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Journal ArticleDOI

Identification and prospective validation of clinically relevant chronic obstructive pulmonary disease (COPD) subtypes

TL;DR: In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated: ‘severe respiratory COPD’, ‘moderate respiratory COPd’ and ‘systemic COPD'.
Abstract: Background Chronic obstructive pulmonary disease (COPD) is increasingly considered a heterogeneous condition. It was hypothesised that COPD, as currently defined, includes different clinically relevant subtypes. Methods To identify and validate COPD subtypes, 342 subjects hospitalised for the first time because of a COPD exacerbation were recruited. Three months after discharge, when clinically stable, symptoms and quality of life, lung function, exercise capacity, nutritional status, biomarkers of systemic and bronchial inflammation, sputum microbiology, CT of the thorax and echocardiography were assessed. COPD groups were identified by partitioning cluster analysis and validated prospectively against cause-specific hospitalisations and all-cause mortality during a 4 year follow-up. Results Three COPD groups were identified: group 1 (n¼126, 67 years) was characterised by severe airflow limitation (postbronchodilator forced expiratory volume in 1 s (FEV1) 38% predicted) and worse performance in most of the respiratory domains of the disease; group 2 (n¼125, 69 years) showed milder airflow limitation (FEV1 63% predicted); and group 3 (n¼91, 67 years) combined a similarly milder airflow limitation (FEV1 58% predicted) with a high proportion of obesity, cardiovascular disorders, diabetes and systemic inflammation. During follow-up, group 1 had more frequent hospitalisations due to COPD (HR 3.28, p<0.001) and higher all-cause mortality (HR 2.36, p¼0.018) than the other two groups, whereas group 3 had more admissions due to cardiovascular disease (HR 2.87, p¼0.014). Conclusions In patients with COPD recruited at their first hospitalisation, three different COPD subtypes were identified and prospectively validated: ‘severe respiratory COPD’, ‘moderate respiratory COPD’, and ‘systemic COPD’.
Citations
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Journal ArticleDOI
TL;DR: It is recommended that spirometry is required for the clinical diagnosis of COPD to avoid misdiagnosis and to ensure proper evaluation of severity of airflow limitation.
Abstract: Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

17,023 citations

Journal ArticleDOI
18 May 2012-PLOS ONE
TL;DR: Overall, the results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment and show associations but do not prove causality.
Abstract: Background: Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies. To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552). Methods and Findings: Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-a levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 nonsmoker controls that were followed-up for three years. We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation. Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p,0.001) and exacerbation frequency (1.5 (1.5) vs. 0.9 (1.1) per year, p,0.001) compared to non-inflamed ones. As a descriptive study our results show associations but do not prove causality. Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice. Conclusions: Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment.

700 citations


Cites result from "Identification and prospective vali..."

  • ...However, our findings are consistent with those of Garcia-Aymerich et al, who using a different methodological approach (cluster analysis) also identified a ‘‘systemic’’ COPD subtype characterized by more systemic inflammation and a higher proportion of obesity in 342 COPD patients followed during 4 years [42]....

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Journal ArticleDOI
TL;DR: Multimorbidity is common in patients with COPD, and different comorbidite clusters can be identified, and low-grade systemic inflammation is mostly comparable among comor bidities.
Abstract: Rationale: Comorbidities contribute to disease severity and mortality in patients with chronic obstructive pulmonary disease (COPD). Comorbidities have been studied individually and were mostly based on self-reports. The coexistence of objectively identified comorbidities and the role of low-grade systemic inflammation in the pathophysiology of COPD remain to be elucidated.Objectives: To cluster 13 clinically important objectively identified comorbidities, and to characterize the comorbidity clusters in terms of clinical outcomes and systemic inflammation.Methods: A total of 213 patients with COPD (FEV1, 51 ± 17% predicted; men, 59%; age, 64 ± 7 yr) were included prospectively. Comorbidities were based on well-known cut-offs identified in the peer-reviewed English literature. Systemic inflammatory biomarkers were determined in all patients. Self-organizing maps were used to generate comorbidity clusters.Measurements and Main Results: A total of 97.7% of all patients had one or more comorbidities and 53.5%...

668 citations

Journal ArticleDOI
03 Dec 2015
TL;DR: In this paper, the authors investigated the mechanisms underlying chronic obstructive pulmonary disease (COPD), which is associated with chronic inflammation that is usually corticosteroid resistant, and accelerated ageing of the lungs and an abnormal repair mechanism driven by oxidative stress.
Abstract: Chronic obstructive pulmonary disease (COPD) is a common disease with high global morbidity and mortality. COPD is characterized by poorly reversible airway obstruction, which is confirmed by spirometry, and includes obstruction of the small airways (chronic obstructive bronchiolitis) and emphysema, which lead to air trapping and shortness of breath in response to physical exertion. The most common risk factor for the development of COPD is cigarette smoking, but other environmental factors, such as exposure to indoor air pollutants - especially in developing countries - might influence COPD risk. Not all smokers develop COPD and the reasons for disease susceptibility in these individuals have not been fully elucidated. Although the mechanisms underlying COPD remain poorly understood, the disease is associated with chronic inflammation that is usually corticosteroid resistant. In addition, COPD involves accelerated ageing of the lungs and an abnormal repair mechanism that might be driven by oxidative stress. Acute exacerbations, which are mainly triggered by viral or bacterial infections, are important as they are linked to a poor prognosis. The mainstay of the management of stable disease is the use of inhaled long-acting bronchodilators, whereas corticosteroids are beneficial primarily in patients who have coexisting features of asthma, such as eosinophilic inflammation and more reversibility of airway obstruction. Apart from smoking cessation, no treatments reduce disease progression. More research is needed to better understand disease mechanisms and to develop new treatments that reduce disease activity and progression.

456 citations

Journal ArticleDOI
TL;DR: In this article, the effects of antibiotics in the management of acute COPD exacerbations on treatment failure and other patient-important outcomes (mortality, adverse events, length of hospital stay) were assessed.
Abstract: Background Many patients with an exacerbation of chronic obstructive pulmonary disease (COPD) are treated with antibiotics. However, the value of antibiotics remains uncertain as systematic reviews and clinical trials have shown conflicting results. Objectives To assess the effects of antibiotics in the management of acute COPD exacerbations on treatment failure as observed between seven days and one month after treatment initiation (primary outcome) and on other patient-important outcomes (mortality, adverse events, length of hospital stay). Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and other electronically available databases up to September 2012. Selection criteria Randomised controlled trials (RCTs) in people with acute COPD exacerbations comparing antibiotic therapy and placebo with a follow-up of at least seven days. Data collection and analysis Two review authors independently screened references and extracted data from trial reports. We kept the three groups of outpatients, inpatients and patients admitted to the intensive care unit (ICU) separate for benefit outcomes and mortality because we considered them to be clinically too different to be summarised in one group. We considered outpatients to have a mild to moderate exacerbation, inpatients to have a severe exacerbation and ICU patients to have a very severe exacerbation. Where outcomes or study details were not reported we requested missing data from the authors of the primary studies. We calculated pooled risk ratios (RR) for treatment failure, Peto odds ratios (OR) for rare events (mortality and adverse events) and weighted mean differences (MD) for continuous outcomes using fixed-effect models. We used GRADE to assess the quality of the evidence. Main results Sixteen trials with 2068 participants were included. In outpatients (mild to moderate exacerbations), there was evidence of low quality that antibiotics did statistically significantly reduce the risk for treatment failure between seven days and one month after treatment initiation (RR 0.75; 95% CI 0.60 to 0.94; I2 = 35%) but they did not significantly reduce the risk when the meta-analysis was restricted to currently available drugs (RR 0.80; 95% CI 0.63 to 1.01; I2 = 33%). Evidence of high quality showed that antibiotics statistically significantly reduced the risk of treatment failure in inpatients with severe exacerbations (ICU not included) (RR 0.77; 95% CI 0.65 to 0.91; I2 = 47%) regardless of whether restricted to current drugs. The only trial with 93 patients admitted to the ICU showed a large and statistically significant effect on treatment failure (RR 0.19; 95% CI 0.08 to 0.45; high-quality evidence). Evidence of low-quality from four trials in inpatients showed no effect of antibiotics on mortality (Peto OR 1.02; 95% CI 0.37 to 2.79). High-quality evidence from one trial showed a statistically significant effect on mortality in ICU patients (Peto OR 0.21; 95% CI 0.06 to 0.72). Length of hospital stay (in days) was similar in the antibiotics and placebo groups except for the ICU study where antibiotics statistically significantly reduced length of hospital stay (mean difference -9.60 days; 95% CI -12.84 to -6.36 days). One trial showed no effect of antibiotics on re-exacerbations between two and six weeks after treatment initiation. Only one trial (N = 35) reported health-related quality of life but did not show a statistically significant difference between the treatment and control group. Evidence of moderate quality showed that the overall incidence of adverse events was higher in the antibiotics groups (Peto OR 1.53; 95% CI 1.03 to 2.27). Patients treated with antibiotics experienced statistically significantly more diarrhoea based on three trials (Peto OR 2.62; 95% CI 1.11 to 6.17; high-quality evidence). Authors' conclusions Antibiotics for COPD exacerbations showed large and consistent beneficial effects across outcomes of patients admitted to an ICU. However, for outpatients and inpatients the results were inconsistent. The risk for treatment failure was significantly reduced in both inpatients and outpatients when all trials (1957 to 2012) were included but not when the analysis for outpatients was restricted to currently used antibiotics. Also, antibiotics had no statistically significant effect on mortality and length of hospital stay in inpatients and almost no data on patient-reported outcomes exist. These inconsistent effects call for research into clinical signs and biomarkers that help identify patients who benefit from antibiotics and patients who experience no effect, and in whom downsides of antibiotics (side effects, costs and multi-resistance) could be avoided.

430 citations

References
More filters
Journal ArticleDOI
TL;DR: It is recommended that spirometry is required for the clinical diagnosis of COPD to avoid misdiagnosis and to ensure proper evaluation of severity of airflow limitation.
Abstract: Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

17,023 citations

Journal ArticleDOI
TL;DR: In this article, it was shown that ignoring the process that causes missing data when making sampling distribution inferences about the parameter of the data, θ, is generally appropriate if and only if the missing data are missing at random and the observed data are observed at random, and then such inferences are generally conditional on the observed pattern of missing data.
Abstract: Two results are presented concerning inference when data may be missing. First, ignoring the process that causes missing data when making sampling distribution inferences about the parameter of the data, θ, is generally appropriate if and only if the missing data are “missing at random” and the observed data are “observed at random,” and then such inferences are generally conditional on the observed pattern of missing data. Second, ignoring the process that causes missing data when making Bayesian inferences about θ is generally appropriate if and only if the missing data are missing at random and the parameter of the missing data is “independent” of θ. Examples and discussion indicating the implications of these results are included.

8,197 citations


"Identification and prospective vali..." refers background in this paper

  • ...From a total of 536 variables obtained, 224 were considered after excluding those with additive relationships or resulting from categorisations. Since missing values made up a small proportion and were considered to be either completely random or random,...

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Journal ArticleDOI
TL;DR: The main goals of the updated document are to improve the quality of care provided to patients with COPD and to develop the project using a disease-oriented approach.
Abstract: The Standards for the Diagnosis and Treatment of Patients with COPD document 2004 updates the position papers on chronic obstructive pulmonary disease (COPD) published by the American Thoracic Society (ATS) and the European Respiratory Society (ERS) in 1995 1, 2. Both societies felt the need to update the previous documents due to the following. 1) The prevalence and overall importance of COPD as a health problem is increasing. 2) There have been enough advances in the field to require an update, especially adapted to the particular needs of the ATS/ERS constituency. 3) It allows for the creation of a “live” modular document based on the web; it should provide healthcare professionals and patients with a user friendly and reliable authoritative source of information. 4) The care of COPD should be comprehensive, is often multidisciplinary and rapidly changing. 5) Both the ATS and the ERS acknowledge the recent dissemination of the Global Initiative of Obstructive Lung Disease (GOLD) 3 as a major worldwide contribution to the battle against COPD. However, some specific requirements of the members of both societies require adaptation of the broad GOLD initiative. Those requirements include specific recommendations on oxygen therapy, pulmonary rehabilitation, noninvasive ventilation, surgery in and for COPD, sleep, air travel, and end-of-life. In addition, special emphasis has been placed on issues related to the habit of smoking and its control. ### Goals and objectives The main goals of the updated document are to improve the quality of care provided to patients with COPD and to develop the project using a disease-oriented approach. To achieve these goals, both organisations have developed a modular electronic web-based document with two components. 1) A component for health professionals that intends to: raise awareness of COPD; inform on the latest advances in the overall pathogenesis, diagnosis, monitoring and management of COPD; and …

4,312 citations


"Identification and prospective vali..." refers methods in this paper

  • ...7).(3) The protocol was approved by the Ethics Committees of all the participating hospitals, and written informed consent was obtained from all subjects....

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Journal ArticleDOI
TL;DR: The BODE index, a simple multidimensional grading system, is better than the FEV1 at predicting the risk of death from any cause and from respiratory causes among patients with COPD.
Abstract: background Chronic obstructive pulmonary disease (COPD) is characterized by an incompletely reversible limitation in airflow. A physiological variable — the forced expiratory volume in one second (FEV 1 ) — is often used to grade the severity of COPD. However, patients with COPD have systemic manifestations that are not reflected by the FEV 1 . We hypothesized that a multidimensional grading system that assessed the respiratory and systemic expressions of COPD would better categorize and predict outcome in these patients. methods We first evaluated 207 patients and found that four factors predicted the risk of death in this cohort: the body-mass index (B), the degree of airflow obstruction (O) and dyspnea (D), and exercise capacity (E), measured by the six-minute–walk test. We used these variables to construct the BODE index, a multidimensional 10-point scale in which higher scores indicate a higher risk of death. We then prospectively validated the index in a cohort of 625 patients, with death from any cause and from respiratory causes as the outcome variables. results There were 25 deaths among the first 207 patients and 162 deaths (26 percent) in the validation cohort. Sixty-one percent of the deaths in the validation cohort were due to respiratory insufficiency, 14 percent to myocardial infarction, 12 percent to lung cancer, and 13 percent to other causes. Patients with higher BODE scores were at higher risk for death; the hazard ratio for death from any cause per one-point increase in the BODE score was 1.34 (95 percent confidence interval, 1.26 to 1.42; P<0.001), and the hazard ratio for death from respiratory causes was 1.62 (95 percent confidence interval, 1.48 to 1.77; P<0.001). The C statistic for the ability of the BODE index to predict the risk of death was larger than that for the FEV 1 (0.74 vs. 0.65).

3,688 citations

Book
01 Jan 2001
TL;DR: Without a way of critically appraising the information they receive, clinicians are relatively helpless in deciding what new information to learn and decide how to modify their practice.
Abstract: Medical practice is constantly changing. The rate of change is accelerating, and physicians can be forgiven if they often find it dizzying. How can physicians learn about new information and innovations, and decide how (if at all) they should modify their practice? Possible sources include summaries from the medical literature (review articles, practice guidelines, consensus statements, editorials, and summary articles in "throwaway" journals); consultation with colleagues who have special expertise; lectures; seminars; advertisements in medical journals; conversations with representatives from pharmaceutical companies; and original articles in journals and journal supplements. Each of these sources of information might be valuable, though each is subject to its own particular biases. 1,2 Problems arise when, as is often the case, these sources of information provide different suggestions about patient care. See also p 2093. Without a way of critically appraising the information they receive, clinicians are relatively helpless in deciding what new information

3,305 citations

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