Time to desaturation in the 6-min walking distance test predicts 24-hour oximetry in COPD patients with a PO2 between 60 and 70mmHg

SummaryBackgroundThe 6-min walking distance (6MWD) test is a useful tool for assessing patients with chronic obstructive pulmonary disease (COPD), but little is known about the changes in oxygen saturation that occur during the test.ObjectiveTo predict the oximetry profile during daily living activities by the time to desaturation in the 6MWD test in COPD-affected patients.Patients and methodsWe studied 67 COPD patients with moderate hypoxemia performing a 6MWD test and a 24-hour ambulatory pulse oximetry (24-hr PO). We determined the time to desaturation (SatO2⩽90%) in the 6MWD test, in the daytime, nighttime and 24-hr PO. We then estimated the time to desaturation that better predicts desaturation in diurnal, nocturnal and 24-hour oximetries using the ROC type II analysis.ResultsThe patients who desaturated after 3′30min have a 100% probability not to desaturate during diurnal, nocturnal and 24-hr PO. Those patients who desaturated during the first minute of the 6MWD test have a 74% probability to desaturate in these oximetries.ConclusionsThe time to desaturation in the 6MWD test can discriminate early desaturators who desaturate during their daily living activities and late desaturators who do not desaturate. Ambulatory oximetry would thus only be necessary in patients with a time to desaturation that ranges between 1 and 3′30″

Epicardial adipose tissue in patients with chronic obstructive pulmonary disease

EAT volume is increased in COPD patients and is independently associated with smoking history, BMI and exercise capacity, all modifiable risk factors of future cardiovascular events. EAT volume could be a non-invasive marker of COPD patients at high risk for future cardiovascular event

Sex differences in mortality in patients with COPD

Little is known about survival and clinical prognostic factors in females with chronic obstructive pulmonary disease (COPD). The aim of the present study was to determine the survival difference between males and females with COPD and to compare the value of the different prognostic factors for the disease. In total, 265 females and 272 males with COPD matched at baseline by BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) and American Thoracic Society/European Respiratory Society/Global Initiative of Chronic Obstructive Lung Disease criteria were prospectively followed. Demographics, lung function, St George’s Respiratory Questionnaire, BODE index, the components of the BODE index and comorbidity were determined. Survival was documented and sex differences were determined using Kaplan–Meier analysis. The strength of the association of the studied variables with mortality was determined using multivariate and receiver operating curves analysis. All-cause (40 versus 18%) and respiratory mortality (24 versus 10%) were higher in males than females. Multivariate analysis identified the BODE index in females and the BODE index and Charlson comorbidity score in males as the best predictors of mortality. The area under the curve of the BODE index was a better predictor of mortality than the forced expiratory volume in one second for both sexes. At similar chronic obstructive pulmonary disease severity by BODE index and forced expiratory volume in one second, females have significantly better survival than males. For both sexes the BODE index is a better predictor of survival than the forced expiratory volume in one second

Plasma metabolomics and clinical predictors of survival differences in COPD patients

Background: Plasma metabolomics profile (PMP) in COPD has been associated with clinical characteristics, but PMP’s relationship to survival has not been reported. We determined PMP differences between patients with COPD who died an average of 2 years after enrollment (Non-survivors, NS) compared to those who survived (S) and also with age matched controls (C). Methods: We studied prospectively 90 patients with severe COPD and 30 controls. NS were divided in discovery and validation cohorts (30 patients each) and the results compared to the PMP of 30 S and C. All participants completed lung function tests, dyspnea scores, quality of life, exercise capacity, BODE index, and plasma metabolomics by liquid and gas chromatography / mass spectometry (LC/MS, LC/MS2 , GC/MS). Statistically, we used Random Forest Analysis (RFA) and Support Vector Machine (SVM) to determine metabolites that differentiated the 3 groups and compared the ability of metabolites vs. clinical characteristics to classify patients into survivors and non-survivors. Results: There were 79 metabolites statistically different between S and NS [p < 0.05 and false discovery rate (q value) < 0.1]. RFA and SVM classification of COPD survivors and non-survivors had a predicted accuracy of 74 and 85% respectively. Elevation of tricyclic acid cycle intermediates branched amino acids depletion and increase in lactate, fructose and xylonate showed the most relevant differences between S vs. NS suggesting alteration in mitochondrial oxidative energy generation. PMP had similar predictive power for risk of death as information provided by clinical characteristics. Conclusions: A plasma metabolomic profile characterized by an oxidative energy production difference between survivors and non-survivors was observed in COPD patients 2 years before death

Chronic obstructive pulmonary disease (COPD) as a disease of early aging: evidence from the epiChron cohort

Background: Aging is an important risk factor for most chronic diseases. Patients with COPD develop more comorbidities than non-COPD subjects. We hypothesized that the development of comorbidities characteristically affecting the elderly occur at an earlier age in subjects with the diagnosis of COPD. Methods and findings: We included all subjects carrying the diagnosis of COPD (n = 27,617), and a similar number of age and sex matched individuals without the diagnosis, extracted from the 727,241 records of individuals 40 years and older included in the EpiChron Cohort (Aragon, Spain). We compared the cumulative number of comorbidities, their prevalence and the mortality risk between both groups. Using network analysis, we explored the connectivity between comorbidities and the most influential comorbidities in both groups. We divided the groups into 5 incremental age categories and compared their comorbidity networks. We then selected those comorbidities known to affect primarily the elderly and compared their prevalence across the 5 age groups. In addition, we replicated the analysis in the smokers' subgroup to correct for the confounding effect of cigarette smoking. Subjects with COPD had more comorbidities and died at a younger age compared to controls. Comparison of both cohorts across 5 incremental age groups showed that the number of comorbidities, the prevalence of diseases characteristic of aging and network's density for the COPD group aged 56-65 were similar to those of non-COPD 15 to 20 years older. The findings persisted after adjusting for smoking. Conclusion: Multimorbidity increases with age but in patients carrying the diagnosis of COPD, these comorbidities are seen at an earlier age

Somatotypes trajectories during adulthood and their association with COPD phenotypes

Rationale: Chronic obstructive pulmonary disease (COPD) comprises distinct phenotypes, all characterised by airflow limitation. Objectives: We hypothesised that somatotype changes – as a surrogate of adiposity – from early adulthood follow different trajectories to reach distinct phenotypes. Methods: Using the validated Stunkard’s Pictogram, 356 COPD patients chose the somatotype that best reflects their current body build and those at ages 18, 30, 40 and 50 years. An unbiased group-based trajectory modelling was used to determine somatotype trajectories. We then compared the current COPD-related clinical and phenotypic characteristics of subjects belonging to each trajectory. Measurements and main results: At 18 years of age, 88% of the participants described having a lean or medium somatotype (estimated body mass index (BMI) between 19 and 23 kg·m−2 ) while the other 12% a heavier somatotype (estimated BMI between 25 and 27 kg·m−2 ). From age 18 onwards, five distinct trajectories were observed. Four of them demonstrating a continuous increase in adiposity throughout adulthood with the exception of one, where the initial increase was followed by loss of adiposity after age 40. Patients with this trajectory were primarily females with low BMI and DLCO (diffusing capacity of the lung for carbon monoxide). A persistently lean trajectory was seen in 14% of the cohort. This group had significantly lower forced expiratory volume in 1 s (FEV1), DLCO, more emphysema and a worse BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) score thus resembling the multiple organ loss of tissue (MOLT) phenotype. Conclusions: COPD patients have distinct somatotype trajectories throughout adulthood. Those with the MOLT phenotype maintain a lean trajectory throughout life. Smoking subjects with this lean phenotype in early adulthood deserve particular attention as they seem to develop more severe COPD

Finding the best thresholds of FEV1 and dyspnea to predict 5-year survival in COPD patients: the COCOMICS study

BACKGROUND: FEV1 is universally used as a measure of severity in COPD. Current thresholds are based on expert opinion and not on evidence. OBJECTIVES: We aimed to identify the best FEV1 (% predicted) and dyspnea (mMRC) thresholds to predict 5-yr survival in COPD patients. DESIGN AND METHODS: We conducted a patient-based pooled analysis of eleven COPD Spanish cohorts (COCOMICS). Survival analysis, ROC curves, and C-statistics were used to identify and compare the best FEV1 (%) and mMRC scale thresholds that predict 5-yr survival. RESULTS: A total of 3,633 patients (93% men), totaling 15,878 person-yrs. were included, with a mean age 66.4 ± 9.7, and predicted FEV1 of 53.8% (± 19.4%). Overall 975 (28.1%) patients died at 5 years. The best thresholds that spirometrically split the COPD population were: mild ≥ 70%, moderate 56-69%, severe 36-55%, and very severe ≤ 35%. Survival at 5 years was 0.89 for patients with FEV1 ≥ 70 vs. 0.46 in patients with FEV1 ≤ 35% (H.R: 6; 95% C.I.: 4.69-7.74). The new classification predicts mortality significantly better than dyspnea (mMRC) or FEV1 GOLD and BODE cutoffs (all p<0.001). Prognostic reliability is maintained at 1, 3, 5, and 10 years. In younger patients, survival was similar for FEV1 (%) values between 70% and 100%, whereas in the elderly the relationship between FEV1 (%) and mortality was inversely linear. CONCLUSIONS: The best thresholds for 5-yr survival were obtained stratifying FEV1 (%) by ≥ 70%, 56-69%, 36-55%, and ≤ 35%. These cutoffs significantly better predict mortality than mMRC or FEV1 (%) GOLD and BODE cutoffs

Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2015 and GOLD 2019 staging: a pooled analysis of individual patient data

In 2019, The Global Initiative for Chronic Obstructive Lung Disease (GOLD) modified the grading system for patients with COPD, creating 16 subgroups (1A–4D). As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aim to compare the mortality prediction of the 2015 and 2019 COPD GOLD staging systems. We studied 17 139 COPD patients from the 3CIA study, selecting those with complete data. Patients were classified by the 2015 and 2019 GOLD ABCD systems, and we compared the predictive ability for 5-year mortality of both classifications. In total, 17 139 patients with COPD were enrolled in 22 cohorts from 11 countries between 2003 and 2017; 8823 of them had complete data and were analysed. Mean±sd age was 63.9±9.8 years and 62.9% were male. GOLD 2019 classified the patients in milder degrees of COPD. For both classifications, group D had higher mortality. 5-year mortality did not differ between groups B and C in GOLD 2015; in GOLD 2019, mortality was greater for group B than C. Patients classified as group A and B had better sensitivity and positive predictive value with the GOLD 2019 classification than GOLD 2015. GOLD 2015 had better sensitivity for group C and D than GOLD 2019. The area under the curve values for 5-year mortality were only 0.67 (95% CI 0.66–0.68) for GOLD 2015 and 0.65 (95% CI 0.63–0.66) for GOLD 2019