Rationale: Patients with chronic obstructive pulmonary disease (COPD) are afflicted by comorbidities. Few studies have prospectively evaluated COPD comorbidities and mortality risk. Objectives: To prospectively evaluate COPD comorbidities and mortality risk. Methods: We followed 1,664 patients with COPD in five centers for a median of 51 months. Systematically, 79 comorbidities were recorded. We calculated mortality risk using Cox proportional hazard, and developed a graphic representation of the prevalence and strength of association to mortality in the form of a “comorbidome.” A COPD comorbidity index (COPD specific comorbidity test [COTE]) was constructed based on the comorbidities that increase mortality risk using a multivariate analysis. We tested the COTE index as predictor of mortality and explored whether the COTE index added predictive information when used with the validated BODE index. Measurements and Main Results: Fifteen of 79 comorbidities differed in prevalence between survivors and nonsurvivors. Of those, 12 predicted mortality and were integrated into the COTE index. Increases in the COTE index were associated with an increased risk of death from COPD-related (hazard ratio [HR], 1.13; 95% confidence interval, 1.08–1.18; P < 0.001) and non–COPD-related causes (HR, 1.18; 95% confidence interval, 1.15–1.21; P < 0.001). Further, increases in the BODE and COTE were independently associated with increased risk of death. A COTE score of greater than or equal to 4 points increased by 2.2-fold the risk of death (HR, 2.26–2.68; P < 0.001) in all BODE quartile. Conclusions: Comorbidities are frequent in COPD and 12 of them negatively influence survival. A simple disease-specific comorbidities index (COTE) helps assess mortality risk in patients with COPD.

The 6-min walk distance (6MWD) predicted values have been derived from small cohorts mostly from single countries. The aim of the present study was to investigate differences between countries and identify new reference values to improve 6MWD interpretation.We studied 444 subjects (238 males) from seven countries (10 centres) ranging 40–80 yrs of age. We measured 6MWD, height, weight, spirometry, heart rate (HR), maximum HR (HR_max) during the 6-min walk test/the predicted maximum HR (HR_max% pred), Borg dyspnoea score and oxygen saturation.The mean±sd6MWD was 571±90 m (range 380–782 m). Males walked 30 m more than females (p<0.001). A multiple regression model for the 6MWD included age, sex, height, weight and HR_max% pred (adjusted r²= 0.38; p<0.001), but there was variability across centres (adjusted r²= 0.09–0.73) and its routine use is not recommended. Age had a great impact in 6MWD independent of the centres, declining significantly in the older population (p<0.001). Age-specific reference standards of 6MWD were constructed for male and female adults.In healthy subjects, there were geographic variations in 6MWD and caution must be taken when using existing predictive equations. The present study provides new 6MWD standard curves that could be useful in the care of adult patients with chronic diseases.

Static lung hyperinflation has important clinical consequences in patients with chronic obstructive pulmonary disease. We analyzed the power of lung hyperinflation as measured by the inspiratory capacity–to-total lung capacity ratio (IC/TLC) to predict mortality in a cohort of 689 patients with chronic obstructive pulmonary disease (95% males; FEV1, 1.17 L) with a mean follow-up of 34 months. We also compared the predictive value of IC/TLC with that of the BODE (body mass index, airflow obstruction, dyspnea, exercise performance) Index. Subjects who died (183; 27%) were older; had lower body mass index, FEV1, and IC/TLC ratio; walked less in the 6-minute walking distance; and had more dyspnea, a higher BODE Index, and comorbidity (p < 0.001). On the basis of logistic regression analysis, IC/TLC was found to be a good and independent predictor of all-cause and respiratory mortality. On the basis of receiver operating characteristic Type II curves, IC/TLC compared favorably with FEV1 and predicted mortality independently of the BODE Index. We conclude that IC/TLC is an independent risk factor for mortality in subjects with chronic obstructive pulmonary disease. We propose that this ratio be considered in the assessment of patients with chronic obstructive pulmonary disease.

Rationale: Little is known about the clinical factors associated with the development of lung cancer in patients with chronic obstructive pulmonary disease (COPD), although airway obstruction and emphysema have been identified as possible risk factors. Objectives: To explore incidence, histologic type, and factors associated with development of lung cancer diagnosis in a cohort of outpatients with COPD attending a pulmonary clinic. Methods: A cohort of 2,507 patients without initial clinical or radiologic evidence of lung cancer was followed a median of 60 months (30–90). At baseline, anthropometrics, smoking history, lung function, and body composition were recorded. Time to diagnosis and histologic type of lung cancer was then registered. Cox analysis was used to explore factors associated with lung cancer diagnosis. Measurements and Main Results: A total of 215 of the 2,507 patients with COPD developed lung cancer (incidence density of 16.7 cases per 1,000 person-years). The most frequent type was squamous cell carcinoma (44%). Lung cancer incidence was lower in patients with worse severity of airflow obstruction. Global Initiative for Chronic Obstructive Lung Disease Stages I and II, older age, lower body mass index, and lung diffusion capacity of carbon monoxide less than 80% were associated with lung cancer diagnosis. Conclusions: Incidence density of lung cancer is high in outpatients with COPD and occurs more frequently in older patients with milder airflow obstruction (Global Initiative for Chronic Obstructive Lung Disease Stages I and II) and lower body mass index. A lung diffusion capacity of carbon monoxide less than 80% is associated with cancer diagnosis. Squamous cell carcinoma is the most frequent histologic type. Knowledge of these factors may help direct efforts for early detection of lung cancer and disease management.