Modified Medical Research Council scale vs Baseline Dyspnea Index to evaluate dyspnea in chronic obstructive pulmonary disease

International audienceBackground: Assessment of dyspnea in COPD patients relies in clinical practice on the modified Medical Research Council (mMRC) scale, whereas the Baseline Dyspnea Index (BDI) is mainly used in clinical trials. Little is known on the correspondence between the two methods. Methods: Cross-sectional analysis was carried out on data from the French COPD cohort Initiatives BPCO. Dyspnea was assessed by the mMRC scale and the BDI. Spirometry, plethysmography, Hospital Anxiety-Depression Scale, St George's Respiratory Questionnaire, exacerbation rates, and physician-diagnosed comorbidities were obtained. Correlations between mMRC and BDI scores were assessed using Spearman's correlation coefficient. An ordinal response model was used to examine the contribution of clinical data and lung function parameters to mMRC and BDI scores. Results: Data are given as median (interquartile ranges, [IQR]). Two-hundred thirty-nine COPD subjects were analyzed (men 78%, age 65.0 years [57.0; 73.0], forced expiratory volume in 1 second [FEV1] 48% predicted [34; 67]). The mMRC grade and BDI score were, respectively, 1 [1-3] and 6 [4-8]. Both BDI and mMRC scores were significantly correlated at the group level (rho = -0.67; P < 0.0001), but analysis of individual data revealed a large scatter of BDI scores for any given mMRC grade. In multivariate analysis, both mMRC grade and BDI score were independently associated with lower FEV1% pred, higher exacerbation rate, obesity, depression, heart failure, and hyperinflation, as assessed by the inspiratory capacity/total lung capacity ratio. The mMRC dyspnea grade was also associated with the thromboembolic history and low body mass index. Conclusion: Dyspnea is a complex symptom with multiple determinants in COPD patients. Although related to similar factors (including hyperinflation, depression, and heart failure), BDI and mMRC scores likely explore differently the dyspnea intensity in COPD patients and are clearly not interchangeable

Tiotropium might improve survival in subjects with COPD at high risk of mortality

Abstract Background Inhaled therapies reduce risk of chronic obstructive pulmonary disease (COPD) exacerbations, but their effect on mortality is less well established. We hypothesized that heterogeneity in baseline mortality risk influenced the results of drug trials assessing mortality in COPD. Methods The 5706 patients with COPD from the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) study that had complete clinical information for variables associated with mortality (age, forced expiratory volume in 1 s, St George’s Respiratory Questionnaire, pack-years and body mass index) were classified by cluster analysis. Baseline risk of mortality between clusters, and impact of tiotropium were evaluated during the 4-yr follow up. Results Four clusters were identified, including low-risk (low mortality rate) patients (n = 2339; 41%; cluster 2), and high-risk patients (n = 1022; 18%; cluster 3), who had a 2.6- and a six-fold increase in all-cause and respiratory mortality compared with cluster 2, respectively. Tiotropium reduced exacerbations in all clusters, and reduced hospitalizations in high-risk patients (p < 0.05). The beneficial effect of tiotropium on all-cause mortality in the overall population (hazard ratio, 0.87; 95% confidence interval, 0.75–1.00, p = 0.054) was explained by a 21% reduction in cluster 3 (p = 0.07), with no effect in other clusters. Conclusions Large variations in baseline risks of mortality existed among patients in the UPLIFT® study. Inclusion of numerous low-risk patients may have reduced the ability to show beneficial effect on mortality. Future clinical trials should consider selective inclusion of high-risk patients

Identification of Clinical Phenotypes Using Cluster Analyses in COPD Patients with Multiple Comorbidities

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation, the severity of which is assessed using forced expiratory volume in 1 sec (FEV1, % predicted). Cohort studies have confirmed that COPD patients with similar levels of airflow limitation showed marked heterogeneity in clinical manifestations and outcomes. Chronic coexisting diseases, also called comorbidities, are highly prevalent in COPD patients and likely contribute to this heterogeneity. In recent years, investigators have used innovative statistical methods (e.g., cluster analyses) to examine the hypothesis that subgroups of COPD patients sharing clinically relevant characteristics (phenotypes) can be identified. The objectives of the present paper are to review recent studies that have used cluster analyses for defining phenotypes in observational cohorts of COPD patients. Strengths and weaknesses of these statistical approaches are briefly described. Description of the phenotypes that were reasonably reproducible across studies and received prospective validation in at least one study is provided, with a special focus on differences in age and comorbidities (including cardiovascular diseases). Finally, gaps in current knowledge are described, leading to proposals for future studies

Patient eligibility criteria for a surgical treatment that enhances tissue sealing by use of a medicated sponge: observational study ELITE

RATIONALE: The application of a haemostatic agent in general surgery, in addition to its effect on bleeding, also provides tissue sealing and adhesion. A sponge drug is used with some actions of resection and wide dissection, without knowledge of the eligibility of patients. In this study, we sought to identify clusters of patients for which the medicated sponge enhances tissue sealing. METHODS: Observational study (ELITE), from a panel of selected surgeons from hospitals in France in several surgical areas: abdominal, gynaecology, urology and thoracic. The survey identified the criteria for using the sponge TachoSil® in their surgical practices involving n = 683 patients. A multiple correspondence analysis (MCA) followed by an ascending hierarchical classification (AHC) was used in order to identify the eligibility criteria for the application of the sponge for tissue sealing in addition to hemostasis. RESULTS: The most relevant classification was based on 9 groups of patients for which the sponge was used. 6 of them are mainly linked with the kind of lesion, 2 with the site of application and the latest one with the type of operation. CONCLUSIONS: The ELITE study revealed that the TachoSil® sponge was used mainly during surgery, requiring a reinforcement of the resection tissue sealing. The expected objective was successfully reached in 97% of the cases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-613) contains supplementary material, which is available to authorized users

Randomized controlled trials of pharmacological treatments to prevent COPD exacerbations: applicability to real-life patients

BackgroundIn patients with chronic obstructive pulmonary disease, all efforts should be made to prevent exacerbations because each event modifies the trajectory of the disease. Treatment recommendations are mostly built on results from randomized controlled trials (RCTs) whose methodology ensure internal validity. However, their relevance may be compromised by the lack of generalizability, due to poor representability of study populations compared to real-life patients.In order to delimit to whom the results of studies on current and future treatments apply, we sought to identify and characterize the fraction of COPD population that would be eligible for inclusion into RCTs aiming at decreasing exacerbation risk.MethodsWe used the Initiatives-BPCO database, a French cohort of 1309 real-life COPD patients monitored in academic centers. We identified industry-sponsored phase III and IV trials that enrolled more than 500 patients, lasted at least one year and used exacerbations related endpoints. Eligibility criteria were extracted from each trial and applied to the patients.ResultsThe eligibility criteria of 16 RCTs were applied to the 1309 patients. The most discriminating eligibility criteria were FEV1, minimum exacerbation rate in the previous year and smoking history, responsible for the exclusion of 39.9, 36.7 and 16.8% of patients, respectively. Altogether, 2.3 to 46.7% of our patients would have satisfied all eligibility criteria.ConclusionThese analyses confirm that an important gap exists between real-life patients and clinical trials populations in COPD, which limits the relevance of results and therefore should be considered when grading levels of evidence and designing future studies

Two Distinct Chronic Obstructive Pulmonary Disease (COPD) Phenotypes Are Associated with High Risk of Mortality

In COPD patients, mortality risk is influenced by age, severity of respiratory disease, and comorbidities. With an unbiased statistical approach we sought to identify clusters of COPD patients and to examine their mortality risk.status: publishe

Two Distinct Chronic Obstructive Pulmonary Disease (COPD) Phenotypes Are Associated with High Risk of Mortality

<div><h3>Rationale</h3><p>In COPD patients, mortality risk is influenced by age, severity of respiratory disease, and comorbidities. With an unbiased statistical approach we sought to identify clusters of COPD patients and to examine their mortality risk.</p> <h3>Methods</h3><p>Stable COPD subjects (n = 527) were classified using hierarchical cluster analysis of clinical, functional and imaging data. The relevance of this classification was validated using prospective follow-up of mortality.</p> <h3>Results</h3><p>The most relevant patient classification was that based on three clusters (phenotypes). Phenotype 1 included subjects at very low risk of mortality, who had mild respiratory disease and low rates of comorbidities. Phenotype 2 and 3 were at high risk of mortality. Phenotype 2 included younger subjects with severe airflow limitation, emphysema and hyperinflation, low body mass index, and low rates of cardiovascular comorbidities. Phenotype 3 included older subjects with less severe respiratory disease, but higher rates of obesity and cardiovascular comorbidities. Mortality was associated with the severity of airflow limitation in Phenotype 2 but not in Phenotype 3 subjects, and subjects in Phenotype 2 died at younger age.</p> <h3>Conclusions</h3><p>We identified three COPD phenotypes, including two phenotypes with high risk of mortality. Subjects within these phenotypes may require different therapeutic interventions to improve their outcome.</p> </div

Dendrogram illustrating the results of the cluster analysis in 527 COPD subjects.

<p>Subjects were classified using agglomerative hierarchical cluster analysis based on the main axes identified by principal component analysis (PCA) and multiple correspondence analyses (MCA, see Methods section). Each vertical line represents an individual subject and the length of vertical lines represents the degree of similarity between subjects. The horizontal lines identify possible cut-off for choosing the optimal number of clusters in the data. When choosing 3 clusters (upper line) the 3 groups (labelled 1 to 3) have differential mortality rates (0.5%, 20.6% and 14.3% for Phenotype 1, 2, and 3, respectively). When choosing 5 clusters (lower line, labelled 1′ to 5′), subjects in clusters 1′ and 2′ had comparable mortality rates (0.7% and 0%, respectively) and subjects in clusters 4′ and 5′ had similar mortality rates (14.3% in each group), suggesting that grouping in 5 phenotypes would not improve patient classification.</p

Cox model analysis of mortality between phenotypes.

<p>CI: confidence interval.</p

Description of the 527 COPD patients based on spirometric GOLD classification.

<p>BMI : body mass index; FEV1: forced expiratory volume in 1 sec, FVC: forced vital capacity, RV: residual volume, TLC: total lung capacity, TGV: thoracic gas volume, Raw: airway resistance, Sgaw: specific airway conductance, DLCO: diffusing capacity of the lung for carbon monoxide, KCO: ratio of DLCO to alveolar volume, mMRC: modified Medical Research Council Scale.</p>*<p>, % missing data: GOLD I 83%, GOLD II 28%.</p