Ables were submitted to multiple correspondence analyses (MCA) to transform them into independent mathematical axes. This latter procedure allowed using in a single cluster analysis (Ward’s procedure) the significant axes identified in the MCA and the significant component identified by PCA. A description of these procedures is presented in Text S1.Processing of Continuous and Categorical VariablesSeven continuous variables were selected for their relevance to COPD natural history: age, body mass index (BMI), FEV1 ( predicted), mMRC scale, CCQ total score, thoracic gas volume (TGV, predicted) and DLCO ( predicted). Subjects with complete data for these 7 variables were submitted to PCA. The first two axes identified in the PCA had eigenvalues .1 and were kept for cluster analysis (Table S4 and S5). All categorical variables available were submitted to MCA. The variables included in these analyses were comorbidities, and data obtained from CT analysis, including emphysema, bronchial thickening 
and bronchiectasis. MCA identified 17 axes of which 3 were excluded because they happened to be correlated mostly with missing information on comorbidities (Table S6 and S7). Thus, we were able to exclude these 3 axes without losing significant information and only 14 axes were kept for cluster analysis.Identification of COPD Phenotypes using Cluster Analysis and Mortality RatesWe performed 
a Ward’s cluster analysis based on the significant mathematical axes identified by PCA and MCA for continuous and categorical variables, respectively. Classification of the 527 COPD SRIF-14 site patients resulted in a dendrogram showing the progressive joining of the clustering process (Figure 2). Based on visual assessment of the dendrogram, data could be optimally grouped into 3 or 5 clusters, each cluster corresponding to a potential phenotype. To decide on the number of phenotypes, we examined mortality rates among clusters. When grouping the data into 3 clusters, there was a clear difference in mortality rates among clusters (Table 2 and Figure 2). Grouping the data into 5 clusters did not improve the ability to predict mortality because this only resulted in the division of clusters 1 and 3 into two new clusters (for each), but mortality was comparable in these newly formed clusters (Figure 2).Vital Status and Survival AnalysesVital status was assessed as per January 1st 2010. For patients followed at the University hospital, mortality data were obtained from medical files. When no data on mortality was retrieved, general practitioners (GP’s) caring for the patient were contacted to check survival. For subjects from the NELSON study, survival was checked by direct telephone contact with GP’s. Subjects who were lost to follow-up (n = 8) were not included in the survival analysis because no information was available on their vital status. Additionally the exact date of death was unavailable in 8 subjects who died during 23388095 follow-up. Thus, the survival analyses were performed in 511/527 (97 ) subjects. Survival analyses were performed on all-cause mortality using Kaplan-Meier and log-rank tests with Tukey-Kramer adjustments for multiple comparisons. Because age was markedly I-BRD9 site different among Phenotypes, we further studied mortality risk using a Cox model adjusted for age.Characterization of COPD PhenotypesCharacteristics of subjects grouped into 3 clusters (phenotypes) are 23115181 presented in Table 2. Phenotype 1 (n = 219 subjects) corresponded to subjects with a median [IQR] ag.Ables were submitted to multiple correspondence analyses (MCA) to transform them into independent mathematical axes. This latter procedure allowed using in a single cluster analysis (Ward’s procedure) the significant axes identified in the MCA and the significant component identified by PCA. A description of these procedures is presented in Text S1.Processing of Continuous and Categorical VariablesSeven continuous variables were selected for their relevance to COPD natural history: age, body mass index (BMI), FEV1 ( predicted), mMRC scale, CCQ total score, thoracic gas volume (TGV, predicted) and DLCO ( predicted). Subjects with complete data for these 7 variables were submitted to PCA. The first two axes identified in the PCA had eigenvalues .1 and were kept for cluster analysis (Table S4 and S5). All categorical variables available were submitted to MCA. The variables included in these analyses were comorbidities, and data obtained from CT analysis, including emphysema, bronchial thickening and bronchiectasis. MCA identified 17 axes of which 3 were excluded because they happened to be correlated mostly with missing information on comorbidities (Table S6 and S7). Thus, we were able to exclude these 3 axes without losing significant information and only 14 axes were kept for cluster analysis.Identification of COPD Phenotypes using Cluster Analysis and Mortality RatesWe performed a Ward’s cluster analysis based on the significant mathematical axes identified by PCA and MCA for continuous and categorical variables, respectively. Classification of the 527 COPD patients resulted in a dendrogram showing the progressive joining of the clustering process (Figure 2). Based on visual assessment of the dendrogram, data could be optimally grouped into 3 or 5 clusters, each cluster corresponding to a potential phenotype. To decide on the number of phenotypes, we examined mortality rates among clusters. When grouping the data into 3 clusters, there was a clear difference in mortality rates among clusters (Table 2 and Figure 2). Grouping the data into 5 clusters did not improve the ability to predict mortality because this only resulted in the division of clusters 1 and 3 into two new clusters (for each), but mortality was comparable in these newly formed clusters (Figure 2).Vital Status and Survival AnalysesVital status was assessed as per January 1st 2010. For patients followed at the University hospital, mortality data were obtained from medical files. When no data on mortality was retrieved, general practitioners (GP’s) caring for the patient were contacted to check survival. For subjects from the NELSON study, survival was checked by direct telephone contact with GP’s. Subjects who were lost to follow-up (n = 8) were not included in the survival analysis because no information was available on their vital status. Additionally the exact date of death was unavailable in 8 subjects who died during 23388095 follow-up. Thus, the survival analyses were performed in 511/527 (97 ) subjects. Survival analyses were performed on all-cause mortality using Kaplan-Meier and log-rank tests with Tukey-Kramer adjustments for multiple comparisons. Because age was markedly different among Phenotypes, we further studied mortality risk using a Cox model adjusted for age.Characterization of COPD PhenotypesCharacteristics of subjects grouped into 3 clusters (phenotypes) are 23115181 presented in Table 2. Phenotype 1 (n = 219 subjects) corresponded to subjects with a median [IQR] ag.