COPD Clinical Control : predictors and long-term follow-up of the CHAIN cohort

Control in COPD is a dynamic concept that can reflect changes in patients' clinical status that may have prognostic implications, but there is no information about changes in control status and its long-term consequences. We classified 798 patients with COPD from the CHAIN cohort as controlled/uncontrolled at baseline and over 5 years. We describe the changes in control status in patients over long-term follow-up and analyze the factors that were associated with longitudinal control patterns and related survival using the Cox hazard analysis. 134 patients (16.8%) were considered persistently controlled, 248 (31.1%) persistently uncontrolled and 416 (52.1%) changed control status during follow-up. The variables significantly associated with persistent control were not requiring triple therapy at baseline and having a better quality of life. Annual changes in outcomes (health status, psychological status, airflow limitation) did not differ in patients, regardless of clinical control status. All-cause mortality was lower in persistently controlled patients (5.5% versus 19.1%, p = 0.001). The hazard ratio for all-cause mortality was 2.274 (95% CI 1.394-3.708; p = 0.001). Regarding pharmacological treatment, triple inhaled therapy was the most common option in persistently uncontrolled patients (72.2%). Patients with persistent disease control more frequently used bronchodilators for monotherapy (53%) at recruitment, although by the end of the follow-up period, 20% had scaled up their treatment, with triple therapy being the most frequent therapeutic pattern. The evaluation of COPD control status provides relevant prognostic information on survival. There is important variability in clinical control status and only a small proportion of the patients had persistently good control. Changes in the treatment pattern may be relevant in the longitudinal pattern of COPD clinical control. Further studies in other populations should validate our results. Trial registration: Clinical Trials.gov: identifier NCT01122758

New GOLD classification: longitudinal data on group assignment

Rationale: Little is known about the longitudinal changes associated with using the 2013 update of the multidimensional GOLD strategy for chronic obstructive pulmonary disease (COPD). Objective: To determine the COPD patient distribution of the new GOLD proposal and evaluate how this classification changes over one year compared with the previous GOLD staging based on spirometry only. Methods: We analyzed data from the CHAIN study, a multicenter observational Spanish cohort of COPD patients who are monitored annually. Categories were defined according to the proposed GOLD: FEV1%, mMRC dyspnea, COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and exacerbations-hospitalizations. One-year follow-up information was available for all variables except CCQ data. Results: At baseline, 828 stable COPD patients were evaluated. On the basis of mMRC dyspnea versus CAT, the patients were distributed as follows: 38.2% vs. 27.2% in group A, 17.6% vs. 28.3% in group B, 15.8% vs. 12.9% in group C, and 28.4% vs. 31.6% in group D. Information was available for 526 patients at one year: 64.2% of patients remained in the same group but groups C and D show different degrees of variability. The annual progression by group was mainly associated with one-year changes in CAT scores (RR, 1.138; 95%CI: 1.074-1.206) and BODE index values (RR, 2.012; 95%CI: 1.487-2.722). Conclusions: In the new GOLD grading classification, the type of tool used to determine the level of symptoms can substantially alter the group assignment. A change in category after one year was associated with longitudinal changes in the CAT and BODE index

New GOLD classification: longitudinal data on group assignment

In the new GOLD grading classification, the type of tool used to determine the level of symptoms can substantially alter the group assignment. A change in category after one year was associated with longitudinal changes in the CAT and BODE index

Metallomic signatures of lung cancer and chronic obstructive pulmonary disease

Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC.Funding: This work has been supported by the project “Heteroatom-tagged proteomics and metabolomics to study lung cancer. Influence of gut microbiota” (Ref.: PY20_00366) (Project of Excellence, Regional Ministry of Economy, Knowledge, Business and University, Andalusia, Spain). The authors are also grateful for grants 651/2018 and 115/2020 from the Spanish Society of Pneumology and Surgery (SEPAR) and grant 08/2018 from the Association of Pneumology and Thoracic Surgery (Neumosur), which were used to facilitate recruitment at the hospitals and biobank registration. The authors also thank Instituto de Salud Carlos III (AES16/01783) and wish to express their gratitude for the unrestricted funding from the Menarini Group and AstraZeneca. Acknowledgments: We thank all the patients who volunteered and donated their biomaterials for the study

Clinical and prognostic impact of low diffusing capacity for carbon monoxide values in patients with global initiative for obstructive lung disease I COPD

Background The Global Initiative for Obstructive Lung Disease (GOLD) does not promote diffusing capacity for carbon monoxide (Dlco) values in the evaluation of COPD. In GOLD spirometric stage I COPD patients, the clinical and prognostic impact of a low Dlco has not been explored. Research Question Could a Dlco threshold help define an increased risk of death and a different clinical presentation in these patients? Study Design and Methods GOLD stage I COPD patients (n = 360) were enrolled and followed over 109 ± 50 months. Age, sex, pack-years’ history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, and history of exacerbations were recorded. A cutoff value for Dlco was identified for all-cause mortality and the clinical and physiological characteristics of patients above and below the threshold compared. Cox regression analysis explored the predictive power of that cutoff value for all-cause mortality. Results A Dlco cutoff value of <60% predicted was associated with all-cause mortality (Dlco ≥ 60%: 9% vs Dlco < 60%: 23%, P = .01). At a same FEV1% predicted and Charlson score, patients with Dlco < 60% had lower BMI, more dyspnea, lower inspiratory capacity (IC)/total lung capacity (TLC) ratio, lower 6-min walk distance (6MWD), and higher BODE. Cox multiple regression analysis confirmed that after adjusting for age, sex, pack-years history, smoking status, and BMI, a Dlco < 60% is associated with all-cause mortality (hazard ratio [HR], 95% CI = 3.37, 1.35-8.39; P = .009) Interpretation In GOLD I COPD patients, a Dlco < 60% predicted is associated with increased risk of death and worse clinical presentation. What the cause(s) of this association are and whether they can be treated need to be determined

Metallomic Signatures of Lung Cancer and Chronic Obstructive Pulmonary Disease

Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC

Clinical Application of the COPD Assessment Test: Longitudinal Data From the COPD History Assessment in Spain (CHAIN) Cohort

OBJECTIVE: The COPD Assessment Test (CAT) has been proposed for assessing health status in COPD, but little is known about its longitudinal changes. The objective of this study was to evaluate 1-year CAT variability in patients with stable COPD and to relate its variations to changes in other disease markers. METHODS: We evaluated the following variables in smokers with and without COPD at baseline and aft er 1 year: CAT score, age, sex, smoking status, pack-year history, BMI, modified Medical Research Council (mMRC) scale, 6-min walk distance (6MWD), lung function, BODE (BMI, obstruction, dyspnea, exercise capacity) index, hospital admissions, Hospital and Depression Scale, and the Charlson comorbidity index. In patients with COPD, we explored the association of CAT scores and 1-year changes in the studied parameters. R ESULTS: A total of 824 smokers with COPD and 126 without COPD were evaluated at baseline and 441 smokers with COPD and 66 without COPD 1 year later. At 1 year, CAT scores for patients with COPD were similar ( ± 4 points) in 56%, higher in 27%, and lower in 17%. Of note, mMRC scale scores were similar ( ± 1 point) in 46% of patients, worse in 36%, and better in 18% at 1 year. One-year CAT changes were best predicted by changes in mMRC scale scores ( β -coefficient, 0.47; P<, .001). Similar results were found for CAT and mMRC scale score in smokers without COPD. CONCLUSIONS: One-year longitudinal data show variability in CAT scores among patients with stable COPD similar to mMRC scale score, which is the best predictor of 1-year CAT changes. Further longitudinal studies should confirm long-term CAT variability and its clinical applicability. © 2014 AMERICAN COLLEGE OF CHEST PHYSICIANS.The authors have reported to CHEST the follow ing conflicts of interest: Dr de Torres received fees for speaking activities for GlaxoSmithKline plc, AstraZeneca, Novartis AG, Merck Sharp & Dohme Corp, and Takeda Pharmaceuticals International GmbH and received consultancy fees for participating on advisory boards for Takeda Pharmaceuticals International GmbH and Novartis AG between 2010 and 2013. Dr Martinez-Gonzalez received fees for speaking activities for Almirall, SA; AstraZeneca; Boehringer Ingelheim GmbH; Pfi zer Inc; GlaxoSmithKline plc; and Chiesi Farmaceutici SpA between 2010 and 2013. Dr de Lucas-Ramos received fees for speaking activities for Almirall, SA; Boehringer Ingelheim GmbH; Takeda Pharmaceuticals International GmbH; and GlaxoSmithKline plc and received grants from Almirall, SA, and Foundation Vital Aire between 2010 and 2013. Dr Cosio received fees for speaking activities for Almirall, SA; Takeda Pharmaceuticals International GmbH; The Menarini Group; Boehringer Ingelheim GmbH; Pfizer Inc; GlaxoSmithKline plc; and Chiesi Farmaceutici SpA between 2010 and 2013. Dr Peces-Barba received fees for speaking activities for Almirall, SA; Takeda Pharmaceuticals International GmbH; Novartis AG; Boehringer Ingelheim GmbH; AstraZeneca; Esteve; GlaxoSmithKline plc, and Chiesi Farmaceutici SpA; received consultancy fees for participating in advisory boards of Takeda Pharmaceuticals International GmbH, Novartis AG, and Ferrer Internacional; and received grants from GlaxoSmithKline plc between 2010 and 2013. Dr Solanes-García received fees for speaking activities for Esteve; AstraZeneca; Th e Menarini Group; Boehringer Ingelheim GmbH; Pfizer Inc; GlaxoSmithKline plc, Biodatos Investigación SL, and Chiesi Farmaceutici SpA between 2010 and 2013. Dr Agüero Balbin received fees for speaking activities for Almirall, SA; AstraZeneca; Novartis AG; Boehringer Ingelheim GmbH; Takeda Pharmaceuticals International GmbH; GlaxoSmithKline plc; and Chiesi Farmaceutici SpA between 2010 and 2013. Dr de Diego-Damia received fees for speaking activities for Boehringer Ingelheim GmbH, AstraZeneca, Pfizer Inc, Merck Sharp & Dohme Corp, GlaxoSmithKline plc, and Chiesi Farmaceutici SpA between 2010 and 2013. Dr Alfageme Michavila received fees for speaking activities for Almirall, SA; Boehringer Ingelheim GmbH; and Pfizer Inc between 2010 and 2013. Dr Irigaray received fees for speaking activities for Novartis AG, Takeda Pharmaceuticals International GmbH, GlaxoSmithKline plc, and Chiesi Farmaceutici SpA between 2010 and 2013. Dr Llunell Casanovas received fees for speaking activities for AstraZeneca, Eli Lilly and Co, and Chiesi Farmaceutici SpA between 2010 and 2013. Dr Galdiz Iturri received fees for speaking activities for Almirall, SA; Novartis AG; AstraZeneca; Boehringer Ingelheim GmbH; GlaxoSmithKline plc; and Chiesi Farmaceutici SpA between 2010 and 2013. Dr Soler-Cataluña participated in speaking activities, on an industry advisory committee, or with other related activities sponsored by Almirall, SA; AstraZeneca; Boehringer Ingelheim GmbH; Pfizer Inc; Ferrer Internacional; GlaxoSmithKline plc; Takeda Pharmaceuticals International GmbH; Merck Sharp & Dohme Corp; Novartis AG; and Grupo Uriach between 2010 and 2013. Dr Soriano received grants from GlaxoSmithKline plc in 2011 and Chiesi Farmaceutici SpA in 2012 through his home institution and participated in speaking activities, on an industry advisory committee, or with other related activities sponsored by Almirall, SA; Boehringer Ingelheim GmbH; Pfizer Inc; Chiesi Farmaceutici SpA; GlaxoSmithKline plc; and Novartis AG between 2010 and 2013. Dr Casanova participated in speaking activities for Almirall, SA; Takeda Pharmaceuticals International GmbH; Chiesi Farmaceutici SpA; GlaxoSmithKline plc; and Novartis AG between 2010 and 2013. Drs Marin, Mir-Viladrich, CalleRubio, Feu-Collado, Balcells, Marín Royo, and Lopez-Campos have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article

Impact of applying the global lung initiative criteria for airway obstruction in GOLD defined COPD cohorts: the BODE and CHAIN experience

Introduction: The Global Lung Function Initiative (GLI) has proposed new criteria for airflow limitation (AL) and recommends using these to interpret spirometry. The objective of this study was to explore the impact of the application of the AL GLI criteria in two well characterized GOLD-defined COPD cohorts. Methods: COPD patients from the BODE (n=360) and the COPD History Assessment In SpaiN (CHAIN) cohorts (n=722) were enrolled and followed. Age, gender, pack-years history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, history of exacerbations and survival were recorded. CT-detected comorbidities were registered in the BODE cohort. The proportion of subjects without AL by GLI criteria was determined in each cohort. The clinical, CT-detected comorbidity, and overall survival of these patients were evaluated. Results: In total, 18% of the BODE and 15% of the CHAIN cohort did not meet GLI AL criteria. In the BODE and CHAIN cohorts respectively, these patients had a high clinical burden (BODE≥3: 9% and 20%; mMRC≥2: 16% and 45%; exacerbations in the previous year: 31% and 9%; 6MWD<350m: 15% and 19%, respectively), and a similar prevalence of CT-diagnosed comorbidities compared with those with GLI AL. They also had a higher rate of long-term mortality - 33% and 22% respectively. Conclusions: An important proportion of patients from 2 GOLD-defined COPD cohorts did not meet GLI AL criteria at enrolment, although they had a significant burden of disease. Caution must be taken when applying the GLI AL criteria in clinical practice