairment. Whether excess exercise ventilation would add to resting lung function in predicting mortality in COPD, however, is currently unknown. After an incremental cardiopulmonary exercise test, 288 patients (forced expiratory volume in one second ranging from 18% to 148% predicted) were followed for a median (interquartile range) of 57 (47) months. Increases in the lowest (nadir) ventilation to CO₂ output (VCO₂) ratio determined excess exercise ventilation. Seventy-seven patients (26.7%) died during follow-up: 30/77 (38.9%) deaths were due to respiratory causes. Deceased patients were older, leaner, had a greater co-morbidity burden (Charlson Index) and reported more daily life dyspnea. Moreover, they had poorer lung function and exercise tolerance (p < 0.05). A logistic regression analysis revealed that ventilation/VCO₂ nadir was the only exercise variable that added to age, body mass index, Charlson Index and resting inspiratory capacity (IC)/total lung capacity (TLC) ratio to predict all-cause and respiratory mortality (p < 0.001). Kaplan–Meier analyses showed that survival time was particularly reduced when ventilation/VCO₂ nadir > 34 was associated with IC/TLC ≤ 0.34 or IC/TLC ≤ 0.31 for all-cause and respiratory mortality, respectively (p < 0.001). Excess exercise ventilation is an independent prognostic marker across the spectrum of COPD severity. Physiological abnormalities beyond traditional airway dysfunction and lung mechanics are relevant in determining the course of the disease.     

Socioeconomic Status and Prognosis of COPD in Denmark

We investigated the association between length of school education and 5-year prognosis of chronic obstructive lung disease (COPD), including exacerbations, hospital admissions and survival. We used sample of general population from two independent population studies: The Copenhagen City Heart Study and Copenhagen General Population Study. A total of 6,590 individuals from general population of Copenhagen with COPD defined by the Global initiative for obstructive lung disease criteria were subdivided into 4 groups based on the length of school education: 1,590 with education < 8 years; 3,131 with education 8–10 years, 1,244 with more than 10 years, but no college/university education and 625 with college/university education. Compared with long education, short education was associated with current smoking (p < 0.001), higher prevalence of respiratory symptoms (p < 0.001) and lower forced expiratory volume in the first second in percent of predicted value (FEV₁%pred) (p < 0.001).

Adjusting for sex, age, FEV₁%pred, dyspnea, frequency of previous exacerbations and smoking we observed that shortest school education (in comparison with university education), was associated with a higher risk of COPD exacerbations (hazards ratio 1.65, 95% CI 1.15–2.37) and higher risk of all-cause mortality (hazards ratio 1.96, 95% CI 1.28–2.99). We conclude that even in an economically well-developed country with a health care system (which is largely free of charge), low socioeconomic status, assessed as the length of school education, is associated with a poorer clinical prognosis of COPD.     

Reanalysis of the Japanese experience using the combined COPD assessment of the 2011 GOLD classification

BackgroundThe Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 consensus report proposed a new classification system, incorporating symptoms with future risk, in subjects with chronic obstructive pulmonary disease (COPD). We hypothesized it could be applied to Japanese COPD patients.MethodsWe previously analyzed clinical factors related to 5-year mortality in 150 male outpatients with COPD. We reviewed the data and reanalyzed the relationships between the new GOLD classification and various outcomes including mortality.ResultsThere were 51 (34.0%), 12 (8.0%), 57 (38.0%), and 30 (20.0%) patients in GOLD A (forced expiratory volume in 1 s [FEV₁]≥50% predicted and modified Medical Research Council [mMRC] 0–1), GOLD B (FEV₁≥50% predicted and mMRC≥2), GOLD C (FEV₁<50% predicted and mMRC 0–1), and GOLD D (FEV₁ <50% predicted and mMRC≥2), respectively. The GOLD 2011 classification correlated significantly with exercise capacity and multi-dimensional disease staging. Cox proportional hazards analysis revealed that, among several methods categorizing symptoms, the GOLD A-D classification was significantly associated with mortality (p=0.0055).ConclusionAlthough the relative number of patients in each category of the combined COPD assessment classification depended on the choice of symptom measures, the categories defined by the mMRC scale (score 0–1 versus ≥2) were most useful for future risk assessed as mortality. GOLD A had the lowest mortality, followed by GOLD B and C, and D had the highest mortality. Exercise capacity was also stratified by the new GOLD classification.     

Different COPD Disease Characteristics are Related to Different Outcomes in the 6-minute Walk Test

Abstract

Background: Chronic obstructive pulmonary disease (COPD) can lead to severe disability as the disease advances. The 6-minute walk test (6MWT) is commonly used to measure functional capacity in COPD patients and has three potential outcomes; walking distance, oxygen desaturation, and self-perceived dyspnea assessed by the Borg scale, all reflecting different aspects of COPD. The aim of this study was to identify predictors of all 3 outcomes of 6MWT in patients with COPD. Methods: 370 COPD patients, aged 40–75 yrs, were included from the first phase of the Bergen COPD cohort study. They were examined with spirometry, bioelectrical impedance measurements, 6MWT, Center for Epidemiologic Studies of Depression (CES-D) Scale, Medical Research Council (MRC) dyspnea scale, Charlson index for co-morbidities, self-reported physical activity questionnaire, plasma levels of C-reactive protein (CRP) and arterial blood gases. Results: Significant predictors in the multivariate analyses were sex, age, FEV₁ in% predicted, symptoms of dyspnea (MRC), co-morbidities (Charlson Index) and self-reported physical activity for walking distance, FEV₁ in% predicted and PaO₂ for oxygen desaturation, and body composition, smoking and co-morbidities for self-perceived dyspnea assessed by the Borg scale. Conclusion: Several COPD characteristics have predictive value for the 6MWT, and some COPD characteristics are more strongly related to specific 6MWT outcomes than others.     

The Rapid FEV1 Decline in Chronic Obstructive Pulmonary Disease Is Associated with Predominant Emphysema: A Longitudinal Study

Abstract

Background: Early identification of patients with COPD and prone to more rapid decline in lung function is of particular interest from both a prognostic and therapeutic point of view. The aim of this study was to identify the clinical, functional and imaging characteristics associated with the rapid FEV₁ decline in COPD. Methods: Between 2001 and 2005, 131 outpatients with moderate COPD in stable condition under maximum inhaled therapy underwent clinical interview, pulmonary function tests and HRCT imaging of the chest and were followed for at least 3 years. Results: Twenty-six percent of patients had emphysema detected visually using HRCT. The FEV₁ decline was 42 ± 66 mL/y in the total sample, 88 ± 76 mL/y among rapid decliners and 6 ± 54 mL/y among the other patients. In the univariable analysis, the decline of FEV₁ was positively associated with pack-years (p < 0.05), emphysema at HRCT (p < 0.001), RV (p < 0.05), FRC (p < 0.05), FEV₁ (p < 0.01) at baseline and with number of hospitalizations per year (p < 0.05) during the follow-up. Using multivariable analysis, the presence of emphysema proved to be an independent prognostic factor of rapid decline (p = 0.001). When emphysema was replaced by RV, the model still remained significant. Conclusions: The rapid decline in lung function may be identified by the presence of emphysema at HRCT or increased RV in patients with a long smoking history.     

The health, activity, dyspnea, obstruction, age, and hospitalization: prognostic score for stable COPD patients

Multidimensional instruments for determining the severity and prognosis of chronic obstructive pulmonary disease (COPD) must be used in daily clinical practice. Objective: To develop and validate a new COPD severity score using variables readily obtained in clinical practice and to compare its predictive capacity with that of other multidimensional indexes.Data collected from a prospective cohort of 611 stable COPD patients were used to derive a clinical prediction rule that was later validated in a separate prospective cohort of 348 patients.In the multivariate analyses, six independent predictive factors were correlated with overall and respiratory mortality: health status, physical activity, dyspnea, airway obstruction (FEV₁), age, and hospitalizations for COPD exacerbations in the previous two years. These create the HADO-AH score. Based on the β parameter obtained in the multivariate model, a score was assigned to each predictive variable. The area under the curve for 5-year mortality was 0.79 (95% CI, 0.74–0.83) in the derivation cohort and 0.76 (95% CI, 0.71–0.81) in the validation cohort. The HADO-AH score was a significantly better predictor of mortality than the HADO-score and the Body-mass index, Obstruction, Dyspnea, Exercise-index were statistically significant (p < 0.0004 and p = 0.021, respectively), but was similar to the Age, Dyspnea, and Obstruction-index (p = 0.345).The HADO-AH score provides estimates of all-cause and respiratory mortality that are equal to, or better than, those of other multidimensional instruments. Because it uses only easily accessible measures, it could be useful at all levels of care.     

Impact of airflow obstruction on long-term mortality in patients with asthma in Japan

BackgroundThe long-term prognosis of asthma with airflow obstruction is poorly understood in Japan. The aim of this retrospective 26-year study was to investigate the long-term mortality risk of airflow obstruction in asthmatics.MethodsUsing data from the Omuta City Air Pollution-related Health Damage Cohort Program, mortality risk ratios of airflow obstruction in Japanese Individuals were analyzed by Cox proportional hazards models. Airflow obstruction was considered to be present when the forced expiratory volume in 1 sec (FEV₁)/forced vital capacity ratio was <0.7 and FEV₁ predicted was <80% based on spirometry.ResultsAmong the 3146 victims with chronic respiratory diseases, 697 with adult asthma were selected. Median follow-up period was 26.3 (range 0.9–40.9) years. The airflow obstruction group (n = 193) showed significantly higher rates of mortality related to respiratory problems (risk ratio [95% confidence interval] 1.51 [1.86–1.93], P = 0.0017) and asthma attacks (1.86 [1.30–2.66], P = 0.0011) than the without airflow obstruction group (n = 504). Airflow obstruction was an independent risk factor for both respiratory-related (1.84 [1.36–2.49], P = 0.0001) and all-cause (1.44 [1.17–1.76], P = 0.0008) mortality after adjustment for age, sex, body mass index, and smoking status. More severe airflow obstruction was significantly associated with poorer prognosis.ConclusionsThis long-term cohort program revealed the impacts of asthma with airflow obstruction as an independent mortality risk. Findings suggest that intervention and prevention of airflow obstruction can reduce long-term mortality in patients with asthma.     

Airway Distensibility by HRCT in Asthmatics and COPD with Comparable Airway Obstruction

Abstract

Introduction: Decreased airway distensibility (AD) in response to deep inspirations, as assessed by HRCT, has been associated with the severity of asthma and COPD. Aims: The current study was designed to compare the magnitude of AD by HRCT in individuals with asthma and COPD with comparable degrees of bronchial obstruction, and to explore factors that may influence it. Results: We enrolled a total of 12 asthmatics (M/F:7/5) and 8 COPD (7/1) with comparable degree of bronchial obstruction (FEV₁% predicted mean±SEM: 69.1 ± 5.2% and 61.2 ± 5.0%, respectively; p = 0.31). Each subject underwent chest HRCT at FRC and at TLC. A total of 701 airways (range 20 to 38 airway per subject; 2.0 to 23.1 mm in diameter) were analyzed. AD did not differ between asthmatics and COPD (mean ± SEM: 14 ± 3.5% and 17 ± 4.3%, respectively; p = 0.58). In asthmatics, AD was significantly associated with FEV₁% predicted (r² = 0.45, p = 0.018). We found a significant correlation between the change in lung volume and the change in AD by HRCT (r² = 0.64, p = 0.002). In COPD, we found significant correlations between AD and the RV% predicted (r² = 0.51, p = 0.046) and the RV/TLC (r² = 0.68, p = 0.01). Conclusions: AD was primarily affected by the dynamic ability to change lung volumes in asthmatics, and by static lung volumes in COPD.     

Bronchial Responsiveness,Spirometry and Mortality in a Cohort of Adults

Objective. Prospective population studies have reported that pulmonary function, measured by forced expiratory volume in one second (FEV₁), is an independent predictor for mortality. Besides, several studies found that death from all causes is higher in asthmatics than in non-asthmatics. However, none of these studies examined whether bronchial hyperresponsiveness (BHR), one of the key features in asthma, can be used as a predictor for mortality. Thus, the aim of this study was to analyze the association between BHR, FEV_1, and all-cause mortality in a population-based cohort of adults. Methods. Within the cross-sectional survey ECRHS-I Erfurt (1990–1992), 1162 adults aged 20–65 years performed lung function tests, including spirometry and BHR testing by methacholine inhalation up to a cumulative dose of 2 mg. BHR was assessed from the methacholine dose nebulized at ≥ 20% fall of FEV₁. After circa 20 years of follow-up, the association between baseline lung function, BHR, and mortality was investigated. Results. A total of 85 individuals (7.3%) died during a mean follow-up period of 17.4 years (SD = 2.4). FEV₁, but not forced vital capacity (FVC), was a predictor for mortality. In men, BHR increased the mortality risk (OR = 2.6, 95% CI: 1.3–5.3; adjusted for age and BMI). Additional adjustment for asthma did not change the results (OR = 2.4, 95% CI: 1.2–5.0). However, after an additional adjustment for pack years of cigarette smoking or airway obstruction, the association was not statistically significant anymore (OR = 1.8, 95% CI: 0.8–4.0, OR = 1.9, 95% CI: 0.9–4.3, respectively). Conclusions. BHR was associated with an increased mortality risk in men. Potential explanatory factors for this association are cigarette smoking, chronic obstructive pulmonary disease (COPD), or asthma. Thus, BHR might be an indirect predictor for all-cause mortality. FEV₁ was an independent predictor for all-cause mortality.     

Lung Function and Respiratory Symptoms in Association with Mortality: The HUNT Study

Whether respiratory symptoms are associated with mortality independent of lung function is unclear. The authors explored the association of the exposures i) lung function, ii) respiratory symptoms, and iii) lung function and respiratory symptoms combined, with the outcomes all-cause and cardiovascular mortality. The study included 10,491 adults who participated in the Nord-Trøndelag Health Study (HUNT) Lung Study in 1995–1997 and were followed through 2009. Cox regression was used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals for all-cause and cardiovascular mortality associated with pre-bronchodilator% predicted forced expiratory volume in 1 second (ppFEV₁), chronic obstructive pulmonary disease (COPD) grades, and respiratory symptoms (chronic bronchitis, wheeze, and levels of dyspnoea). Lung function was inversely associated with all-cause mortality. Compared to ppFEV₁ ≥100, ppFEV₁ <50 increased the HR to 6.85 (4.46–10.52) in women and 3.88 (2.60–5.79) in men. Correspondingly, compared to normal airflow, COPD grade 3 or 4 increased the HR to 6.50 (4.33–9.75) in women and 3.57 (2.60–4.91) in men. Of the respiratory symptoms, only dyspnoea when walking remained associated with all-cause mortality after controlling for lung function (HR 1.73 [1.04–2.89] in women and 1.57 [1.04–2.36] in men). Analyses of lung function and dyspnoea when walking as a combined exposure further supported this finding. Overall, associations between lung function and cardiovascular mortality were weaker, and respiratory symptoms were not associated with cardiovascular mortality. In conclusion, lung function was inversely associated with all-cause and cardiovascular mortality, and dyspnoea when walking was associated with all-cause mortality independent of lung function.     

Efficacy and Safety of Aclidinium Bromide Compared with Placebo and Tiotropium in Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease: Results from a 6-week,Randomized, Controlled Phase Iiib Study

Abstract

Background: This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Methods: Patients received aclidinium 400 μg twice daily (morning and evening), tiotropium 18 μg once daily (morning), or placebo for 6 weeks. The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV₁ AUC_0–24) at week 6. Secondary and additional endpoints included FEV₁ AUC_12–24, COPD symptoms (EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [E-RS] total score and additional symptoms questionnaire), and safety. Results: Overall, 414 patients were randomized and treated (FEV₁ 1.63 L [55.8% predicted]). Compared with placebo, FEV₁ AUC_0–24 and FEV₁ AUC_12–24 were significantly increased from baseline with aclidinium (? = 150 mL and 160 mL, respectively; p < 0.0001) and tiotropium (? = 140 mL and 123 mL, respectively; p < 0.0001) at week 6. Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium (p < 0.0001) than tiotropium (p < 0.05) versus placebo. Only aclidinium significantly reduced the severity of early-morning cough, wheeze, shortness of breath, and phlegm, and of nighttime symptoms versus placebo (p < 0.05). Adverse-event (AE) incidence (28%) was similar between treatments. Few anticholinergic AEs (<1.5%) or serious AEs (<3%) occurred in any group. Conclusions: Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks. Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium. Aclidinium was generally well tolerated.     

Longitudinal Lung Volume Changes in Patients with Chronic Obstructive Pulmonary Disease

Background

The progression of lung hyperinflation in patients with chronic obstructive pulmonary disease (COPD) has not been studied in a long-term prospective cohort. We explored the longitudinal changes in lung volume compartments with the aim of identifying predictors of a rapid decline of the inspiratory capacity to total lung capacity ratio (IC/TLC).

Methods

The study population comprised 324 patients with COPD who were recruited prospectively. Annual rates of changes in pulmonary function, including forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC), total lung capacity (TLC), functional residual capacity (FRC), residual volume (RV), vital capacity (VC), IC, and IC/TLC, were estimated using the random coefficient models.

Results

The mean annual rates of changes in pre- and post-bronchodilator FEV₁ were ?23.0 mL/year (p < 0.001) and ?26.5 mL/year (p = 0.004). The mean annual rates of changes in VC, IC, TLC, and IC/TLC were ?33.7 mL/year (p = 0.007), ?53.9 mL/year (p < 0.001), ?43.7 mL/year (p = 0.012), and ?0.65 %/year (p = 0.001), respectively. RV, FRC, and RV/TLC did not change significantly during the study period. Multivariate logistic regression analysis showed that a high modified Medical Research Council (MMRC) dyspnea scale score, a high Charlson comorbidity index value, and low post-bronchodilator FEV₁ were associated with rapid decline in IC/TLC.

Conclusion

MMRC dyspnea scale, post-bronchodilator FEV_1, and the Charlson comorbidity index at baseline were independent predictors of a rapid decline in IC/TLC.     

Is static hyperinflation a limiting factor during exercise in adolescents with cystic fibrosis?

Increased work of breathing is considered to be a limiting factor in patients with cystic fibrosis (CF) performing aerobic exercise. We hypothesized that adolescents with CF and with static hyperinflation are more prone to a ventilatorily limited exercise capacity than non‐static hyperinflated adolescents with CF. Exercise data of 119 adolescents with CF [range 12–18 years], stratified for static hyperinflation, defined as ratio of residual volume to total lung capacity (RV/TLC) > 30%, were obtained during a progressive bicycle ergometer test with gas analysis and analyzed for ventilatory limitation. Static hyperinflation showed a significant, though weak association (Φ 0.38; P < 0.001) with a ventilatorily limited exercise capacity (breathing reserve index at maximal effort >0.70; FEV₁ < 80% predicted and reduced exercise capacity, defined as VO_2peak < 85% predicted). Analysis of association for increasing degrees of hyperinflation showed an increase to Φ 0.49 (P < 0.001) for RV/TLC > 50%. In adolescents with static hyperinflation, peak work rate (W_peak; 3.1 ± 0.7 W/kg (75.1 ± 17.3% of predicted), peak oxygen uptake (VO_2peak/kg (ml/min/kg); 39.2 ± 9.2 ml/min/kg (91.0 ± 20.3% of predicted), peak heart rate (HR_peak; 176 ± 19 beats/min) were significantly (P < 0.05) decreased when compared with non‐static hyperinflated adolescents (W_peak 3.5 ± 0.5 W/kg (81.4 ± 10.0% of predicted)); VO_2peak/kg (ml/min/kg); 43.1 ± 7.5 ml/min/kg (98.0 ± 15.1% of predicted); and HR_peak 185 ± 14 beats/min). Additionally, no difference was found in the degree of association of FEV₁ (%) and RV/TLC (%) with VO_2peak/kg_pred and W_peak/kg_Pred, but we found the RV/TLC (%) to be a slightly stronger predictor of VO_2peak/kg_pred and W_peak/kg_Pred than FEV₁ (%). These results indicate that the presence of static hyperinflation in adolescents with CF by itself does not strongly influence ventilatory constraints during exercise and that static hyperinflation is only a slightly stronger predictor of W_peak/kg_Pred and VO_2peak/kg_Pred than airflow obstruction (FEV₁ (%)). Pediatr. Pulmonol. 2011; 46:119–124. © 2011 Wiley‐Liss, Inc.     

Predictors of Mortality in Patients with Stable COPD

OBJECTIVES  To determine which easily available clinical factors are associated with mortality in patients with stable COPD and if health-related quality of life (HRQoL) provides additional information. DESIGN  Five-year prospective cohort study. SETTING  Five outpatient clinics of a teaching hospital. PARTICIPANTS  Six hundred stable COPD patients recruited consecutively. MEASUREMENTS  The variables were age, FEV_1%, dyspnea, previous hospital admissions and emergency department visits for COPD, pack-years of smoking, comorbidities, body mass index, and HRQoL measured by Saint George’s Respiratory Questionnaire (SGRQ), Chronic Respiratory Questionnaire (CRQ), and Short-Form 36 (SF-36). Logistic and Cox regression models were used to assess the influence of these variables on mortality and survival. RESULTS  FEV_1%(OR: 0.62, 95% CI 0.5 to 0.75), dyspnea (OR 1.92, 95% CI 1.2 to 3), age (OR 2.41, 95% CI 1.6 to 3.6), previous hospitalization due to COPD exacerbations (OR 1.53, 1.2 to 2) and lifetime pack-years (OR 1.15, 95% CI 1.1 to 1.2) were independently related to respiratory mortality. Similarly, these factors were independently related to all-cause mortality with dyspnea having the strongest association (OR 1.54, 95% CI 1.1 to 2.2). HRQoL was an independent predictor of respiratory and all-cause mortality only when dyspnea was excluded from the models, except scores on the SGRQ were associated with all-cause mortality with dyspnea in the model. CONCLUSIONS  Among patients with stable COPD, FEV_1% was the main predictor of respiratory mortality and dyspnea of all-cause mortality. In general, HRQoL was not related to mortality when dyspnea was taken into account, and CRQ and SGRQ behaved in similar ways regarding mortality. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Sources of support: Grant no. 97/0326 from the Fondo de Investigación Sanitaria. Research Committee of Galdakao-Usansolo Hospital.     

Frequency of Multi-dimensional COPD Indices and Relation with Disease Activity Markers

Abstract

Our aim was to describe the population-based distribution of several COPD multi-dimensional indices and to evaluate their relationship with daily physical activity, co-morbidity, health status and systemic inflammatory biomarkers. From a population-based sample of 3,802 subjects aged 40–80 from the EPI-SCAN study, 382 subjects (10.2%) with a post-bronchodilator FEV₁/FVC<0.7 were identified as COPD. Smoking habits, respiratory symptoms, quality of life, co-morbidities, lung function and inflammatory biomarkers were recorded. Health status and daily physical activity were assessed using the EQ-5D and LCADL questionnaires, respectively. The new GOLD grading and the BODE, ADO, DOSE, modified DOSE, e-BODE, BODEx, CPI, SAFE and HRS indices were determined.

A notable dispersion in the total scores was observed, although 83–88% of the COPD patients were classified into the mildest level and 1–3% in the most severe. The SAFE index was the best independent determinant of daily physical activity; the SAFE and ADO indices were associated with presence of co-morbidity; and the SAFE and modified DOSE indices were independently related to health status. The systemic biomarkers showed a less consistent relation with several indices. In a population-based sample of COPD patients, the SAFE index reaches the highest relation with physical activity, co-morbidity and health status.     

Comorbidity, Hospitalization, and Mortality in COPD: Results from a Longitudinal Study

We evaluated comorbidity, hospitalization, and mortality in chronic obstructive pulmonary disease (COPD), with special attention to risk factors for frequent hospitalizations (more than three during the follow-up period), and prognostic factors for death. Two hundred eighty-eight consecutive COPD patients admitted to respiratory medicine wards in four hospitals for acute exacerbation were enrolled from 1999 to 2000 in a prospective longitudinal study, and followed up until December 2007. The Charlson index without age was used to quantify comorbidity. Clinical and biochemical parameters and pulmonary function data were evaluated as potential predictive factors of mortality and hospitalization. FEV₁, RV, PaO₂, and PaCO₂ were used to develop an index of respiratory functional impairment (REFI index). Hypertension was the most common comorbidity (64.2%), followed by chronic renal failure (26.3%), diabetes mellitus (25.3%), and cardiac diseases (22.1%). Main causes of hospitalization were exacerbation of COPD (41.2%) and cardiovascular disease (34.4%). Most of the 56 deaths (19.4%) were due to cardiovascular disease (67.8%). Mortality risk depended on age, current smoking, FEV₁, PaO₂, the REFI index, the presence of cor pulmonale, ischemic heart disease, and lung cancer. Number and length of hospital admissions depended on the degree of dyspnea and REFI index. The correct management of respiratory disease and the implementation of aggressive strategies to prevent or treat comorbidities are necessary for better care of COPD patients.     

Aerobic Exercise Training Improves Right- and Left Ventricular Systolic Function in Patients with COPD

Abstract

Objective: The aim of this study was to investigate the effects of moderate continuous training (MCT) and high intensity aerobic interval training (AIT) on systolic ventricular function and aerobic capacity in COPD patients. Methods: Seventeen patients with COPD (64 ± 8 years, 12 men) with FEV₁ of 52.8 ± 11% of predicted, were randomly assigned to isocaloric programs of MCT at 70% of max heart rate (HR) for 47 minutes) or AIT (～90% of max HR for 4×4 minutes) three times per week for 10 weeks. Baseline cardiac function was compared with 17 age- and sex-matched healthy individuals. Peak oxygen uptake (VO_2-peak) and left (LV) and right ventricular (RV) function examined by echocardiography, were measured at baseline and after 10 weeks of training. Results: At baseline, the COPD patients had reduced systolic function compared to healthy controls (p < 0.05). After the training, AIT and MCT increased VO_2-peak by 8% and 9% and work economy by 7% and 10%, respectively (all p < 0.05). LV and RV systolic function both improved (p < 0.05), with no difference between the groups after the two modes of exercise training. Stroke volume increased by 17% and 20%, LV systolic tissue Doppler velocity (S’) by 18% and 17% and RV S’ by 15% after AIT and MCT, respectively (p < 0.05). Conclusion: Systolic cardiac function is reduced in COPD. Both AIT and MCT improved systolic cardiac function. In contrast to other patient groups studied, higher exercise intensity does not seem to have additional effects on cardiac function or aerobic capacity in COPD patients.     

Co-morbidities and 90-day Outcomes in Hospitalized COPD Exacerbations

COPD exacerbations resulting in hospitalization are accompanied by high mortality and morbidity. The contribution of specific co-morbidities to acute outcomes is not known in detail: existing studies have used either administrative data or small clinical cohorts and have provided conflicting results. Identification of co-existent diseases that affect outcomes provides opportunities to address these conditions proactively and improve overall COPD care. Cases were identified prospectively on admission then underwent retrospective case note audit to collect data including co-morbidities on up to 60 unselected consecutive acute COPD admissions between March and May in each hospital participating in the 2008 UK National COPD audit. Outcomes recorded were death in hospital, length of stay, and death and readmission at 90 days after index admission. 232 hospitals collected data on 9716 patients, mean age 73, 50% male, mean FEV₁ 42% predicted. Prevalence of co-morbidities were associated with increased age but better FEV₁ and ex-smoker status and with worse outcomes for all four measures. Hospital mortality risk was increased with cor pulmonale, left ventricular failure, neurological conditions and non-respiratory malignancies whilst 90 day death was also increased by lung cancer and arrhythmias. Ischaemic and other heart diseases were important factors in readmission. This study demonstrates that co-morbidities adversely affect a range of short-term patient outcomes related to acute admission to hospital with exacerbations of COPD. Recognition of relevant accompanying diseases at admission provides an opportunity for specific interventions that may improve short-term prognosis.     

Advanced glycation end products in the skin are enhanced in COPD

Background

Cigarette smoking is the main cause of chronic obstructive pulmonary disease (COPD) inducing oxidative stress and local tissue injury, resulting in pulmonary inflammation. Advanced glycation end products (AGEs) are produced by glycation and oxidation processes and their formation is accelerated in inflammatory conditions. In this study we assessed whether AGE accumulation in the skin is elevated in COPD and associates with disease severity.

Methods

202 mild-to-very-severe COPD patients and 83 old (40–75 years) and 110 young (18–40 years) healthy smokers and never-smokers were included. AGEs were measured by skin autofluorescence (SAF). Demographic variables, smoking habits, co-morbidities and lung function values were obtained.

Results

COPD patients (FEV₁ = 55% predicted) had significantly higher SAF values than old and young healthy controls: 2.5 vs. 1.8 and 1.2 (arbitrary units, p < 0.05). No differences in SAF values were found between GOLD stages I-IV (2.4, 2.3, 2.5, 2.5 respectively). Lower function (FEV₁/FVC, MEF₅₀/FVC, RV/TLC) and higher number of packyears were significantly associated with SAF (p < 0.05).

Conclusions

SAF is increased in mild-to-very severe COPD patients compared with healthy controls. Interestingly, SAF was not associated with disease severity as values were comparable between different GOLD stages (stage I-IV) of COPD. This may suggest that AGEs play a role in the induction phase of COPD in susceptible smokers. Future studies should further investigate the mechanisms underlying AGEs formation and accumulation in COPD.