Rationale: Chronic obstructive pulmonary disease (COPD) is thought to result in rapid and progressive loss of lung function usually expressed as mean values for whole cohorts. Objectives: Longitudinal studies evaluating individual lung function loss and other domains of COPD progression are needed. Methods: We evaluated 1,198 stable, well-characterized patients with COPD (1,100 males) recruited in two centers (Florida and Tenerife, Spain) and annually monitored their multidomain progression from 1997 to 2009. Patients were followed for a median of 64 months and up to 10 years. Their individual FEV1 (L) and BODE index slopes, expressed as annual change, were evaluated using regression models for repeated measures. A total of 751 patients with at least three measurements were used for the analyses. Measurements and Main Results: Eighteen percent of patients had a statistically significant FEV1 slope decline (−86 ml/yr; 95% confidence interval [CI], −32 to −278 ml/yr). Higher baseline FEV1 (relative risk, 1.857; 95% CI, 1.322–2.610; P < 0.001) and low body mass index (relative risk, 1.071; 95% CI, 1.035–1.106; P < 0.001) were independently associated with FEV1 decline. The BODE index had a statistically significant increase (0.55, 0.20–1.37 point/yr) in only 14% of patients and these had more severe baseline obstruction. Concordance between FEV1 and BODE change was low (κ Cohen, 16%). Interestingly, 73% of patients had no significant slope change in FEV1 or BODE. Only the BODE change was associated with mortality in patients without FEV1 progression. Conclusions: The progression of COPD is very heterogeneous. Most patients show no statistically significant decline of FEV1 or increase in BODE. The multidimensional evaluation of COPD should offer insight into response to COPD management.

The impact of blood eosinophilia in chronic obstructive pulmonary disease (COPD) remains controversial.To evaluate the prevalence and stability of a high level of blood eosinophils (≥300 cells·μL^–1) and its relationship to outcomes, we determined blood eosinophils at baseline and over 2 years in 424 COPD patients (forced expiratory volume in 1 s (FEV₁) 60% predicted) and 67 smokers without COPD from the CHAIN cohort, and in 308 COPD patients (FEV₁60% predicted) in the BODE cohort. We related eosinophil levels to exacerbations and survival using Cox hazard analysis.In COPD patients, 15.8% in the CHAIN cohort and 12.3% in the BODE cohort had persistently elevated blood eosinophils at all three visits. A significant proportion (43.8%) of patients had counts that oscillated above and below the cut-off points, while the rest had persistent eosinophil levels <300 cells·μL^–1. A similar eosinophil blood pattern was observed in controls. Exacerbation rates did not differ in patients with and without eosinophilia. All-cause mortality was lower in patients with high eosinophils compared with those with values <300 cells·μL^–1(15.8%versus33.7%; p=0.026).In patients with COPD, blood eosinophils ≥300 cells·μL^–1persisting over 2 years was not a risk factor for COPD exacerbations. High eosinophil count was associated with better survival.

Rationale: Microalbuminuria (MAB), a marker of endovascular dysfunction, is a predictor of cardiovascular events and all-cause mortality in the general population. There is evidence of vascular dysfunction in patients with chronic obstructive pulmonary disease (COPD). Objectives: To assess the prevalence and relationship of MAB with clinical and physiological parameters in stable patients with COPD. Methods: We measured urinary albumin rate (urinary albumin to creatinine ratio: UACR), smoking history, arterial blood pressure, gas exchange, body mass index, lung function, BODE index (body mass index, airflow obstruction, dyspnea, exercise performance), and comorbidity index in 129 patients with stable COPD and 51 smokers with normal spirometry without known cardiovascular disease. MAB levels were compared between groups. A multivariate analysis was performed to determine the best determinants of MAB levels. Measurements and Main Results: MAB was higher in patients with COPD than in control smokers (8 [5th−95th percentile (P5–95), 2.9–113] vs. 4.2 [P5–95, 1.8–22.7] mg/g, P < 0.001]). The difference remained significant even after using the standard pathologic threshold (MAB, 30–299 mg/g in women and 20–299 mg/g in men; 24% in patients with COPD vs. 6% in control smokers; P = 0.005). In patients with COPD, there was a negative correlation between PaO2 and MAB (r = −0.40, P < 0.001). Using multivariate analysis, MAB was only associated with the PaO2 (relative risk, 0.934; 95% confidence interval, 0.880–0.992; P < 0.001) and with the systolic arterial blood pressure (relative risk, 1.034; 95% confidence interval, 1.011–1.057; P = 0.003). Conclusions: MAB is frequent in patients with COPD and is associated with hypoxemia independent of other cardiovascular risk factors. Further studies are necessary to investigate whether MAB could be an early simple biomarker of cardiovascular compromise in patients with COPD.

The relationship between serum biomarkers and clinical expressions of COPD is limited. We planned to further describe this association using markers of inflammation and injury and repair.

Rationale: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) document has modified the grading system directing pharmacotherapy, but how this relates to the previous one from 2015 and to comorbidities, hospitalizations, and mortality risk is unknown. Objectives: The aim of this study was to evaluate the changes in the GOLD groups from 2015 to 2017 and to assess the impact on severity, comorbidities, and mortality within each group. Methods: We prospectively enrolled and followed, for a mean of 5 years, 819 patients with chronic obstructive pulmonary disease (84% male) in clinics in Spain and the United States. We determined anthropometrics, lung function (FEV1%), dyspnea score (modified Medical Research Council scale), ambulatory and hospital exacerbations, and the body mass index, obstruction, dyspnea, and exercise capacity (BODE) and Charlson indexes. We classified patients by the 2015 and 2017 GOLD ABCD system, and compared the differential realignment of the same patients. We related the effect of the reclassification in BODE and Charlson distribution as well as chronic obstructive pulmonary disease and all-cause mortality between the two classifications. Measurements and Main Results: Compared with 2015, the 2017 grading decreased by half the proportion of patients in groups C and D (20.5% vs. 11.2% and 24.6% vs. 12.9%; P < 0.001). The distribution of Charlson also changed, whereas group D was higher than B in 2015, they become similar in the 2017 system. In 2017, the BODE index and risk of death were higher in B and D than in A and C. The mortality risk was better predicted by the 2015 than the 2017 system. Conclusions: Compared with 2015, the GOLD ABCD 2017 classification significantly shifts patients from grades C and D to categories A and B. The new grading system equalizes the Charlson comorbidity score in all groups and minimizes the differences in BODE between groups B and D, making the risk of death similar between them.